Alzheimer's Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

ALZHEIMER’S DISEASE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES ...

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ALZHEIMER’S DISEASE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Alzheimer’s Disease: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83691-4 1. Alzheimer’s Disease-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on Alzheimer’s disease. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON ALZHEIMER’S DISEASE ............................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Alzheimer’s Disease ...................................................................... 8 E-Journals: PubMed Central ....................................................................................................... 66 The National Library of Medicine: PubMed ................................................................................ 71 CHAPTER 2. NUTRITION AND ALZHEIMER’S DISEASE ................................................................. 159 Overview.................................................................................................................................... 159 Finding Nutrition Studies on Alzheimer’s Disease ................................................................... 159 Federal Resources on Nutrition ................................................................................................. 176 Additional Web Resources ......................................................................................................... 177 CHAPTER 3. ALTERNATIVE MEDICINE AND ALZHEIMER’S DISEASE ........................................... 181 Overview.................................................................................................................................... 181 National Center for Complementary and Alternative Medicine................................................ 181 Additional Web Resources ......................................................................................................... 198 General References ..................................................................................................................... 203 CHAPTER 4. DISSERTATIONS ON ALZHEIMER’S DISEASE ............................................................. 205 Overview.................................................................................................................................... 205 Dissertations on Alzheimer’s Disease........................................................................................ 205 Keeping Current ........................................................................................................................ 218 CHAPTER 5. CLINICAL TRIALS AND ALZHEIMER’S DISEASE ........................................................ 219 Overview.................................................................................................................................... 219 Recent Trials on Alzheimer’s Disease........................................................................................ 219 Keeping Current on Clinical Trials ........................................................................................... 231 CHAPTER 6. PATENTS ON ALZHEIMER’S DISEASE ........................................................................ 233 Overview.................................................................................................................................... 233 Patents on Alzheimer’s Disease ................................................................................................. 233 Patent Applications on Alzheimer’s Disease ............................................................................. 240 Keeping Current ........................................................................................................................ 241 CHAPTER 7. BOOKS ON ALZHEIMER’S DISEASE............................................................................ 243 Overview.................................................................................................................................... 243 Book Summaries: Federal Agencies............................................................................................ 243 Book Summaries: Online Booksellers......................................................................................... 247 The National Library of Medicine Book Index ........................................................................... 261 Chapters on Alzheimer’s Disease ............................................................................................... 263 Directories.................................................................................................................................. 265 CHAPTER 8. MULTIMEDIA ON ALZHEIMER’S DISEASE ................................................................. 267 Overview.................................................................................................................................... 267 Video Recordings ....................................................................................................................... 267 Bibliography: Multimedia on Alzheimer’s Disease.................................................................... 268 CHAPTER 9. PERIODICALS AND NEWS ON ALZHEIMER’S DISEASE .............................................. 271 Overview.................................................................................................................................... 271 News Services and Press Releases.............................................................................................. 271 Newsletter Articles .................................................................................................................... 275 Academic Periodicals covering Alzheimer’s Disease ................................................................. 276 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 277 Overview.................................................................................................................................... 277 U.S. Pharmacopeia..................................................................................................................... 277 Commercial Databases ............................................................................................................... 279 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 283

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Overview.................................................................................................................................... 283 NIH Guidelines.......................................................................................................................... 283 NIH Databases........................................................................................................................... 285 Other Commercial Databases..................................................................................................... 289 The Genome Project and Alzheimer’s Disease ........................................................................... 289 APPENDIX B. PATIENT RESOURCES ............................................................................................... 295 Overview.................................................................................................................................... 295 Patient Guideline Sources.......................................................................................................... 295 Finding Associations.................................................................................................................. 307 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 309 Overview.................................................................................................................................... 309 Preparation................................................................................................................................. 309 Finding a Local Medical Library................................................................................................ 309 Medical Libraries in the U.S. and Canada ................................................................................. 309 ONLINE GLOSSARIES................................................................................................................ 315 Online Dictionary Directories ................................................................................................... 317 ALZHEIMER’S DISEASE DICTIONARY ................................................................................ 319 INDEX .............................................................................................................................................. 393

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with Alzheimer’s disease is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about Alzheimer’s disease, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to Alzheimer’s disease, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on Alzheimer’s disease. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to Alzheimer’s disease, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on Alzheimer’s disease. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON ALZHEIMER’S DISEASE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Alzheimer’s disease.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and Alzheimer’s disease, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “Alzheimer’s disease” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Acetyl L-Carnitine Slows Decline in Younger Patients With Alzheimer's Disease: a Reanalysis of a Double-Blind, Placebo-Controlled Study Using the Source: International Psychogeriatrics. 10(2): 193-203. June 1998. Summary: This article assesses the longitudinal effects of acetyl-L-carnitine (ALC) on patients diagnosed with Alzheimer's disease (AD). Researchers studied 334 diagnosed subjects from 24 sites across the United States by administering the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) every 3 months for 1 year. Data showed that both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS. Analysis revealed a statistically significant Age x Drug interaction characterized by younger subjects benefiting more from ALC treatment than older subjects. Further analyses suggested that the optimal, though not statistically significant,

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cutoff point for ALC benefits was age 61. The authors concluded that ALC slows the progression of AD in younger subjects, and the use of a trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials. 3 figures, 3 tables, 20 references. •

Extrapyramidal Side Effects in Patients With Alzheimer's Disease Treated With LowDose Neuroleptic Medication Source: American Journal of Geriatric Psychiatry. 6(1): 75-82. Winter 1998. Summary: This article describes a study to determine whether extrapyramidal motor function, measured before the start of neuroleptic treatment, could be used to predict the development and severity of neuroleptic-induced parkinsonism (NIP) in patients with Alzheimer's disease (AD). Twenty-four community-dwelling patients with AD, mean age 75.1 years, were recruited from the Geropsychiatry Clinical Research Center at the University of California, San Diego. Sixteen patients were treated with haloperidol and eight with thioridazine, at dosages determined by their primary physicians. They were assessed before treatment and after 3 months and 9 months of treatment. Pretreatment extrapyramidal motor function and NIP were assessed with a modified version of the Simpson-Angus Rating Scale for Extrapyramidal Side Effects (SAS). Postural tremor, rigidity, and bradykinesia also were quantified with instrument-based measures. Sixteen patients (66.7 percent) developed NIP at some point during the 9month followup. These patients exhibited more severe pretreatment bradykinesia on instrument-based measures, but not on the SAS, than patients who did not develop NIP. The authors conclude that instrumented measures of pretreatment motor function may be useful for identifying patients at greater risk for NIP. 1 figure, 1 table, 21 references.

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The Contribution of Gaetano Perusini to the Definition of Alzheimer's Disease Source: Italian Journal of Nerological Sciences. 19: 49-52. 1998. Summary: This article discusses Gaetano Perusini's contribution to the definition of Alzheimer's disease (AD). Shortly after Alzheimer presented the seminal case of a 51year old woman with dementia, he suggested that Perusini undertake a more detailed study of the clinical notes and neuropathological specimens. Perusini studied that case along with three others, and subsequently produced three papers that more clearly defined the clinical and histopathological features of AD. The third paper, published in 1911, centered on the diagnostic value of the senile plaques and neurofibrillar alterations originally described by Alzheimer. Throughout his works, Perusini was careful to credit Alzheimer with his discovery and to express gratitude that Alzheimer entrusted him with further study of the disease. 2 figures, 17 references.

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Cognitive Models of Physicians' Legal Standard and Personal Judgments of Competency in Patients With Alzheimer's Disease Source: JAGS. Journal of the American Geriatrics Society. 48(8): 919- 927. August 2000. Summary: This article explores cognitive predictors of physician judgements of competency in patients with Alzheimer's disease (AD). Five physicians with extensive experience in dementia and competency assessment were asked to make judgments of 10 older controls and 21 AD patients based on videotapes of their performance on the Capacity to Consent to Treatment Instrument (CCTI). The CCTI consists of two clinical vignettes that test competency under five different, increasing difficult legal standards (LS). Each physician made a judgment of competent or incompetent under each LS as well as a personal competency judgment for both vignettes. Results showed that

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multiple cognitive functions predicted physicians' LS and personal competency judgments. Declines in semantic knowledge, short-term verbal recall, and simple reasoning ability predicted physicians' judgments on the three most difficult and clinically relevant LS as well as their personal competency judgments. The findings suggest that clinical assessment of competency should include evaluation of semantic knowledge, verbal recall, and simple reasoning abilities. 3 tables, 29 references. •

Is Smoking Associated With the Risk of Developing Alzheimer's Disease? Results From Three Canadian Data Sets Source: Annals of Epidemiology. 10(7): 409-416. October 2000. Summary: This article investigates the association between smoking and Alzheimer's disease (AD). Three Canadian data sets were analyzed: the University of Western Ontario Dementia Study (200 cases, 163 controls), the Canadian Study of Health and Aging (258 cases, 258 controls), and the patient database from the Clinic for Alzheimer Disease and Related Disorders at the Vancouver Hospital and Health Sciences Center (566 cases, 277 controls). The association between smoking and AD was examined using bivariate analyses and multiple logistic regression models with adjustment for age, sex, educational level, family history of dementia, head injury, and hypertension. The results of bivariate analyses were inconsistent across the three data sets, with smoking found to be a significant protective factor, a significant risk factor, or not associated with AD. Results of the multiple logistic regression models were consistent; no significant association remained after adjusting for potential confounders. The authors conclude that failure to adjust for appropriate confounders may explain the inconsistent reports of an association between smoking and AD in the literature. 7 tables, 41 references. (AAM).

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First International Pharmacoeconomic Conference on Alzheimer's Disease: Report and Summary Source: Alzheimer Disease and Associated Disorders. 12(4): 266-280. 1998. Summary: This article presents a report on the First International Pharmacoeconomic Conference on Alzheimer's disease (AD), which was held under the auspices of the International Working Group for Harmonization of Dementia Drug Guidelines. The conference brought together researchers, clinicians, and industry representatives. In this report, the authors discuss the role of longer life expectancy on quality of life, integrating care systems, and the economics of AD. They look at guidelines, current trends, and methodological issues of pharmacoeconomic studies in dementia as well as economic models of drug treatments for AD. The authors hope that the models described may become more available to politicians, clinicians, and caregivers to help them make better decisions about AD treatment. 4 tables, 73 references.

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Alzheimer's Disease International and International Working Group for Harmonization of Dementia Drug Guidelines for Research Involving Human Source: Alzheimer Disease and Associated Disorders. 13(2): 71-79. 1999. Summary: This consensus statement addresses the Working Group's mission, of global drug development efforts in dementia, focusing on the ethical considerations relevant to dementia research proposal review. The statement emphasizes that ethical review committees must consider a proposal's scientific design; it would be unethical to permit a study that presents risk to subjects with cognitive impairment if the study, whether biomedical or behavioral, is flawed in a way that would make the results invalid. Fifteen

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guidelines directed at the application of ethical principles to research involving human subjects are presented. The guidelines address the following categories: informed consent of subjects, selection of research subjects, confidentiality of data, compensation of research subjects for accidental injury, review procedures, and externally sponsored research. 18 references. •

Descriptive Analysis of Emergency Hospital Admissions of Patients With Alzheimer's Disease Source: Alzheimer Disease and Associated Disorders. 15(1): 21-25. 2001. Summary: This journal article describes a study that examined the reasons for emergency hospital admissions among people with dementia of the Alzheimer type (DAT) and noted patient characteristics. Information was collected prospectively on 118 patients with DAT, most from two emergency departments of one British hospital. Data analysis indicated that the two main reasons for admission were behavioral problems and falls. Patients with DAT were usually at an advanced stage of the disease and had poor nutritional status and loss of activities of daily living. Approximately one-third of the patients had been admitted to the hospital for the same reason in previous months. The main medications taken were psychotropic drugs. Discharge reports indicated that medications were a contributing factor in the disorders of 25 percent of the patients. The researchers concluded that improved information for caregivers and early management and treatment of patients with DAT are crucial. 3 tables, 21 references.

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Assessing the Impact of Neuropsychiatric Symptoms in Alzheimer's Disease: The Neuropsychiatric Inventory Caregiver Distress Scale Source: Journal of the American Geriatrics Society. 46(2): 210-215. February 1998. Summary: This journal article describes an evaluation of the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D), an adjunct scale to the Neuropsychiatric Inventory (NPI) designed to assess caregiver distress associated with neuropsychiatric symptoms in patients with Alzheimer's disease (AD. The participants were 85 patients with AD, aged 58 to 88 years, and their caregivers (54 spouses and 31 children), enrolled in ambulatory Memory Disorder Clinics at the University of California at Los Angeles and the University of Pittsburgh, Pennsylvania. The NPI was used to assess neuropsychiatric symptoms in the patients, and the NPI-D was used to assess caregiver distress related to those symptoms. Criterion validity of the NPI-D was examined in 69 participants by comparison with an abridged version of the Relatives' Stress Scale (RSS). Test-retest validity was examined in 20 caregivers, and interrater validity in 16 caregivers. The NIPD scale had adequate test-retest and interrater reliability, and NIP-D ratings were significantly correlated with RSS scores. Caregiver distress was associated more strongly with neuropsychiatric symptoms than with cognitive symptoms. The authors conclude that the NIP-D may be useful in both clinical and research settings to assess the effects of neuropsychiatric symptoms on caregiver distress. 3 tables, 42 references.

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Paradise Garden: A Model Garden Design for Those With Alzheimer's Disease Source: Activities, Adaptation, and Aging. 22(1-2): 3-16. 1997. Summary: This journal article describes the design of garden spaces for people with Alzheimer's disease (AD), using the paradise garden as a model for a restorative environment. The concept of the paradise garden originated in ancient times in the Middle East and is characterized by four key elements: an enclosing wall, water, a canopy (tree or trellis), and a hill. This article explores how these elements, together with

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paving, can serve the needs of people with AD. It describes how these components of the paradise garden were integrated into the design of three therapeutic gardens at the Alois Alzheimer Center in Cincinnati, Ohio. The center accommodates 82 residents with AD and dementia, and provides a continuum of care. Three garden spaces were designed to meet the unique environmental, social, and physical needs of residents at different stages of AD. All of the garden spaces feature an enclosing wall for safety and security, a trellis to filter harsh sunlight, a raised area to provide visual interest and variety, a small pool and fountain, and nontoxic plants for sensory stimulation. Two of the gardens have looped walkways to permit wandering by active residents; and one is configured to accommodate wheelchairs and sturdy, comfortable garden furniture for more impaired residents. 1 figure, 11 references. •

Features of Alzheimer's Disease: Crystallized and Fluid Intelligence in Elderly Patients With Mild Dementia of the Alzheimer Type Source: International Psychogeriatrics. 10(2): 147-154. June 1998. Summary: This journal article discusses a study that examined early intellectual deficits in elderly patients by using the Japanese version of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) to compare 25 elderly patients with Alzheimer's disease (AD) and 25 normal controls. The two groups were similar in age, years of education, and gender. Researchers classified the WAIS-R subtests into two categories: fluid intelligence and crystallized intelligence. Fluid intelligence describes the ability to acquire new concepts and adapt to unfamiliar situations; crystalized intelligence refers to knowledge accumulated over a lifetime. Data revealed that the AD patients had significantly lower crystallized intelligence scores; subtests for crystallized intelligence (information, comprehension, and similarities) showed the most significant deficits. The fluid intelligence scores did not differ significantly between the two groups. These results demonstrate that elderly subjects with mild AD have crystallized intelligence that is more impaired than that of subjects without dementia. These results suggest that it may be possible through a prospective cohort study, to clarify more precisely the intellectual deficits in AD. 2 tables, 40 references (AA-M).

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Apolipoprotein E Genotype and Progression of Alzheimer's Disease: The Rotterdam Study Source: Journal of Neurology. 246: 304-308. 1999. Summary: This journal article examines the effect of the apolipoprotein E4 allele on the progression of Alzheimer's disease (AD). A sample of AD patients (n=97) was drawn from a population-based study of people aged 55 years and older living in a suburb of Rotterdam, The Netherlands. All patients were free of dementia at study entry, and were followed for up to 5 years. ApoE genotyping was performed for all participants. Cognitive function was assessed with the Dutch version of the Mini-Mental State Examination (MMSE), and stage of AD with the Clinical Dementia Rating (CDR) scale. Changes in MMSE and CDR scores were similar in carriers and noncarriers of the apoE4 allele. Overall survival also did not differ between the two groups. The findings suggest that the progression of AD is not related to the presence or absence of the apoE4 allele. 1 figure, 2 tables, 26 references.

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Right-Side Neglect in Alzheimer's Disease Source: Neurology. 51: 1207-1209. October 1998.

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Summary: This journal article reports on a 73-year-old woman with probable Alzheimer's disease (AD) who showed signs of right-side neglect and extinction. Unilateral neglect, or the inability to pay attention to events occurring on one side of space, usually occurs for left-side events after focal right-hemisphere damage. In this case, the signs of unilateral neglect for the right hemispace were consistent throughout several tasks and became more severe at retest after 1 year. Neuroimaging techniques demonstrated asymmetry of cortical involvement, with cortical atrophy and hypoperfusion predominant in the left posterior regions. The authors state that unilateral neglect should be assessed systematically in AD. This assessment could help determine more precisely the pattern of cognitive impairment in each patient and could help identify patients at risk for spatial disorientation and wandering. 2 figures, 1 table, 10 references (AA-M).

Federally Funded Research on Alzheimer’s Disease The U.S. Government supports a variety of research studies relating to Alzheimer’s disease. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to Alzheimer’s disease. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore Alzheimer’s disease. The following is typical of the type of information found when searching the CRISP database for Alzheimer’s disease: •

Project Title: A MULTIDIMENSIONAL ALZHEIMER'S DISEASE BRAIN ATLAS Principal Investigator & Institution: Toga, Arthur W.; Professor; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-MAY-1995; Project End 31-JUL-2006 Summary: This competitive renewal application has an overall goal, the creation of an atlas of Alzheimer's disease. The neuroscience and informatics efforts proposed here will result in a tool set and product that is applicable not only to the basic and clinical science of Alzheimer's disease, but to the general problem of mapping the structure and function of any dynamic process in health or disease in whole populations of subjects. Leveraging the accomplishments achieved during the last period of this project and building upon our high-resolution post mortem anatomic framework, the development of atlas construction methodology and the ability to create 3D visual models of anatomy, we will construct the first multimodality probabilistic atlas of the brain representing a diseased population. Including both histologically processed post mortem tissue as well as high- resolution 3D MR images acquired from subjects in various stages of

2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Alzheimer's disease, we will generate the average geometry and 3D variability of the anatomic structures of these populations. Further, we will describe the anatomy as cytoarchitectural features from histology and gyral sulcal features from MRI. There are 7 specific aims in this project. The first will be the collection of a cohort of post mortem specimens from an Alzheimer's disease population. Second, we will create detailed individual probabilistic maps describing the architectural boundaries in AD and matched controls. Third, we will create an MRI probabilistic atlas based upon data that has been previously acquired or will be acquired with funding from other active projects. Fourth, we will develop and refine appropriate registration deformation correction atlasing strategies to create a comprehensive multimodality atlas of Alzheimer's disease. This will enable the development of data at different spatial resolutions and representing different aspects of brain structure and function. Fifth, individualized data analysis utilizing mathematical strategies to compare individual MRI data with the probabilistic atlas will enable access by the neuroscience community to this multimodality atlas. Sixth, we will develop dynamic 4D mapping tools to express the spatial and temporal profiles of degeneration heretofore unavailable in static single time point representations of anatomy or physiology. Seventh, these will be combined into an interactive visualizable and analytic tool set made available to the neuroscientific community. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A PROGRAM OF COLLABORATIVE CARE FOR ALZHEIMER DISEASE Principal Investigator & Institution: Callahan, Christopher M.; Associate Professor; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: Alzheimer Disease and related disorders are common among older adults attending primary care clinics. Unfortunately, many of these vulnerable older adults do not receive an adequate diagnosis, evaluation, education treatment, or long-term management. Also, primary care practices are rarely designed to provide education and support for the caregivers of patients with dementia. Fragmentation of care within the health care system and poor communication among the health care providers and between local social support agencies contribute to frustration, poorer outcomes, and increased costs. Indeed, primary care practitioners appear to have tremendous difficulty in delivering a systematic program of care for older adults with dementia. In our earlier studies, we found that nearly 1 in 6 patients over the age 60 attending a large primary care practice suffered from cognitive impairment. Unfortunately, 75 percent of the patients with moderate to severe cognitive impairment had not been diagnosed with a dementing disorder. Patients with moderate to severe cognitive impairment were more likely to be seen in the emergency room, more likely to be hospitalized, and more likely to die over the following year. Even controlling for the impact of comorbid conditions, cognitive impairment in these older adults was significantly associated with mortality after 5-7 years of follow-up. We are proposing a four-year randomized controlled clinical trial designed to test the efficacy of an Integrated Program of Collaborative Care as compared to usual care in improving the outcomes of care for older adults with Alzheimer Disease in a primary care setting. Although guidelines for the care of patients with Alzheimer Disease and related disorders have been published, there are no clinical trials that test the impact of close adherence to these guidelines on the outcomes of care for a group of vulnerable older adults in an urban primary care setting. We are

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hypothesizing that the integrated program of collaborative care, managed by a geriatric nurse practitioner who is empowered to facilitate published guidelines for care, will result in: a reduction in psychopathology and disruptive behavior among patients; a reduction in stress and depression among caregiver; a reduction in the use of skilled nursing home services; and an improvement in satisfaction with care. The study design will also allow us to describe the prevalence of dementing disorders and associated comorbidity in primary care and to measure utilization, costs, use of community services, and the costs associated with the intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ADAPT NEURODEGENERATION

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Principal Investigator & Institution: Davies, Kelvin J.; Gerontology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: We are interested in a possible link between oxidative stress, aging and neurodegenerative diseases. In recent studies of adaptation to oxidative stress we have identified several previously unknown genes (in addition to confirming the overexpression of several known genes) that appear to provide stress protection in isolated hamster cells in culture. These "adapt" genes include: adapt15, adapt33, adapt66, adapt73, adapt78, and adapt 116. Although our studies indicate that full adaptation depends upon both transcription and translation, it is not clear which genes are actually required. Although each of these newly discovered genes is worthy of detailed study, adapt78 whose mRNA levels increase more than 50 fold in adaptation, in particular stands out. In screening studies employing autopsy samples from human brains, we have now found that the human homologue of adapt78 exhibits extremely high levels of expression in brain autopsy samples from Alzheimer's disease patients, and low levels of expression in brain samples encompassing the substantia nigra from patients who died with Parkinson's disease. Recently, it has become clear that our adapt78 is identical to (or at least highly homologous with) the simultaneously independently discovered Down syndrome critical region 1 (DSCR1) gene of chromosome 21. Furthermore, two different isoforms of both adapt78 and DSCR1 are differentially expressed; corresponding to differentially spliced forms of exons 1-5, 6, 7 and exons 4-5, 6, 7. We propose to now carefully study expression of both isoforms of the human adapt78 gene in different brain regions, using the more sensitive techniques of RT-PCR and in situ hybridization. We plan to study adapt78 expression as a function of age, in brain autopsy samples from otherwise healthy individuals, since adapt78 expression may well vary with age. We will perform detailed studies of brain samples from Alzheimer's disease patients, Parkinson's disease patients, and Down syndrome patients in order to carefully determine both qualitative and quantitative differences in expression of both isoforms of adapt78 mRNA. Localization of adapt78 mRNA expression by cell type will also be studied. We also will synthesize and characterize the (1-5, 6, 7 and 4-5, 6, 7) Adapt78 proteins and generate antibodies to them in order to study expression of the actual proteins in all cell and brain samples. In cell culture studies, with PC-12 cells, we will test the hypothesis that inducible overexpression of adapt78 may confer an oxidative stress resistance phenotype. We will also test the ability of inducible adapt78 overexpressing cells to overcome the lethal oxidizing effects of glutathione deficiency, caused by expression of antisense message to gamma glutamylcysteine synthetase. These studies will allow us to begin to investigate our hypothesis that aging, and perhaps certain neurodegenerative diseases, involving

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defects in the expression of adapt78 and other adaptive genes required to cope with the deleterious effects of oxidative stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALZHEIMER'S DISEASE AND ANIMAL MODELS Principal Investigator & Institution: Price, Donald L.; Professor of Neurology; Pathology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 28-SEP-1984; Project End 31-MAR-2004 Summary: The Alzheimer's Disease Research Center (ADRC) at The Johns Hopkins Medical Institutions (JHMI) is committed to investigations of aging and Alzheimer's disease (AD). Age and genes are important risk factors for AD, and our principal goal is to examine the impact of age and mutations in the amyloid precursor protein (APP) in the cognition/memory abnormalities occurring in elderly humans and in our mouse/human-APPswe (Mo/Hu- APP) transgenic (Tg) mice. Thus, with the support of Cores A and D, Cores B and C focus on behavior-brain correlations in intact, mildly impaired, and demented aged individuals, particularly by those in the cohorts of the Baltimore Longitudinal Study of Aging (BLSA). This extraordinarily well characterized with serial imaging studies; many of these individuals have entered our prospective autopsy program. Supported by Cores B and C, Project 4 takes advantage of this material to examine early brain lesions focusing on: glial cell responses and the production of inflammatory mediators. complement factors, cytokines, etc.) capable of influencing neurons and synapses. These findings will be correlated with detailed assessments of the neuropathology, quantitative estates of synaptic markers, and evidence of cell death and neuronal loss. In parallel to the studies of aging and AD in humans, Projects 1-3 take advantage of our lines of Mo/Hu-APPswe Tg mice that express mutant APP at levels approximately threefold greater than endogenous MoAPP; these animals develop Abeta deposits, we hypothesize that elevated levels of Abeta42 damage synapses before over deposits of Abeta species. In project 1, we will examine the performances of these Tg mice on tasks designed to assess cognition/memory. In Project 2, we will correlate these findings with studies of biochemical marker (e.g. levels of Abeta peptide species, synaptic proteins, neurotransmitters and their enzymes) and the character/severity of the cellular pathology (e.g., abnormalities in synapses, Abeta deposition, loss of synapses, activation of glial cells, subsets of neurons, evidence of cell death, etc.) in specific regions of brain. In Project 3, we believe that these parallel clinical-neurochemical-pathological correlative studies of humans and Tg mice will help to define the biological substrates of impairments. In the intervention studies of our Tg mice, we will assess the responsivity (to age, genotype, and toxins) to the basal forebrain cholinergic and monoaminergic systems that are vulnerable in cases of AD; attempt to provoke glial cells to enhance amyloid; and to test the effects of estrogen on Abeta deposits. Finally, Core D will serve to disseminate information concerning ageassociated diseases to families, caregivers, and other health professionals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ALZHEIMERS DISEASE RESEARCH CENTER Principal Investigator & Institution: Doody, Rachelle S.; Neurology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 1998; Project Start 29-SEP-1989; Project End 31-MAY-2004 Summary: The Baylor College of Medicine's ADRC will now focus on detailed evaluation and longitudinal assessment of a well-characterized population of

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Alzheimer's disease patients and controls including related neurodegenerative disorders to be correlated with neuropathological studies and parallel research investigations of the mechanisms of selective neuronal vulnerability and prevention of cell death. The Administrative Core will coordinate and help foster the goals of the Clinical Core, the Neuropathology Core, and the Information Core and promote interactions between the Cores and the three research projects and the two pilot projects. It will help foster the growth of Alzheimer's disease clinical care and research in the Southwestern par tof the United States. The Clinical Core will promote and facilitate the recruitment, follow up, and detailed evaluation of patients with Alzheimer's disease as well as appropriate controls, including minatory populations. It will monitor rates of progression with special emphasis on defining populations with slow an with fast progression, and will encourage clinical pathologic correlations. The Neuropathology Core will establish the histopathology of Alzheimer's disease, maintain a rapid autopsy protocol, provide special histologic stains and quantitative measures, and support eh Brain Donation Program. The Information Core will provide Alzheimer's disease educational outreach program and consultation to healthcare providers, caregivers, and the Houston lay community. Data management now assures improved communication between Cores an projects under the aegis of our biostatistician. Research Project 1 will investigate mechanisms of selective vulnerability and the role of increased intracellular calcium and limited calcium buffering capacity. Specific studies will explore the direct toxic effects of IgG from amyotrophic lateral sclerosis patients on a motor neuron cell line and the toxic effects of beta amyloid on a substantia nigra cell line. Research Project 9 will test a model for neuronal rescue by implanting cells with an amplifiable regulatable gene. Cells can be activated to produce tyrosine hydroxylase in 6-OH. Dopamine lesioned animals and nerve growth factor in fimbria-fornix lesioned animals. Research Project 10 will investigate interactions between mononuclear phagocytes and AD plaques, and will assess possible consequences of these interactions, including neuronal cell death. Plot Project 1 is a study of implicit semantic memory, and is related to past and present interests of the Clinical Core. Pilot Project 2, further delineates the role of calcium in cell death employing electrophysiologic techniques to study beta amyloid-induced toxicity and clearly relates tot he ongoing activities of Research Projects 1 and 3. The common aims of the Cores, Research Projects and pilot Projects will enhance ongoing interactions and help translate the ADRC activity into improved care and therapy for patients afflicted with Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALZHEIMERS DISEASE RESEARCH CENTER Principal Investigator & Institution: Thal, Leon J.; Professor and Chair; Neurosciences; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 28-SEP-1984; Project End 31-MAR-2004 Summary: This proposal is for a five-year renewal of the Alzheimer's Disease Research Center (ADRC) at the University of California San Diego in consortium with The Salk and The Burnham Institutes. The major goals of the Center over the next five years will be to expand our efforts into early clinical identification of Alzheimer's disease (AD) and studying mechanisms of neurodegeneration and repair. Projects will focus on semantic memory in AD, potential mechanisms of neurodegeneration in AD, alphasynuclein biology, and mechanisms whereby hormones or environment may enhance neuronal survival. In addition, we will continue to carry out detailed clinicopathological correlations and studies of the course of AD. This Center will continue to maintain extremely strong Clinical and Neuropathology Cores. The Clinical Core will continue to

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longitudinally characterize a cohort of approximately 475-500 subjects to study early changes in cognition and semantic memory, and to provide other AD investigators and the San Diego community as a whole with a well- characterize clinical cohort of both Caucasian and Hispanic volunteer who undergo annual evaluations and are willing to participate in clinical research. The Clinical Core will also recruit special subjects and controls to support the special needs of many of the individual projects. Subjects will also participate in multi-center drug trials. Data derived from subjects will be used in collaborative research. We will place increasing emphasis in identifying genetic influence that either accelerate or protect individuals from the development of AD. In addition, we will continue to focus our studies on the 15-20% of individuals with AD who also have Lewy bodies in their cortex and represent the second most common form of dementia in the United States. The Neuropathology ore will continue to refine the diagnosis of AD and LBD, provide diagnoses, clinicopathological correlations, and brain tissue. The Center as a whole will continue to provide brain tissue, fibroblasts, plasma, DNA, and cerebrospinal fluid to investigators upon request. The ADRC provides a setting to facilitate research training of investigators and will transfer information to the profession and lay communities through our mini-residency program, conferences and other educational activities. The Biostatistics Core will continue to modernize the database and will: 1) maintain the database for the Center, 2) transmit data as requested for the Alzheimer's Disease Data Coordinating Center, 3) provide consultations and statistical expertise for projects emanating from the cores, projects and pilots. Our specific research projects in this renewal include: the role of caspase cleavage in neurodegenerative disease (Bredesen), regulation of neurogenesis in the adult mammalian hippocampus (Gage), NACP/alpha-synuclein and the mechanism of neurodegeneration in Lewy body disease (Masliah), cognitive studies of semantic memory in AD (Salmon), and estrogen mediated neuronal plasticity in the brain (Tuszynski). A mechanism is also outlined for the awarding of pilot feasibility studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALZHEIMRE'S DISEASE ANTIAMYLOID NEUROPROTECTIVE TMT Principal Investigator & Institution: Manyam, Bala V.; Professor of Neurology; Scott and White Memorial Hospital 2401 S 31St St Temple, Tx 76508 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2004 Summary: Alzheimer's disease (AD) is the leading cause of cognitive impairment in the geriatric population. Deposition of the beta-amyloid peptide (Abeta) in the brain parenchyma and cerebral blood vessel walls is one of the distinguishing neuropathological features of AD. Abeta has been hypothesized to be the primary culprit triggering the neurodegenerative changes responsible for the memory loss and behavioral changes in AD. Increased Abeta production and deposition occurs with mutations in all three genes linked to early onset AD, the amyloid precursor protein, Presenilin 1 and Presenilin 2. Doubly transgenic mice with mutations in the amyloid precursor protein and Presenilin 1 rapidly develop AD-like changes in the brain including fibrillar Abeta deposits, glial reactivity and dystrophic neurites and will provide a means of screening treatments that alter AD production or which ameliorate its effects in the brain. Centella asiatica (Syn. Gota Cola, Luei Gong Gen, Indian Pennywort) is an ethnophytotherapeutic agent reputed to have a beneficial effect on cognition. However, the mode of action of Centella asiatica has not been fully established. The object of this application is to test the central hypothesis that Centella asiatica extract (CAE) may exert a therapeutic effect on both cognition and neuropathology in a doubly transgenic mouse model of AD by modulating amyloid

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deposition in the brain. Specific aims: 1) Determine the effect of 3 different doses of CAE on learning and memory performance at young (3 month), mature (6 month), and aging (12 month) old doubly transgenic mice when treatment is started prior to onset of Abeta deposition (2 months). 2) Assay the effect of CAE on the production and deposition of Abeta 40 and 42 isoforms using ELISA as well as antibodies to Abeta and standard histological techniques known to detect fibrillar amyloid at each of the three age groups tested. 3) Perform secondary analysis of neuronal loss, dystrophic neurite formation, glial activation and markers of oxidative stress to test the neuronal and glial response to both AD and CAE treatment with aging. The efficacy of CAE to improve working and spatial memory will be studied using the object recognition task that has previously been shown to discriminate between transgenic mice carrying mutations linked to early onset AD and controls. Expected results are improvement in performance of CAEtreated group in the behavioral task, and reduction in the levels of Abeta(3 deposition in the brain. Our proposal meets the criteria of R21 application of NCCAM that will generate preliminary data on possible mechanism of action of a traditional herbal drug for Alzheimer's disease with eventual development of a therapeutic agent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTI-ABETA IMMUNITY AGAINST ALZHEIMER'S DISEASE Principal Investigator & Institution: Ugen, Kenneth E.; Associate Professor; Medical Microbiol & Immunology; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2004 Summary: (provided by applicant): Alzheimer's disease (AD) is a neurodegenerative disease characterized by overproduction of Abeta-amyloid from amyloid precursor protein (APP), with the subsequent pathologic deposition of Abeta into extracellular plaques in regions of the brain which are important for memory. Recently we, as well as others, have demonstrated that vaccination of a transgenic (Tg) mouse which expresses mutant presenilin-1 and APP (and serves as a model for AD) with an Abeta(1-42) peptide, resulted in amelioration of neural pathology and protection of these mice from functional memory deficits. Others have indicated that humoral immunity plays a major role in at least ameliorating the neural pathology. However, the exact role of cellular immunity, whether beneficial or deleterious, has not been addressed. We have recently demonstrated that vaccination of Tg mice with Abeta results in the induction of antibodies indicative of a T helper 2 response. We have also shown strong T cell proliferative activity in mice vaccinated with Abeta stimulated with specific antigen. A chimeric mouse line has recently been developed which expresses human MHC I and II molecules and is called CHAD (chimeric human A2DR). We propose to use this mouse to cross mate with the doubly transgenic mice described above to ask important questions about human immune responses to Abeta. The specific aims of this proposal are as follows: (a) evaluation of the CD4 T cell responses to Abeta in a Tg mouse model for AD; (b) evaluation of the potential role of CD4 T cell responses after Abeta vaccination; (c) evaluation of the CD8 T cell responses in Tg mouse models; and (d) engineering of specific immune responses in AD Tg mice. These studies will comprehensively address the potential role of cellular immune responses to Abeta vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: APP TRAFFICKING AND THE PATHWAYS OF A BETA FORMATION Principal Investigator & Institution: Koo, Edward H.; Professor; Neurosciences; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2002 Summary: Alzheimer's disease is characterized by the presence of both beta- amyloid plaques and neurofibrillary tangles in cortex. Increasing evidence favors the deposition of amyloid beta-protein (Abeta) in plaques as an early and possibley primary event in the pathogenesis of Alzheimer's disease, a process that may be related to altered expression or processing of the amyloid precursor protein (APP). Recent studies have further implicated the longer Abeta species, specifically Abeta peptides of 42 amino acids long (Abeta42) as potentially critical for amyloid deposition and fibril formation. The pathways that lead to the generation of Abeta and Abeta42 have not been clearly defined. The foundation that guides this ongoing project is that processing of APP in the endocytic pathway is important to Abeta production. Accordingly, we have formulated two working hypotheses to direct our continuing research efforts: 1) the APP internalization pathway is the primary route for Abeta production and subsequent release into the medium, and 2) familial Alzheimer's disease mutations alter APP trafficking and, in turn, Abeta production. Three Specific Aims are proposed for the next granting period to test the two working hypotheses. The first Specific Aim examines the role of endocytic processing in the production and release of Abeta42. The second Specific Aim will analyze the relationship between presenilin-1 mutations, APP trafficking and Abeta42 production. In the third Specific Aim, the mechanism by which the APP codon 717 mutations increases Abeta42 production will be explored with regards to the relationship between internalization and gamma-secretase APP cleavage. This investigation of the APP trafficking pathways in a cell culture system will examine fundamental processes that are critical for Abeta (Abeta42) production. Results from these studies may provide important insight into the pathogenesis of Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ATTENTION AND MEMORY INFLUENCES ON NAVIGATION IN AD Principal Investigator & Institution: Mapstone, Mark E.; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Spatial disorientation is a primary manifestation of Alzheimer's disease (AD) greatly impacting functional independence. While the amnesic features of AD are well described, relatively little is known about the deficits underlying spatial disorientation. Spatial disorientation in AD has been attributed to pervasive memory dysfunction, but it can present without evident memory deficits. Alternatively, spatial disorientation in AD may reflect a reduction in the size of the spatial window of attention; the area of the visual field that is simultaneously accessed by cognition. Narrowing the attentional window might limit access to orientation cues in global patterns of optic flow and force reliance on less informative object motion cues. I propose to immerse myself in the study of spatial disorientation in Alzheimer's disease for the next five years. Through formal instruction, hands-on laboratory experience, and completion of the research plan described within. l will further develop skills in patient-oriented research leading to competence as an independent investigator.

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The strength of my approach is a core group of mentors selected for their expertise in addressing the proposed research topic and for their commitment to developing young investigators. Charles Dully, MD, PhD (visual psychophysics), Roger Kurlan, MD (neurological disease clinical trials), and Suzanne Corkin, PhD (behavioral studies of memory) have agreed to share their specific expertise and serve as mentors in my transition to independent investigator. The specific aims of the proposed research are 1 ) To quantify the size of the window of attention in patients with AD and investigate its effect on the use global motion (optic flow) and local motion (object) cues for determining heading, 2) To determine the contributions of spatial attention and memory systems for path integration, and 3) To explore the role of the cholinergic system as a neuro-modulator for spatial attention and global motion processing using pharmacological challenge. This funding will provide for my further development in behavioral studies of spatial attention in aging and AD and commence my programmatic approach to the study of brain-behavior relationships. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BETA AMYLOID DERIVATION IN BRAIN IN ALZHEIMERS DISEASE Principal Investigator & Institution: Dewji, Nazneen N.; Associate Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-AUG-1989; Project End 31-MAR-2003 Summary: Mutations in the genes for the beta-amyloid precursor protein (beta- APP), a type 1 single-membrane spanning integral protein, and the more recently identified closely homologous seven-membrane spanning integral proteins S182 and STM2, together account for all early-onset familial Alzheimer's disease. The normal functions of the three proteins are not known nor do we know how their functions are implicated in the disease. They recently proposed (Science, 271, 159-160, 1996) based on precedents in other system of an integral proteins, that one or more forms of beta-APP and S182 (or STM2) may normally be components of an intercellular signaling system. Beta-APP and S182 or STM2 on the surfaces of neighboring cells would bind to one another specifically through their extra-cellular domains protruding from the dell membranes, beta-amyloid (Abeta) being a proteolytic by-product of this interaction. To test this proposal fulllength cDNAs for S182 and STM2 were cloned by PCR and subcloned into pcDNA3. Beta- APP695 cDNA was also subcloned into pcDNA3 and the constructs were used to transiently transfect cultured cells. Polyclonal antibodies raised to peptide sequences of STM2 and S182 demonstrated the presence of the two proteins at the surface of transfected cells. In order to determine if STM2 or S182 on one cell interacts with betaAPP on another, transfected cells expressing STM2 or S182 were mixed with cells expressing beta-APP. Heterotypic cell aggregates were formed, as shown by double labeling with antibodies to beta-APP and STM2 (or S182). Furthermore, this aggregation could be inhibited by excess soluble beta-APP, indicating specificity of the interaction. Our work provides evidence for the direct physical interaction of beta- APP with STM2 and S182, which may be crucial to the generation of Abeta and the genesis of Alzheimer's disease. To further test our hypothesis, in this application we propose, among other things, to investigate if transcellular binding between beta-APP and S182/STM2 results in vesicular internalization of the two proteins, the release of more or longer form of Abeta and normal signaling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BRAIN IMAGING & COGNITION IN SUBJECTS AT RISK FOR AD Principal Investigator & Institution: Bassett, Susan S.; Associate Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: Alzheimer's disease (AD) is a major health problem facing this country. The destruction of brain tissue in this degenerative disease likely begins decades before the onset of clinical symptoms. Identification of preclinical markers for AD would be extremely valuable for both intervention and treatment. Recent work suggests that decrements in cognition and changes on neuroimaging in asymptomatic individuals may identify those who go on to develop AD. The aim of this project is to study both cognition and structural and functional neuroimaging longitudinally in a sample of adults who are at increased risk for development of AD and contrast these findings with those of a matched control group. Specifically we will examine cognitive performance on tests of memory and learning, generalized and regional brain measures from conventional MRI and changes in activation with a memory fMRI paradigm. In a small subsample, we will investigate activation changes using olfactory fMRI. In addition, participants will be referred to NIH for assay of amyloid in cerebral spinal fluid. Participants, all at least 50 years of age, will include adult offspring (N=100) of autopsyconfirmed AD cases who are members of multiplex families with extensively characterized pedigrees, currently enrolled in a genetic study of AD, and adults matched for age and gender (N=100) who are presently followed in a study of normal aging. Approximately equal numbers of males and females will be enrolled. All participants will be evaluated twice, three years apart to examine change over time on these measures. In addition, all participants will be typed on two genetic markers (APOE, Alpha2 Macroglobulin) for correlation of allele status with the above measures. The results of this study will provide information on the identification of preclinical markers for late-onset AD. It is hoped that the findings here will prove of significant value as future interventions for Alzheimer's disease are developed. In addition, the proposed studies will provide valuable data for planned long-term longitudinal studies of persons at-risk for AD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CANDIDATE GENES FOR ALZHEIMER'S DISEASE RISK IN BLACKS Principal Investigator & Institution: Evans, Rebecca M.; Neurology; Indiana UnivPurdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2001; Project Start 19-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted From The Applicant's Abstract): The primary objective of this Mentored Patient-Oriented Research Career Development Award is to permit Rebecca M. Evans (the candidate) to develop her full potential as a clinical investigator in dementia research. Dr Evans has completed a 2-year fellowship in neurodegenerative disease and has initiated research into vascular aspects of dementia. She has been, and will continue to be actively involved in the hands-on examination of participants in the Indianapolis-Ibadan Dementia Study (IIDS), a cross-cultural, longitudinal, populationbased study of dementia in elderly Africans and African Americans. As the APOE epsilon 4 allele is not associated with AD risk in blacks, Dr Evans' initial research project will focus on examining three candidate genes for AD risk. Given that hypertension is very prevalent in the black population, and is a major vascular risk factor, and the emerging recognition that vascular factors increase AD risk, the genetic polymorphisms

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chosen to study for AD risk are all associated with hypertension in blacks. Dr. Evans will study the angtiotensin I converting enzyme (ACE) gene insertion/deletion polymorphism, the angiotensinogen allele T235, and epithelial sodium channel variants for association with Alzheimer's disease (AD) in each cohort of the IIDS. During the award period, she will work with her mentors to design and implement preliminary case control studies to assess the significance of vascular risk factors in AD patients and patients with post-stroke dementia. Dr. Evans' future goal is to obtain independent grant funding to develop and implement 1.) larger studies of vascular risk factors for AD, and 2.) interventional trials of therapy to modify vascular risk factors which might prevent or delay dementia onset or slow disease progression. Didactic courses are planned in epidemiology, clinical trial design, statistical analysis, and the ethical conduct of research. This career enhancement plan will enable Dr. Evans to develop expertise in patient-oriented research, and help her accomplish her goal of becoming an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARRIER MEDIATED UPTAKE OF ABETA IN VIVO & IN VITRO Principal Investigator & Institution: Harris-White, Marni E.; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): There is increasing evidence for soluble Amyloidbeta peptide (Abeta) uptake into neurons being an early event in the pathogenesis of Alzheimer's Disease (AD). Identification of the early events leading to neurotoxicity is key to preventing or curing Alzheimer's disease. In this proposal, we examine a very specific, receptor-mediated mechanism of Abeta uptake into neurons. Aim 1 will examine the role of the Low Density Lipoprotein Receptor Related Protein (LRP) in mediating Transforming Growth Factor-beta2 (TGFbeta2) targeting of Abeta to neurons. TGFbeta2 has been shown to be upregulated in AD brain and recent evidence points to TGFbeta2 being upregulated very early in the course of the disease. In Aim 1 we will investigate the mechanism by which TGFbeta2 impacts Abeta uptake, clearance and degradation. Another protein known to be genetically linked to AD is Apolipoprotein E (ApoE). Aim 2 examines the role of ApoE, an LRP ligand, in TGFbeta2-mediated targeting of Abeta to neurons. Aim 3 completes the protocol by testing our mechanism in vivo using human ApoE transgenics and ApoE knockout mice. The Aims outlined in the proposal utilize primary cell cultures, organotypic hippocampal slice cultures (OHSC) and in vivo methods, giving us a symmetrical and powerful approach to studying receptor-mediated uptake and neurotoxicity of Abeta. Another advantage to our mouse infusion model of AD is that, as opposed to transgenic models that overproduce Abeta, we can dissect Abeta clearance away from issues of Abeta production in our mouse infusion model of Alzheimer's disease. There are few published reports that focus on receptor-mediated pathways for Abeta toxicity in Alzheimer's Disease. Understanding this mechanism may help to resolve the paradox that "Abeta plaque deposition is not sufficient to cause Alzheimer's" and could lead to new and better targets of intervention in Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHOLESTEROL AND AMYLOIDOGENESIS Principal Investigator & Institution: Pappolla, Miguel A.; Professor; Pathology; University of South Alabama Mobile, Al 366880002

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Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Recent studies have shown that increased levels of Ab peptides are among the earliest detectable abnormalities in Alzheimer's disease and may mediate a chain of downstream events leading to neuronal degeneration and cognitive decline. There is increasing evidence from clinical, epidemiological and laboratory studies that cholesterol plays a role in the pathogenesis of Alzheimer's disease. This body of evidence includes in vitro studies indicating that cellular cholesterol levels modulate Ab production and the enzymatic processing of APP, animal studies demonstrating that cholesterol levels modulate Ab accumulation in the brain (preliminary data) and several observational, clinical studies suggesting that the prevalence and incidence of probable Alzheimer's disease was significantly lower in patients taking cholesterol-lowering drugs. Taken together the studies support the hypothesis that Alzheimer's disease may be a disease in which cholesterol homeostasis is altered and that cholesterol may participate in a chain of events that modulate the disease neuropathology. The application proposes to test the following hypotheses: 1that in the human brain increased cholesterol content contributes to amyloid accumulation by changing APP processing in a more amyloidogenic manner. 2-that there are correlative interactions between levels of apoE expression, cholesterolemia and amyloid pathology. 3-that certain apoE promoter polymorphisms act in concert with cholesterol levels influencing the extent of apoE expression and amyloid accumulation. Preliminary and recently published data from our laboratory suggest that cholesterol content in plasma and brain of Alzheimer's transgenic mice is strongly correlated with rate of development of amyloid pathology and with apoE expression. These hypotheses are amenable to testing as outlined in the corresponding sections of the proposal and their study will advance our understanding of the pathogenesis of Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLONING OF LATE-ONSET ALZHEIMER'S DISEASE GENES Principal Investigator & Institution: Schellenberg, Gerard D.; Research Professor; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2007 Summary: (provided by the applicant): Alzheimer's disease (AD) is the most common cause of dementia in the elderly. In the U.S., this disease affects approximately 3-4 million persons, costing the U.S. economy more than $50 billion per year. The cause(s) of this debilitating neurodegenerative disease is/are presently unknown. However, a large body of evidence indicates that at least some, if not all, AD cases are due to genetic factors. Genetic analysis of families with multiple cases of early-onset AD has shown that 3 autosomal-dominant genes are responsible for at least some occurrences of the disease. In these families, offspring of affected persons are at least at 50% risk of inheriting a Familial AD (FAD) gene and developing AD. Late-Onset FAD (LOFAD) appears to involve other genes, and is a more complex disease. Using linkage analysis, other sophisticated statistical genetic methods and positional cloning approaches, the long-range goal of this project is to identify the underlying causes of AD by identifying the genes responsible for genetic forms of late-onset AD. Using genetic-linkage analysis, based on Monte Carlo Markov Chain methods, we identified a quantitative trait locus on chromosome-19p 13.2 that affects AD risk. This locus was identified as a quantitative trait that affects age-of-onset. The 19p locus targeted by this project is distinct from ApoE, another LOFAD gene located at 19q13. To identify this new LOFAD gene by positional cloning, the following steps will be performed. First, a physical, sequence, and gene-map of 19p13.2 spanning the region, indicated by linkage analysis, will be

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generated. Second, genes in this region will be screened for polymorphic sites by database analysis and DNA sequence analysis. Third, polymorphisms spanning the region will be used to test for linkage disequilibrium in the region. Polymorphic sites tested will include short tandem repeat polymorphic sites and single nucleotide polymorphism (SNP) sites. Fourth, SNP's in genes in the region will be tested as pathogenic sites in multiple familial and case-control samples to identify the true pathogenic allele. Fifth, when the gene and pathogenic alleles are found, functional assays will be devised to determine the mechanism of pathogenesis leading to AD. Identification of additional LOFAD genes should greatly enhance our understanding of AD, and potentially lead to new types of therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPLEMENT PATHOGENESIS

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INFLAMMATORY

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AD

Principal Investigator & Institution: Tenner, Andrea J.; Professor; Molecular Biology and Biochem; University of California Irvine Campus Dr Irvine, Ca 92697 Timing: Fiscal Year 2001; Project Start 01-FEB-1997; Project End 31-MAY-2004 Summary: (Adapted from the Investigator's Abstract): Alzheimer's disease (AD) is a common dementia or loss of cognitive abilities, which is linked to degeneration of brain tissue. The cause of this neurodegeneration is under intense investigation, as a critical step toward designing therapies for this debilitating and costly disease. In a variety of test systems, fibrillar beta-amyloid displays neurotoxic properties via its direct interaction with neurons but also via its interaction(s) with microglia and its ability to activate the complement system. Multiple studies have demonstrated that reactive microglia and astrocytes and proteins of the complement system are associated with the senile plaques in AD brain, suggesting that inflammation initiated by or exacerbated by activation of the complement system may be one of the major processes involved in the generation of pathology that leads to the cognitive loss. The complement (C') system is a powerful effector mechanism of the immune system. Tissue damage can result however, from chronic or unregulated activation of this system. However, it is also becoming increasingly evident that some complement components provide protective functions in areas of injury. Thus, in this research program novel mouse models will be generated to more closely mimic the human complement system to test the hypothesis that complement plays a role in the pathogenesis of Alzheimer's Disease. Organotypic culture systems will be used to assess the ability of specific complement components to modify amyloid-induced microglia-mediated neuronal cell death/degeneration. In addition, potential protective effects of specific complement components in this disorder will be defined and the specific ligand-receptor interactions that regulate these functions will be determined. These studies should provide solid data on the significance of complement activation and inflammatory events in AD--events which could be targeted to slow the progression of the disease, as well as develop relevant animal models for testing potential therapies in vivo. Since complement has been implicated in a number of other neurodegenerative diseases, it is likely that the investigators' findings will be relevant to other diseases as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONFERENCE ON NEURONAL AND VASCULAR STRESS Principal Investigator & Institution: Stern, David M.; Dean and Chief; Keystone Symposia Drawer 1630, 221 Summit Pl #272 Silverthorne, Co 80498

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Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2002 Summary: Recent findings have focused attention on amyloid beta-peptide (Abeta) as a key element in the pathogenicity of cell stress and, ultimately, cytotoxicity to neurons and the vasculature in Alzheimer's disease and cerebrovascular amyloid angiopathy. Although dense extracellular plaque-like deposits of Abeta are abundant late in the course of Alzheimer's disease, it has become evident that much earlier events in the generation and toxicity of Abeta, especially within the endoplasmic reticulum, will be critical to fully understand in order to design therapies that block the disease at a stage when cellular dysfunction is still reversible. Biology of the presenilins, cell surface and intracellular targets of Abeta converge on microglial-neuronal interactions and the vasculature to create a milieu of sustained and destructive inflammation, as well as an exaggerated and adverse response to ischemic stress. Insights from new animal models and clinical studies will be described, and related to an emerging cell biology of Alzheimer's disease and cerebrovascular amyloid angiopathy; namely, that of cellular dysfunction is driven by Abeta-induced engagement of specific molecular targets, rather than the previously held notion of passive cellular disruption by massive fibrils nonspecifically and inexorably destabilizing cell membranes. This altered view of the pathogenesis of Alzheimer's disease suggests multiple sites for future therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--CLINICAL Principal Investigator & Institution: Foster, Norman L.; Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2002 Summary: The Clinical Core promotes the goals of the MADRC and s3erves individual projects by recruiting patients for clinical research studies. Patients with Alzheimer' s disease and Alzheimer's mimics are identified at the University of Michigan with the help of collaborators in the Neurology and Geropsychiatry Clinics and the Neuropsychology Division and at Satellite Diagnostic and Treatment Centers located in Detroit and in rural Northern Michigan. This provides an ethnically diverse research population including rural and urban residing subjects reflecting the full range of disease severity from minimally symptomatic to severely impaired. Recruitment of normal control subjects is coordinated with the Human Subjects Core of the Pepper Older Americans Independence Center at the University of Michigan. Potential research subjects receive exclusion criteria. Demographic and caregiver data, dementia severity, neuropsychological performance, motor signs and behavior are characterized using standardized procedures. A subset of these patients who have named a health care advocate and are given provisional consent for an autopsy, and a cohort of normal individuals who have consented to an autopsy are periodically reassessed and serve as a resource for studies examining the clinical course of dementing disorders and clinicopathological correlations Nurses and social workers help recruit patients to research studies and provide patient and caregiver support and telephone contacts that encourage research participation and the cooperation of families in obtaining postmortem brain examinations. They assure appropriate subject selection and patient safety by coordinating participation in multiple studies. The Clinical Core provides consultation about clinical aspects of dementia to investigators and other Cores and plays a major role in educational and outreach activities of the Center. It promotes collaboration with other Alzheimer Disease Centers for datasharing and joint projects such as the Alzheimer Disease Cooperative Study. Data collected are linked to ongoing

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epidemiological studies of aging at the University of Michigan including the Assets and Health Dynamics Study of community dwelling elderly and the National Nursing Home Resident Assessment Instrument for elderly receiving institutional care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--CLINICAL RESEARCH Principal Investigator & Institution: Wilson, Robert S.; Associate Professor of Psychology; Rush-Presbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 01-APR-1991; Project End 31-MAR-2004 Summary: The proposed Clinical Core will identify and recruit persons who are eligible for the two proposed clinical projects, and follow a subset of participants in the clinical projects with annual clinical evaluations to identify incident cases of dementia and Alzheimer's diseases and to assess change in cognitive function. To accomplish these goals, the Core will have the following Specific Aims. 1. Recruit the following four groups of persons: a. older persons meeting accepted clinical criteria for Alzheimer's disease, b. older persons meeting clinical criteria for mild cognitive impairment, c. older persons without cognitive impairment, d. younger persons without cognitive impairment. 2. At initial evaluation, gather uniform clinical and neuropsychological data, in a highly structured fashion, applying uniform structure diagnostic criteria for Alzheimer's disease mild cognitive impairment and non cognitive impairment. 3. Review clinical data from the initial evaluation and distribute eligible subjects to the proposed clinical projects. 4. Follow older persons meeting clinical criteria for Alzheimer's disease, mild cognitive impairment and no cognitive and non cognitive impairment with annual clinical evaluations to assess change in cognitive function and, in those with mild or no cognitive impairment, to identify incident dementia and Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--NEUROPATHOLOGY Principal Investigator & Institution: Cochran, Elizabeth; Rush-Presbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 01-APR-1991; Project End 31-MAR-2004 Summary: The Neuropathology Core will provide brain tissue and diagnostic neuropathology evaluations on Alzheimer's disease patients and elderly individuals, both controls and those with mild cognitive impairment, to the researchers of the Program Project. This tissue will be obtained from subjects of the Rush Alzheimer's Disease Center Clinical and Religious Orders Study Cores. These individuals are closely following with annual neurological and neuropsychological examinations. There are four projects requiring brain tissue: project R07, Dr. J. Kordower, Dopaminergic mesocortical and nigrostrial system in mild cognitive impairment and Alzheimer's disease; project RO8, Dr. E. Mufson, Galanin remodeling in the progression of Alzheimer's disease; project R09, Dr. L. Binder, Tau truncation and conformation in Alzheimer's disease progression, and project RO10, Dr. J. Kuret, Protein kinase markers of Alzheimer's disease progression. Each project requires both frozen and fixed tissue from the following clinical categories: severe Alzheimer's disease, moderate Alzheimer's disease, mild Alzheimer's disease, mild cognitive impairment, and no cognitive impairment will be the Religious Orders Study Core. The Rush ADC Clinical Core and Religious Orders Study Core have provided an average of 36 and 20 cases, respectively, annually, over the last grant period. The Neuropathology Core will

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provide state-of-the-art neuropathological evaluation for Alzheimer's disease, using the NIA Consensus/Reagan diagnostic criteria. These criteria are uniformly applied and all data is directly entered into a computerized program at the time of collection. In addition, all stored tissue is indexed using a specimen tracking software program (FreezerWorks) facilitating reliable tissue distribution. The brain tissue and neuropathological data provided to the investigators of Projects 7, 8, 9, and 10 by the Neuropathology Core is critical for the success of the projects, and for the provision of seminal information about changes in the dopaminergic system and the functions of tau protein kinases and galanin in the progression of cognitive impairment in the elderly and those with Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE-NEUROTOXICOLOGY/NEURODEGENERATIVE DISEASE RESEARCH Principal Investigator & Institution: Graziano, Joesph H.; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: The developing nervous system is vulnerable to adverse effects due to exposures to a variety of substances in the environment, particularly metals and pesticides. At the same time, chronic exposure to low levels of neurotoxicants throughout life can lead to impaired neurologic functioning later in life, particularly in the elderly. As life expectancy increases, and the baby-boom generation approaches retirement age, neurodegenerative diseases such as IPD, Essential Tremor and Alzheimer's Disease will have a significant impact on quality of life, and will represent significant financial costs to the health care system. Collectively, the investigators in this research core are interested in understanding the extent to which, and mechanisms 295 whereby, populations exposed to known quantities of neurotoxicants suffer adverse consequences on the nervous system. The populations under investigation, which include birth cohorts in Yugoslavia and northern Manhattan, populations of adults and children chronically exposed to arsenic in drinking water in Bangladesh, and populations of the elderly in northern Manhattan, represent groups of individuals who have been remarkably well characterized for a variety of chemical exposures and other risk factors for adverse neurologic outcomes. At the same time, laboratory based scientists are exploring the mechanisms whereby the compounds of interest alter normal function. The overall goals of the Neurotoxicology/Neurodegenerative Disease Research Core are: I) to promote and facilitate interdisciplinary neuroscience-related research that will define the magnitude of effect of exposure to substances in the environment that are believed to be involved in the etiology of neurologic disease. These substances include metals (Pb, Mn, Fe and As), pesticides (chlorpyrifos, diazinon, propoxur, and others), 13- carboline alkaloids (harmane and harmine), and other factors; and 2) to unravel the cellular and molecular mechanisms whereby these substances exert their effects. The core is responsible for furthering the development of existing and new investigations of environmental exposures that affect the incidence and/or progression of diseases of the central and peripheral nervous systems. The Specific Aims currently under investigation include: 1) to define the cellular and molecular events involved in chemical models of Parkinsonism and in IPD, with the goal of defining those that are common to each; 2) to elucidate the environmental risk factors associated with the onset of IPD, Essential Tremor, and Alzheimer's Disease; 3) to examine, in both humans and animal models, the relationship between environmental Pb exposure and brain function, with particular interest in the possible mediating effects of Pb on thyroid

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hormone fate and transport; 4) to determine whether exposure to arsenic in drinking water is associated with adverse neuropsychologic effects in children, and polyneuropathy in adults; and 5) to develop biomarkers of prenatal pesticide exposure in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYCLOOXYGENASE AND ANTI-INFLAMMATORY DRUGS IN AD Principal Investigator & Institution: Pasinetti, Giulio M.; Professor; Psychiatry; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: Non steroidal anti-inflammatory drugs are among the most promising classes of drugs for the prevention and possibly treatment of Alzheimer's disease (AD). A rapidly increasing number of large-scale therapeutic trials of such drugs are being initiated. The most likely target of NSAIDs in the brain is cyclooxygenase (COX)-2. We found that COX-2, but not COX-1 expression, is elevated in the neurons of AD brain, where it correlates with amyloid plaque density and neuronal atrophy. In this revised application, using a combination of in situ hybridization and immunocytochemical techniques, we will further study the regional distribution and cell-type expression of COX-2 and other inflammatory markers in the AD brain. To determine the relationship between COX-2 expression in the AD brain and clinical measures of disease activity, COX-2 expression will be correlated with antemortem assessment of dementia. Because therapeutic trials of potential disease-modifying regimens select patients at one or more stages of clinical disease, these studies will determine the relationship between AD clinical stage and COX-2 expression. In parallel studies the effect of COX inhibitors on COX-2 mediated responses in the brain will be explored using a transgenic mouse model of human (h)COX-2 overexpression in neurons. In preliminary studies using primary neuron cultures derived from these transgenic mice, we found that hCOX-2 overexpression potentiates beta amyloid (Abeta) neurotoxicity in vitro through potentiation of oxidative stress mechanisms. We will use this model system to compare the neuroprotective activity of various COX inhibitors on Abeta toxicity in vitro, and to study the mechanism of such neuroprotection. Based in part on the outcome of these studies, we will then test the brain activity of NSAID regimens administered systemically. We have established in our preliminary studies that transgenic mice with neuronal overexpression of hCOX-2 show increased lipid peroxidation in brain as measured by levels of malondialdehyde (MDA) along with elevated prostaglandin (PG)F2alpha. Preliminary studies also indicate increased expression of components of the complement cascade in the brain of hCOX-2 transgenics. Based on our evidence that COX-2 in neurons is indeed the appropriate target for NSAID regimens in AD, this transgenic model provides a unique method of measuring relevant brain activity of COX inhibitors. The outcome of the proposed studies will be immediately relevant to the design of human trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYTOSKELETAL PROTEIN PHOSPHORYLATION IN APOPTOSIS Principal Investigator & Institution: Johnson, Gail V W.; Professor; Psychiatry; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-MAY-2004 Summary: (Verbatim from the Applicant's Abstract) During apoptosis the cytoskeleton of the cell undergoes dynamic alterations which result in the characterisitic

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morphological changes common to most apoptotic cells. Recently, using the classical paradigm of inducing apoptosis differentiated PC12 cells by withdrawal of serum and nerve growth factor (NGF), we demonstrated that the neuronal cytoskeletal protein tau is hyperphosphorylated at specific epitopes during apoptosis. Further, there are associated functional changes, as the microtubule-bindng capacity of tau from apoptotic cells is significantly reduced, and it is restored after dephosphorylation. This demonstrates directly that the increased phosphorylation of tau in cells undergoing apoptosis impairs the function of tau, and thus may contribute to the microtubule instability and the cytoskeletal based morphological changes of apoptotic cells. These findings are exciting both for the insight they provide for understanding the drastic morphological changes associated with apoptosis, and for the potential links between apoptosis in Alzheimer's disease and hyperphosphorylated tau. There is increasing evidence that apoptotic-like processes may contribute to the neuronal death in Alzheimer's disease, as well as other neurodegenerative disorders. In Alzheimer's disease brain, extensively hyperphosphorylated tau forms paired helical filaments (PHFs). In addition, the microtubule binding of PHF-tau is impaired, but can be restored at least partially by dephosphorylation. Thus, apoptosis during Alzheimer's disease may contribute to the formation of hyperphosphorylated tau that accumulated in this disease, thereby further emphasising the need to clarify the mechanisms that control tau phosphorylation in these conditions. In AD brain, cdc2, casein kinase1d (CK1d ) and cdk5 are elevated, and the investigators have found them to be increased during apoptosis as well. Considering these and other findings, the comprehensive working hypothesis is that during apoptosis tau is hyperphosphorylated at specific sites by specific protein kinases and this hyperphosphorylation results in compromised tau function, which contributes to the structural changes that occur during apoptosis. Elucidation of the changes in tau phosphorylation that occur during apoptosis will contribute towards the understanding of the processes that result in the hyperphosphorylation of tau in AD and other neurodegenerative disorders. The specific aims of this proposal are to test the hypotheses that: (1) during apoptosis tau is phosphorylated at specific sites and the increases in the activities of cdc2, CK1d and cdk5 are essential components of this process, (2) that the specific sites on tau that are phosphorylated in apoptotic cells modulate tau function and localization, and (3) that during apoptosis, tau with frontal temporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) mutations is differentially phosporylated and localized compared to wild type tau. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEMENTIA IN SWEDISH TWINS Principal Investigator & Institution: Gatz, Margaret J.; Professor; Psychology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 15-FEB-1990; Project End 31-JUL-2004 Summary: (Adapted from Applicant's Abstract). This application seeks continued support for the Study of Dementia in Swedish Twins to expand the sample by means of total ascertainment of all cases of Alzheimer's disease and other late-life dementias in the entire Swedish Twin Registry. The estimate is to complete data for over 200 pairs in which one or both is diagnosed with Alzheimer's disease, and 350 pairs in which one or both has any dementia diagnosis. Case identification will use telephone screening with all individuals in the sample, followed by informant interviews for those with evidence impairment, resulting in cognitive screening data from over 6000 complete pairs. Record linkage to health care utilization will be carried out as a parallel case identification

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strategy. Diagnostic assessment for those with a positive screening outcome will include medical evaluation, neuropsychological measures, neuroimaging, and informant interviews. Partners will receive the identical protocol, as will an independent sample of individuals who screened negative. Risk and protective factors will be obtained from the informant interview, medical records, and twin registry database, with occupational history linked to measured exposures. One longitudinal follow-up is included, and permission for autopsy will be requested. Data analyses using quantitative genetic approaches will address six questions: 1) What is the relative importance of genetic and environmental effects of Alzheimer's disease? 2) What are the best indices of the underlying genetic liability and of quantitative variability? 3) What non-genetic risk factors can be identified? 4) What influences age of onset? 5) Are there interactions between genetic and environmental risk factors? and 6) What is the covariation of liability to different types of disorder? Analytic techniques will include expansion of liability threshold models to mixed models, sex limitation models, use of measured genotype, bivariate models, and case-control methods using matched twin designs. Different diagnostic criteria will be compared. Quantitative indices will be derived from neuropsychological scores and from neuroimaging data subjected to quantitative mapping. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEMENTIA OF PARKINSON TYPE: CLINICOPATHOLOGIC PHENOTYPE Principal Investigator & Institution: Galvin, James E.; Assistant Professor; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: Parkinson's disease and Dementia with Lewy bodies (DLB) together comprise the second most common form of dementia after Alzheimer's Disease (AD). The signature pathologic lesions in these disorders are Lewy bodies (Lbs) found in cortical (DLB) and nigral (PD) neurons. Furthermore, a significant number of AD patients develop parkinsonian signs during the course of disease and many of these patients also are found to have Lbs on autopsy. Whether previously diagnosed with PDassociated dementia now would be classified as DLB is unknown. It is also unclear that PD alone can cause dementia occurs only in the presence of critical Lbs or AD-related pathology. The goal of this project is to characterize the clinicopathologic phenotypes of Dementia of the Parkinson Type (DPT). We propose to analyze the longitudinal studies of the Alzheimer's Disease Research Center (ADRC) for the clinical, motor, cognitive, behavioral, and pathologic characteristics of autopsy defined case of AD, PD and DLB in order to: 1) determine those clinical features that differentiate pathologically diagnosed DLB and PD from AD and from each other to establish the DPT phenotype; 2) identify differences between groups in pathologic features other than those used in the diagnosis by exploring the neuroanatomical correlates of the unique clinical symptomatology of DPT; and 3) to determine the best short set of clinical features for the diagnosis of pathologically defined DPT groups. The ADRC and the Department of Neurology at Washington University School of Medicine provide the candidate with an outstanding environment to develop his skills as an independent clinician-scientist. This K08 award will make available to the candidate protected time to complete the Specific Aims of the project and complete didactic courses in the ethical conduct of research, biostatistics and epidemiological study design. The research career development plan of the candidate is to use the mentored period to establish in the field of dementia research, specifically examining the role co-existent pathologies play in the onset, progression and unique

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characteristics of dementing disorders. At the completion of the award period, candidate plans to develop an independent R01 project derived from the data generated by the experiments described in this proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETECTION OF PRESYMPTOMATIC ALZHEIMER'S DISEASE BY FMRI Principal Investigator & Institution: Smith, Charles D.; Neurology; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2003; Project Start 30-SEP-1997; Project End 31-DEC-2007 Summary: (provided by applicant): Alzheimer's disease (AD) is preceded by a period when detectable changes in brain function occur without warning symptoms. This period may be twenty years or longer. Activation measured by functional magnetic resonance imaging is reduced during confrontation naming in normal women who have increased risk of late-onset Alzheimer's disease, at an average age of only 53 years. These same individuals have reduced activation in the posterior cingulate cortex during a memorization task, among other disparities. Our hypothesis is that the altered functional MRI responses in naming, working memory and memorization will quantifiably worsen with age, due to progressive underlying Alzheimer's disease pathology. Disease-modifying treatments applied in this early, pre-symptomatic stage of AD could have profound impact, by preventing the onset of cognitive symptoms. Millions are currently being spent on large-scale prevention trials, with AD symptoms as end-points. By providing a biomarker of pre-symptomatic AD progression, fMRI could potentially reduce the duration and costs of such trials. This continuation proposal is designed to detect changes in brain function in high-AD risk individuals over time. We will study normal education-matched groups of high- and low-AD risk subjects in the age ranges 40-65 and 65-90 years, using fMRI stimulus tasks which have previously demonstrated regional disparities in high-AD risk individuals. In addition, we will repeat the naming and fluency fMRI studies performed previously in high- and low-AD risk individuals after an interval of five years, in order to detect longitudinal changes in activation. The convergence of evidence from these cross-sectional and longitudinal studies could provide powerful evidence for a model of Alzheimer's disease as a relentless, slowly progressive brain pathology that begins early in adult life, but remains compensated until it produces clinical symptoms in its late stages. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEVELOPMENT OF NOVEL MUSCARINIC AGONISTS Principal Investigator & Institution: Messer, William S.; Medicinal & Biological Chemistry; University of Toledo 2801 W Bancroft St Toledo, Oh 43606 Timing: Fiscal Year 2001; Project Start 08-AUG-1994; Project End 31-JUL-2003 Summary: Applicant's Abstract) The neurotransmitter acetylcholine mediates a variety of responses within the central nervous system and plays an important role in memory function and cognition. Cholinergic cells within the basal forebrain denerate in Alzheimer's disease, a disorder associated with memory dysfunction and progressive cognitive decline. Research efforts have focused on developing selective M1 muscarinic agonists for the treatment of Alzheimer's disease. Over the past few years, several putative M1 agonists have been identified. The proposal focuses on the design, synthesis, and biological testing of novel compounds as selective muscarinic ligands. Chemical synthesis focuses on exploring a radically new approach to the development

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of muscarinic agonists, based on a novel series of bis-thiadiazole derivatives that display very high potency and activity at M1 receptors. Structure activity and molecular modeling studies will help identify the molecular features that contribute to activity and provide a basis for the rational design and synthesis of new ligands. In addition to pharmacological characterization of new compounds, biological studies will compare the affinity and efficiacy of several putative slective M1 muscarinic agonists at muscarinic receptors expressed in cultured cell lines and in the brain. Further studies will examine the ability of a few active and slective compounds to penetrate into the brain and reverse memory deficits associated with lesions of the septohippocampal cholinergic system. The overall goals of the project are to identify ligands with improved selectivity for muscarinic receptor subtypes, thereby providing important new pharmacological tools. A compound with high M1 agonists activity and the ability to penetrate into the brain also could become a drug candidate for the treatment of Alzheimer's disease. These studies will help determine the therapeutic utility of selective muscarinic agonists in the treatment of Alzheimer's disease. In addition the research could provide new approaches to the synthesis of compounds useful in a variety of neurological disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISSECTING PATHOGENIC DOMAINS OF APP IN TRANSGENIC MICE Principal Investigator & Institution: Ashe, Karen H.; Professor; Neurology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-AUG-1994; Project End 31-JAN-2004 Summary: The broad, long-range objective of these studies is to define the molecular basis of neuronal dysfunction in Alzheimer's disease. We have developed transgenic mice expressing the amyloid precursor protein (APP) for animal studies of Alzheimer's disease (Hsiao et al., 1996). These mice simulate several behavioral and neuropathological features of Alzheimer's disease. We propose to delineate the molecular domains of APP responsible for these behavioral and neuropathological abnormalities. Because hundreds of researchers around the world have begun using these mice as a model for Alzheimer's disease, we feel compelled to dispel even the slightest doubts about the reproducibility of the phenotypic traits we observed. Therefore, we shall embark upon producing another line of mice over-expressing mutant human APP exhibiting both age-related behavioral and pathological abnormalities simulating Alzheimer's disease in humans in AIM #1. In AIM #2 we shall examine the role of alphabeta in producing age-related neural dysfunction in the brain. By comparing the behavioral and neuropathological profiles of transgenic mice expressing wild-type APP and APP lacking the alphabeta domain to transgenic mice over-expressing mutant APP we shall determine which biological and behavioral abnormalities are due to alphabeta accumulation and which can be attributed solely to APP over-expression. Elucidating the role of alphabeta in functional brain abnormalities in Alzheimer's disease is a critical and timely question that can now be approached by studying neural dysfunction in transgenic APP mice. We shall also distinguish between the more and less amyloidogenic forms of alphabeta, alphabeta40 and alphabeta42(43), by comparing, by comparing behavioral and neuropathological profiles of transgenic mice expressing APP with the Swedish (KM670/671 NL) and London (V717I) mutations. In Aim #3 we shall determine whether the KPI domain in APP influences the onset and rate of amyloid formation. In different laboratories APP isoforms with or without KPI domains have both been used to generate transgenic mice developing

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amyloid plaques (Games et al., 1995; Hsiao et al., 1996; Sturchler-Pierrat et al., 1997). Although the topographical and morphological features of the amyloid deposits are remarkably similar in these mice, the presence or absence of the KPI domain in the APP transgene might account for differences in the chronological appearance and amount of alpha/beta deposition. Whether the KPI domain alone can explain these differences remains unresolved because of slight potential variations in APP levels and differences in promoters used to drive APP expression in the two lines of mice. To answer this question we shall compare alphabeta levels, temporal patterns and extent of alphabeta deposits, as well as profiles of behavioral impairment in transgenic mice, expressing mutated APP with and without the KPI domain driven at comparable levels by the identical promoter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EARLY EVENTS IN ALZHEIMER PATHOGENESIS Principal Investigator & Institution: Griffin, Sue T.; Professor; Geriatrics; University of Arkansas Med Scis Ltl Rock 4301 W Markham St Little Rock, Ar 72205 Timing: Fiscal Year 2001; Project Start 01-JUN-1995; Project End 31-MAY-2002 Summary: The objective of this Program Project is to critically evaluate a hypothesized cytokine cycle of molecular and cellular events that we propose is important in the pathogenesis of Alzheimer disease. Effector- stimulated microglial activation with synthesis and release of the glial inflammatory cytokine interleukin-1 (IL-1) is seminar in this cycle. IL- 1-based actions include (i) induction of over-expression and processing of beta-amyloid precursor protein (betaAPP) in neurons (leading to beta- amyloid deposition, cell death and release of secreted APP, stimulating further expression of IL1); and (ii) activation of astrocytes and release of S100beta (increasing the potential for cell death by promoting increases in intraneuronal calcium, by promoting synthesis of beta-APP, and by inducing overgrowth of dystrophic neurites) and with synthesis and release of ApoE (which may bind to beta-amyloid and stabilize it). Alzheimer's disease is inherently progressive, and any sequence of events hypothesized to significantly contribute to the pathogenesis of this disease must explain this progression., and any sequence of events hypothesized to significantly contribute to the pathogenesis of this disease must explain this progression. We postulate, in view of IL-1 based actions, and the potential of chronic IL-1 over-expression to promote neuronal injury and death, that the progression of Alzheimer's disease may be driven by this potentially self propagating, self sustaining sequence events. We will determine the role of glial inflammatory processes in neuronal cell injury and death in Alzheimer's disease and in epilepsy, which predisposes to early Alzheimer-type changes. We will also determine temporal and spatial relationships between glial inflammatory processes and neuronal cell injury and death in Down's syndrome and following head injury, and the modulating effects of genotype on these processes. We will also use transgenic animals over-expressing S100beta or betaAPP to define mechanisms responsible for these relationships. Cell culture models will be used to define mechanisms by which glial inflammatory proteins modulate neuronal cell injury and death. Accomplishment of the goals of this Program will yield results of direct benefit to the identification of basic elements in Alzheimer pathogenesis and provide targets for development of therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENVIRONMENTAL CAUSES OF SPORADIC ALZHEIMER'S DISEASE Principal Investigator & Institution: Charlton, Clivel G.; Professor and Chairman; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: This study will test a proposition that environmental toxins are involved in the cause of Sporadic AIzheimer's disease (AD) by inducing, early in life, a less resilient but functional set of Nucleus Basalis of Meynert (NBM) acetylcholinergic (Ach) neurons that cannot withstand the stress placed on them later in life. Two stages of afflictions, therefore, are involved. The 1st is a predisposing or sensitizing stage that occurs early in life, causes mostly epigenetic changes that impair the phenotype and/or reduce the number of the NBM Ach neurons. The 2nd superimposing/precipitating stage occurs when age-related wear-and-tear or other interventions damage the already susceptible NBM neurons and precipitate AD. The project will identify interventions that will mimic the two stages. The plant-derived tubulin assembling inhibitors, colchicines; the fungal-derived protein synthesis inhibitor, puromycin, and the fungal and plantsderived mitochondrial toxin, 3-nitroproprionic acid (3-NP) will be administered during the period of differentiation of the NBM Ach neurons of the embryos in timed-pregnant mice to induce the 1st stage. Age-related studies will verify the trans-placental or indirect in utero changes related to memory functions and the anatomy and histochemistry of the NBM Ach neurons, thus testing the vulnerability of the neurons to the wear-and-tear of life. The anticholinergic agent, scopolamine, that causes amnesia will be used, also, to mimic the 2nd stage and rationally to precipitate Alzheimer's disease-like changes in the pups. It is proposed that the ED50 for the induction of amnesia will be lower in the 1st stage treated mice, as compare to control. A new model for AD may be identified, based on chemically producing a less resilient but functional NBM Ach neuronal phenotype early in life and stressing those susceptible neurons later in life. Interventions that prevent or delay the toxic responses will be tested. This concept is relevant to the role of the environmental in about 90% of AD cases, and it may be used to study other neurodegenerative disorders but focusing on other neuronal sets. The mechanisms that underlie the proposed sensitization and precipitating stages, such as DNA and RNA editing and protein modifications, will be studied in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY, PATHOLOGY, AND PARKINSONISM IN AGING Principal Investigator & Institution: Schneider, Julie A.; Rush-Presbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: This 5-year clinical scientist development award proposes the use of quantitative epidemiologic principles to relate post-mortem findings to neurologic conditions associated with aging. A spectrum of parkinsonian signs, including bradykinesia, rigidity, tremor, and gait imbalance are common in older persons without Parkinson's disease, and are associated with increased morbidity and mortality. The nigrostriatal system also shows a spectrum of change with age. Preliminary data suggest that nigral neurofibrillary pathology is more common than previously recognized and is related to parkinsonian signs in older persons with and without Alzheimer's disease. The proposed studies will relate nigral neurofibrillary pathology and biochemical nigrostriatal changes to quantitative measures of global and specific parkinsonian signs in older persons with and without Alzheimer's disease. We will test the hypotheses that

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neurofibrillary pathology, specifically within the pars compacta of the substantia nigra, rather than the ventral tegmental or retrorubral areas, accounts for parkinsonian signs in older persons with and without AD, and that the mechanism by which neurofibrillary pathology produces parkinsonian signs involves decreased gene expression of tyrosine hydroxylase and a reduction in striatal dopamine, but not neuronal loss. We will also determine the role of mitochondrial mutations in the pathogenesis of neurofibrillary pathology and parkinsonian signs. The proposed project will use brain tissue of 80 older persons, without Parkinson's disease, in The Religious Order Study, a longitudinal study of over 650 catholic clergy who have agreed to annual examinations and brain donation after death. The proposed study will provide the Candidate in the opportunity to work with senior colleagues and allow the development of a unique research area that integrates the clinical neurology and neuropathology training. Through the course of these studies and analyses, through didactic sessions with her sponsors and consultants, and related course work, the candidate will develop the skills necessary to become an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ERP INVESTIGATIONS OF NOVELTY PROCESSING IN AGING AND AD Principal Investigator & Institution: Daffner, Kirk R.; Chief, Division of Cognitive and Behavio; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant) Attention to novel events facilitates adaptation to a changing environment and may increase engagement with one?s surroundings and enhance cognitive abilities. Despite its importance, there has been limited study of ageand disease-related changes in how the brain processes novel events. Based on the PI?s research, a provisional model of a neurally-based novelty processing system is presented. Building upon this work, the proposed research will investigate age-related changes in the novelty P3 response and subsequent allocation of attention to novel stimuli (as measured by viewing durations) in order to elucidate the relationship between responsiveness to novelty and different patterns of cognitive aging. The research aims to distinguish between changes in response to novelty that appear to be inevitable (observed with even the most successful cognitive aging), changes that are most commonly seen with usual cognitive aging, and changes that are associated with the most frequent degenerative disease of the brain (Alzheimer?s disease). A carefully designed series of experiments will test hypotheses about: 1) age-related changes in response to novelty among groups of cognitively high performing individuals; 2) differences in response to novelty between cognitively high and mid performing older individuals; 3) age-related changes in response to novelty among groups of individuals that differ in level of cognitive performance; 4) differences in response to novelty between cognitively normal individuals and cognitively impaired ones (with mild Alzheimer?s disease); and 5) the relationship between the novelty P3 response and subsequent attention to novel events in the laboratory and level of engagement in daily activities. These integrative functional and cognitive neuroscientific studies will extend previous work on the neurology of attention to novel events and provide new insights into the ways in which this fundamental aspect of human behavior is related to normal aging and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONAL ANALYSIS OF ASTROCYTE DERIVED APOE3 AND APOE4 Principal Investigator & Institution: Niven, Anne F.; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 15-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from the application) The candidate (Anne Fagan Niven) received her Ph.D. in Neuroscience from the University of California, San Diego in 1992, and has a history of productive research investigating neuronal plasticity in the developing and injured nervous system. The candidate has expertise in cognitive neuroscience, neuronal development, neuroanatomy, and molecular neurobiology. Recent work at Washington University School of Medicine (WUSM) has fostered an interest in the etiology of neurodegenerative disease, in particular, the mechanism(s) by which apolipoprotein (ApoE) E4 is a risk factor for Alzheimer's disease (AD). Since ApoE is known to be an important regulator of plasma cholesterol metabolism, proper investigation of its role in AD, as well as in the normal brain, will require knowledge of: 1) AD, 2) cell biology, and 3) cholesterol/lipid metabolism, areas in which the candidate has little background. The proposed plan will provide the candidate with an additional period of mentored research in order to gain expertise in these three areas. The immediate career goal is to initiate a research program investigating the connection between ApoE4 and AD. Importantly, the scientific and technical expertise gained in the course of these studies will allow the candidate to attain her long-term goal; to establish an independent, multidisciplinary research career in neuroscience, with an emphasis on neuronal growth and repair as it relates to neurodegenerative disease. In the proposed study, it is hypothesized that brain-derived lipoproteins containing ApoE4 are inherently different in their composition/structure than those containing ApoE3, which in turn affects their ability to transport cholesterol/lipid, and/or affect AB metabolism. Utilizing transgenic mice which express human ApoE3 or ApoE4 by astrocytes, the candidate will characterize the composition/structure of astrocyte-derived lipoprotein particles and test their ability to transport cholesterol/lipid and affect AB metabolism in vitro and in vivo. David M. Holtzman, M.D (mentor) will provide training in AD, models of neurodegenerative disease, and cell biology; Alan L. Schwartz, M.D., Ph.D. (co-mentor), cell biology; and consultants, cell biology and lipid metabolism. WUSM, the Department of Neurology, and its associated Alzheimer's Disease Research Center has wellestablished research programs and a renowned group of faculty committed to research, education, and training. The many educational and technical resources available to the candidate at WUSM, in combination with the strong research programs of the mentor, co-mentor, and consultants, will provide the comprehensive training necessary to achieve her career goals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC KNOWLEDGE AND ATTITUDES IN ALZHEIMER'S DISEASE Principal Investigator & Institution: Blacker, Deborah L.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: This is a resubmission of Genetic Knowledge and Attitudes in Alzheimer's Disease (1 R01 HG0183), which addresses the ethical, legal, and social implications Alzheimer's disease (AD) genetics from the critical perspective of a group at high risk for the disease: currently unaffected relatives in families with AD. The applicants--at

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Mass General Hospital/Harvard Medical School and the University of Alabama--have been working together since 1990 as part of the NIMH Genetics Initiative to identify families with Alzheimer's disease for a genetic linkage study. Nearly 350 such families, predominantly affected sibling pairs and over 300 of their unaffected siblings, have been collected. Regular follow- up of unaffected subjects is in process in order to monitor them for disease onset and assess the role of risk factors for AD, and there are approximately 200 additional unaffected siblings in study families. In the present proposal, the two centers will study knowledge, attitudes, and behavior related to genetic studies and genetic testing in the unaffected individuals in these AD families and their primary care physicians, and will develop and pilot educational materials designed to address their needs for genetic information. Information about the ethical, legal, and social implications is just as critical as that about inheritance patterns and risk probabilities. We will employ a broad approach including qualitative as well as quantitative methods in order to capture the complexity, uncertainty, and subjectivity in this new realm. Given the growing prevalence, devastating symptoms, and prodigious social cost of AD, the recent flurry of developments in AD genetics has received extensive attention both from the popular press and from advertisers touting putative genetic tests. Those whose family history puts them at increased risk for AD are especially vulnerable to misinformation. Their primary care physicians are also illprepared to address these issues. The genetic educational materials for laypeople and physicians to be developed and tested in the present proposal strive to meet their current needs for accurate information, to prepare them for future challenges, and to supply models for genetic education in other complex diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENOMIC SCREEN TO IDENTIFY ALZHEIMERS DISEASE GENES Principal Investigator & Institution: Vance, Jeffery M.; Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 20-FEB-1997; Project End 31-JAN-2008 Summary: (provided by applicant): To identify genes influencing age at onset (AAO) in two common neurodegenerative diseases, we performed a genomic screen for AAO in families with Alzheimer disease (AD;) and Parkinson disease (PD. (Li et al, AJHG, April, 2002). Heritabilities between 40 percent-60 percent were found in both the AD and PD datasets. For PD, significant evidence for linkage to AAO was found on chromosome 1p (LOD =3.41). In addition, evidence for AAO linkage on chromosomes 6 and 10 was identified independently in both the AD and PD data sets. Subsequent unified analyses of these regions identified a single peak on chromosome 10q between D10S 1239 and D10S 1237, with a maximum LOD score of 2.62. These data suggest that a common gene affects AAO in these two common complex neurodegenerative diseases. We propose to further map and identify the genes contributing to this age-of-onset effect. We will continue to collect new AD and PD families to further map the peaks, and test candidate genes within the region for association to age of onset in these two disorders. Candidates will be prioritized using initially obvious biological candidates, then candidates that lie within the linkage peaks that are identified through Serial Analysis of Gene Expression and Microarray studies in both AD and PD (being performed in our lab in concurrent studies) and finally through fine mapping of the linkage peak for high areas of association using a DNA pooling approach and a new Single base pairdenaturing high performance liquid chromatography methodology. Candidates lying within these high association areas will be investigated further. Once identified, the genes will be investigated in collaboration with known mouse models, at present the

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Parkin model of Dr. Jian Feng and the APOE models of Dr. Don Schmechel of the DUMC Alzheimer Disease Research Center. Identifying age-of-onset genes may lead to treatment and delay of these late-onset disorders and a better understanding of the pathological processes they share. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENOMIC SCREEN TO IDENTIFY ALZHEIMERS DISEASE GENES Principal Investigator & Institution: Pericak-Vance, Margaret A.; Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 20-FEB-1997; Project End 31-JAN-2003 Summary: This proposal is a continuation of our grant to delineate the genetics of Alzheimer disease [AD], the most common form of dementia after age 40. Within the past five years, four AD genes have been described. APP, PS-I and II are autosomal dominant causative loci in early (<60) familial AD but represent <2% of all AD cases. The vast majority of cases are late- onset familial or sporadic AD. Through the present grant, the laboratories of Drs. Pericak-Vance and Haines were the first to describe the increased risk related to the APOE-4 allele and the protective effect of the APOE-2 allele. By all estimations, APOE accounts for approximately 50% of the total predicted genetic effect and is the single most important biological risk factor yet identified in AD. Although this finding has dramatically changed the focus of AD research, another 50% of genetic etiology of AD remains unexplained. In addition to delineating the APOE effect, we have completed a genome screen using our initial set of extended late-onset pedigrees and have identified several regions deserving more scrutiny. We have now expanded our data set from 52 to 200+ multiplex late-onset AD families (250+ sampled affected sibpairs) and have 500+ sporadic AD patients and 300+ spouse controls. We also have identified the genetically isolated Indiana Amish population who, despite having a lower prevalence of AD and a decreased frequency of APOE-4, maintain familial aggregation. The above resources permit a more detailed and sophisticated genome screening and analyses to identify all major and moderate genetic effects in AD, something not possible even three years ago. We will use newly described sibpair and affected- relative-pair analyses in conjunction with lod score analysis to make greatest use of the screening data. We will also examine gene/gene interactions between the regions we (or others) conform as harboring AD genes. The ultimate goal of our proposal is the identification of all major loci involved in AD, the first step in combating this devastating neurodegenerative disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENOMIC SEARCH FOR SUSCEPTIBILITY--ALZHEIMER DISEASE Principal Investigator & Institution: Goate, Alison M.; Professor; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: Studying the genetics of Alzheimer's Disease (AD) has added significantly to our understanding of the disease. During the last six years it has been established that familial early onset Alzheimer's disease (FAD) is a genetically heterogenous disease that can be caused by mutations in at least three different genes: the beta-amyloid protein precursor (APP) gene on chromosome 21, the presenilin 1 (PS-1) gene on chromosome 14 and the presenilin 2 (PS-2) gene on chromosome 1 (1-3). Since other families exist that do not carry mutations within any of these genes it is very likely that there are other as yet unidentified FAD genes. In vitro experiments suggest that

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mutations in each of the known genes cause AD through changes in APP processing that lead to elevated levels of total Abeta or specifically increase Abeta42 (4). This provides strong support for the "Amyloid Hypothesis" of AD pathogenesis. The study of the genetics of late onset AD has also led to the identification of the first genetic risk factor for AD. The epsilon 4 allele of the apolipoprotein E (ApoE) gene has been shown to increase risk for AD in every population studied although the magnitude of the increase in risk varies between populations. Although it is still uncertain how the ApoE4 allele increases risk for AD there is some evidence to support the hypothesis that ApoE4 modifies amyloid deposition by an unknown mechanism. However, since there are many individuals with AD who have no ApoE4 alleles there must be other risk factors for late onset AD. We hypothesize that at least some of these risk factors are genetic and that they may also modify amyloid deposition. The aim of this proposal is to use a genetic linkage strategy to identify new genetic risk factors for late onset AD. As our test sample we will use three hundred caucasian sib pairs with an age of onset of AD over the age of sixty five years to perform a 20cM genome-wide screen using microsatellite markers. Genomic regions showing evidence of linkage will be followed up with flanking markers in the same sample and in a second sample of equivalent size also selected on the basis of racial origin and age of onset. It is anticipated that by restricting the racial origin and age of onset of our initial samples we will reduce the likely genetic heterogeneity and increase our chances of detecting a second risk factor. Candidate genes in genomic regions that continue to show evidence of linkage will then be followed up using a case control association approach in caucasians and in other ethnic groups. Finally, we will complete a 20cM genome screen in the replication sample increasing the effective sample size to 600 sib pairs, enabling us to look for genes of smaller effect size. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLIAL CYTOKINES AND NEURONAL DEATH Principal Investigator & Institution: Van Eldik, Linda J.; Professor; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: This Project will examine the link between selected glial neuroinflammatory responses and neuronal cell death. The hypothesis to be tested is: Overproduction or sustained production of potentially detrimental biomolecules (NO and proinflammatory cytokines) by activated glia contribute to neuronal death. Insight into which of these pathways can be readily modulated by endogenous factors or synthetic ligands will provide a firm foundation for future drug discovery efforts towards developing new therapeutics for Alzheimer's Disease (AD). We will address several fundamental questions about glial cytokine production and its linkage to neuronal cell death. These include: what glial cytokines contribute to neuronal death and what pathways are potential targets for inhibition of cytokine-dependent neuronal cell death? The focus will be on: (i) beta-amyloid (Abeta)-induced upregulation of inducible nitric oxide synthase (iNOS), and its potentially neurotoxic product, nitric oxide (NO) and NO metabolites such as peroxynitrite; (ii) the Abeta-induced increases in proinflammatory cytokines interleukin (IL)-1beta, tumor necrosis factor (TNF)alpha, and S 100B; (iii) comparison of the neurotoxic effects of these glial derived products to those of direct Abeta effects on neurons; and (iv) discovery of ligand modulators of signaling pathways key to neuronal cell death. In aim 1, we will define at the molecular level what is meant by glial cytokine-dependent neuronal cell death. Glial/neuronal co-culture models, in vivo administration of cytokines, and animal models of neuroinflammation and disease

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will be utilized. We will determine the potential common and distinct elements between cytokine-dependent and -independent neuronal death by focusing on key elements of standard themes that have been implicated previously in cell death mechanisms, particularly MAP kinase (MAPK)-regulated pathways and death domain signaling pathways involving death receptors like TNF receptorl (TNFR1) and death kinases like death associated protein kinase (DAPK). In aim 2, we will discover ligand modulators of cytokine-dependent neuronal cell death. Chemical genomics approaches will allow the discovery of small molecule modulators of neuronal cell death and death kinases. Pathway selective inhibitors will allow probing of the relative contribution of distinct signaling pathways to common biological end points. Potentially efficacious synthetic compounds will be tested in animal models of neuroinflammation and disease. Our results will have a potential broad impact on basic restarch in areas such as signal transduction and glialneuronal interactions as well as provide insight into possible new therapeutic approaches to neurodegenerative disorders such as Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLIAL NEURONAL INTERACTION IN ALZHEIMERS DISEASE Principal Investigator & Institution: Griffin, W S.; University of Arkansas Med Scis Ltl Rock 4301 W Markham St Little Rock, Ar 72205 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2002 Summary: The objective of Project 1 is to address the idea that glial inflammatory changes with over-expression of glia-derived cytokines, in particular interleukin-1 (IL-1) and S100beta, are primer movers in a cascade of events that lead to neuronal cell injury and death in the early pathogenesis of Alzheimer's disease (AD). These cytokine-driven cascades of neuronal dysfunctions include early over-expression of betaAPP, accumulation of neurofibrillary tangles, overgrowth of betaAPP- over-expressing neurites, appearance of neuropil threads, and eventually cell death. Chronic activation of these cytokine-drive neurodegenerative cascades can in turn promote further overexpression of IL-1. In this way these cytokine-driven cascades may become selfpropagating as illustrated in the "cytokine cycle". To elucidate aspects of this cycle, we will use molecular techniques to: 1) Define the relationship of glial inflammation to neuronal cell injury (as evidenced by betaAPP over- expression and neurofibrillary tangle formation in neurons, neurites and in neuropil threads, as well as by synaptic changes) and neuronal cell death (as evidenced by TUNEL positivity) in Alzheimer's disease. These will be correlated with the incidence of: i) associated activated microglial over-expression IL-i); ii) associated activated microglia over-expressing IL-1; ii) associated activated astrocytes over- expressing S100beta; iii) associated beta-amyloid plaques of different types; and iv) stages of neurofibrillary tangle formation. 2) Define the temporal and spatial relationships of glial inflammation to neuronal cell injury and death in conditions predisposing to Alzheimer's disease or to accelerated Alzheimertype senile changes. For this we will use material from patients with Braak and Braak stages of I-IV of Alzheimer- related changes, with Down's syndrome, with head injury, and with epilepsy. 3) Examine the extent and nature of altered glial cytokine expression and of neuronal cell injury and death in genetic animal models with altered expression of cytokine cycle elements. These include betaAPP transgenic mice and S100beta transgenic mice. 4) Assess the local and remote effects of exogenous glial cytokines in vivo, using intracerebral implants of timed-release pellets containing specific glial cytokines and other cytokine cycle molecules. Successful completion of these specific aims will provide information regarding the progression of neuropathological changes

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and highlight targets for therapeutic strategies to slow the clinical progression of Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GSK3BETA: SIGNALING AND APOPTOSIS Principal Investigator & Institution: Jope, Richard S.; Psychiatry; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Glycogen synthase kinase-3beta (GSK3b) is linked to most key aspects of Alzheimer's disease. These include: GSK3b phosphorylates tau and amyloid precursor protein, Abeta peptide activates GSK3b and inhibition of GSK3b protects from Ab-toxicity, and presenilin-1 binds and regulates the activity of GSK3b, actions altered by mutant presenilin-l. Also, GSK3b impairs neural plasticity, facilitates apoptotic signaling cascades, and inhibits the activities of multiple transcription factors (CREB, AP-1, NFkB, myc, b-catenin, and others), all actions likely important in Alzheimer's disease. These actions and associations indicate that GSK3b may be an important modulator of neuropathological processes associated with Alzheimer's disease as well as other neurodegenerative conditions, but much remains to be learned about the actions of GSK3b. The overall goal of this project is to investigate mechanisms regulating GSK3b and to delineate its effects on cell function, especially neural plasticity and apoptosis. The aims are based on our findings that (i) thapsigargin, which increases intracellular calcium levels and causes endoplasmic reticulum (ER)-stress, conditions associated with Alzheimer's disease, activates GSK3b, and GSK3b is obligatory for thapsigargin-induced apoptosis, (ii) apoptotic stimuli cause intranuclear accumulation of GSK3b, and (iii) GSK3b inhibits the function of the key transcription factor CREB. Specific Aim 1 will test the hypothesis that GSK3b is activated by, and is a critical mediator of, toxicity induced by thapsigargin and other agents perturbing calcium or the ER, and will identify the mechanisms involved in GSK3b activation and assess the regulatory roles of GSK3b-binding proteins. Specific Aim 2 will test the hypothesis that apoptotic stimuli induce nuclear accumulation of GSK3b, identify the mechanisms controlling the intranuclear distribution of GSK3b, and test if nuclear GSK3b contributes to apoptotic signaling. Specific Aim 3 will test the hypothesis that GSK3b has dual functions in apoptosis, both attenuating antiapoptotic signals, with a focus on survivalpromoting transcription factors, and facilitating proapoptotic signals connecting ER stress to caspase activation. Overall, these experiments will clarify mechanisms regulating GSK3b and its effects on neural plasticity and survival. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IL-1 INDUCED MEDIATORS OF CNS INFLAMMATION AND AD-COXPrincipal Investigator & Institution: O'banion, Michael Kerry.; Associate Professor; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 28-APR-2000; Project End 31-MAR-2003 Summary: (adapted from applicant's abstract): Inflammation-related changes are a prominent part of the CNS response to acute injury, infection, and chronic neurodegenerative disease. Numerous studies indicate that attenuation of CNS inflammation may be beneficial in treating CNS disorders, including Alzheimer's disease (AD). Microglia and astrocytes play a significant role in the initiation and maintenance of CNS inflammation by producing a wide-range of inflammation-related

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gene products. Elaboration of inflammatory responses elicited by both acute and chronic stimuli depends on key molecular players that drive interactions among cells. One of these players is IL-1 beta proinflammatory cytokine strongly implicated in acute CNS inflammation as well as AD. Based on studies of peripheral inflammation, another key player is likely to be prostaglandin E2 (PGE2) produced by the inflammation-responsive protein, cyclooxygenase-2 (COX-2), one of two isoforms of the obligate enzyme for prostaglandin biosynthesis. COX-2 is made in brain and can be induced by IL-1 beta and other proinflammatory cytokines in astrocytes and microglia. Moreover, preliminary studies indicate that selective inhibition of COX-2 attenuates the expression of inflammation-related genes following acute CNS injury. Based on these findings and epidemiological evidence that inhibitors of cyclooxygenase may be beneficial in AD, this competitive renewal focuses on the role of COX-2 in CNS inflammation. The hypothesis that COX-2 derived prostaglandins are required for elaboration of acute as well as chronic local inflammatory responses in the central nervous system will be tested in three different model systems. The first specific aim will characterize direct influences of COX-2 and PGE2 on expression of IL-1 beta responsive genes in primary cultures of human and murine astrocytes. In the second specific aim, the contributions of COX-2 and PGE2 to an acute inflammatory cascade elicited by cortical injection of IL-1 beta will be established. In the third and fmal specific aim, COX-2 specific inhibitors will be employed in double transgenic PS-1/APP mice to ascertain the role of COX-2 in chronic CNS inflammation secondary to Abeta deposition. Together, these studies examine the role of COX-2 and increased prostaglandin production in CNS inflammation and a model of Alzheimer's disease. This work will provide a clearer understanding of the mechanisms by which anti-inflammatory drugs influence AD and may reveal new avenues for therapeutic intervention. Moreover, these studies have relevance to pathological processes occurring in head trauma, stroke, and other neurodegenerative diseases where gliosis and inflammation-related changes take place. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOTHERAPY OF ALZHEIMER'S DISEASE Principal Investigator & Institution: Raso, Victor A.; Senior Scientist; Boston Biotechnology Corporation Watertown, Ma 02472 Timing: Fiscal Year 2001; Project Start 15-APR-1998; Project End 31-DEC-2003 Summary: The beta-amyloid peptide and the cerebral plaques that it forms are likely either the direct or indirect cause of Alzheimer's disease. This peptide is produced in both the brain and peripheral tissues by cleavage from a common cell-surface precursor protein. Soluble beta-amyloid exists free in the blood and cerebrospinal fluid while "insoluble" aggregates are deposited in the brain as amyloid plaques. The soluble and insoluble forms of beta-amyloid present within Alzheimer's patients appear to be in dynamic equilibrium. In the Phase I proposal we described how to displace this equilibrium away from the brain by generating peptide-specific antibodies in a transgenic mouse model of Alzheimer's disease. Recent studies have shown that, as we predicted, this beta-amyloid vaccine approach can prevent plaque formation in young mice and dissipate preestablished plaques in older mice. Those preclinical experiments used complete Freund's adjuvant to help elicit an immune response but such preparations are not approved for use in humans. Therefore Phase II will focus on producing and testing in animals several alternative adjuvant and antigen formulations which are compatible with clinical standards. Our expressly designed beta-amyloid antigens and adjuvants would form a basis for the immunotherapy of Alzheimer's disease using highly specific beta-amyloid vaccines. PROPOSED COMMERCIAL

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APPLICATIONS: The high-potency, human-compatible vaccines produced in this Phase II project have tremendous potential for use in either treating or preventing Alzheimer's disease. If successful the vaccine approach could help the large number of patients who are already suffering from the disease. It might also be used to prevent or delay the onset of disease in those who are at high risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IN VITRO IN VIVO MODELS OF ALZHEIMER'S DISEASE Principal Investigator & Institution: Lee, Virginia M.; Professor; Pathology and Lab Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-SEP-1997; Project End 31-AUG-2008 Summary: (provided by applicant): The competing renewal of this Program Project grant (PPG) builds on important research conducted during the last 10 years in the development of in vitro and in vivo models of Alzheimer's Disease (AD) amyloidosis for the purpose of elucidating mechanisms leading to the regulation of amyloid beta (Abeta) pathogenesis. These studies are sharply focused on addressing a novel hypothesis that emerged from studies conducted in the previous funding cycle of this PPG to account for the neurotoxicity of Abeta. A "two hit" hypothesis is proposed which states that the "first hit" (i.e., elevation of full length Abeta) is necessary but not sufficient to induce neurodegeneration, and that a "second hit" (i.e. genetic and epigenetic factors) is required to render neurons susceptible to the toxic effects of Abeta. In addition to being plausible and compatible with our own preliminary data and the published literature on the biological effects of Abeta in vitro and in vivo, this hypothesis can be rigorously tested by accomplishing the goals of Projects 1-4 in this PPG application where so-called "second hit" events that augment Abeta toxicity could be oxidative stress, lipid peroxidation, traumatic brain injury, the involvement of other Abeta fragments in senile plaque formation, neurofibrillary tangles, Lewy bodies or other processes identified to occur in the AD brain. To test this hypothesis, the investigators use complementary research strategies to pursue four separate projects: 1) Cell Biology of Abeta Production (RW Doms); 2) Novel Abeta Fragments as Mediators of Alzheimer's Disease (V. M.-Y. Lee); 3) Lipid peroxidation and Alzheimer's disease phenotypes (D. Pratico); and 4) Traumatic Brain Injury and Alzheimer's Disease (J. Q. Trojanowski). With the support of the Administrative and Neuroscience Cores, the investigators will use a multi-disciplinary approach to work synergistically to advance understanding of mechanisms of Abeta-mediated neuron degeneration in AD at the molecular, cellular and in vivo levels. It is anticipated that information derived from this research could provide a rationale for the development of novel therapeutic interventions for AD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFLUENCE OF APOLIPOPROTEIN E2 & E4 ON DVPMT OF HALLMARKS OF ALZHEIMER'S DISEASE Principal Investigator & Institution: Martinez, Andrew O.; Professor; University of Texas San Antonio San Antonio, Tx 78249 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: Transgenic mouse models for Alzheimer's disease (AD) offer the best hope for understanding and developing effective means of treating this dreadful disease. A number of laboratories, including ours, are working to develop useful models for this polygenic disease. Familial AD is often associated with mutations in the amyloid

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precursor protein (APP); one of the mutations is found in a Swedish population (APPSWED). Several groups have developed transgenic mice carrying the APPSWED gene but to date the most successful model is one developed by Hsaio/Ashe et al. (1995) called Tg2576. The proposed work is to cross the Tg2576 mice with mice generated in our laboratory that carry two common alleles for human apolipoprotein E (APOE), APOE-2 and APOE-4. APOE-4 is a risk factor for AD, and APOE-2 is reported to be beneficial in somehow retarding the development of AD. The ultimate goal is to obtain two mouse lines that each carry three transgenes; one carrying APOE-4, APPSWED, and mouse APOE-knockout (E-KO); the other carrying APOE-2, APPSWED, and E-KO. In addition, we also plan to similarly use a new APPSWED transgenic line recently developed in our laboratory to cross with APOE-2 and APOE-4 mouse lines. The new APPSWED line may be needed to elucidate any defects that may be due to mouse background strain. Once the proper crosses are obtained, the mice will be tested for (1) memory deficits and the age at which any deficits occur, (2) presence in brain of amyloidosis and content of b-amyloid peptide which is derived from APP and strongly implicated in the pathogenesis of AD, and (3) the presence of cerebral angiopathy which is found in AD. After demonstration of neuropathology in the mice, the effects of both diet restriction and high cholesterol diets will be tested to determine if the course of the pathology can be altered. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LEADERSHIP AWARD FOR ALZHEIMER'S DISEASE RESEARCH Principal Investigator & Institution: Mirra, Suzanne S.; Professor and Chair; Pathology; Suny Downstate Medical Center 450 Clarkson Ave New York, Ny 11203 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: The overall goal of this Academic Career Leadership Award is to develop an outstanding research and educational program on Alzheimer's disease (AD) and other neurodegenerative disorders at the State University of New York, Health Science Center at Brooklyn (Downstate). We plan to build upon the existing strengths at Downstate and the unique demographics of its surrounding community. These include the neuroscience program with its emphasis on hippocampal pathophysiology, the large population of Caribbean American, African American, and other minority groups in Brooklyn, and the special interests of the PI, including the overlap and heterogeneity of AD, Parkinson's disease and other neurodegenerative disorders. Our specific aims are to (1) establish an infrastructure to support the development of an institutional research center on AD and related neurodegenerative disorders; (2) develop mechanisms that will bring new investigators to the field, enable established investigators to channel their expertise towards the field, encourage collaborations, and support pilot studies; (3) stimulate interest and collaborations in AD-related research within the scientific community through educational programs and related experiences; and (4) promote awareness of AD in the lay and professional community through outreach and educational programs. The candidate, Dr. Suzanne Mirra, is well qualified to lead this initiative. An experienced and respected neuropathologist working on AD and other neurodegenerative disorders, Dr. Mirra was the director and principal investigator of the Alzheimer's Disease Center at her former institution. She led the neuropathology arm of CERAD (Consortium to Establish a Registry for AD), the NIA longitudinal study, in standardizing the neuropathological evaluation of AD. A nationally recognized leader in neuropathology, she is Founding Chair of the Neuropathology Committee of the College of American Pathologists and President-Elect of the American Association of Neuropathologists. Dr. Mirra has forged strong ties in the lay community, such as her

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involvement with the national board and regional chapters of the Alzheimer's Association. Moreover, she is an outstanding communicator as well as a committed and innovative educator with a demonstrated track record of outreach to non-white minorities. This Academic Career Leadership Award, along with strong institutional commitment, will enable Dr. Mirra and collaborators to build a thriving research program on Alzheimer's disease and related neurodegenerative disorders at Downstate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF NEUROTROPHIN-IMPROVED COGNITION IN AGING Principal Investigator & Institution: Granholm, Ann-Charlotte E.; Associate Professor; Physiology and Neuroscience; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 29-SEP-1991; Project End 31-AUG-2008 Summary: (provided by applicant): Aging and Alzheimer's disease are correlated with a progressive loss of cognitive function. Even though a significant increase in resources and research emphasis have been spent on investigating memory loss, it is still not known which biological events in the brain that lead to age-related cognitive impairment. Studies have demonstrated that altered function of the neurotrophic factors nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) may lead to age-related cognitive impairment. Likewise, many investigators believe that faulty processing of the amyloid precursor protein (APP), leading to production of the deadly beta-amyloid, is the culprit in age-related neuronal loss and cognitive dysfunction, especially in Alzheimer's disease. Amyloid is formed by gamma-secretase mediated cleavage of the APP pre-protein. In the past grant period we investigated effects of NGF upon cholinergic neurotransmission during aging. We would like to continue this work, and expand our focus to include BDNF, since this growth factor has been shown to be involved in memory. We propose a hypothesis that NGF and BDNF play important roles in neurotransmission in the hippocampus. In addition, we postulate that this neurotrophic influence is altered by APP and/or amyloid processing during aging, leading to lost neurotrophic function and, eventually, memory loss. In order to investigate this hypothesis we propose the following specific aims: 1. To determine if release, uptake, or retrograde transport of BDNF and/or NGF are altered in aged animals. 2. To determine if amyloid synthesis and/or gamma-secretase activity is altered in aged rodents, and if so: if this is correlated with age-related memory impairment or neurotrophic loss. The overall goal is to determine if NGF and BDNF activity is altered during aging because of altered release, uptake, or transport, and also to determine if this altered neurotrophic activity is related to alterations in amyloidenzyme activities. We hope that these findings will ultimately lead to better treatment paradigms for patients with neurodegenerative diseases, in particular Alzheimer's disease, and provide a more mechanistic base for knowledge regarding this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MICHIGAN ALZHEIMERS DISEASE RESEARCH CENTER Principal Investigator & Institution: Gilman, Sid; Director, Michigan Alzheimer's Disease c; Neurology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 29-SEP-1989; Project End 31-MAY-2004

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Summary: In this application for continuation of the MADRC, we propose to initiate new projects and extend two ongoing projects and maintain research cores. All projects involve investigations of Alzheimer's disease (AD) and AD mimics. The proposed projects include positron emission tomography (PET) studies of glucose metabolism and monoaminergic pathways in AD and dementia with Lewy disease (DLB); presynaptic neurochemical markers in AD, Parkinson's disease, and DLB; strategies for inhibition of Abeta protein aggregation; protein-protein interactions in amyloid precursor protein processing; and telephone counseling intervention to promote caregiver self-care behavior. Pilot projects are included in the proposal to stimulate innovative research in AD. The proposed Clinical, Neuropathology, Education and Information Transfer, and Biostatistics Cores will support these and a large number of other continuing and externally funded AD projects. Two successful satellite diagnostic and treatment centers in Detroit and Norther Michigan will continued to recruit under-represented urban, predominantly African American, and rural-resident patients to research studies The scientific approaches utilize major strengths in neurology and neuroscience at the longitudinal studies with autopsy verification, biostatistics, PET, molecular biology, molecular pharmacology, and survey research. The MADRC interacts with multiple components of the University to achieve its scientific and educational objectives, particularly the Schools of Medicine, Public Health, and Nursing, the Pepper Older Americans Independence Center, the Institute of Gerontology, the Geriatrics Center, and the Geriatric Research Education and Clinical Center at the Ann Arbor Veterans Medical Center. It collaborates with other ADCs on research projects and in datasharing. It plays a leadership role in statewide dementia initiatives and works closely with Michigan chapters of the Alzheimer Association. The scientific program proposed involves interdisciplinary collaboration of scientists and educators with many backgrounds and a strong training environment for predoctoral and postdoctoral students, medical students, and visiting scholars. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICROGLIAL SIGNALING MECHANISMS IN ALZHEIMER'S DISEASE Principal Investigator & Institution: Landreth, Gary E.; Professor; Neurology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 31-JAN-2005 Summary: (adapted from applicant's abstract) Alzheimer's Disease (AD) is characterized by the extracellular deposition of compacted fibrillar forms of B-amyloid (AB) protein within the brain. These senile plaques are the focus of a complex cellular reaction, the most prominent which is the presence of abundant reactive microglial cells that are found adjacent to and invest in the senile plaques. Microglia are derived from a monocytic lineage and are the sole immune cell in the brain. Microglial activation is accompanied by enhanced expression of numerous cell surface proteins an elaboration of a complex array of proinflammatory and acute phase products. There is compelling evidence that there is a significant inflammatory component in Alzheimer's disease as evidenced by a diverse range of clinical studies which have shown that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) substantially reduces the incidence of AD-related dementia delays disease progression. The central hypothesis guiding these studies is that microglia can detect and respond to fibrillar forms of amyloid by activation of intracellular signaling pathways which subserve the "activation" of the cells and the consequent secretion of proinflammatory products. The Specific Aims of this proposal are: 1. The characterization of membrane proteins that interact with AB fibrils

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and serve as primary signal transducing elements linked to intracellular signaling pathways. We demonstrate that the B-class scavenger receptor, CD36, and an integrin mediate the adhesion of monocytes to AB fibrils and activation of tyrosine kinase based signaling cascades. We propose to identify the relevant integrin and ascertain how these cell surface molecules are linked to intracellular signal transduction complexes. 2. Identification of the signal transduction pathways activated in response to AB which subserve the production of proinflammatory products and the acquisition of an activated phenotype by the microglia. Specifically, we will investigate signaling pathways that mediate the activation of the transcription factors NFkB and the peroxisome proliferation activated receptor, PPARy. We will also investigate ABinducted expression of cyclooxygenase-2. 3. We propose to employ an animal model of Alzheimer's disease to the effects of anti-inflammatory drugs on microglial activation. Transgenic mice expressing mutant forms of both the amyloid precursor gene and the presenelin 1 gene develop amyloid plaques and exhibit dramatic activation of plaqueassociated microglia. We will test the efficacy of the classical NSAID, indomethacin, as well a PPARy agonists and a COX-2 specific inhibitor in blocking the acquisition of a reactive phenotype by microglial cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODELS OF ALZHEIMER'S DISEASE Principal Investigator & Institution: Andreasson, Katrin I.; Neurology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2003 Summary: adapted from applicant's abstract): Alzheimer's disease is a neurodegenerative disorder affecting the elderly and accounts for two thirds of all dementia. Recent epidemiological studies suggest that the use of non-steroidal antiinflammatory agents is associated with a significantly lower risk of developing Alzheimer's disease. The primary targets of NSAIDs are the prostaglandin synthases, also known as cyclooxygenases. The cyclooxygenases catalyze the conversion of arachidonic acid to PGH2, which becomes the substrate for prostaglandin and thromboxane synthases. The conclusion raised by the recent epidemiological studies is that inhibition of cyclooxygenases activity is protective against development of Alzheimer's disease. There are two isoforms of cyclooxygenase (cox). Cox-1 is expressed constitutively in most tissues and at very low levels in the brain. Cox-2 is expressed in neurons of hipppocampus, amygdala and layers II/III of cortex. From our previous studies of genes involved in the adaptive responses of neurons to synaptic activity, we have identified cox-2 as an N-methyl D-aspartate (NMDA)-dependent activity-regulated gene in brain. Cox-2 is also highly expressed in neurons in paradigms of excitotoxicity, such as ischemia, trauma, and kindling. Because of its regulation by excitatory synaptic activity, and because of recent evidence implicating excitotoxic mechanisms in neurodegenerative diseases, we propose to study the role of cox-2 in the pathogenesis of Alzheimer's disease. We have generated transgenic C57Bl6/J founder mice that express the human form of cox-2 driven by the neuronal specific thy-1. An initial line of transgenic hcox-2 mice demonstrates immunoreactive hcox-2 and an 8 to 12-fold increase in PGE2 synthesis. In Aim 1 we will complete our immunohistochemical and biochemical characterization of remaining lines generated from our founder mice and select 3-5 additional lines for further study. In Aim 2 we will examine the contribution of cox-2 activity to the pathogenesis of Alzheimer's disease by crossing hcox-2 mice to a murine model of familial Alzheimer's disease that overexpresses mutant APP and PS-1 and analyzing the pathological phenotype of

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resultant double and triple transgenic mice. In Aim 3, we will test the effect of a selective cox-2 inhibitor on the development of a pathological AD phenotype in single, bigenic and trigenic mice generated in Aims 1 and 2. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODULATION OF ALZHEIMER'S AMYLOIDOSIS BY STATINS Principal Investigator & Institution: Petanceska, Suzana S.; Assistant Professor; Nathan S. Kline Institute for Psych Res Psychiatric Research Orangeburg, Ny 10962 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Cerebral accumulation of Amyloid beta (Abeta) peptides is an early event in establishing of Alzheimer's disease (AD) pathology. Based on the epidemiological evidence pointing to a link between cholesterol metabolism and AD and the numerous laboratory studies implicating cholesterol in the process of Abeta production and accumulation, it is now believed that cholesterol-lowering therapies will be of value as disease modifying agents. Several epidemiological studies revealed that statin use for the treatment of coronary arterial disease is associated with a decreased prevalence or a decreased risk of developing AD. The major objectives of this proposal are: to test the ability of different statins to delay the onset or retard the progression of brain Abeta deposition in the PSAPP transgenic mouse model of Alzheimer's amyloidosis, and to investigate the mechanisms by which statin treatment modulates brain Abeta accumulation. Our goal is to examine how the lipid-lowering as well as the anti-inflammatory/immunomodulatory activities of statins contribute to their effect on brain Abeta accumulation. To this end we will employ in vivo experimental paradigms using the PSAPP transgenic mouse model of Alzheimer's amyloidosis, as well as in vitro experimental paradigms using microglial and neuronal cultures. In the first specific aim we will compare the relative efficacy with which statins with different BBB permeability attenuate early as well as advanced Abeta deposition. We will then examine how statin treatments modulate APP processing and ApoE expression in brain (specific aim 2). Finally, we will evaluate the effects of statins on the inflammatory response in brain in the context of different paradigms of microglial activation and we will test their ability to prevent or attenuate Abeta-induced microglial neurotoxicity (specific aim 3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MULTIPHOTON MICROSCOPY FOR IN VIVO NEURAL IMAGING. Principal Investigator & Institution: Bacskai, Brian J.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): In vivo imaging of cellular and molecular structures in the intact brain provides a powerful tool for wideranging investigations in normal physiology, or in experimental models of disease processes. We have recently developed methods using a light microscope-based technique, multiphoton microscopy, to image microscopic structures in the brains of living transgenic mice over periods of months. Multiphoton microscopy utilizes a near-infrared laser for excitation of fluorophores deep within scattering tissue, with high spatial and temporal resolution. The spatial resolution of this imaging technique is about 1micrometer, several orders of magnitude better than other in vivo techniques, like PET, or MRI. In this application, we propose to develop new techniques that will provide important in rive readouts for biological imaging. This research will also lay the groundwork for development of contrast reagents suitable for use in human brain imaging with PET or MRI. We will develop, in

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Aim 1, techniques for high-resolution, in vivo imaging of structural reporters in the brain. We will investigate procedures to image individual neurons and microglia with high spatial resolution in the intact brain. In Aim 2, we propose to develop imaging techniques that exploit functional reporters in these living cells in the brain. Development of these molecular imaging techniques will build upon techniques accomplished in Aim 1. We have been using an experimental, transgenic mouse model of Alzheimer's disease that develops senile similar to those found in patients with Alzheimer's disease (AD). Our imaging techniques have allowed us to image the senile plaques in vivo in these mice with high spatial resolution. We will apply our new imaging techniques to this mouse model and address important questions that will provide insight into the pathophysiology of this disease. Our current techniques, however, rely on invasive procedures to gain access to the brain for imaging. In Aim 3, we will develop new techniques for non-invasive, in rive detection of senile plaques. New techniques using nearinfrared contrast reagents, and IR-sensitive detectors will allow non-invasive detection of plaques in the intact animal, and may also lead to clinically relevant diagnostic procedures for AD patients. In summary, the proposals outlined in this application will lead to generally applicable new techniques for cellular and molecular imaging in the intact brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROBIOLOGY OF ALZHEIMER'S DISEASE AND AGING Principal Investigator & Institution: Rosenberg, Roger N.; Professor; Neurology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2001; Project Start 01-MAY-1994; Project End 31-MAR-2005 Summary: The Alzheimer's Disease Center (ADC) has as its long-range goal to continue to develop and expand its Clinical Core functions to evaluate and follow comprehensively, selected patients with memory loss, Alzheimer's Disease (AD), and other dementias, and similarly to longitudinally follow and evaluate control subjects and encode pertinent data in a central database. Patients will be assigned to appropriate follow- up and study protocols and a computerized tracking system to monitor and document progress will be employed. Minority recruitment has been emphasized to increase our number of patients who are African- American, Hispanic, and NativeAmerican. It is our plan to evaluate potential predisposing events to AD, clinical course and complications of AD, clinical course and complications of AD, quantify emotional/behavioral symptoms and quality of life, utilization of imaging studies in the diagnosis of AD, and obtain clinical pathologic correlations. It will be our intent to achieve an 80% follow-up rate for persons designated for long-term studies. Wellstudied subjects, clinical data and body fluids will be supplied to investigators, and in particular ante- mortem and perimortem information to investigators using postmortem tissues from our controls and patients. Patients and control subjects will be evaluated with comprehensive neuropsychological testing, brain imaging, CSF and neuropathologic findings, in order to detect and assess preclinical and early AD. A Memory Disorders for Native Americans will be developed in Dallas to study their prevalence and clinical features of AD. The collaboration with the Alzheimer's Disease Clinical Studies Unit will continue. ADC patients and controls will be autopsied to provide an accurate diagnosis of AD or other basis of dementia. The Brain Bank will be expanded over the next five years from these autopsy studies and banked tissues will be made available to be utilized by investigators on our campus and at other ADC's. The Clinical Core will also supply information about the ante mortem state of control and AD patients for correlation with cellular and molecular analyses. Genotyping of AD

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autopsied cases for apolipoprotein E will be conducted as will ELISA assays for synaptophysin and tau proteins, and quantification of neocortical neuritic dystrophy in immunostained sections using image analysis. It is our intent as well to expand the isolation and banking of DNA from frozen and fixed autopsied tissue samples to facilitate ongoing and new studies of molecular alterations in AD and aging. The Statistics and Data Management Core will enter, store and analyze additional new patient data for comparative studies. The functionality of the existing centralized database will be enhanced with appropriate security over a central network to authorized ADC investigators at our institutions. The Education Core has extensive plans that have been developed over the past five years to extend knowledge about AD and specifically, availability of patient services to minority populations and also to primary health care providers. Educational videotapes and TV announcements will be developed both in English and Spanish. The Alzheimer's Researcher Newsletter will be published semi-annually and distributed to our 5000 subscribers in this five-state region. The number and scope of research projects will be increased during the next five years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROGENOMICS OF ALZHEIMER'S DISEASE AND AGING Principal Investigator & Institution: Stephan, Dietrich A.; Assistant Professor; Translational Genomics Research Inst 400 N 5Th St, Ste 1600 Phoenix, Az 85004 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Alzheimer's disease (AD) affects a large proportion of the world's population and is primarily a disease of old age. There is little known about the early molecular pathogenesis of AD leading to the characteristic dementia. Increased knowledge of the etiologic processes leading to dementia would allow improved diagnostics and targeted therapeutics. This proposal is multifaceted and seeks to elucidate 1) what differentiates AD from normal aging processes and other dementias of old age, 2) why individuals with certain genetic backgrounds (ApoE4 alleles) are more likely to become affected (inter-individual differences), 3) and what happens at the cellular and subcellular level in response to dementia-inducing stimuli (plaques and tangles)(intra-individual differences). Taken together the expression profiling data set generated on laser capture microdissected (LCM) cells from carefully stratified patient cohorts should provide unique insight into the AD phenotype. Specific hypotheses related to energy metabolism will be validated by multiple techniques (by immunohistochemistry on independent tissues and at the functional level using neuronal cell cultures and siRNAs). These results will be made available to the general public within 6 months of generation via the most established relational database for array data, the NINDS/NIMH array consortium repository. The applicants are uniquely qualified to perform a large-scale collaborative study of this type. Working closely in collaboration with 3 Alzheimer's Disease Centers (ADCs), the PIs will have access to tissue sections from the appropriate cohorts. The use of tissue sections (as opposed to large heterogeneous pieces of brain) and LCM as the starting reagents for the expression profiling will allow generation of high quality data while not depleting the banked national resource of brains. The PI is the Chairman of a National consortium of expression profiling facilities which generate extremely high quality data on large numbers of neurological phenotypes. Integration of this data set into that repository will increase the value of the AD data set exponentially because of the increased number of comparisons which can be generated using pre-existing data. The group also has access to sophisticated validation technologies. In all, the partnership of leaders in the AD

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field, the national resources within the ADCs, and the genomics expertise at TGen should allow rapid progress in understanding the etiology of AD dementia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROPEPTIDES 2003 SYMPOSIUM: ALZHEIMER'S DISEASE Principal Investigator & Institution: Seroogy, Kim B.; Neurology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2004 Summary: (provided by applicant): On behalf of the American Summer Neuropeptide Conference request is being made from the National Institute on Aging to partially sponsor the symposium titled "Alzheimer's Disease" to be held as part of NEUROPEPTIDES 2003, the 3rd Joint Meeting of the American Summer Neuropeptide Conference and the European Neuropeptide Club. This joint international meeting will be held in Montauk, New York, USA from June 8-12, 2003. The goal of the symposium is to bring together leaders in the field of peptides and aging disorders to discuss their latest findings on the roles of neuropeptides in Alzheimer's disease. This symposium will provide important, state-of-the-art research on the pathophysiology and biochemical basis of AIzheimer's disease in the context of neuropeptides. Topics will range from basic molecular mechanisms to potential neuroprotective and therapeutic applications of neuropeptides in neurodegenerative disorders, with an emphasis on Alzheimer's disease. Specifically, we are requesting funds to help defray meeting expenses of several invited speakers in this symposium and of several graduate student and postdoctoral trainees who will participate in the conference and interact with established leaders in fields related to the mission of the National Institute on Aging. The total amount requested is $11,650. The American Summer Neuropeptide Conference, now in its thirteenth year, and its counterpart the European Neuropeptide Club. The conferences highlight major new advances in neuropeptide research and attract a good mixture of senior and junior participants from academia and industry from throughout the world. Active participation by graduate and postdoctoral trainees, as well as by women and minority scientists, is strongly encouraged. The format of the present joint conference involves morning, afternoon and evening symposia, poster sessions Club, also in its thirteenth year, have become the premier international meetings for neuropeptide research, an award ceremony and conference banquet, and special lectures by distinguished international scientists. This format, coupled with the informal setting, provides an ideal forum for the dissemination and exchange of current information and the development of new collaborations among the participants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEW INHIBITORS OF BETA-AMYLOID TOXICITY Principal Investigator & Institution: Murphy, Regina M.; Professor; Chemical Engineering; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 10-APR-2000; Project End 31-MAR-2004 Summary: (From the applicant's abstract): Alzheimer's disease is a devastating neurodegenerative disease that afflicts over 4 million people in the United States. Two defining pathological features of the disease are extracellular senile plaques and intraneuronal fibrillary tangles, both abnormal features found in the brain of patients upon autopsy. The senile plaques consist of a proteinaceous amyloid deposit surrounded by degenerating neurites. The predominant protein component of the amyloid deposit is beta-amyloid (Abeta), a 4 kDa peptide derived from a much larger

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transmembrane precursor protein. Abeta deposits are fibrillar, with a diameter of 5-10 nm and a cross-beta structural motif. Mounting in vitro and transgenic mouse data support the hypothesis that Abeta, and more specifically, aggregated (fibrillar) Abeta, is neurotoxic and thus likely plays an essential role in the onset and/or progression of Alzheimer's pathology. This hypothesis leads to a proposed strategy for therapeutic intervention: compounds which can interfere with assembly of Abeta monomer into toxic fibrils should provide protection from Abeta toxicity. Abeta is an amphiphilic selfassociating peptide whose sequence is known. To self-associate, Abeta must be able to "recognize" other copies of itself. This leads to the intriguing possibility that molecules which borrow partial sequences from Abeta could also associate specifically with, or recognize, Abeta. Such sequences would be useful as means to target Abeta. These recognition elements could then be coupled to elements that were capable of disrupting Abeta aggregation. The hybrid compounds, containing both recognition and disrupting functionality, could potentially prevent Abeta neurotoxicity. In preliminary work, four such hybrid compounds were synthesized. These compounds disrupted Abeta aggregation and protected cells in vitro from Abeta toxicity. In the proposed research, this modular design strategy is explored in much greater depth. A library of peptidyl and organopeptidyl compounds will be synthesized, drawing on knowledge of the amino acids in Abeta that are responsible for the Abeta-Abeta interaction. Those compounds which prove to be effective recognition elements will be coupled to a palette of peptide- or saccharide-based disrupting elements. Such compounds will be evaluated extensively for their effect on Abeta aggregation and their ability to interfere with Abeta cellular toxicity. By repeated rounds of synthesis and evaluation, compounds which are highly effective at interfering with Abeta aggregation will be generated. Such compounds may serve as useful probes of the role of Abeta aggregation in neurotoxicity and may provide leads for developing clinically effective therapies for the treatment of Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OLFACTION AND EARLY DIAGNOSIS OF AD:FMRI STUDIES Principal Investigator & Institution: Tabert, Matthias H.; Psychiatry; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): This is an application for a Mentored Research Scientist Development Award. In Alzheimer's disease (AD), degeneration due to amyloid plaques and neurofibrillary tangles occurs early in the entorhinal-hippocampalsubicular complex as well as in the olfactory bulb and tract. AD patients consistently show deficits in olfactory identification compared to age-matched controls, as do patients with mild cognitive impairment (MCI), who are thought to be in the preclinical stages of the illness. While progress is being made in understanding the neuroanatomical and neurophysiological basis of olfaction, there has been a lack of clinical studies examining the neural correlates of AD-related olfactory deficits. The primary goal of the current research project will be to examine the degree to which odorant-induced brain activation in olfactory-related brain regions can be used as a reliable index that differentiates mild AD patients, MCI patients, and healthy agematched elders. To implement this goal, the proposed project will conduct an olfactory fMRI study. The focus will be on cross-sectional analyses of the fMRI response to odorants in olfactory-related brain regions. Ultimately, the clinical goal is to use differential odorant-induced activation profiles in MCI patients as an early diagnostic marker of AD. Such markers are critical for the development of effective treatments that

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can slow disease progression early in its course. The proposal provides for a staged training schedule designed to build on the candidate's background in neuropsychology and develop expertise in olfaction and neuroimaging, within a clinical research context. The career development activities and research plan capitalize on the resources of Columbia University to aid in achieving the candidate's long-term goal of becoming an independent investigator, focusing on early detection of psychiatric and neurological disease, limbic system functions, and brain imaging. In the training plan, he will receive expert mentorship in key areas, including psychophysics and neuroscience of olfaction, technical and theoretical aspect of fMRI, research design and quantitative methods, clinical assessment and diagnosis, and in the ethical treatment of patients and research conduct. This will be complemented by a comprehensive didactic program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OREGON ALZHEIMER DISEASE CENTER Principal Investigator & Institution: Kaye, Jeffrey A.; Professor and Director of Adcc; Neurology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 06-JUL-1990; Project End 31-MAR-2005 Summary: The overall mission of the Oregon Alzheimer's Disease Center (OADC) is to facilitate and advance research in Alzheimer's disease (AD) and related dementias. This will be achieved by maintaining 6 core facilities in associated with expert Core personnel to support both current research strengths, as well as to be responsive to the developing potential of new knowledge and discoveries in the field. The Center is organized and coordinated by the Administrative ore to be an efficient unit, working in concert with the research community to facilitate investigations in several major thematic areas such as studies of preclinical or incipient dementia in the very elderly, the genetics of AD, and the relationship between AD and Parkinson's disease. The Clinical Core provides well-characterized, longitudinally followed research subjects of several kinds: 1) AD and related dementias; 2) Healthy elderly at high risk for developing dementia, emphasizing those older than 85 years of age; 3) Dementia of Parkinson's disease; and 4) Subjects reflecting social and racial diversity (African American, Native American, and isolated rural populations). The Clinical Core is linked to the Neuropathology Core through programs such as the Community Brain Donor Program designed to enhance tissue donation. The Neuropathology Core uses modern histopathologic and morphometric techniques to characterized donated tissues which in turn are utilized by a diverse array of basic and clinical scientists both locally and nationally. The Genetics Core response to the needs of both Clinical and Neuropathology Cores and their missions of sophisticated characterization of research subjects and tissues by family history and genotype. The Genetics Core is also responsive to basic scientists in potential ability to facilitate study of candidate genes causing AD or genes which are protective and promote successful aging. Liking all these units is the Data Core which maintains an efficient relational database containing a unique catalogue record system allowing easy revision and modification of protocols as is inevitable in any longitudinal program. The Data Core further provides important assistance and advice in design and statistical analysis to investigators developing new projects. New information and knowledge of the field is disseminated through the Education and Information Transfer Core. This Core provides regular educational forums of many types ranging from small seminars to interactive television broadcasts. The Core's professional education programs and curricula are informed by new research spearheaded by this Core on how primary care physicians diagnose dementia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PET STUDIES OF CHOLINERGIC MODULATION IN ALZHEIMERS Principal Investigator & Institution: Smith, Gwenn S.; Associate Professor; Long Island Jewish Medical Center 270-05 76Th Ave New Hyde Park, Ny 11040 Timing: Fiscal Year 2000; Project Start 01-APR-1997; Project End 31-MAR-2004 Summary: Primary symptomatology in Alzheimer~s disease (AD) has been attributed to a presynaptic cholinergic deficit, based mainly on post- mortem examination of the brain at the end stages of the illness. Pharmacologic enhancement of the cholinergic system has not been consistently efficacious and does not stop disease progression. Animal and human models of AD based on inducted cholinergic hypofunction only mimic some aspects of symptomatology in AD. More recent neuropathologic studies have reported deficits in other neurotransmitter systems (e.g. dopamine, serotonin, norepinephrine). As an integration of the present knowledge concerning the neurochemistry of AD and the observation that neurotransmitter systems function synergistically, not in isolation, the proposed studies will test the novel hypothesis that the cognitive and behavioral symptomatology in AD represents a failure of acetylcholine to modulate other functionally-linked neurotransmitters, and that these deficits occur prior to the clinical diagnosis of AD. A recently developed research approach with Positron Emission Tomography (PET) will be used to combine neuroreceptor radiotracer studies with pharmacologic challenges to measure cholinergic modulation (Smith et al., 1996, Dewey et al., 1993). This approach is the most direct, non-invasive and quantitative method of measuring neurotransmitter activity and modulation in the living brain. These studies will measure cholinergic modulation of monoamine function (serotonin, dopamine) in the normal elderly, and in AD patients. A well- characterized pharmacologic challenge paradigm (administration of the selective muscarinic cholinegic antagonist scopolamine) will be used with PET and radiotracers for dopaminergic (D2, [1]C]- raclopride) and serotonergic (5-HT2A, [18F]-altanserin) receptors. Having performed the proposed studies, unique information will be obtained regarding cholinergic modulation of dopamine and serotonin receptor systems. These studies will provide a baseline for subsequent longitudinal follow-up of patients and for correlation with genetics and post-mortem findings (by the Alzheimer~s Disease Research Center) to determine how differences in monoaminergic responsiveness relate to AD subgroups (e.g. Lewy Body Dementia) A better understanding of the neurochemical deficits in AD may direct the development of novel treatment interventions that would improve symptomatology and perhaps stop disease progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POST-TRANSCRIPTIONALLY ACTING ALZHEIMER'S DRUGS Principal Investigator & Institution: Utsuki, Tada; Scientist; Message Pharmaceuticals, Inc. 30 Spring Mill Dr Malvern, Pa 19355 Timing: Fiscal Year 2001; Project Start 15-AUG-1997; Project End 31-DEC-2002 Summary: Alzheimer's disease (AD) is a major concern as the population ages, with no truly effective treatments available. One of the hallmarks of the disease is the deposition of insoluble plaques composed of a peptide derived from Amyloid Precursor Protein (APP). Message has established a drug discovery program focused on regulating protein expression by altering the interaction of an RNA binding protein with its target RNA. The overall goal of this project is to use this technology to develop drugs that decrease levels of APP. The current proposal seeks to (1) identify all the necessary components involved in these interactions; (2) screen for compounds that alter the interactions; (3)

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analyze effects of the compounds in cell culture; and (4) determine the in vivo efficacy in animal models of AD. Successful completion of this work will result in preclinical drug candidates and ultimately in a novel treatment targeting AD progression. To date, we have demonstrated that Message is regulated at the post-transcriptional level and that phenserine can block translation of the APP mRNA in a specific fashion. Analogs are currently being tested for more potent molecules and a high throughput screen will be developed once the regulatory regions are better understood. PROPOSED COMMERCIAL APPLICATION: Successful completion of this project will provide compounds for preclinical development as AD therapeutics. All current treatments for AD treat the symptoms (cognition) whereas this strategy would target a key factor believed to play a role in causing the disease. In addition, validation of posttranscriptional drug targeting would have broad implications for the treatment of other diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESONANCE

PREDICTING

ALZHEIMERS

DISEASE

WITH

MAGNETIC

Principal Investigator & Institution: Jack, Clifford R.; Professor of Radiology; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-JUN-1993; Project End 31-MAY-2003 Summary: (Adapted from Applicant's Abstract): The overall aim of this application is to identify magnetic resonance imaging (MRI) and 1H magnetic resonance spectroscopic (1HMRS) measurements which will aid in prospectively identifying individuals who subsequently develop Alzheimer's Disease (AD). We will study three clearly distinguishable clinical groups: 1) cognitively normal elderly controls, 2) patients with probably AD, and 3) risk for developing AD. Patients and controls will be drawn from the Mayo Alzheimer's Disease Registry (AG06786) and Alzheimer's Disease Center (AG0803). Aim #1: We will develop age and gender specific normative values for the MRI/MRS measurements. Aim #2: A multivariate model will be developed with the distinction between AD and controls as the dependent variable. Independent variable swill be hippocampal volume, temporal horn volume, brain volume, ventricular volume, 1HMRS metabolic ratios (NAA/Cr, mI/Cr, NAA/mI), leukoariosis volume, the annual percent change in each of the preceding MR variables, age, family history, education, and apolipoprotein E genotype. Aim #2 will entail testing the hypothesis that each of the preceding variables is significantly associated with the diagnosis of AD. Aim #3: Univariate analyses will be performed testing the hypothesis that a significant association exists between crossover of MCI patients to AD and each of the independent variables which were demonstrated to be significant in Specific Aim #2. Crossover is defined as the conversion of a patient from the diagnostic category of MCI to the diagnosis of AD. Aim #4: Using only those MRI/MRS, clinical, and laboratory predictor variables which were significant in Aim #3, we will develop a multivariate mathematical model for predicting crossover of MCI patients to AD. This will allow us to test the hypothesis that each MRI/MRS variables has power to predict crossover which is independent of an additive to other predictor variables. Aim #5: Decline in cognition will be modeled as a function of the MRI/MRS, clinical, and laboratory variables listed in Aim #2 for the controls and MCI patients. We will test the hypothesis that specific MR measures are associated with decline in specific measures of cognition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROTEIN RADICAL, PROTEIN NITRATION, MITOCHONDRIA, AND AD Principal Investigator & Institution: Chen, Yeong-Renn; Internal Medicine; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 13-SEP-2002; Project End 31-JUL-2005 Summary: (Taken from the Investigator's Abstract) The causative factors of Alzheimer's disease (AD) involve aging, genetics, and environmental exposures. At the neuronal level, a defect of energy metabolism associated with mitochondrial cytochrome C oxidase (CcO) deficiency was marked in AD brain. The mitochondrial abnormality caused by oxidative damage of CcO has been suggested as a part of causative events in AD. The long-term objective of this proposed research is to identify the molecular mechanism related to oxidative damage of AD-associated mitochondrial CcO. The proteincentered radical(s) in CcO, as detected with ESR spin-trapping technique, is formed by reacting with peroxides, such as hydrogen peroxide, organic peroxides, and lipid peroxides. Available evidence indicates that a specific tyrosine in mitochondrial cytochrome C may be nitrated to form 3- nitrotyrosine. The candidate hypothesizes that a specific amino acid residue(s) in CcO is involved in the radical formation and that 3nitrotyrosine can be detected when the purified CcO is exposed to a reactive nitrogen species (RNS) such as nitric oxide (NO) or peroxynitrite. The radioisotope-labeled spin trap, [14C]-labeled 2-methyl-2-nitrosopropane (MNP), will be synthesized and used to trap the protein-centered radical(s) in CcO. The subunit (location) of CcO associated with the spin trap will be visualized by SDS-PAGE and radioisotope distribution. NO and peroxynitrite will be used to test the nitration of tyrosine in purified CcO. The nitration of CcO will be characterized by immunoblotting using the antibody against 3nitrotyrosine. Peptide chemistry/mapping and mass spectrometry will be used to identify specific amino residue(s) associated with the above events of oxidative damage. The functional domains involved in the above radical formation and nitration will be identified. The essential role of the identified domains will be studied by immunochemistry. The results will provide fundamental information concerning the pathological relevance of neurodegenerative disease, such as AD, associated with mitochondrial dysfunction caused by oxidative damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROTEOME MARKERS FOR ALZHEIMER'S DISEASE DIAGNOSIS Principal Investigator & Institution: Lee, Kelvin H.; Associate Professor; Chemical and Biomedical Engineering; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Adapted from applicant's abstract): The objective of this project is to identify CSF molecular markers associated with the antemortem diagnosis of Alzheimer's disease which can be used as a measure for disease pathology. In contrast to brain based studies of the molecular mechanism of disease progression, this investigation with use proteomics technology to identify and characterize CSF proteins of interest. This information can be used to categorize disease pathology or can be used to develop immunoassays for diagnosis. In order to achieve these long-term objectives, the investigator plans to: identify and obtain CSF blood samples and clinical information from an appropriate sample population of patients with different forms of dementia, probable Alzheimer's disease at various stages and controls (Specific Aim 1). Analyze the samples for AD specific protein markers used in proteome analysis that includes

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high solution two-dimensional electrophoresis, laser densitometry, fluorescence imaging, and computer aided in each analysis (Specific Aim 2). He employs multivariate statistics to establish a correlation between relevant changes in disease diagnosis and establish qualitative and quantitative bar code for diagnosis of Alzheimer's disease. This includes the validation of other proposed CSF markers such as tau and Abeta 42 as well as the preliminary identification of other major differential diagnosis such as vascular dementia, dementia with Lewy bodies (Specific Aim 3). Use microchemical characterization of important proteins to elucidate the genetic basis of the molecular markers and other reference proteins. This information can also be used to develop immunoassays (Specific Aim 4). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REVEALING EPISTASIS IN ALZHEIMER DISEASE Principal Investigator & Institution: Martin, Eden R.; Assistant Research Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Alzheimer disease (AD) is a leading cause of dementia in the elderly. Identifying susceptibility genes for AD will aid in risk assessment, diagnosis and understanding the etiology of the disease. Several chromosomal regions have been identified as harboring genes for late-onset AD, but only one gene, APOE, has been demonstrated consistently to be directly involved in disease risk. While APOE may explain up to half of the genetic effect in late-onset AD, the remaining susceptibility genes have been difficult to identify. A large number of candidate genes have been tested for association using either case-control tests in unrelated individuals or familybased association tests, but the results have varied greatly between studies. It is our hypothesis that epistatic effects among multiple genes play a more important role in determining risk of AD than the independent effects of any single gene. The multiple positive and negative reports for numerous candidate gene association studies may in fact be due to study designs that only evaluate each candidate gene for main effects that are independent of all other genes. The goal of this proposal is to determine the role of epistasis or nonadditive gene-gene interactions on the risk of late-onset AD. To accomplish this goal, we propose to identify and genotype several single nucleotide polymorphisms in ten AD candidate genes for which there have been conflicting association studies. We will use a family-based design using affected and unaffected siblings and propose to study 800 sibships containing approximately 1600 individuals. We will extend the recently developed pedigree disequilibrium test (PDT) to test for associations at the genotypic level and allow its incorporation into the new multifactor dimensionality reduction (MDR) method. To test for complex genetic interactions in these data, we will use this modified MDR-PDT method. We anticipate that these results will explain at least some of the inconsistency arising from Alzheimer disease candidate gene association studies. Further, knowledge gained from the proposed research will be invaluable for public health efforts to prevent and treat the initiation, progression, and severity of Alzheimer disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RISK FACTORS FOR INCIDENT ALZHEIMERS DISEASE Principal Investigator & Institution: Evans, Denis A.; Director, Rush Institute for Healthy Agi; Rush-Presbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 01-MAR-1993; Project End 31-MAY-2004

54 Alzheimer’s Disease

Summary: (Adapted from the Investigator's Abstract) This is a revision of a previous application that was not funded. It proposes to continue the Chicago Health and Aging Project (CHAP), a study of incident clinically diagnosed Alzheimer's Disease among 6,162 residents of a geographically defined, urban, biracial community of the south side of Chicago. Recent data from the studies suggest that prevalence of Alzheimer's Disease is 2.65-fold higher among blacks than whites after adjustment for age, education and APOE genotype. The proposed work examines potentially modifiable risk factors, especially ones that might explain racial differences in risk. The primary questions are: (1) whether vascular factors, especially elevated blood pressure, increase risk of clinically manifest Alzheimer's Disease itself, in addition to their accepted role in predicting risk of vascular dementia, (2) whether this is mediated through small brain infarcts and non-infarct related white matter changes, and (3) to what extent do vascular factors account for racial differences in risk of disease? Secondary issues include potential protective effects of anti-inflammatory drugs and estrogens, effects of early life exposure on risk of Alzheimer's Disease, and the extent to which vascular factors predict risk of vascular dementia. To achieve these goals, a proposed second follow up (incidence) data collection cycle will detect Alzheimer's Disease occurring in the three year interval since the previous cycle, and all clinical evaluations will include magnetic resonance imaging and magnetic resonance and geography. In addition, enrollment of successive age cohorts of community residents as they reach age 65 is proposed to enable the study, in the future, to examine three important issues that cannot be examined by existing studies: whether effects of risk factors for Alzheimer's Disease vary greatly with age, the need for exposure information at multiple points over an extended period of time, and differences in the occurrence and effects of risk factors in different age cohorts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF CASPASE CLEAVAGE IN NEURODEGENERATIVE DISEASES Principal Investigator & Institution: Bredesen, Dale E.; Director; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 15-APR-2001; Project End 31-MAR-2002 Summary: The mechanisms that contribute to death of neurons in Alzheimer's disease remain to be defined. This is a particularly important process because loss of neurons and synapses likely play a critical role in cognitive impairment and indeed, may even precede clinical manifestations of the disease. Recent studies consistently showed that many mutations associated with neurodegenerative disease result in a pro-apoptotic phenotype in culture and, furthermore, many of the neurodegeneration-associated gene products are generally believed to be the "executioners" of the cell death program. We have recently found that the mutant androgen receptor associated with Kennedy's syndrome (spinobulbar muscular atrophy) is a caspase substrate, and, more importantly, that mutation of the caspase cleavage site blocks the pro-apoptotic effects of the mutant gene. This result argues that caspase cleavage in this case is an important event in the induction of cell death. Recently, it has been shown that three important Alzheimer's disease associated-genes, amyloid precursor protein, presenilin-1, and presenilin-2, are all caspase substrates. Therefore, the working hypothesis that guides this project is that caspase cleavage of these three gene products is required for cell death promoting properties associated with the familial Alzheimer's disease (FAD) mutations. In this application, we propose to explore the relationship between caspase cleavage of these three proteins and cell death. The results of these studies should help

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determine whether caspase cleavage represents an important signaling event in cell death in culture included by these mutant proteins. Furthermore, an understanding of this relationship will affect the development of new therapeutic strategies to treat Alzheimer disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF NO SYNTHASE-2 IN MURINE ALZHEIMER'S DISEASE Principal Investigator & Institution: Nathan, Carl F.; Professor & Chair; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 19-SEP-2000; Project End 31-JUL-2005 Summary: Alzheimer's disease (AD) can be viewed as a chronic degenerative and inflammatory disease leading to neuronal dysfunction and loss that are critically linked to accumulation of fibrillogenic fragments (Abeta[1-42/43]) of beta-amyloid precursor protein (APP). One leading possibility to explain how Abeta accumulation leads to neurotoxicity is that Abeta triggers oxidative and/or nitrosative injury. Fibrillogenic Abeta can generate oxidants in vitro and can elicit production of reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI) from microglia, astrocytes, neurons and monocytes in vitro (alone or with cytokines) and when injected into the brain. Biochemical and histochemical hallmarks of oxidative/nitrosative injury have been documented in lesions of AD. Among these, expression of the inducible isoform of nitric oxide synthase (NOS2; iNOS) is of special interest because its presence in brain is abnormal and implies inflammation; its production of NO is usually more sustained and destructive than that of other NOS's; it can produce ROI simultaneously with RNI, both by its own enzymatic action and by damaging mitochondria; and the resulting production of NO and superoxide in the same time and place favors the formation of peroxynitrite. Peroxynitrite is more toxic than either of its precursors, and there is strong histochemical evidence for its formation in AD. The PI has collaborated in demonstrating the presence of NOS2 in brains of patients with AD, associated with tangle-bearing neurons and neuropil. The advent of mice bearing AD-associated transgenes and the PI's generation of mice with disrupted alleles for NOS2 now permit a genetic test of the hypothesis that NOS2 may be an important enzymatic contributor to the oxidative/nitrosative neuronal injury characteristic of AD. Preliminary studies in 4 transgenic mouse models of AD using well-characterized antibodies for NOS2 have demonstrated NOS2 immunoreactivity in each type of AD-prone mouse. In contrast, cyclooxygenase 2 was scarcely detectable. In this proposal, mice carrying two ADassociated transgenes will be bred to retain or lose functional alleles of NOS2. These two strains will be compared with each other and with littermate- derived wild type mice as a function of age. If inability to express NOS2 decreases, delays, slows, or reduces the incidence, onset, progression or severity of neuronal loss or oxidative injury in mice with AD-associated transgenes, then NOS2 will emerge as an important target for experimental therapy in AD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF TGF B1 IN CEREBROVASCULAR AMYLOIDOSIS Principal Investigator & Institution: Wyss-Coray, Tony; Assistant Professor; J. David Gladstone Institutes 365 Vermont St San Francisco, Ca 94103 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: (From Abstract): Cerebrovascular deposition of amyloid, or cerebral amyloid angiopathy (CAA), is a prime cause of normotensive intracerebral hemorrhages in the

56 Alzheimer’s Disease

elderly. CAA is also a major neuropathological lesion in Alzheimer's disease (AD) and is accompanied by degenerating cells of the vascular wall. Because cerebrovascular amyloidosis has implications for the pathogenesis of Alzheimer's disease and for central nervous system (CNS) function in general, understanding its etiology is of great importance. Although it is known that single amino acid substitutions in several different proteins can cause rare autosomal dominant forms of CAA and that the apolipoprotein (apo) E e4 allele is a genetic risk factor for CAA, the cause of this disease in the majority of cases remains elusive. Through studies addressing the role of injury in neurodegenterative diseases, we have identified transforming growth factor (TGF)ß1 as an inducer of cerebrovascular amyloidosis and as a potential pathogenic factor for CAA in human Alzheimer's disease cases. The cytokine TGF-ß1 is rapidly produced after all forms of CNS injury and may function as an organizer of the responses to brain injury. Overexpression of TGF-ß1 in astrocytes of transgenic mice caused cerebrovasular amyloid deposition and prominent perivascular astrocyte activation along with a degeneration of cortical capillaries reminiscent of Alzheimer's disease. Here we propose experiments to define the role of TGF-ß1 in cerebrovascular amyloidosis at the molecular level. We will determine whether chronic activation of astrocytes by TGF-ß1 is necessary and sufficient to cause cerebrovascular amyloidosis in vivo and whether this process is modulated by different human apoe isoforms. We will use transgenic mice that overexpress dominant-active or dominant-negative TGF-ß receptors in astrocytes or comparable levels of apoE3 or apoE4 in neurons. In addition, we will initiate studies to determine if chronic TGFß1 production and astrocytosis cause the capillary degeneration that precedes amyloid deposition and whether these processes can be modulated by apoE3 or apoE4. The proposed studies will allow us to better understand the etiology and pathogenesis of cerebrovascular amyloidosis in vivo and clarify the roles of TGF-ß1, CNS injury, and astrocyte activation in this process. Our findings will have implications for the pathogenesis of human CAA and Alzheimer's disease in general and will help to assess whether TGF-ß1 could be a future target of therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SCREENING FOR NOVEL ALZHEIMER'S DISEASE DRUGS Principal Investigator & Institution: Marques, Marcos A.; Apologic, Inc. 3130 Highland Ave, Ste 3265 Cincinnati, Oh 45219 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-MAR-2002 Summary: There are four million people with Alzheimer's disease (AD) in the U.S. alone and the cost of their care is currently estimated at 100 billion dollars. Available therapy is limited to symptomatic relief without affecting the underlying cause of the disease. Recent evidence indicates that apolipoprotein E (apoE) may play a direct role in neuropathological changes that occur in AD. In particular, apoE has been shown to exhibit neurotoxic activity with isoform specificity that parallels the risk of disease. We have found that the neurotoxic activity of apoe can be blocked by specific compounds, suggesting a novel approach to the design of new therapeutic agents for treatment of Alzheimer's disease. Phase I has been successful. The feasibility of screening novel compounds has been demonstrated. Many of these show efficacy in an in vitro assay designed to mimic the proposed neurotoxic properties associated with apoE. The goals of phase II are to: accelerate in vitro screening, carry out refined analysis of positive compounds, synthesize novel compounds based on positive results, and screen for nontarget properties of effective compounds. PROPOSED COMMERCIAL APPLICATION: There are currently no effective treatments for Alzheimer's disease. The identification

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and development of an agent that significantly delays either the onset or progression of the disease would address a current healthcare cost of several billion dollars. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNALING FUNCTION BY APP PROCESSING AND RELEASE OF AID Principal Investigator & Institution: D'adamio, Luciano; Chief; Microbiology and Immunology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): The Familial Alzheimer's disease gene product Amyloid beta Precursor Protein (APP) undergoes extensive processing. APP cleavage by secretases has been studied in great detail because it generates Abeta peptides that are implicated in the pathogenesis of Alzheimer's disease. Recent data indicate that the intracellular domain of APP (AID), released together with Abeta, has signaling functions. AID can induce cell death, plays a role in the regulation of gene transcription and regulates calcium release from endoplasmic reticulum stores. We have found that AID can repress Notch-dependent transcription and that this restraint may be mediated by the interaction of AID with the Notch inhibitors Numb/Numblike (Nbl). Numb has also been involved in receptors endocytosis and endocytosis of APP is known to regulate APP processing. Based on these findings, we hypothesize that Numb/Nbl proteins mediate the inhibitory effect of AID on Notch signaling and regulate APP endocytosis and processing. In this application, we propose to study the role of Numb/Nbl proteins in inhibition of Notch by AID, in APP endocytosis and APP processing. Aside for their relevance to the biology of APP. these studies may have implications pertinent to the therapy and pathology of Alzheimer's disease. Drugs designed to lower Abeta production might also alter the levels of AID. Therefore a clear understanding of the biological functions of AID may help in predicting and preventing toxic effects due to alterations in AID production by these inhibitors. Furthermore, inhibition of Notch signaling by AID might accelerate the neurodegenerative process of Alzheimer's disease by enhancing synapse loss, neurite dystrophy and neuronal degeneration. Lastly, regulation of APP endocytosis and processing by Numb/Nbl proteins might provide potential new targets for compounds aimed to reduce Abeta production. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TARGETED MOUSE MODELS OF ALZHEIMER DISEASE Principal Investigator & Institution: Fukuchi, Ken-Ichiro; Genomics and Pathobiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: Alzheimer Disease (AD) is a neurodegenerative disorder characterized by the progressive loss of memory and cognitive functions. Cardinal pathological changes found in the brain of patients with AD are neurofibrillary tangles and deposits of aggregated amyloid protein (Abeta) in neuritic plaques and cerebral vessels (cerebrovascular amyloid angiopathy). The pathogenetic mechanisms that lead to development of AD are not clearly understood. There is no satisfactory treatment for AD. Approximately 10% of AD cases are classified as early onset familial AD (FAD) and show autosomal dominant inheritance. Inherited mutations in the gene coding for presenilin 1 (PS1) cause 18 to 50% of the early onset FAD cases. Although PS1 may be a transmembrane aspartyl protease that generates Abeta by cleaving its precursor

58 Alzheimer’s Disease

proteins, neither the physiological functions nor normal metabolism of PS1 are fully understood. Such understanding is essential to establishing the logical basis for therapy and prevention of the disease. Attempts to clarify the physiological functions of PS1 by constructing PS1 deficient (knockout) mice resulted in embryonic lethality. Thus, it is impossible to study the physiological functions and pathogenetic roles of PS1 in the adult using the "conventional" knockout mice. The primary goal of this pilot project is to establish new lines of PS1 knockout mice where expression of the PS1 gene is tightly regulated by the tetracycline (Tc) controllable transactivator system. The Specific Aims of the current research project are to: (Aim 1) isolate targeted embryonic stem (ES) cell lines with a PS1 gene under control of the Tc transactivator system and (Aim 2) establish mutant mouse lines for the PS1 gene using the targeted ES cell lines established in Aim 1 and test the tight regulation of the targeted PS1 genes in the mice. In these new lines of mice, expression of the PS1 gene will be turned on during embryogenesis and completely turned off by administration of doxycycline (a derivative of Tc) when the mice become adult. The long-term goal of this research is to elucidate the role of PS1 in the pathogenesis of AD via a thorough understanding of the physiological functions and normal metabolism of PS1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF CASPASE-8 IN ALZHEIMER'S DISEASE Principal Investigator & Institution: Rohn, Troy T.; Biology; Boise State University 1910 University Dr Boise, Id 83725 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (Adapted from applicant's abstract): A prominent feature of Alzheimer's disease (AD) is the loss of neurons by apoptotic cell death. Apoptosis is characterized by plasma membrane blebbing, nuclear condensation, and DNA fragmentation and is initiated by the activation of caspases, a family of aspartate proteases. The initiation of apoptosis involves the sequential activation of pro-caspases to their active form by proteolysis. Two key members of this family are caspase-8, the most apical member of the caspases, and caspase-3 that is commonly referred to as the executioner member of this family. Because caspases are specific, cleaving after aspartic residues, this generates caspase cleavage products (CCPs) that are antigenically distinct and therefore, represent desirable targets for cleavage site-directed antibodies. Using this approach, we designed an antibody to CCPs of fodrin, a neuronal cytoskeleton protein, and showed widespread accumulation of these products in Alzheimer's disease. Thus, while no staining was observed in control cases, labeling of neurons was observed in the hippocampus and entorhinal cortex of all AD cases, which increased as a function of disease progression. This study along with others has demonstrated a prominent role for the activation of apoptotic mechanisms in neurons of the AD brain. Presently, there are two major pathways of apoptosis: the death receptor pathway in which caspase-8 plays a critical initiator role and the mitochondrial pathway involving oxidative stress and activation of caspase-9. Induction of cell death via the Fas/TNFR super family of death receptors is mediated by adapter proteins (e.g., Fas-associated death domain, FADD) and initiation caspases (e.g., caspase-8). In the present application we test the role of the death receptor pathway and caspase-8 in Alzheimer's disease. To examine the role of caspase-8 in Alzheimer's disease we will propose to 1) develop cleavage site-directed antibodies against the active fragments of caspase-8; 2) characterize these antibodies using model systems of apoptosis; 3) use this antibody together with the fodrin CCP antibody to determine the role of caspase-8 in mediating the activation of caspase-3 in neurons of the AD brain. Elucidation of the exact apoptotic pathway involved in the eventual

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activation of caspase-3 will lead to the identification of newer, more specific targets for pharmacological intervention that may be useful for the treatment of Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSGENIC MODELS OF ALZHEIMERS DISEASE Principal Investigator & Institution: Irizarry, Michael C.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-MAY-2002 Summary: Alzheimer's disease (AD) is a progressive neurodegenerative dementing disorder affecting over 3.5 million Americans for which there is not known effective therapy. Genetic, cell culture, and animal studies support a key role of the amyloid precursor protein (APP) and amyloid beta protein (alpha beta) in the pathogenesis of AD, and related disorder, congophilic amyloid angiopathy (CAA). The applicant proposes to study two existing transgenic mouse models of cerebral amyloid deposition and to contribute the development of a transgenic model of vascular APP production to examine specific hypotheses relevant to the pathophysiology and neuropathology of AD and CAA. The objective of this Mentored Clinical Scientist proposal is to study whether APP transgene expression and/or Abeta deposition is associated with neuronal loss, vascular damage, synaptic alterations, gliotic changes, or loss of functional integrity of neural systems. Stereologically based statistically unbiased techniques will be used to assess neuronal counts, amyloid burden, and vascular amyloid in the entorhinal cortex, cingulate cortex, and hippocampal subfields to transgenic mice an non-transgenic littermate controls. The regional distribution and morphology of amyloid plaques will be analyzed immunohistochemically with light and confocal microscopy. The relation of transgene APP splice form expression to Abeta deposition will be assessed through in situ hybridization. Functional integrity of neural systems will be evaluated by cytochrome oxidase histochemistry and in situ hybridization, and synaptic integrity will be evaluated by immunohistochemistry and in situ hybridization. The applicant proposes to assess the effects of APP over-expression in vascular smooth muscle by producing and evaluating a new transgenic model of cerebral amyloid angiopathy. The candidate is a board certified neurologist who has completed two productive years of fellowship training in the well established neuroscience laboratory of Bradley T. Hyman. The laboratory includes experience and facilities for stereological techniques, molecular biology, immunohistochemistry, and confocal microscopy as well as access to human pathological specimens through the Alzheimer Disease Research Center. The additional basic science training in an exciting and novel project with direct clinical relevance will allow the candidate to develop into an independent academic neuroscientist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSGENIC MODELS TO STUDY ALZHEIMER'S DISEASE Principal Investigator & Institution: Mucke, Lennart; Associate Professor; J. David Gladstone Institutes 365 Vermont St San Francisco, Ca 94103 Timing: Fiscal Year 2002; Project Start 01-SEP-1992; Project End 31-MAR-2007 Summary: (Adapted from applicant's abstract): Alzheimer' s disease (AD) is the main cause of dementia in the elderly. Its increasing prevalence and enormous cost threaten the health and economic stability of people in the United States and many other nations. Thus, there is an urgent need to deepen our understanding of this illness and to develop

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better strategies to treat and prevent it. In this project, we use transgenic (tg) mouse models to study the roles of amyloid proteins and apolipoprotein (apo) E in the pathogenesis of Alzheimer's disease. During the last funding cycle, we overexpressed human amyloid protein precursors (APPs) and APP-derived amyloid peptides (A13) in neurons of tg mice. Similar to people with AD, APP mice showed progressive deposition of At3 in amyloid plaques and degeneration of neurons and synapses. Plaque formation depended not only on absolute levels of the fibrillogenic AB1-42 peptide but also on a number of key modifiers. High AB1-4O/AB1-42 ratios and ablation of apoE prevented neuritic plaques, whereas a1-antichymotrypsin doubled the plaque load. The cytokine transforming growth factor Bi had complex effects, decreasing the overall plaque burden while promoting amyloid deposition in blood vessels. Synaptic deficits correlated with AB levels but not with plaque load, suggesting a plaque-independent role for AB in Alzheimer's disease. Expression of apoE3, but not of apoE4, prevented or delayed synaptic deficits and memory impairments in APP/apoE doubly tg mice, consistent with observations by others that apoE4 increases AD risk, accelerates AD onset, and is found in the majority of people with Alzheimer's disease. This application follows up on our previous results, extends our project from AD pathogenesis to treatments, and addresses several important unanswered questions. We propose to determine whether nondeposited forms of AB such as AB-derived diffusible ligands (ADDLs) cause the plaque-independent neuronal deficits we identified in APP tg mice; whether these deficits can be prevented and ameliorated by vaccination with ADDLs; whether apoE3 suppresses ADDLs more effectively than apoE4 in APP/apoE mice, tg glial cultures, and cell-free conditions; and whether transient expression of apoE3 in adult regulatable APP/apoE mice can decrease ADDL levels and inhibit neuronal deficits. We also propose to use DNA microarrays to identify additional mechanisms by which apoE isoforms might affect AB/ADDL-induced neuronal deficits. Achieving these aims could shed light on the molecular pathways that culminate in AD-associated cognitive decline and assist in the preclinical evaluation of novel treatments for the most common neurodegenerative disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSGENIC RAT MODELS OF ALZHEIMER'S DISEASE Principal Investigator & Institution: Herrera, Victoria L.; Profesor of Medicine; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 15-FEB-2000; Project End 31-JAN-2003 Summary: Animal models are proven investigative tools for study of complex human diseases such as Alzheimer s Disease (AD) and atherosclerosis. Trangenic and bigenic mouse models for presenilin-1 (PS1) and amyloid precursor protein (APP) human gene variants have been instrumental in delineating their roles in AD pathogenesis. However, to date these mouse models have not exhibited key AD pathology such as neurofibrillary tangles, neuronal loss and AD-associated cognitive/neurobehavioral deficits. We hypothesize that a more phenotypically robust and experimentally accessible model of Alzheimer s disease will be obtained in the rat based on key observations: a) rat ApoE is more homologous to human ApoE4 compared with mouse; b) rat complement, like the human has greater levels compared with the mouse and might be a key determinant to the development of neurofibrillary tangles; c) neurobehavioral studies assessing aging and hippocampal-specific learning and memory deficits have been validated in the rat; d) the size of the rat allows lesioning and imaging studies; f) the more robust atherosclerotic phenotype in transgenic rats compared with mice given the same human cholesteryl ester transfer (hCETP) transgene

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indicates valid modeling for complex diseases. This proposal focuses on the following specific aims. (1) Develop three key inbred Fischer 344 rat AD models with the highest probability for a robust AD phenotype: a) homozygous high-expresser of mutant human APPSWE AD gene, TgAPP, b) homozygous bigenic with both mutant human PSIM146L and hAPPSWE, 2TG[PS1xAPP], and a trigenic rat model, 3Tg]PS1 x APAP x hCETP], which imposes, if not test, hypercholesterolemia-induced exacerbaytion of amyloidogenic APP processing in vivo. (2) Investigate the degree of cognitive deficits in the combinational transgenic rat AD models by measuring hippocampal-dependent working memory and spatial learning and memory at 12, 18, 24 months. 3) Correlate observed hippocampal-dependent neurobehavioral alterations with AD- associated neuropathological alterations at 12, 18, and 24 months. (4) Correlate key neurobehavioral and neuropathological alterations with molecular and cellular markers of AD pathogenesis at 12, 18, and 24 months. Comparative analysis of the proposed rat models will not only address an accessible AD model for mechanistic dissection and therapy development, but also provide insight into the role of complement- and hypercholesterolemia-mediated disease paradigms in AD pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSMITTER NEUROANATOMY IN ALZHEIMERS DISEASE Principal Investigator & Institution: Armstrong, David M.; Scientific Review Administrator; Lankenau Institute for Medical Research Wynnewood, Pa 19096 Timing: Fiscal Year 2001; Project Start 01-AUG-1988; Project End 31-DEC-2002 Summary: (Applicant's Abstract): The proposed studies will address the issue of selective vulnerability of neurons in Alzheimer's disease. Underlying these studies is the hypothesis that excitotoxicity, particularly that which is mediated via stimulation of ionotropic glutamate receptors, contributes to the neuro-degeneration of Alzheimer's disease. Moreover, we predict that in Alzheimer's disease the perturbation of specific glutamate receptor subunits, particularly those involved in the gating of calcium, may contribute significantly to the viability of the cell. The current investigation focuses on the N-methyl- D-aspartate (NMDA) receptor. Notably, previous work of ours has focused on the distribution and expression of specific non-NMDA (i.e. AMPA) receptor subunits in the hippocampus of patients with Alzheimer's disease pathology. Collectively, these investigations attempt to provide a comprehensive understanding of the anatomy of the ionotropic glutamate receptor in the hippocampus of normal subjects and in subjects with Alzheimer's disease. In this application, we propose a series of highly correlated immunohistochemical (Specific Aims 1&2), biochemical (Specific Aim 3) and in situ hybridization studies investigating the distribution and level of expression of specific NMDA receptor subunits (e.g., NMDAR1, NR2A, NR2B, & NR2D). Studies will focus on the human hippocampus, in part, because this region is known to be affected very early within the progression of the disease. Subjects representing a broad range of neuropathologic severity (i.e. Braak stages I-VI) will be studied thus providing us with the opportunity of examining alterations in glutamate receptor expression throughout various stages of the disease. Moreover, the use of specific antibodies identifying early events in the evolution of neurofibrillary pathology provides an additional opportunity of correlating alterations in NMDA receptor subunit expression with initiating events of neurodegeneration. An understanding of the anatomical organization of NMDA and AMPA receptors and the mechanism underlying glutamatemediated excitotoxicity is important before appropriate drugs aimed at halting Alzheimer's disease-associated neuronal degeneration can be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRIPLE TRANSGENIC MODEL OF ALZHEIMER'S DISEASE Principal Investigator & Institution: Vitek, Michael P.; Associate Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2007 Summary: (Adapted from applicant's abstract): The National Institutes on Aging and Reagan Institute consensus criteria for the diagnosis of Alzheimer's disease includes a clinical evaluation of progressive dementia and a post-mortem observation of both amyloid plaques and neurofibrillary tangles in the brains of AD patients. Age of the patient is the largest risk for the presence of AD followed by the presence of one or more epsilon-4 alleles of the apolipoprotein-E gene (APOE4) in about 45 percent of all AD patients. The presence of APOE4 is also associated with an increase in the numbers of neurofibrillary tangles and amyloid plaques compared to those AD patients that lack APOE4 alleles. These data imply that increased numbers of plaques and tangles are associated with a gain of Alzheimer's dementia. An animal model that displays progressive dementia, amyloid plaques and neurofibrillary tangles is a critical step forward toward developing a safe and effective drug for the treatment of Alzheimer's disease. Based on reported studies of AD patients, an animal model should also display increased numbers of neurofibrillary tangles and amyloid plaques when APOE4 gene products are present. We propose to make a mouse model of Alzheimer's disease to meet the National Institute of Aging-Reagan Institute criteria for Alzheimer's disease. This triple transgenic mouse (APP + TAU + APOE) is designed to display both neurofibrilary tangles and amyloid plaques in their brains. To be an accurate model of human AD, we hypothesize that the numbers of neurofibrillary tangles and amyloid plaques should increase in the presence of human APOE4 gene products compared to human APOE3 gene products. Although work on plaque-only or tangle-only mice needs to continue, if we are really going to develop a mouse model of Alzheimer's disease, we must have progressive dementia, plaques, and tangles. Such a model would facilitate exploration of the basic mechanisms that cause neurodegeneration and dementia, in the 'presence of plaques, tangles and apoE proteins, and thus, greatly facilitate the finding of a safe and effective drug to block Alzheimer's dementia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: UCLA ALZHEIMERS DISEASE RESEARCH CENTER Principal Investigator & Institution: Cummings, Jeffrey L.; Director; Neurology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 05-APR-1999; Project End 31-MAR-2004 Summary: This application proposes the establishment of an Alzheimer's Disease Research Center (ADRC) at UCLA. The theme of the ADRC is "understanding the mechanisms and optimizing the treatment of Alzheimer's disease". An ADRC would add a basic science dimension to established activities of the current UCLA Alzheimer's Disease Core Center (ADCC), use tissues and antibodies from the ADCC Neuropathology Core, and facilitate an invigorating interchange between clinical scientists and the growing cadre of basic scientists at UCLA. The ADCC has accomplished its original goals and established a flow of well characterized patients that are being followed longitudinally (Clinical Core); accessioned 148 brains into the ADCC brain bank (Neuropathology Core); created an imaging archive with sophisticated image analysis techniques available to investigators (Imaging Subcore of Imaging and Genetics Core); developed mechanisms for routine genotyping and established a DNA

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bank for genetic investigations (Genetics Subcore of Imaging and Genetics Core); and engaged ore than 3600 clinicians in education programs (Education/Information Transfer Core). The ADCC database contains information on 1261 patients and control, in the past year we have achieved an annualized follow-up rate of 90%. In the past five years, we have awarded funding for 12 Pilot Projects; these projects have contributed to 10 funded grants and 22 publications. The ADCC has three clinical sites, each serving a different ethnic population: UCLA (primarily majority culture patients), Martin Luther King Medical Center/Drew Medical School (primarily an African-American population), and Olive View Medical Center (an Hispanic population). UCLA investigators using data from the Cores have advanced understanding of frontotemporal dementias, dementia with Lewy bodies, behavioral aspects of AD, the role of vascular disease in AD and vascular dementia, and the role of imaging and genetics in the diagnosis and characterization of AD. ADCC investigators published 375 articles and 338 abstracts on dementia-related topics between 1993 and 1997. Three basic science projects are being proposed: 1) apolipoprotein influences on amyloid deposition (Greg Cole, Ph.D.), 2) amyloid deposition, toxicity, and inflammation in an amyloid infusion model of AD (Sally Frautschy Ph.D.) and intracellular amyloid signaling (Istvan Mody, Ph.D.). The activities of the Cores will be continued an expanded in the ADRC and the Project Leaders will be integrated into all aspects of the ADRC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UHC/CWRU ALZHEIMER'S DISEASE RESEARCH CENTER Principal Investigator & Institution: Herrup, Karl F.; Professor; Neurology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 21-SEP-1988; Project End 31-MAY-2005 Summary: The three-part of the Alzheimer Center of University Hospitals of Cleveland/Case Western Reserve University Medical School is 1) to provide clinical service, 2) to promote research and 3) to educate health professionals and the lay public into the causes and treatments of Alzheimer's disease (AD). We have learned much about the biological basis of AD in the past six years, yet the disease persists. The pace of discovery gives us hope, but the persistence of the disease is a reminder that much more needs to be done. To approach this task, this application proposes four research projects. Dr. Lamb will investigate the behavioral and pathological deficits of mice engineered to mimic early onset forms of AD. Dr. Landreth will explore the role of inflammatory processes and ectopic cell cycle components in the neurodegenerative processes of AD. Dr. Smyth will examine the dynamics and effectiveness of various forms of computermediated support to caregivers of persons with AD. Dr. Whitlatch will study the congruence between the treatment preferences of persons with dementia and their caregivers. These four studies plus the projects of many researchers throughout Greater Cleveland depend on the support services offered by the eight Cores. Dr. Herrup will direct the Administration Core that oversees the operations of the entire ADRC. The Clinical Core, under Dr. Geldmacher, will recruit and characterize AD research subjects. The Neuropathology Core, under Dr. Gambetti, will perform pathological diagnosis of dementia cases and controls and assist in the analyses of animal models. Dr. Neundorfer will run our Minority Recruitment Satellite. Dr. Smyth will lead the Management and Analysis Core that stores and helps to analyze the data sets collected during the previous 12 years. Dr. Stuckey will direct the Education & Information Transfer Core to disseminate reliable information on AD and its treatment to students, professionals and the public. Dr. Herrup will run the Laboratory Services Core that will offer access to a range of AD animal models. This renewal application describes the structure of an

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ADRC aimed at further our knowledge of Alzheimer's disease itself and developing the most effective means of easing the burden of AD for both its sufferers and their caregivers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UROKINASE-TYPE PLASMINOGEN ACTIVATOR/ALZHEIMER'S DISEASE Principal Investigator & Institution: Estus, Steven S.; Associate Professor; Physiology; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-MAY-2005 Summary: (provided by applicant): Genetic factors that contribute to Alzheimer's disease (AD) susceptibility are critical to our understanding and early diagnosis of the disease. A chromosome 10 region contains at least one susceptibility locus for late onset Alzheimer's disease, and is associated with increased amyloid-B (ADi) plasma levels. The gene encoding urokinase-type plasminogen activator (uPA) is within this implicated region. UPA is induced by AB-treated neurons in vitro and in the Hsiao mouse model of AB burden in vivo. Moreover, uPA converts plasminogen to the active protease plasmin, which degrades both nonaggregated and aggregated AB with physiologic efficiency. In summation, ADi induces uPA, which can in turn lead to AB degradation, suggesting a self-regulated system for clearance of AB aggregates. Considering these data overall we hypothesize that the chromosome 10 loci includes a uPA polymorphism(s) that modulates uPA's ability to contribute to AD clearance. To evaluate this hypothesis, we propose to (i) identify uPA polymorphisms that segregate with Alzheimer's disease. In preliminary work we have identified two uPA polymorphisms that significantly segregate with AD susceptibility and are in strong linkage disequilibrium, including (i) a substitution of leu for pro at position 141 within uPA, which alters binding of the uPA zymogen to aggregated fibrin and (ii) a SNP two basepairs 3' to an AP-I site that is known to be critical for uPA induction. We also propose to (ii) Gain insight into the possible role of the at-risk uPA haplotype by comparing individuals homozygous for each genotype for relevant clinical and neuropathologic markers of Alzheimer's disease, (iii) Evaluate the effect of the uPA polymorphisms associated with AD risk on uPA expression and function, and (iv) Evaluate the role of uPA in AB clearance in vivo by quantifying AB accumulation in mice that are wildtype or genetically deficient for uPA. Overall, the focused approach proposed here will (i) directly evaluate the possible role of uPA polymorphisms as a risk factor(s) for Alzheimer's disease, and (ii) provide insights into possible mechanisms underlying differential uPA actions. These studies are significant in that the identification of additional genetic risk factors for Alzheimer's disease will aid in early AD diagnosis, and thereby facilitate drug discovery by identifying patients at high risk for AD prior to symptomology. Moreover, by evaluating possible mechanisms underlying the enhanced susceptibility to Alzheimer's disease, these studies may lead to the discovery of novel insights into the molecular mechanisms underlying Alzheimer's disease, and thereby suggest new therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: UTILITY OF MUSCARINIC AGONISTS FOR ALZHEIMER'S DISEASE Principal Investigator & Institution: Ghosh, Debasis; Cognitive Pharmaceuticals, Ltd 333 14Th St Toledo, Oh 43624

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Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-OCT-2003 Summary: (provided by applicant): The purpose of the present study is to assess the utility of muscarinic agonists in treating Alzheimer's disease. Levels of acetylcholine decrease in Alzheimer's disease, resulting in memory deficits. Efforts to treat Alzheimer's disease have been based on compounds that mimic acetylcholine without producing side effects such as salivation or diarrhea. Unfortunately, muscarinic agonists have shown limited clinical utility due to low efficacy, poor selectivity or high toxicity. Recent studies suggest however, that muscarinic agonists might be useful in treating not only memory impairments, but also the underlying causes of Alzheimer's disease. In particular, muscarinic agonists promote a-secretase activity, thereby limiting the production of b-amyloid, and stimulate Akt , which prevents the phosphorylation of tau proteins. Thus administration of efficacious, selective and safe muscarinic agonists could be beneficial in the early stages of Alzheimer's disease. 5-(3-Ethyl-1,2 4-oxadiazol-5-yl)-1 ,4,5,6-tetrahydropyrimidine (CDD-0 102) activates muscarinic receptors in brain and improves memory function with few side effects and low toxicity in the present study, CDD-01 02 will be examined for its ability to promote a-secretase and Akt activity. Metabolites of CDD-0102 will be determined and examined for receptor activity to assess safety. Together, the studies will assess the utility of CDD-01 02 in treating not only cognitive and memory deficits, but also the progression of Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VASCULAR RISK FACTORS IN ALZHEIMER'S DISEASE Principal Investigator & Institution: Li, Gail; Psychiatry and Behavioral Scis; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Candidate's Plan/Training: The Candidate plans a career as a patient-oriented clinical research investigator and academic geriatric psychiatrist bridging dementia, vascular risk factors and clinical epidemiology. Training will include formal didactics in lipid metabolism and augmentation of the Candidate's previous epidemiology training with additional advanced biostatistics and epidemiology courses and closely supervised completion of the research plan. Environment: The University of Washington Alzheimer's Disease Patient Registry (ADPR)/Adult Changes in Thought (ACT) and Alzheimer's Disease Research Center (ADRC) provide expertise in epidemiology, clinical dementia evaluation, and biostatistics to form an ideal research environment for epidemiological investigation of Alzheimer's disease (AD) and related dementias. Research: Recent studies suggest midlife hypercholesterolemia and hypertension increase risk of dementia and specifically AD in late life. Cholesterol-lowering medications, the 3-hydroxy-3-methylglutarylcoenzyme-A reductase inhibitors, i.e., statins, may reduce the risk of AD. We hypothesize that vascular risk factors increase the risk of AD and/or vascular dementia (VaD) and use of statins reduces this risk. To address these hypotheses, Specific Aim 1 will determine whether the use of statins decreases the risk of AD and/or VaD, and whether these effects are modified by the presence of the Apolipoprotein Ee4 allele. We also investigate whether high serum low-density lipoprotein (LDL) and low serum highdensity lipoprotein (HDL) are associated with increased risk for AD and/or VaD. Specific Aim 2 will determine if hypertension in older age (> 65 years) increases the risk of AD and/or VaD; we will also investigate blood pressure changes prior to the diagnosis of AD and/or VaD. A prospectively enrolled community-based cohort of 2581 initially cognitively normal elderly will provide the framework for this study. Results from the research project will provide insights into vascular risk factors for AD, thus

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providing additional information toward development of new prevention and treatment strategies. This research plan, together with the didactic and mentored instruction proposed, will provide the career development necessary for the candidate to conduct scientifically rigorous, independently funded, patient-oriented research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “Alzheimer’s disease” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Alzheimer’s disease in the PubMed Central database: •

[beta]-Amyloid peptides enhance [alpha]-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease. by Masliah E, Rockenstein E, Veinbergs I, Sagara Y, Mallory M, Hashimoto M, Mucke L.; 2001 Oct 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59799

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A polymorphic gene nested within an intron of the tau gene: Implications for Alzheimer's disease. by Conrad C, Vianna C, Freeman M, Davies P.; 2002 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124341

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A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and A[beta]. by Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I.; 2001 May 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33469

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Advances in the pharmacotherapy of Alzheimer's disease. by Gauthier S.; 2002 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=99406

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Aggravated decrease in the activity of nucleus basalis neurons in Alzheimer's disease is apolipoprotein E-type dependent. by Salehi A, Dubelaar EJ, Mulder M, Swaab DF.; 1998 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21662

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Agrin in Alzheimer's disease: Altered solubility and abnormal distribution within microvasculature and brain parenchyma. by Donahue JE, Berzin TM, Rafii MS, Glass DJ, Yancopoulos GD, Fallon JR, Stopa EG.; 1999 May 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26905

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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Alzheimer's disease and herpes. by Itzhaki RF, Dobson CB.; 2002 Jul 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=116625

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Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons. by Huang Y, Liu XQ, Wyss-Coray T, Brecht WJ, Sanan DA, Mahley RW.; 2001 Jul 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37522

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Apolipoprotein E is essential for amyloid deposition in the APP V717F transgenic mouse model of Alzheimer's disease. by Bales KR, Verina T, Cummins DJ, Du Y, Dodel RC, Saura J, Fishman CE, DeLong CA, Piccardo P, Petegnief V, Ghetti B, Paul SM.; 1999 Dec 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24803

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Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. by Holtzman DM, Bales KR, Tenkova T, Fagan AM, Parsadanian M, Sartorius LJ, Mackey B, Olney J, McKeel D, Wozniak D, Paul SM.; 2000 Mar 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16026

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Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes. by Hirano M, Shtilbans A, Mayeux R, Davidson MM, DiMauro S, Knowles JA, Schon EA.; 1997 Dec 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25134

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Canadians' awareness of Alzheimer's disease lacking. by Martin S.; 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=152713

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Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. by Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, Lavretsky H, Miller K, Siddarth P, Rasgon NL, Mazziotta JC, Saxena S, Wu HM, Mega MS, Cummings JL, Saunders AM, Pericak-Vance MA, Roses AD, Barrio JR, Phelps ME.; 2000 May 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18554

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Clusterin promotes amyloid plaque formation and is critical for neuritic toxicity in a mouse model of Alzheimer's disease. by DeMattos RB, O'dell MA, Parsadanian M, Taylor JW, Harmony JA, Bales KR, Paul SM, Aronow BJ, Holtzman DM.; 2002 Aug 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125060

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Correlates of response to acetylcholinesterase inhibitor therapy in Alzheimer's disease. by Lanctot KL, Herrmann N, LouLou MM.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161722

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Declining brain activity in cognitively normal apolipoprotein E [var epsilon]4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease. by Reiman EM, Caselli RJ, Chen K, Alexander GE, Bandy D, Frost J.; 2001 Mar 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30654

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Detection of Alzheimer's disease and dementia in the preclinical phase: population based cohort study. by Palmer K, Backman L, Winblad B, Fratiglioni L.; 2003 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140758

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Detection of neuritic plaques in Alzheimer's disease by magnetic resonance microscopy. by Benveniste H, Einstein G, Kim KR, Hulette C, Johnson GA.; 1999 Nov 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24193

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Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies. by Etminan M, Gill S, Samii A.; 2003 Jul 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165707

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Efficacy and safety of cholinesterase inhibitors in Alzheimer's disease: a metaanalysis. by Lanctot KL, Herrmann N, Yau KK, Khan LR, Liu BA, LouLou MM, Einarson TR.; 2003 Sep 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=191283

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Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial. by Wilcock GK, Lilienfeld S, Gaens E.; 2000 Dec 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27547

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Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial. by Rosler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, Stahelin HB, Hartman R, Gharabawi M.; 1999 Mar 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27767

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Expression profiles of multiple genes in single neurons of Alzheimer's disease. by Chow N, Cox C, Callahan LM, Weimer JM, Guo L, Coleman PD.; 1998 Aug 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21388

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Failure To Detect Chlamydia pneumoniae in Brain Sections of Alzheimer's Disease Patients. by Gieffers J, Reusche E, Solbach W, Maass M.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=86233

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Familial multiple system tauopathy with presenile dementia: A disease with abundant neuronal and glial tau filaments. by Spillantini MG, Goedert M, Crowther RA, Murrell JR, Farlow MR, Ghetti B.; 1997 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20577

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From Alzheimer's disease to skin tumors: The catenin connection. by Hartmann D.; 2001 Sep 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58494

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Functional brain imaging to identify affected subjects genetically at risk for Alzheimer's disease. by Rapoport SI.; 2000 May 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33991

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Functional integrity of mitochondrial genomes in human platelets and autopsied brain tissues from elderly patients with Alzheimer's disease. by Ito S, Ohta S, Nishimaki K, Kagawa Y, Soma R, Kuno SY, Komatsuzaki Y, Mizusawa H, Hayashi JI.; 1999 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26743

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Galanin transgenic mice display cognitive and neurochemical deficits characteristic of Alzheimer's disease. by Steiner RA, Hohmann JG, Holmes A, Wrenn CC, Cadd G, Jureus A, Clifton DK, Luo M, Gutshall M, Ma SY, Mufson EJ, Crawley JN.; 2001 Mar 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31200

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Immune hyporesponsiveness to amyloid [beta]-peptide in amyloid precursor protein transgenic mice: Implications for the pathogenesis and treatment of Alzheimer's disease. by Monsonego A, Maron R, Zota V, Selkoe DJ, Weiner HL.; 2001 Aug 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56951

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In vivo detection of amyloid plaques in a mouse model of Alzheimer's disease. by Skovronsky DM, Zhang B, Kung MP, Kung HF, Trojanowski JQ, Lee VM.; 2000 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16593

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Inhibition of the ubiquitin-proteasome system in Alzheimer's disease. by Lam YA, Pickart CM, Alban A, Landon M, Jamieson C, Ramage R, Mayer RJ, Layfield R.; 2000 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27620

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Interhemispheric disconnection syndrome in Alzheimer's disease. by Lakmache Y, Lassonde M, Gauthier S, Frigon JY, Lepore F.; 1998 Jul 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21199

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Mapping the evolution of regional atrophy in Alzheimer's disease: Unbiased analysis of fluid-registered serial MRI. by Scahill RI, Schott JM, Stevens JM, Rossor MN, Fox NC.; 2002 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123711

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Mechanism of the cleavage specificity of Alzheimer's disease [gamma]-secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein. by Lichtenthaler SF, Wang R, Grimm H, Uljon SN, Masters CL, Beyreuther K.; 1999 Mar 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15893

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Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. by Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A.; 2001 Jun 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=32306

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Multiplex fluorescence-based primer extension method for quantitative mutation analysis of mitochondrial DNA and its diagnostic application for Alzheimer's disease. by Fahy E, Nazarbaghi R, Zomorrodi M, Herrnstadt C, Parker WD, Davis RE, Ghosh SS.; 1997 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146869

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Opposite roles of apolipoprotein E in normal brains and in Alzheimer's disease. by Russo C, Angelini G, Dapino D, Piccini A, Piombo G, Schettini G, Chen S, Teller JK, Zaccheo D, Gambetti P, Tabaton M.; 1998 Dec 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28089

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Overexpression of hAPPswe Impairs Rewarded Alternation and Contextual Fear Conditioning in a Transgenic Mouse Model of Alzheimer's Disease. by Corcoran KA, Lu Y, Turner RS, Maren S.; 2002 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=187133

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Past exposure to vaccines and subsequent risk of Alzheimer's disease. by Verreault R, Laurin D, Lindsay J, Serres GD.; 2001 Nov 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81665

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Patients with Alzheimer's disease have reduced activities in midlife compared with healthy control-group members. by Friedland RP, Fritsch T, Smyth KA, Koss E, Lerner AJ, Chen CH, Petot GJ, Debanne SM.; 2001 Mar 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30672

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Peripheral anti-A[beta] antibody alters CNS and plasma A[beta] clearance and decreases brain A[beta] burden in a mouse model of Alzheimer's disease. by DeMattos RB, Bales KR, Cummins DJ, Dodart JC, Paul SM, Holtzman DM.; 2001 Jul 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37524

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Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. by Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K, Kholodenko D, Malenka RC, Nicoll RA, Mucke L.; 1999 Mar 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15924

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Plaque-induced neurite abnormalities: Implications for disruption of neural networks in Alzheimer's disease. by Knowles RB, Wyart C, Buldyrev SV, Cruz L, Urbanc B, Hasselmo ME, Stanley HE, Hyman BT.; 1999 Apr 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21854

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Presenilin, Notch, and the genesis and treatment of Alzheimer's disease. by Selkoe DJ.; 2001 Sep 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58679

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Simvastatin strongly reduces levels of Alzheimer's disease [beta]-amyloid peptides A[beta]42 and A[beta]40 in vitro and in vivo. by Fassbender K, Simons M, Bergmann C, Stroick M, Lutjohann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther K, Hartmann T.; 2001 May 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33303

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Specific intercellular binding of the [beta]-amyloid precursor protein to the presenilins induces intercellular signaling: Its significance for Alzheimer's disease. by Dewji NN, Singer SJ.; 1998 Dec 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24574

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Testosterone prevents the heat shock-induced overactivation of glycogen synthase kinase-3[beta] but not of cyclin-dependent kinase 5 and c-Jun NH2-terminal kinase and concomitantly abolishes hyperphosphorylation of [tau]: Implications for Alzheimer's disease. by Papasozomenos SC, Shanavas A.; 2002 Feb 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122157

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The Endogenous and Cell Cycle-dependent Phosphorylation of tau Protein in Living Cells: Implications for Alzheimer's Disease. by Illenberger S, Zheng-Fischhofer Q, Preuss U, Stamer K, Baumann K, Trinczek B, Biernat J, Godemann R, Mandelkow EM, Mandelkow E.; 1998 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25374

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The galvanization of [beta]-amyloid in Alzheimer's disease. by Bush AI, Tanzi RE.; 2002 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124227

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Three-dimensional structure of the lithostathine protofibril, a protein involved in Alzheimer's disease. by Gregoire C, Marco S, Thimonier J, Duplan L, Laurine E, Chauvin JP, Michel B, Peyrot V, Verdier JM.; 2001 Jul 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=125531

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Unusual phenotypic alteration of [beta] amyloid precursor protein ([beta]APP) maturation by a new Val-715 [right arrow] Met [beta]APP-770 mutation responsible for probable early-onset Alzheimer's disease. by Ancolio K, Dumanchin C, Barelli H, Warter JM, Brice A, Campion D, Frebourg T, Checler F.; 1999 Mar 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22430

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When should one stop cholinesterase inhibitors in patients with Alzheimer's disease? by Bogardus ST Jr.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=167204

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Alzheimer’s disease, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Alzheimer’s disease” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Alzheimer’s disease (hyperlinks lead to article summaries): •

A case report: doctor, my daughter has Alzheimer's disease. Author(s): Rozzini L, Borroni B, Chilovi BV, Trabucchi M, Padovani A. Source: Journal of the American Geriatrics Society. 2003 February; 51(2): 283-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558736&dopt=Abstract

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A collaborative study of the emergence and clinical features of the major depressive syndrome of Alzheimer's disease. Author(s): Zubenko GS, Zubenko WN, McPherson S, Spoor E, Marin DB, Farlow MR, Smith GE, Geda YE, Cummings JL, Petersen RC, Sunderland T. Source: The American Journal of Psychiatry. 2003 May; 160(5): 857-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727688&dopt=Abstract

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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A comprehensive study of gray matter loss in patients with Alzheimer's disease using optimized voxel-based morphometry. Author(s): Karas GB, Burton EJ, Rombouts SA, van Schijndel RA, O'Brien JT, Scheltens P, McKeith IG, Williams D, Ballard C, Barkhof F. Source: Neuroimage. 2003 April; 18(4): 895-907. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725765&dopt=Abstract

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A critical review of memory stimulation programs in Alzheimer's disease. Author(s): Grandmaison E, Simard M. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Spring; 15(2): 130-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724453&dopt=Abstract

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A risk for early-onset Alzheimer's disease associated with the APBB1 gene (FE65) intron 13 polymorphism. Author(s): Cousin E, Hannequin D, Ricard S, Mace S, Genin E, Chansac C, Brice A, Dubois B, Frebourg T, Mercken L, Benavides J, Pradier L, Campion D, Deleuze JF. Source: Neuroscience Letters. 2003 May 15; 342(1-2): 5-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727304&dopt=Abstract

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A study of stereotypic behaviours in Alzheimer's disease and frontal and temporal variant frontotemporal dementia. Author(s): Nyatsanza S, Shetty T, Gregory C, Lough S, Dawson K, Hodges JR. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 October; 74(10): 1398402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14570833&dopt=Abstract

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Absence of association between codon 129/219 polymorphisms of the prion protein gene and Alzheimer's disease in Japan. Author(s): Ohkubo T, Sakasegawa Y, Asada T, Kinoshita T, Goto Y, Kimura H, Mizusawa H, Hachiya NS, Kaneko K. Source: Annals of Neurology. 2003 October; 54(4): 553-4; Author Reply 555. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14520676&dopt=Abstract

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Accelerated memory decline in Alzheimer's disease with apolipoprotein epsilon4 allele. Author(s): Hirono N, Hashimoto M, Yasuda M, Kazui H, Mori E. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Summer; 15(3): 354-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928512&dopt=Abstract

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Accidental fatal hypothermia in elderly people with Alzheimer's disease. Author(s): Kibayashi K, Shojo H. Source: Med Sci Law. 2003 April; 43(2): 127-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741656&dopt=Abstract

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Activation of the cell stress kinase PKR in Alzheimer's disease and human amyloid precursor protein transgenic mice. Author(s): Peel AL, Bredesen DE. Source: Neurobiology of Disease. 2003 October; 14(1): 52-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678666&dopt=Abstract

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Advances in the development of biomarkers for Alzheimer's disease: from CSF total tau and Abeta(1-42) proteins to phosphorylated tau protein. Author(s): Hampel H, Goernitz A, Buerger K. Source: Brain Research Bulletin. 2003 August 15; 61(3): 243-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909294&dopt=Abstract

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Age-dependent association between interleukin-1A (-889) genetic polymorphism and sporadic Alzheimer's disease. A meta-analysis. Author(s): Combarros O, Llorca J, Sanchez-Guerra M, Infante J, Berciano J. Source: Journal of Neurology. 2003 August; 250(8): 987-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928921&dopt=Abstract

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Age-dependent cerebrovascular abnormalities and blood flow disturbances in APP23 mice modeling Alzheimer's disease. Author(s): Beckmann N, Schuler A, Mueggler T, Meyer EP, Wiederhold KH, Staufenbiel M, Krucker T. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 September 17; 23(24): 8453-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679413&dopt=Abstract

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Age-dependent impairment of somatosensory response in the amyloid precursor protein 23 transgenic mouse model of Alzheimer's disease. Author(s): Mueggler T, Baumann D, Rausch M, Staufenbiel M, Rudin M. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 September 10; 23(23): 8231-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967984&dopt=Abstract

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Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer's disease brains examined by in situ hybridization. Author(s): Perez-Torres S, Cortes R, Tolnay M, Probst A, Palacios JM, Mengod G. Source: Experimental Neurology. 2003 August; 182(2): 322-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12895443&dopt=Abstract

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Alzheimer's disease and total plasma aminothiols. Author(s): McCaddon A, Hudson P, Hill D, Barber J, Lloyd A, Davies G, Regland B. Source: Biological Psychiatry. 2003 February 1; 53(3): 254-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559659&dopt=Abstract

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Alzheimer's disease as a disconnection syndrome? Author(s): Delbeuck X, Van der Linden M, Collette F. Source: Neuropsychology Review. 2003 June; 13(2): 79-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12887040&dopt=Abstract

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Alzheimer's disease disrupts arithmetic fact retrieval processes but not arithmetic strategy selection. Author(s): Duverne S, Lemaire P, Michel BF. Source: Brain and Cognition. 2003 August; 52(3): 302-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907175&dopt=Abstract

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Alzheimer's disease versus normal ageing: a review of the efficiency of clinical and experimental memory measures. Author(s): Spaan PE, Raaijmakers JG, Jonker C. Source: J Clin Exp Neuropsychol. 2003 April; 25(2): 216-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754679&dopt=Abstract

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Alzheimer's disease. Hope for the future. Author(s): Morrison-Bogorad M. Source: Caring. 2002 August; 21(8): 12-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739346&dopt=Abstract

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Alzheimer's disease: differences in technetium-99m HMPAO SPECT scan findings between early onset and late onset dementia. Author(s): Kemp PM, Holmes C, Hoffmann SM, Bolt L, Holmes R, Rowden J, Fleming JS. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 June; 74(6): 715-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754337&dopt=Abstract

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Amyloid beta pathology in Alzheimer's disease and schizophrenia. Author(s): Religa D, Laudon H, Styczynska M, Winblad B, Naslund J, Haroutunian V. Source: The American Journal of Psychiatry. 2003 May; 160(5): 867-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727689&dopt=Abstract

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Amyloid precursor protein gene mutations responsible for early-onset autosomal dominant Alzheimer's disease. Author(s): Kowalska A. Source: Folia Neuropathol. 2003; 41(1): 35-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862394&dopt=Abstract

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Amyloid-beta immunization in Alzheimer's disease transgenic mouse models and wildtype mice. Author(s): Lemere CA, Spooner ET, Leverone JF, Mori C, Iglesias M, Bloom JK, Seabrook TJ. Source: Neurochemical Research. 2003 July; 28(7): 1017-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737526&dopt=Abstract

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Antibody therapy for Alzheimer's disease. Author(s): Morgan D. Source: Expert Rev Vaccines. 2003 February; 2(1): 53-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901597&dopt=Abstract

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Anti-inflammatory drug therapy alters beta-amyloid processing and deposition in an animal model of Alzheimer's disease. Author(s): Yan Q, Zhang J, Liu H, Babu-Khan S, Vassar R, Biere AL, Citron M, Landreth G. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 August 20; 23(20): 7504-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930788&dopt=Abstract

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Anti-inflammatory drugs and Alzheimer's disease. Author(s): Martyn C. Source: Bmj (Clinical Research Ed.). 2003 August 16; 327(7411): 353-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919966&dopt=Abstract

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Anti-inflammatory therapy in Alzheimer's disease: is hope still alive? Author(s): van Gool WA, Aisen PS, Eikelenboom P. Source: Journal of Neurology. 2003 July; 250(7): 788-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883918&dopt=Abstract

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APOE epsilon 3/ epsilon 4 heterozygotes have an elevated proportion of apolipoprotein E4 in cerebrospinal fluid relative to plasma, independent of Alzheimer's disease diagnosis. Author(s): Fukumoto H, Ingelsson M, Garevik N, Wahlund LO, Nukina N, Yaguchi Y, Shibata M, Hyman BT, Rebeck GW, Irizarry MC. Source: Experimental Neurology. 2003 September; 183(1): 249-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957508&dopt=Abstract

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Apolipoprotein D levels are elevated in prefrontal cortex of subjects with Alzheimer's disease: no relation to apolipoprotein E expression or genotype. Author(s): Thomas EA, Laws SM, Sutcliffe JG, Harper C, Dean B, McClean C, Masters C, Lautenschlager N, Gandy SE, Martins RN. Source: Biological Psychiatry. 2003 July 15; 54(2): 136-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873803&dopt=Abstract

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Apolipoprotein E genotype and early Alzheimer's disease: a longitudinal SPECT study. Author(s): Sakamoto S, Matsuda H, Asada T, Ohnishi T, Nakano S, Kanetaka H, Takasaki M. Source: Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging. 2003 April; 13(2): 113-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722493&dopt=Abstract

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App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16 mouse model of down syndrome. Author(s): Cataldo AM, Petanceska S, Peterhoff CM, Terio NB, Epstein CJ, Villar A, Carlson EJ, Staufenbiel M, Nixon RA. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 July 30; 23(17): 6788-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890772&dopt=Abstract

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Are they grieving? A qualitative analysis examining grief in caregivers of individuals with Alzheimer's disease. Author(s): Sanders S, Corley CS. Source: Social Work in Health Care. 2003; 37(3): 35-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14526875&dopt=Abstract

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Artificial grammar learning in Alzheimer's disease. Author(s): Reber PJ, Martinez LA, Weintraub S. Source: Cognitive, Affective & Behavioral Neuroscience. 2003 June; 3(2): 145-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943329&dopt=Abstract

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Assessing the health of adult daughter former caregivers for elders with Alzheimer's disease. Author(s): Berg-Weger M, Rauch SM, Rubio DM, Tebb SS. Source: Am J Alzheimers Dis Other Demen. 2003 July-August; 18(4): 231-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955788&dopt=Abstract

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Assessment of health economics in Alzheimer's disease (AHEAD): treatment with galantamine in the UK. Author(s): Ward A, Caro JJ, Getsios D, Ishak K, O'Brien J, Bullock R; AHEAD Study Group. Source: International Journal of Geriatric Psychiatry. 2003 August; 18(8): 740-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891643&dopt=Abstract

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Association analysis between anterior-pharynx defective-1 genes polymorphisms and Alzheimer's disease. Author(s): Poli M, Gatta LB, Archetti S, Padovani A, Albertini A, Finazzi D. Source: Neuroscience Letters. 2003 October 23; 350(2): 77-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972157&dopt=Abstract

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Association of the C766T polymorphism of the low-density lipoprotein receptorrelated protein gene with Alzheimer's disease. Author(s): Kolsch H, Ptok U, Mohamed I, Schmitz S, Rao ML, Maier W, Heun R. Source: American Journal of Medical Genetics. 2003 August 15; 121B(1): 128-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898587&dopt=Abstract

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Association study between Alzheimer's disease and genes involved in Abeta biosynthesis, aggregation and degradation: suggestive results with BACE1. Author(s): Clarimon J, Bertranpetit J, Calafell F, Boada M, Tarraga L, Comas D. Source: Journal of Neurology. 2003 August; 250(8): 956-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928915&dopt=Abstract

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Barriers to remember: brain-targeting chemical delivery systems and Alzheimer's disease. Author(s): Bodor N, Buchwald P. Source: Drug Discovery Today. 2002 July 15; 7(14): 766-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547033&dopt=Abstract

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Behavioral and electrical brain measures of semantic priming in patients with Alzheimer's disease: implications for access failure versus deterioration hypotheses. Author(s): Auchterlonie S, Phillips NA, Chertkow H. Source: Brain and Cognition. 2002 March-April; 48(2-3): 264-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030448&dopt=Abstract

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Behavioral characterization of the Tg2576 transgenic model of Alzheimer's disease through 19 months. Author(s): King DL, Arendash GW. Source: Physiology & Behavior. 2002 April 15; 75(5): 627-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020728&dopt=Abstract

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Behavioral issues in Alzheimer's disease. Author(s): Grace J, Cahn-Weiner D. Source: Medicine and Health, Rhode Island. 2002 July; 85(7): 213-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182093&dopt=Abstract

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Behavioural pathology in Alzheimer's disease with special reference to apolipoprotein E genotype. Author(s): Gabryelewicz T, Religa D, Styczynska M, Peplonska B, Pfeffer A, Wasiak B, Luczywek E, Golebiowski M, Androsiuk W, Czyzewski K, Przekop I, Barcikowska M. Source: Dementia and Geriatric Cognitive Disorders. 2002; 14(4): 208-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411763&dopt=Abstract

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Beta-amyloid (Abeta) protein in cerebrospinal fluid as a biomarker for Alzheimer's disease. Author(s): Andreasen N, Blennow K. Source: Peptides. 2002 July; 23(7): 1205-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12128078&dopt=Abstract

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Beta-amyloid aggregation inhibitors for the treatment of Alzheimer's disease: dream or reality? Author(s): Talaga P. Source: Mini Reviews in Medicinal Chemistry. 2001 July; 1(2): 175-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369982&dopt=Abstract

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Beta-amyloid fragment 25-35 selectively damages platelets from patients with Alzheimer's disease. Author(s): Casoli T, Di Stefano G, Delfino A, Solazzi M, Fattoretti P, Bertoni-Freddari C, Guidi M, Scarpino O, Giunta S, Galeazzi L. Source: Annals of the New York Academy of Sciences. 2002 November; 977: 296-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480764&dopt=Abstract

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Beta-amyloid production, aggregation, and clearance as targets for therapy in Alzheimer's disease. Author(s): De Felice FG, Ferreira ST. Source: Cellular and Molecular Neurobiology. 2002 December; 22(5-6): 545-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585679&dopt=Abstract

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Beta-amyloid, neuronal death and Alzheimer's disease. Author(s): Carter J, Lippa CF. Source: Current Molecular Medicine. 2001 December; 1(6): 733-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11899259&dopt=Abstract

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Beta-secretase (BACE) as a drug target for Alzheimer's disease. Author(s): Vassar R. Source: Advanced Drug Delivery Reviews. 2002 December 7; 54(12): 1589-602. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453676&dopt=Abstract

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Beta-secretase as a target for the treatment of Alzheimer's disease. Author(s): Citron M. Source: Journal of Neuroscience Research. 2002 November 1; 70(3): 373-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391600&dopt=Abstract

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Beta-secretase processing in the trans-Golgi network preferentially generates truncated amyloid species that accumulate in Alzheimer's disease brain. Author(s): Huse JT, Liu K, Pijak DS, Carlin D, Lee VM, Doms RW. Source: The Journal of Biological Chemistry. 2002 May 3; 277(18): 16278-84. Epub 2002 February 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847218&dopt=Abstract

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Better preservation of memory span relative to supraspan immediate recall in Alzheimer's disease. Author(s): Cherry BJ, Buckwalter JG, Henderson VW. Source: Neuropsychologia. 2002; 40(7): 846-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900735&dopt=Abstract

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Biochemical analysis of tau proteins in argyrophilic grain disease, Alzheimer's disease, and Pick's disease : a comparative study. Author(s): Zhukareva V, Shah K, Uryu K, Braak H, Del Tredici K, Sundarraj S, Clark C, Trojanowski JQ, Lee VM. Source: American Journal of Pathology. 2002 October; 161(4): 1135-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368187&dopt=Abstract

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Biochemical and therapeutic effects of antioxidants in the treatment of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Author(s): Di Matteo V, Esposito E. Source: Current Drug Targets. Cns and Neurological Disorders. 2003 April; 2(2): 95-107. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769802&dopt=Abstract

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Biochemical markers of Alzheimer's disease: wish and reality. Author(s): Papassotiropoulos A, Hock C. Source: Neurobiology of Aging. 2002 July-August; 23(4): 513-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12009497&dopt=Abstract

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Biogenesis and metabolism of Alzheimer's disease Abeta amyloid peptides. Author(s): Evin G, Weidemann A. Source: Peptides. 2002 July; 23(7): 1285-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12128085&dopt=Abstract

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Biological correlates of clinical subgroups of Alzheimer's disease. Author(s): Sjogren M, Wikkelso C, Ostling S, Wallin A, Blennow K. Source: Dementia and Geriatric Cognitive Disorders. 2002; 14(4): 191-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411761&dopt=Abstract

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Biological markers for therapeutic trials in Alzheimer's disease. Proceedings of the biological markers working group; NIA initiative on neuroimaging in Alzheimer's disease. Author(s): Frank RA, Galasko D, Hampel H, Hardy J, de Leon MJ, Mehta PD, Rogers J, Siemers E, Trojanowski JQ; National Institute on Aging Biological Markers Working Group. Source: Neurobiology of Aging. 2003 July-August; 24(4): 521-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714109&dopt=Abstract

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Biomarkers of Alzheimer's disease and mild cognitive impairment: are we there yet? Author(s): Turner RS. Source: Experimental Neurology. 2003 September; 183(1): 7-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957483&dopt=Abstract

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Bradykinin receptor modulation in cellular models of aging and Alzheimer's disease. Author(s): Jong YJ, Dalemar LR, Seehra K, Baenziger NL. Source: International Immunopharmacology. 2002 December; 2(13-14): 1833-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12489797&dopt=Abstract

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Brain aging and Alzheimer's disease; use it or lose it. Author(s): Swaab DF, Dubelaar EJ, Hofman MA, Scherder EJ, van Someren EJ, Verwer RW. Source: Prog Brain Res. 2002; 138: 343-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432778&dopt=Abstract

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Brain biopsy prior to treatment of Alzheimer's disease. Author(s): Holm A, Savolainen S, Alafuzoff I. Source: Minimally Invasive Neurosurgery : Min. 2003 June; 46(3): 161-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872193&dopt=Abstract

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Brain hydrogen sulfide is severely decreased in Alzheimer's disease. Author(s): Eto K, Asada T, Arima K, Makifuchi T, Kimura H. Source: Biochemical and Biophysical Research Communications. 2002 May 24; 293(5): 1485-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12054683&dopt=Abstract

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Brain SPET abnormalities in Alzheimer's disease before and after atrophy correction. Author(s): Matsuda H, Kanetaka H, Ohnishi T, Asada T, Imabayashi E, Nakano S, Katoh A, Tanaka F. Source: European Journal of Nuclear Medicine and Molecular Imaging. 2002 November; 29(11): 1502-5. Epub 2002 August 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397471&dopt=Abstract

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Brain SPET perfusion in early Alzheimer's disease: where to look? Author(s): Goethals I, Van De Wiele C, Slosman D, Dierckx R. Source: European Journal of Nuclear Medicine and Molecular Imaging. 2002 August; 29(8): 975-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296285&dopt=Abstract

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Brain to plasma amyloid-beta efflux: a measure of brain amyloid burden in a mouse model of Alzheimer's disease. Author(s): DeMattos RB, Bales KR, Cummins DJ, Paul SM, Holtzman DM. Source: Science. 2002 March 22; 295(5563): 2264-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910111&dopt=Abstract

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Brain-membrane cholesterol in Alzheimer's disease. Author(s): Eckert GP, Kirsch C, Muller WE. Source: J Nutr Health Aging. 2003; 7(1): 18-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679836&dopt=Abstract

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Brainstem and cortical Lewy bodies in patients presenting clinically with Alzheimer's disease. Author(s): SantaCruz KS, Tasaki CS, Kim RC, Cotman CW. Source: Journal of Alzheimer's Disease : Jad. 2002 February; 4(1): 11-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12214014&dopt=Abstract

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Brazilian version of the Mattis dementia rating scale: diagnosis of mild dementia in Alzheimer's disease. Author(s): Porto CS, Fichman HC, Caramelli P, Bahia VS, Nitrini R. Source: Arquivos De Neuro-Psiquiatria. 2003 June; 61(2B): 339-45. Epub 2003 July 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894264&dopt=Abstract

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Broad therapeutic benefits in patients with probable vascular dementia or Alzheimer's disease with cerebrovascular disease after treatment with galantamine. Author(s): Erkinjuntti T. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2002 September; 9(5): 545. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220392&dopt=Abstract

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Burden among family caregivers of persons with Alzheimer's disease in nursing homes. Author(s): Tornatore JB, Grant LA. Source: The Gerontologist. 2002 August; 42(4): 497-506. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145377&dopt=Abstract

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Butyrylcholinesterase: an important new target in Alzheimer's disease therapy. Author(s): Greig NH, Lahiri DK, Sambamurti K. Source: Int Psychogeriatr. 2002; 14 Suppl 1: 77-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636181&dopt=Abstract

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By the way, doctor. I read in the paper that cholesterol might be good for the brain and prevent Alzheimer's disease. So I'm wondering if taking a statin is really such a good idea. Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2002 June; 27(8): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079818&dopt=Abstract

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c954C-->T polymorphism in the Fe65L2 gene is associated with early-onset Alzheimer's disease. Author(s): Tanahashi H, Asada T, Tabira T. Source: Annals of Neurology. 2002 November; 52(5): 691-3. Erratum In: Ann Neurol. 2003 July; 54(1): 137. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12402277&dopt=Abstract

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Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice. Author(s): Harris FM, Brecht WJ, Xu Q, Tesseur I, Kekonius L, Wyss-Coray T, Fish JD, Masliah E, Hopkins PC, Scearce-Levie K, Weisgraber KH, Mucke L, Mahley RW, Huang Y. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 September 16; 100(19): 10966-71. Epub 2003 August 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939405&dopt=Abstract

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Carer impressions of participation in Alzheimer's disease clinical trials: what are their hopes? And is it worth it? Author(s): Mastwyk M, Ritchie CW, LoGiudice D, Sullivan KA, Macfarlane S. Source: Int Psychogeriatr. 2002 March; 14(1): 39-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094906&dopt=Abstract

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Caspase activation in the limbic cortex of subjects with early Alzheimer's disease. Author(s): Gastard MC, Troncoso JC, Koliatsos VE. Source: Annals of Neurology. 2003 September; 54(3): 393-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953274&dopt=Abstract

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Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer's disease. Author(s): Gamblin TC, Chen F, Zambrano A, Abraha A, Lagalwar S, Guillozet AL, Lu M, Fu Y, Garcia-Sierra F, LaPointe N, Miller R, Berry RW, Binder LI, Cryns VL. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 August 19; 100(17): 10032-7. Epub 2003 July 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888622&dopt=Abstract

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Categorization of object descriptions in Alzheimer's disease and frontotemporal dementia: limitation in rule-based processing. Author(s): Grossman M, Smith EE, Koenig PL, Glosser G, Rhee J, Dennis K. Source: Cognitive, Affective & Behavioral Neuroscience. 2003 June; 3(2): 120-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943327&dopt=Abstract

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Cathepsin D polymorphism in Italian elderly subjects with sporadic late-onset Alzheimer's disease. Author(s): Ingegni T, Nocentini G, Mariani E, Spazzafumo L, Polidori MC, Cherubini A, Catani M, Cadini D, Senin U, Mecocci P. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(3): 151-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826741&dopt=Abstract

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Causative and susceptibility genes for Alzheimer's disease: a review. Author(s): Rocchi A, Pellegrini S, Siciliano G, Murri L. Source: Brain Research Bulletin. 2003 June 30; 61(1): 1-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788204&dopt=Abstract

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Cerebral atherosclerosis and mild Alzheimer's disease. Author(s): Rafael H. Source: Stroke; a Journal of Cerebral Circulation. 2003 August; 34(8): E106. Epub 2003 July 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855821&dopt=Abstract

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Cerebral correlates of the progression rate of the cognitive decline in probable Alzheimer's disease. Author(s): Nagahama Y, Nabatame H, Okina T, Yamauchi H, Narita M, Fujimoto N, Murakami M, Fukuyama H, Matsuda M. Source: European Neurology. 2003; 50(1): 1-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824705&dopt=Abstract

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Changes in metabolic activity and estrogen receptors in the human medial mamillary nucleus: relation to sex, aging and Alzheimer's disease. Author(s): Ishunina TA, Kamphorst W, Swaab DF. Source: Neurobiology of Aging. 2003 October; 24(6): 817-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927764&dopt=Abstract

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Chemotactic signaling, microglia, and Alzheimer's disease senile plaques: is there a connection? Author(s): Luca M, Chavez-Ross A, Edelstein-Keshet L, Mogilner A. Source: Bulletin of Mathematical Biology. 2003 July; 65(4): 693-730. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875339&dopt=Abstract

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Cholesterol and Alzheimer's disease. Author(s): Hoyer S. Source: Neurology. 2002 July 9; 59(1): 150; Author Reply 150-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105333&dopt=Abstract

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Cholesterol, oxidative stress, and Alzheimer's disease: expanding the horizons of pathogenesis. Author(s): Pappolla MA, Smith MA, Bryant-Thomas T, Bazan N, Petanceska S, Perry G, Thal LJ, Sano M, Refolo LM. Source: Free Radical Biology & Medicine. 2002 July 15; 33(2): 173-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106813&dopt=Abstract

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Cholinergic function and Alzheimer's disease. Author(s): Giacobini E. Source: International Journal of Geriatric Psychiatry. 2003 September; 18(Suppl 1): S1-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12973744&dopt=Abstract

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Clinical and biomarker investigation of a patient with a novel presenilin-1 mutation (A431V) in the mild cognitive impairment stage of Alzheimer's disease. Author(s): Matsushita S, Arai H, Okamura N, Ohmori T, Takasugi K, Matsui T, Maruyama M, Iwatsubo T, Higuchi S. Source: Biological Psychiatry. 2002 November 1; 52(9): 907-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399144&dopt=Abstract

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Clinical characteristics of Alzheimer's disease. Author(s): Asada T. Source: Intern Med. 2003 March; 42(3): 310-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705808&dopt=Abstract

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Clinical practice. Early Alzheimer's disease. Author(s): Kawas CH. Source: The New England Journal of Medicine. 2003 September 11; 349(11): 1056-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968090&dopt=Abstract

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Clinical trials in Alzheimer's disease. Calculating Alzheimer's Disease Assessment Scale-cognitive subsection with the data from the consortium to establish a registry for Alzheimer's disease. Author(s): Gillen TE, Gregg KM, Yuan H, Kurth MC, Krishnan KR. Source: Psychopharmacology Bulletin. 2001 Spring; 35(2): 83-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397889&dopt=Abstract

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Clinically tested drugs for Alzheimer's disease. Author(s): McGeer EG, McGeer PL. Source: Expert Opinion on Investigational Drugs. 2003 July; 12(7): 1143-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831349&dopt=Abstract

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Coexistence of CADASIL and Alzheimer's disease. Author(s): Thijs V, Robberecht W, De Vos R, Sciot R. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 June; 74(6): 790-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754354&dopt=Abstract

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Cognitive asymmetries associated with apolipoprotein E genotype in patients with Alzheimer's disease. Author(s): Finton MJ, Lucas JA, Rippeth JD, Bohac DL, Smith GE, Ivnik RJ, Petersen RC, Graff-Radford NR. Source: Journal of the International Neuropsychological Society : Jins. 2003 July; 9(5): 751-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901781&dopt=Abstract

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Cognitive estimation in patients with probable Alzheimer's disease and alcoholic Korsakoff patients. Author(s): Brand M, Kalbe E, Fujiwara E, Huber M, Markowitsch HJ. Source: Neuropsychologia. 2003; 41(5): 575-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559150&dopt=Abstract

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Cognitive rehabilitation as a component of early intervention in Alzheimer's disease: a single case study. Author(s): Clare L, Wilson BA, Carter G, Hodges JR. Source: Aging & Mental Health. 2003 January; 7(1): 15-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554310&dopt=Abstract

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Comorbidity of psychopathological domains in community-dwelling persons with Alzheimer's disease. Author(s): Tractenberg RE, Weiner MF, Patterson MB, Teri L, Thal LJ. Source: Journal of Geriatric Psychiatry and Neurology. 2003 June; 16(2): 94-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801159&dopt=Abstract

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Complement C5a receptor-mediated signaling may be involved in neurodegeneration in Alzheimer's disease. Author(s): Farkas I, Takahashi M, Fukuda A, Yamamoto N, Akatsu H, Baranyi L, Tateyama H, Yamamoto T, Okada N, Okada H. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 June 1; 170(11): 5764-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759460&dopt=Abstract

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Conformational changes and truncation of tau protein during tangle evolution in Alzheimer's disease. Author(s): Garcia-Sierra F, Ghoshal N, Quinn B, Berry RW, Binder LI. Source: Journal of Alzheimer's Disease : Jad. 2003 April; 5(2): 65-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719624&dopt=Abstract

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Connecting with the cognitively impaired: dementia and Alzheimer's disease. Author(s): Ledoux N. Source: Caring. 2003 August; 22(8): 30-2; Quiz 33-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556377&dopt=Abstract

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Contribution of APOE promoter polymorphisms to Alzheimer's disease risk. Author(s): Lambert JC, Araria-Goumidi L, Myllykangas L, Ellis C, Wang JC, Bullido MJ, Harris JM, Artiga MJ, Hernandez D, Kwon JM, Frigard B, Petersen RC, Cumming AM, Pasquier F, Sastre I, Tienari PJ, Frank A, Sulkava R, Morris JC, St Clair D, Mann DM, Wavrant-DeVrieze F, Ezquerra-Trabalon M, Amouyel P, Hardy J, Haltia M, Valdivieso F, Goate AM, Perez-Tur J, Lendon CL, Chartier-Harlin MC. Source: Neurology. 2002 July 9; 59(1): 59-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105308&dopt=Abstract

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Contribution of informant and patient ratings to the accuracy of the mini-mental state examination in predicting probable Alzheimer's disease. Author(s): Tierney MC, Herrmann N, Geslani DM, Szalai JP. Source: Journal of the American Geriatrics Society. 2003 June; 51(6): 813-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757568&dopt=Abstract

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Corpus callosum atrophy, white matter lesions, and frontal executive dysfunction in normal aging and Alzheimer's disease. A community-based study: the Tajiri Project. Author(s): Meguro K, Constans JM, Shimada M, Yamaguchi S, Ishizaki J, Ishii H, Yamadori A, Sekita Y. Source: Int Psychogeriatr. 2003 March; 15(1): 9-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834197&dopt=Abstract

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Correlation of oxidative stress and the loss of the nicotinic receptor alpha 4 subunit in the temporal cortex of patients with Alzheimer's disease. Author(s): Yu WF, Nordberg A, Ravid R, Guan ZZ. Source: Neuroscience Letters. 2003 February 20; 338(1): 13-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12565129&dopt=Abstract

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Co-use of donepezil and hypnotics among Alzheimer's disease patients living in the community. Author(s): Stahl SM, Markowitz JS, Gutterman EM, Papadopoulos G. Source: The Journal of Clinical Psychiatry. 2003 April; 64(4): 466-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716251&dopt=Abstract

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CSF markers for incipient Alzheimer's disease. Author(s): Blennow K, Hampel H. Source: Lancet. Neurology. 2003 October; 2(10): 605-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505582&dopt=Abstract

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CSF markers for pathogenic processes in Alzheimer's disease: diagnostic implications and use in clinical neurochemistry. Author(s): Blennow K, Vanmechelen E. Source: Brain Research Bulletin. 2003 August 15; 61(3): 235-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909293&dopt=Abstract

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CSF phosphorylated tau--does it constitute an accurate biological test for Alzheimer's disease? Author(s): Mitchell A, Brindle N. Source: International Journal of Geriatric Psychiatry. 2003 May; 18(5): 407-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766916&dopt=Abstract

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Current treatments for Alzheimer's disease: cholinesterase inhibitors. Author(s): Doody RS. Source: The Journal of Clinical Psychiatry. 2003; 64 Suppl 9: 11-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934969&dopt=Abstract

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Cyclooxygenase-2 in the hippocampus is up-regulated in Alzheimer's disease but not in variant Alzheimer's disease with cotton wool plaques in humans. Author(s): Yokota O, Terada S, Ishizu H, Ishihara T, Ujike H, Nakashima H, Nakashima Y, Kugo A, Checler F, Kuroda S. Source: Neuroscience Letters. 2003 June 12; 343(3): 175-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12770691&dopt=Abstract

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Cytogenetic alterations in lymphocytes of Alzheimer's disease and Parkinson's disease patients. Author(s): Petrozzi L, Lucetti C, Scarpato R, Gambaccini G, Trippi F, Bernardini S, Del Dotto P, Migliore L, Bonuccelli U. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2002 September; 23 Suppl 2: S97-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548361&dopt=Abstract

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DC11: a novel monoclonal antibody revealing Alzheimer's disease-specific tau epitope. Author(s): Vechterova L, Kontsekova E, Zilka N, Ferencik M, Ravid R, Novak M. Source: Neuroreport. 2003 January 20; 14(1): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544837&dopt=Abstract

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Decreased nigral neuromelanin in Alzheimer's disease. Author(s): Reyes MG, Faraldi F, Rydman R, Wang CC. Source: Neurological Research. 2003 March; 25(2): 179-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635519&dopt=Abstract

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Defects in expression of genes related to synaptic vesicle trafficking in frontal cortex of Alzheimer's disease. Author(s): Yao PJ, Zhu M, Pyun EI, Brooks AI, Therianos S, Meyers VE, Coleman PD. Source: Neurobiology of Disease. 2003 March; 12(2): 97-109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667465&dopt=Abstract

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Defining the role of the caregiver in Alzheimer's disease treatment. Author(s): Brodaty H, Green A. Source: Drugs & Aging. 2002; 19(12): 891-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495365&dopt=Abstract

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Delusional thoughts and regional frontal/temporal cortex metabolism in Alzheimer's disease. Author(s): Sultzer DL, Brown CV, Mandelkern MA, Mahler ME, Mendez MF, Chen ST, Cummings JL. Source: The American Journal of Psychiatry. 2003 February; 160(2): 341-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562582&dopt=Abstract

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Delusions and hallucinations in Alzheimer's disease: review of the brain decade. Author(s): Bassiony MM, Lyketsos CG. Source: Psychosomatics. 2003 September-October; 44(5): 388-401. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954913&dopt=Abstract

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Delusions of Japanese patients with Alzheimer's disease. Author(s): Ikeda M, Shigenobu K, Fukuhara R, Hokoishi K, Nebu A, Maki N, Nomura M, Komori K, Tanabe H. Source: International Journal of Geriatric Psychiatry. 2003 June; 18(6): 527-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789674&dopt=Abstract

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Depression and Alzheimer's disease: symptom or comorbidity? Author(s): Moretti R, Torre P, Antonello RM, Cazzato G, Bava A. Source: Am J Alzheimers Dis Other Demen. 2002 November-December; 17(6): 338-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12501480&dopt=Abstract

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Depression in Alzheimer's disease: heterogeneity and related issues. Author(s): Lee HB, Lyketsos CG. Source: Biological Psychiatry. 2003 August 1; 54(3): 353-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893110&dopt=Abstract

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Detection of Alzheimer's disease and dementia in the preclinical phase: population based cohort study. Author(s): Palmer K, Backman L, Winblad B, Fratiglioni L. Source: Bmj (Clinical Research Ed.). 2003 February 1; 326(7383): 245. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560271&dopt=Abstract

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Development of a scale to predict decline in patients with mild Alzheimer's disease. Author(s): Santillan CE, Fritsch T, Geldmacher DS. Source: Journal of the American Geriatrics Society. 2003 January; 51(1): 91-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534852&dopt=Abstract

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Dexamethasone inhibits TNF-alpha synthesis more effectively in Alzheimer's disease patients than in healthy individuals. Author(s): Dziedzic T, Wybranska I, Dembinska-Kiec A, Klimkowicz A, Slowik A, Pankiewicz J, Zdzienicka A, Szczudlik A. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(4): 283-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512725&dopt=Abstract

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DHEA for Alzheimer's disease: a modest showing by a superhormone. Author(s): Knopman D, Henderson VW. Source: Neurology. 2003 April 8; 60(7): 1060-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682305&dopt=Abstract

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DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebocontrolled study. Author(s): Wolkowitz OM, Kramer JH, Reus VI, Costa MM, Yaffe K, Walton P, Raskind M, Peskind E, Newhouse P, Sack D, De Souza E, Sadowsky C, Roberts E; DHEAAlzheimer's Disease Collaborative Research. Source: Neurology. 2003 April 8; 60(7): 1071-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682308&dopt=Abstract

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Diagnose and treat mild to moderate Alzheimer's disease. Author(s): Griffith VT. Source: The Nurse Practitioner. 2002 December; 27(12): 13-25; Quiz 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493946&dopt=Abstract

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Diagnosis and treatment of Alzheimer's disease. Author(s): Grossberg GT. Source: The Journal of Clinical Psychiatry. 2003; 64 Suppl 9: 3-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934967&dopt=Abstract

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Diagnostic utility of visual evoked potential changes in Alzheimer's disease. Author(s): Coburn KL, Arruda JE, Estes KM, Amoss RT. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Spring; 15(2): 175-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724458&dopt=Abstract

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Differences in the behavioral and psychological symptoms between Alzheimer's disease and vascular dementia: are the different pharmacologic treatment strategies justifiable? Author(s): Kim JM, Lyons D, Shin IS, Yoon JS. Source: Human Psychopharmacology. 2003 April; 18(3): 215-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672174&dopt=Abstract

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Different immunoreactivities of the microtubule-binding region of tau and its molecular basis in brains from patients with Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration. Author(s): Arai T, Ikeda K, Akiyama H, Tsuchiya K, Iritani S, Ishiguro K, Yagishita S, Oda T, Odawara T, Iseki E. Source: Acta Neuropathologica. 2003 May; 105(5): 489-98. Epub 2003 February 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677450&dopt=Abstract

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Different pattern of association of paraoxonase Gln192-->Arg polymorphism with sporadic late-onset Alzheimer's disease and coronary artery disease. Author(s): Scacchi R, Gambina G, Martini MC, Broggio E, Vilardo T, Corbo RM. Source: Neuroscience Letters. 2003 March 13; 339(1): 17-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618290&dopt=Abstract

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Differential regulation of glutamate receptors in Alzheimer's disease. Author(s): Lee HG, Zhu X, Ghanbari HA, Ogawa O, Raina AK, O'Neill MJ, Perry G, Smith MA. Source: Neuro-Signals. 2002 September-October; 11(5): 282-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566929&dopt=Abstract

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Differentiation of geriatric major depression from Alzheimer's disease with CSF tau protein phosphorylated at threonine 231. Author(s): Buerger K, Zinkowski R, Teipel SJ, Arai H, DeBernardis J, Kerkman D, McCulloch C, Padberg F, Faltraco F, Goernitz A, Tapiola T, Rapoport SI, Pirttila T, Moller HJ, Hampel H. Source: The American Journal of Psychiatry. 2003 February; 160(2): 376-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562590&dopt=Abstract

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Diffusion tensor in posterior cingulate gyrus: correlation with cognitive decline in Alzheimer's disease. Author(s): Yoshiura T, Mihara F, Ogomori K, Tanaka A, Kaneko K, Masuda K. Source: Neuroreport. 2002 December 3; 13(17): 2299-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488815&dopt=Abstract

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Direct determination of the proportion of intra- and extra-cellular neocortical neurofibrillary tangles in Alzheimer's disease. Author(s): Vickers JC, Tan A, Dickson TC. Source: Brain Research. 2003 May 2; 971(1): 135-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691846&dopt=Abstract

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Distribution, levels, and activation of MEK1 in Alzheimer's disease. Author(s): Zhu X, Sun Z, Lee HG, Siedlak SL, Perry G, Smith MA. Source: Journal of Neurochemistry. 2003 July; 86(1): 136-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807433&dopt=Abstract

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Do cognitive patterns of brain magnetic activity correlate with hippocampal atrophy in Alzheimer's disease? Author(s): Maestu F, Arrazola J, Fernandez A, Simos PG, Amo C, Gil-Gregorio P, Fernandez S, Papanicolaou A, Ortiz T. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 February; 74(2): 20812. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531952&dopt=Abstract

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Do dietary antioxidants prevent Alzheimer's disease? Author(s): Sano M. Source: Lancet. Neurology. 2002 October; 1(6): 342. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849394&dopt=Abstract

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Do leisure activities protect against Alzheimer's disease? Author(s): Fabrigoule C. Source: Lancet. Neurology. 2002 May; 1(1): 11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849540&dopt=Abstract

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Does caffeine intake protect from Alzheimer's disease? Author(s): Maia L, de Mendonca A. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2002 July; 9(4): 377-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099922&dopt=Abstract

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Does insulin dysfunction play a role in Alzheimer's disease? Author(s): Gasparini L, Netzer WJ, Greengard P, Xu H. Source: Trends in Pharmacological Sciences. 2002 June; 23(6): 288-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084635&dopt=Abstract

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Does my mouse have Alzheimer's disease? Author(s): Dodart JC, Mathis C, Bales KR, Paul SM. Source: Genes, Brain, and Behavior. 2002 August; 1(3): 142-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884970&dopt=Abstract

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Does proteasome inhibition play a role in mediating neuropathology and neuron death in Alzheimer's disease? Author(s): Ding Q, Keller JN. Source: Journal of Alzheimer's Disease : Jad. 2003 June; 5(3): 241-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897408&dopt=Abstract

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Donepezil and athetosis in an elderly patient with Alzheimer's disease. Author(s): Tanaka M, Yokode M, Kita T, Matsubayashi K. Source: Journal of the American Geriatrics Society. 2003 June; 51(6): 889-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757588&dopt=Abstract

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Donepezil for dementia due to Alzheimer's disease. Author(s): Birks JS, Harvey R. Source: Cochrane Database Syst Rev. 2003; (3): Cd001190. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917900&dopt=Abstract

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Donepezil is associated with delayed nursing home placement in patients with Alzheimer's disease. Author(s): Geldmacher DS, Provenzano G, McRae T, Mastey V, Ieni JR. Source: Journal of the American Geriatrics Society. 2003 July; 51(7): 937-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834513&dopt=Abstract

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Donepezil use for advanced Alzheimer's disease--a case study from a long-term care facility. Author(s): Tariot PN, Jakimovich L. Source: Journal of the American Medical Directors Association. 2003 July-August; 4(4): 216-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837144&dopt=Abstract

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Drugs targeting Alzheimer's disease: some things old and some things new. Author(s): Michaelis ML. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 March; 304(3): 897-904. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604663&dopt=Abstract

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Dynamics of gray matter loss in Alzheimer's disease. Author(s): Thompson PM, Hayashi KM, de Zubicaray G, Janke AL, Rose SE, Semple J, Herman D, Hong MS, Dittmer SS, Doddrell DM, Toga AW. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 February 1; 23(3): 994-1005. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574429&dopt=Abstract

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Dysregulation of calcium in Alzheimer's disease. Author(s): Brzyska M, Elbaum D. Source: Acta Neurobiol Exp (Wars). 2003; 63(3): 171-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14518509&dopt=Abstract

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Early and persistent alterations in prefrontal cortex MAO A and B in Alzheimer's disease. Author(s): Kennedy BP, Ziegler MG, Alford M, Hansen LA, Thal LJ, Masliah E. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2003 July; 110(7): 789801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811639&dopt=Abstract

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Early diagnosis of Alzheimer's disease. Author(s): Singhal MK. Source: Indian J Exp Biol. 2002 March; 40(3): 373. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635716&dopt=Abstract

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Early diagnosis of Alzheimer's disease: clinical and economic benefits. Author(s): Leifer BP. Source: Journal of the American Geriatrics Society. 2003 May; 51(5 Suppl Dementia): S281-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801384&dopt=Abstract

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Early olfactory involvement in Alzheimer's disease. Author(s): Christen-Zaech S, Kraftsik R, Pillevuit O, Kiraly M, Martins R, Khalili K, Miklossy J. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2003 February; 30(1): 20-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619779&dopt=Abstract

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Early onset familial Alzheimer's disease: Mutation frequency in 31 families. Author(s): Janssen JC, Beck JA, Campbell TA, Dickinson A, Fox NC, Harvey RJ, Houlden H, Rossor MN, Collinge J. Source: Neurology. 2003 January 28; 60(2): 235-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552037&dopt=Abstract

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Early-onset Alzheimer's disease with presenilin-1 M139V mutation: clinical, neuropsychological and neuropathological study. Author(s): Larner AJ, du Plessis DG. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2003 May; 10(3): 319-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752408&dopt=Abstract

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Economic evaluation of galantamine in the treatment of mild to moderate Alzheimer's disease in the United States. Author(s): Migliaccio-Walle K, Getsios D, Caro JJ, Ishak KJ, O'Brien JA, Papadopoulos G; AHEAD Study Group. Source: Clinical Therapeutics. 2003 June; 25(6): 1806-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860500&dopt=Abstract

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Ectopic localization of phosphorylated histone H3 in Alzheimer's disease: a mitotic catastrophe? Author(s): Ogawa O, Zhu X, Lee HG, Raina A, Obrenovich ME, Bowser R, Ghanbari HA, Castellani RJ, Perry G, Smith MA. Source: Acta Neuropathologica. 2003 May; 105(5): 524-8. Epub 2003 February 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677454&dopt=Abstract

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EEG harmonic responses to photic stimulation in normal aging and Alzheimer's disease: differences in interhemispheric coherence. Author(s): Kikuchi M, Wada Y, Takeda T, Oe H, Hashimoto T, Koshino Y. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2002 July; 113(7): 1045-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088698&dopt=Abstract

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EEG synchronization in mild cognitive impairment and Alzheimer's disease. Author(s): Stam CJ, van der Made Y, Pijnenburg YA, Scheltens P. Source: Acta Neurologica Scandinavica. 2003 August; 108(2): 90-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859284&dopt=Abstract

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Effect of advanced glycation endproducts on cell cycle and their relevance for Alzheimer's disease. Author(s): Munch G, Gasic-Milenkovic J, Arendt T. Source: Journal of Neural Transmission. Supplementum. 2003; (65): 63-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946049&dopt=Abstract

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Effect of age on regional cerebral blood flow patterns in Alzheimer's disease patients. Author(s): Hanyu H, Shimuzu T, Tanaka Y, Takasaki M, Koizumi K, Abe K. Source: Journal of the Neurological Sciences. 2003 May 15; 209(1-2): 25-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686398&dopt=Abstract

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Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies. Author(s): Etminan M, Gill S, Samii A. Source: Bmj (Clinical Research Ed.). 2003 July 19; 327(7407): 128. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869452&dopt=Abstract

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Effect of NSAIDs on risk of Alzheimer's disease: conclusions on NSAIDs and Alzheimer's disease were overstated. Author(s): Price D. Source: Bmj (Clinical Research Ed.). 2003 September 27; 327(7417): 752. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512499&dopt=Abstract

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Effect of NSAIDs on risk of Alzheimer's disease: confounding factors were not discussed. Author(s): Robertson M. Source: Bmj (Clinical Research Ed.). 2003 September 27; 327(7417): 751; Author Reply 751-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512494&dopt=Abstract

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Effects of normal aging and Alzheimer's disease on emotional memory. Author(s): Kensinger EA, Brierley B, Medford N, Growdon JH, Corkin S. Source: Emotion (Washington, D.C.). 2002 June; 2(2): 118-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899186&dopt=Abstract

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Effects of toy stimulation on the cognitive, communicative, and emotional functioning of adults in the middle stages of Alzheimer's disease. Author(s): Murray LL, Dickerson S, Lichtenberger B, Cox C. Source: Journal of Communication Disorders. 2003 March-April; 36(2): 101-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609577&dopt=Abstract

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Efficacy and safety of cholinesterase inhibitors in Alzheimer's disease: a metaanalysis. Author(s): Lanctot KL, Herrmann N, Yau KK, Khan LR, Liu BA, LouLou MM, Einarson TR. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 September 16; 169(6): 557-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975222&dopt=Abstract

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Efficacy and safety of rivastigmine in patients with Alzheimer's disease who failed to benefit from treatment with donepezil. Author(s): Auriacombe S, Pere JJ, Loria-Kanza Y, Vellas B. Source: Current Medical Research and Opinion. 2002; 18(3): 129-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094822&dopt=Abstract

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Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease. Author(s): Gauthier S, Feldman H, Hecker J, Vellas B, Ames D, Subbiah P, Whalen E, Emir B; Donepezil MSAD Study Investigators Group. Source: Int Psychogeriatr. 2002 December; 14(4): 389-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670060&dopt=Abstract

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Efficacy of donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer's disease and the effect on caregiver burden. Author(s): Feldman H, Gauthier S, Hecker J, Vellas B, Emir B, Mastey V, Subbiah P; Donepezil MSAD Study Investigators Group. Source: Journal of the American Geriatrics Society. 2003 June; 51(6): 737-44. Erratum In: J Am Geriatr Soc. 2003 September; 51(9): 1331. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757558&dopt=Abstract

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El Portal Latino Alzheimer's Project: model program for Latino caregivers of Alzheimer's disease-affected people. Author(s): Aranda MP, Villa VM, Trejo L, Ramirez R, Ranney M. Source: Social Work. 2003 April; 48(2): 259-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718421&dopt=Abstract

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Electrophysiological analysis of context effects in Alzheimer's disease. Author(s): Schwartz TJ, Federmeier KD, Van Petten C, Salmon DP, Kutas M. Source: Neuropsychology. 2003 April; 17(2): 187-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803424&dopt=Abstract

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Enhanced production of amyloid precursor protein mRNA by peripheral mononuclear blood cell in Alzheimer's disease. Author(s): Jiang S, Zhang M, Ren D, Tang G, Lin S, Qian Y, Zhang Y, Jiang K, Li F, Wang D. Source: American Journal of Medical Genetics. 2003 April 1; 118B(1): 99-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627474&dopt=Abstract

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Enhancement of declarative memory by emotional arousal and visual memory function in Alzheimer's disease. Author(s): Kazui H, Mori E, Hashimoto M, Hirono N. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Spring; 15(2): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724465&dopt=Abstract

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Epitope and isotype specificities of antibodies to beta -amyloid peptide for protection against Alzheimer's disease-like neuropathology. Author(s): Bard F, Barbour R, Cannon C, Carretto R, Fox M, Games D, Guido T, Hoenow K, Hu K, Johnson-Wood K, Khan K, Kholodenko D, Lee C, Lee M, Motter R, Nguyen M, Reed A, Schenk D, Tang P, Vasquez N, Seubert P, Yednock T. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 February 18; 100(4): 2023-8. Epub 2003 Feb 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566568&dopt=Abstract

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Estrogen and Alzheimer's disease. Author(s): LeBlanc A. Source: Curr Opin Investig Drugs. 2002 May; 3(5): 768-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090551&dopt=Abstract

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Estrogen receptor alpha-immunoreactive astrocytes are increased in the hippocampus in Alzheimer's disease. Author(s): Lu YP, Zeng M, Hu XY, Xu H, Swaab DF, Ravid R, Zhou JN. Source: Experimental Neurology. 2003 October; 183(2): 482-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14552888&dopt=Abstract

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Estrogen-induced cell signalling in a cellular model of Alzheimer's disease. Author(s): Goodenough S, Schafer M, Behl C. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 February; 84(23): 301-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711016&dopt=Abstract

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Everyday problem solving in African Americans and European Americans with Alzheimer's disease: an exploratory study. Author(s): Ripich DN, Fritsch T, Ziol E. Source: Int Psychogeriatr. 2002 March; 14(1): 83-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094911&dopt=Abstract

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Evidence for defective retinoid transport and function in late onset Alzheimer's disease. Author(s): Goodman AB, Pardee AB. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 March 4; 100(5): 2901-5. Epub 2003 February 25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604774&dopt=Abstract

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Evidence linking neuronal cell death to autoimmunity in Alzheimer's disease. Author(s): D'Andrea MR. Source: Brain Research. 2003 August 22; 982(1): 19-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915236&dopt=Abstract

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Expanding the association between the APOE gene and the risk of Alzheimer's disease: possible roles for APOE promoter polymorphisms and alterations in APOE transcription. Author(s): Laws SM, Hone E, Gandy S, Martins RN. Source: Journal of Neurochemistry. 2003 March; 84(6): 1215-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614323&dopt=Abstract

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Exploring professional caregivers' perceptions. Balancing self-care with care for patients with Alzheimer's disease. Author(s): McCarty EF, Drebing C. Source: Journal of Gerontological Nursing. 2003 September; 29(9): 42-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14528748&dopt=Abstract

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Exploring the effect of action familiarity on SPTs recall performance in Alzheimer's disease. Author(s): Lekeu F, Van der Linden M, Moonen G, Salmon E. Source: J Clin Exp Neuropsychol. 2002 December; 24(8): 1057-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650231&dopt=Abstract

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F175S change and a novel polymorphism in presenilin-1 gene in late-onset familial Alzheimer's disease. Author(s): Colacicco AM, Panza F, Basile AM, Solfrizzi V, Capurso C, D'Introno A, Torres F, Capurso S, Cozza S, Flora R, Capurso A. Source: European Neurology. 2002; 47(4): 209-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12037434&dopt=Abstract

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Facilitating acquisition and transfer of a continuous motor task in healthy older adults and patients with Alzheimer's disease. Author(s): Dick MB, Hsieh S, Bricker J, Dick-Muehlke C. Source: Neuropsychology. 2003 April; 17(2): 202-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803425&dopt=Abstract

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Factor structure of a modified version of the wisconsin card sorting test: an analysis of executive deficit in Alzheimer's disease and mild cognitive impairment. Author(s): Nagahama Y, Okina T, Suzuki N, Matsuzaki S, Yamauchi H, Nabatame H, Matsuda M. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(2): 103-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784035&dopt=Abstract

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Factorial validation of the Severe Impairment Battery for patients with Alzheimer's disease. A pilot study. Author(s): Pelissier C, Roudier M, Boller F. Source: Dementia and Geriatric Cognitive Disorders. 2002; 13(2): 95-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844891&dopt=Abstract

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Failure to correlate C. pneumoniae with late onset Alzheimer's disease. Author(s): Taylor GS, Vipond IB, Paul ID, Matthews S, Wilcock GK, Caul EO. Source: Neurology. 2002 July 9; 59(1): 142-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105327&dopt=Abstract

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False recognition of pictures versus words in Alzheimer's disease: the distinctiveness heuristic. Author(s): Budson AE, Sitarski J, Daffner KR, Schacter DL. Source: Neuropsychology. 2002 April; 16(2): 163-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949708&dopt=Abstract

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Fast axonal transport misregulation and Alzheimer's disease. Author(s): Morfini G, Pigino G, Beffert U, Busciglio J, Brady ST. Source: Neuromolecular Medicine. 2002; 2(2): 89-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428805&dopt=Abstract

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Fertility and number of children in patients with Alzheimer's disease. Author(s): Ptok U, Barkow K, Heun R. Source: Archives of Women's Mental Health. 2002 October; 5(2): 83-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510204&dopt=Abstract

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Fighting Alzheimer's disease. Author(s): Mintz E. Source: Ncsl Legisbrief. 2000 June-July; 8(29): 1-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11850883&dopt=Abstract

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Fine mapping of susceptibility genes by Lewontin's linkage disequilibrium measure with application to Alzheimer's disease. Author(s): Gong G, Haynatzki G, Deng HW, Recker RR, Mordeson J, Cheng SC, Fong N. Source: Chin Med J (Engl). 2002 August; 115(8): 1233-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215300&dopt=Abstract

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First clinical evaluation of ganstigmine in patients with probable Alzheimer's disease. Author(s): Jhee SS, Fabbri L, Piccinno A, Monici P, Moran S, Zarotsky V, Tan EY, Frackiewicz EJ, Shiovitz T. Source: Clinical Neuropharmacology. 2003 May-June; 26(3): 164-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782920&dopt=Abstract

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First non-ATP competitive glycogen synthase kinase 3 beta (GSK-3beta) inhibitors: thiadiazolidinones (TDZD) as potential drugs for the treatment of Alzheimer's disease. Author(s): Martinez A, Alonso M, Castro A, Perez C, Moreno FJ. Source: Journal of Medicinal Chemistry. 2002 March 14; 45(6): 1292-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11881998&dopt=Abstract

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Five-year retrospective changes in hippocampal atrophy and cognitive screening test performances in very mild Alzheimer's disease: the Tajiri Project. Author(s): Yamaguchi S, Meguro K, Shimada M, Ishizaki J, Yamadori A, Sekita Y. Source: Neuroradiology. 2002 January; 44(1): 43-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11942499&dopt=Abstract

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Focal temporoparietal slow activity in Alzheimer's disease revealed by magnetoencephalography. Author(s): Fernandez A, Maestu F, Amo C, Gil P, Fehr T, Wienbruch C, Rockstroh B, Elbert T, Ortiz T. Source: Biological Psychiatry. 2002 October 1; 52(7): 764-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372668&dopt=Abstract

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Folic acid and Alzheimer's disease. Author(s): Tsolaki M, Kartali N. Source: International Journal of Geriatric Psychiatry. 2003 February; 18(2): 187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571831&dopt=Abstract

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Formation of hydrogen peroxide and hydroxyl radicals from A(beta) and alphasynuclein as a possible mechanism of cell death in Alzheimer's disease and Parkinson's disease. Author(s): Tabner BJ, Turnbull S, El-Agnaf OM, Allsop D. Source: Free Radical Biology & Medicine. 2002 June 1; 32(11): 1076-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031892&dopt=Abstract

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Fractal analysis of cerebral blood flow distribution in Alzheimer's disease. Author(s): Kuikka JT. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2002 December; 43(12): 1727-8; Author Reply 1728. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468525&dopt=Abstract

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Frequency and characteristics of anxiety among patients with Alzheimer's disease and related dementias. Author(s): Porter VR, Buxton WG, Fairbanks LA, Strickland T, O'Connor SM, Rosenberg-Thompson S, Cummings JL. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Spring; 15(2): 180-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724459&dopt=Abstract

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Frequency and distribution of TUNEL-positive neurons in brains of dementia with Lewy bodies: comparison with those in brains of Alzheimer's disease. Author(s): Katsuse O, Iseki E, Suzuki K, Kosaka K. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. 2001 December; 21(4): 272-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11837533&dopt=Abstract

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Frequency of Alzheimer's disease and other dementias in a community outreach sample of Hispanics. Author(s): Fitten LJ, Ortiz F, Ponton M. Source: Journal of the American Geriatrics Society. 2001 October; 49(10): 1301-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890488&dopt=Abstract

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From anticholinesterase toxicity to Alzheimer's disease: important interactions of cholinergic and NMDA receptor systems. Author(s): Popke EJ. Source: Toxicological Sciences : an Official Journal of the Society of Toxicology. 2003 April; 72(2): 185-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685427&dopt=Abstract

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From cDNA microarrays to high-throughput proteomics. Implications in the search for preventive initiatives to slow the clinical progression of Alzheimer's disease dementia. Author(s): Pasinetti GM, Ho L. Source: Restorative Neurology and Neuroscience. 2001; 18(2-3): 137-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847436&dopt=Abstract

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From epidemiology to therapeutic trials with anti-inflammatory drugs in Alzheimer's disease: the role of NSAIDs and cyclooxygenase in beta-amyloidosis and clinical dementia. Author(s): Pasinetti GM. Source: Journal of Alzheimer's Disease : Jad. 2002 October; 4(5): 435-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446975&dopt=Abstract

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Frontal impairment in subcortical ischemic vascular dementia in comparison to Alzheimer's disease. Author(s): Cannata AP, Alberoni M, Franceschi M, Mariani C. Source: Dementia and Geriatric Cognitive Disorders. 2002; 13(2): 101-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844892&dopt=Abstract

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Functional ability in executive variant Alzheimer's disease and typical Alzheimer's disease. Author(s): Back-Madruga C, Boone KB, Briere J, Cummings J, McPherson S, Fairbanks L, Thompson E. Source: Clin Neuropsychol. 2002 August; 16(3): 331-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607146&dopt=Abstract

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Functional imaging of visuospatial processing in Alzheimer's disease. Author(s): Prvulovic D, Hubl D, Sack AT, Melillo L, Maurer K, Frolich L, Lanfermann H, Zanella FE, Goebel R, Linden DE, Dierks T. Source: Neuroimage. 2002 November; 17(3): 1403-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414280&dopt=Abstract

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Functional, cognitive and behavioral effects of donepezil in patients with moderate Alzheimer's disease. Author(s): Gauthier S, Feldman H, Hecker J, Vellas B, Emir B, Subbiah P; Donepezil MSAD Study Investigators' Group. Source: Current Medical Research and Opinion. 2002; 18(6): 347-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12442882&dopt=Abstract

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Galanin receptor over-expression within the amygdala in early Alzheimer's disease: an in vitro autoradiographic analysis. Author(s): Perez S, Basile M, Mash DC, Mufson EJ. Source: Journal of Chemical Neuroanatomy. 2002 July; 24(2): 109-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12191727&dopt=Abstract

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Galantamine hydrobromide: an agent for Alzheimer's disease. Author(s): Zarotsky V, Sramek JJ, Cutler NR. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 March 1; 60(5): 446-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635450&dopt=Abstract

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Galantamine population pharmacokinetics in patients with Alzheimer's disease: modeling and simulations. Author(s): Piotrovsky V, Van Peer A, Van Osselaer N, Armstrong M, Aerssens J. Source: Journal of Clinical Pharmacology. 2003 May; 43(5): 514-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751272&dopt=Abstract

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Galantamine provides broad benefits in patients with 'advanced moderate' Alzheimer's disease (MMSE < or = 12) for up to six months. Author(s): Wilkinson DG, Hock C, Farlow M, van Baelen B, Schwalen S. Source: Int J Clin Pract. 2002 September; 56(7): 509-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296613&dopt=Abstract

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Galantamine provides sustained benefits in patients with 'advanced moderate' Alzheimer's disease for at least 12 months. Author(s): Blesa R, Davidson M, Kurz A, Reichman W, van Baelen B, Schwalen S. Source: Dementia and Geriatric Cognitive Disorders. 2003; 15(2): 79-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566596&dopt=Abstract

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Galantamine: a pharmacoeconomic review of its use in Alzheimer's disease. Author(s): Lyseng-Williamson KA, Plosker GL. Source: Pharmacoeconomics. 2002; 20(13): 919-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381243&dopt=Abstract

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Galantamine: a review of its use in Alzheimer's disease and vascular dementia. Author(s): Corey-Bloom J. Source: Int J Clin Pract. 2003 April; 57(3): 219-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723727&dopt=Abstract

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Gamma-secretase inhibitors and Alzheimer's disease. Author(s): Roberts SB. Source: Advanced Drug Delivery Reviews. 2002 December 7; 54(12): 1579-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453675&dopt=Abstract

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Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer's disease model. Author(s): Link CD, Taft A, Kapulkin V, Duke K, Kim S, Fei Q, Wood DE, Sahagan BG. Source: Neurobiology of Aging. 2003 May-June; 24(3): 397-413. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600716&dopt=Abstract

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Gene expression in Alzheimer's disease. Author(s): Ermak G, Davies KJ. Source: Drugs Today (Barc). 2002 July; 38(7): 509-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582468&dopt=Abstract

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Gene expression profiles of cholinergic nucleus basalis neurons in Alzheimer's disease. Author(s): Mufson EJ, Counts SE, Ginsberg SD. Source: Neurochemical Research. 2002 October; 27(10): 1035-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462403&dopt=Abstract

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Generalized synchronization of MEG recordings in Alzheimer's Disease: evidence for involvement of the gamma band. Author(s): Stam CJ, van Cappellen van Walsum AM, Pijnenburg YA, Berendse HW, de Munck JC, Scheltens P, van Dijk BW. Source: Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society. 2002 December; 19(6): 562-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488788&dopt=Abstract

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Generation of a recombinant Fab antibody reactive with the Alzheimer's diseaserelated Abeta peptide. Author(s): Tammer AH, Coia G, Cappai R, Fuller S, Masters CL, Hudson P, Underwood JR. Source: Clinical and Experimental Immunology. 2002 September; 129(3): 453-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197886&dopt=Abstract

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Genetic analysis of vascular factors in Alzheimer's disease. Author(s): Wakutani Y, Kowa H, Kusumi M, Yamagata K, Wada-Isoe K, Adachi Y, Takeshima T, Urakami K, Nakashima K. Source: Annals of the New York Academy of Sciences. 2002 November; 977: 232-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480755&dopt=Abstract

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Genetic and environmental risk factors for Alzheimer's disease in Israeli Arabs. Author(s): Bowirrat A, Friedland RP, Farrer L, Baldwin C, Korczyn A. Source: Journal of Molecular Neuroscience : Mn. 2002 August-October; 19(1-2): 239-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12212789&dopt=Abstract

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Genetic polymorphisms and cerebrospinal fluid levels of tissue inhibitor of metalloproteinases 1 in sporadic Alzheimer's disease. Author(s): Wollmer MA, Papassotiropoulos A, Streffer JR, Grimaldi LM, Kapaki E, Salani G, Paraskevas GP, Maddalena A, de Quervain D, Bieber C, Umbricht D, Lemke U, Bosshardt S, Degonda N, Henke K, Hegi T, Jung HH, Pasch T, Hock C, Nitsch RM. Source: Psychiatric Genetics. 2002 September; 12(3): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218659&dopt=Abstract

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Genetic variability in the insulin signalling pathway may contribute to the risk of late onset Alzheimer's disease. Author(s): Liolitsa D, Powell J, Lovestone S. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 September; 73(3): 261-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185156&dopt=Abstract

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Genetically selected baby free of inherited predisposition to early-onset Alzheimer's disease. Author(s): Spriggs M. Source: Journal of Medical Ethics. 2002 October; 28(5): 290. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356954&dopt=Abstract

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Genotype-related differences of hippocampal apolipoprotein E levels only in early stages of neuropathological changes in Alzheimer's disease. Author(s): Glockner F, Meske V, Ohm TG. Source: Neuroscience. 2002; 114(4): 1103-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379263&dopt=Abstract

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Glaucoma: ocular Alzheimer's disease? Author(s): McKinnon SJ. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2003 September 1; 8: S1140-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957857&dopt=Abstract

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Glial levels determine severity of white matter disease in Alzheimer's disease: a neuropathological study of glial changes. Author(s): Sjobeck M, Englund E. Source: Neuropathology and Applied Neurobiology. 2003 April; 29(2): 159-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662323&dopt=Abstract

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Glutamate receptors as a target for Alzheimer's disease--are clinical results supporting the hope? Author(s): Winblad B, Mobius HJ, Stoffler A. Source: Journal of Neural Transmission. Supplementum. 2002; (62): 217-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456065&dopt=Abstract

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Glutamatergic systems in Alzheimer's disease. Author(s): Francis PT. Source: International Journal of Geriatric Psychiatry. 2003 September; 18(Suppl 1): S1521. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12973746&dopt=Abstract

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Glycation of the amyloid beta-protein by a nicotine metabolite: a fortuitous chemical dynamic between smoking and Alzheimer's disease. Author(s): Dickerson TJ, Janda KD. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 July 8; 100(14): 8182-7. Epub 2003 June 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12815102&dopt=Abstract

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Glycogen synthase kinase-3 is associated with neuronal and glial hyperphosphorylated tau deposits in Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration. Author(s): Ferrer I, Barrachina M, Puig B. Source: Acta Neuropathologica. 2002 December; 104(6): 583-91. Epub 2002 July 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410379&dopt=Abstract

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Glycosylation of acetylcholinesterase and butyrylcholinesterase changes as a function of the duration of Alzheimer's disease. Author(s): Saez-Valero J, Fodero LR, Sjogren M, Andreasen N, Amici S, Gallai V, Vanderstichele H, Vanmechelen E, Parnetti L, Blennow K, Small DH. Source: Journal of Neuroscience Research. 2003 May 15; 72(4): 520-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704813&dopt=Abstract

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Glycoxidative stress creates a vicious cycle of neurodegeneration in Alzheimer's disease--a target for neuroprotective treatment strategies? Author(s): Munch G, Deuther-Conrad W, Gasic-Milenkovic J. Source: Journal of Neural Transmission. Supplementum. 2002; (62): 303-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456073&dopt=Abstract

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Goal setting and attainment in Alzheimer's disease patients treated with donepezil. Author(s): Rockwood K, Graham JE, Fay S; ACADIE Investigators. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 November; 73(5): 500-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397141&dopt=Abstract

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GSK3beta signalling: casting a wide net in Alzheimer's disease. Author(s): Bhat RV, Budd SL. Source: Neuro-Signals. 2002 September-October; 11(5): 251-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566926&dopt=Abstract

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Guidelines for managing Alzheimer's disease: Part II. Treatment. Author(s): Cummings JL, Frank JC, Cherry D, Kohatsu ND, Kemp B, Hewett L, Mittman B. Source: American Family Physician. 2002 June 15; 65(12): 2525-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086242&dopt=Abstract

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Harnessing the immune system to battle Alzheimer's: some of the most promising approaches to fight Alzheimer's disease aim to develop vaccines. Author(s): Brower V. Source: Embo Reports. 2002 March; 3(3): 207-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882536&dopt=Abstract

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Have cholinergic therapies reached their clinical boundary in Alzheimer's disease? Author(s): Jones RW. Source: International Journal of Geriatric Psychiatry. 2003 September; 18(Suppl 1): S7S13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12973745&dopt=Abstract

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Head circumference and incident Alzheimer's disease: modification by apolipoprotein E. Author(s): Gurwitz D, Chapman J, Weizman A. Source: Neurology. 2002 May 14; 58(9): 1440. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12011307&dopt=Abstract

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Head injury and Alzheimer's disease. Author(s): Wilson JT. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 July; 74(7): 841. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810761&dopt=Abstract

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Head injury as a risk factor for Alzheimer's disease: the evidence 10 years on; a partial replication. Author(s): Fleminger S, Oliver DL, Lovestone S, Rabe-Hesketh S, Giora A. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 July; 74(7): 857-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810767&dopt=Abstract

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Head trauma and Alzheimer's disease. Author(s): Nandoe RD, Scheltens P, Eikelenboom P. Source: Journal of Alzheimer's Disease : Jad. 2002 August; 4(4): 303-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446932&dopt=Abstract

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Headache and Alzheimer's disease. Author(s): Moretti R, Torre P, Antonello RM, Bisin Z, Relja G, Cazzato G, Bava A. Source: Age and Ageing. 2002 January; 31(1): 79-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11850316&dopt=Abstract

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Health care utilization and costs of Alzheimer's disease: the role of co-morbid conditions, disease stage, and pharmacotherapy. Author(s): Fillit H, Hill JW, Futterman R. Source: Family Medicine. 2002 July-August; 34(7): 528-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12144008&dopt=Abstract

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Health service utilization by Alzheimer's disease patients: a 2-year follow-up of primary versus subspecialty care. Author(s): Aupperle PM, MacPhee ER, Coyne AC, Blume J, Sanchez B. Source: Journal of Geriatric Psychiatry and Neurology. 2003 March; 16(1): 15-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641367&dopt=Abstract

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Hemodynamic aspects of Alzheimer's disease. Author(s): Nagata K, Sato M, Satoh Y, Watahiki Y, Kondoh Y, Sugawara M, Box G, Wright D, Leung S, Yuya H, Shimosegawa E. Source: Annals of the New York Academy of Sciences. 2002 November; 977: 391-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480778&dopt=Abstract

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Herpesviruses in brain and Alzheimer's disease. Author(s): Lin WR, Wozniak MA, Cooper RJ, Wilcock GK, Itzhaki RF. Source: The Journal of Pathology. 2002 July; 197(3): 395-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115887&dopt=Abstract

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High occurrence rate of glaucoma among patients with Alzheimer's disease. Author(s): Bayer AU, Ferrari F, Erb C. Source: European Neurology. 2002; 47(3): 165-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914555&dopt=Abstract

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Highly conserved and disease-specific patterns of carboxyterminally truncated Abeta peptides 1-37/38/39 in addition to 1-40/42 in Alzheimer's disease and in patients with chronic neuroinflammation. Author(s): Wiltfang J, Esselmann H, Bibl M, Smirnov A, Otto M, Paul S, Schmidt B, Klafki HW, Maler M, Dyrks T, Bienert M, Beyermann M, Ruther E, Kornhuber J. Source: Journal of Neurochemistry. 2002 May; 81(3): 481-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065657&dopt=Abstract

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Hippocampal atrophy and neocortical dysfunction in early Alzheimer's disease. Author(s): Baron JC. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 November; 73(5): 470-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397133&dopt=Abstract

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Hippocampal dopamine D2 receptors correlate with memory functions in Alzheimer's disease. Author(s): Kemppainen N, Laine M, Laakso MP, Kaasinen V, Nagren K, Vahlberg T, Kurki T, Rinne JO. Source: The European Journal of Neuroscience. 2003 July; 18(1): 149-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859348&dopt=Abstract

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Hippocampal sclerosis in a case of Alzheimer's disease-like dementia with late onset intractable epilepsy. Author(s): Josephs KA, Wai DF, Parisi JE. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2003 May; 10(3): 333-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752417&dopt=Abstract

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Homocysteine, apolipoproteine E and methylenetetrahydrofolate reductase in Alzheimer's disease and mild cognitive impairment. Author(s): Religa D, Styczynska M, Peplonska B, Gabryelewicz T, Pfeffer A, Chodakowska M, Luczywek E, Wasiak B, Stepien K, Golebiowski M, Winblad B, Barcikowska M. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(2): 64-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784029&dopt=Abstract

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Hormone replacement therapy in postmenopausal women with Alzheimer's disease: a randomized, prospective study. Author(s): Yoon BK, Kim DK, Kang Y, Kim JW, Shin MH, Na DL. Source: Fertility and Sterility. 2003 February; 79(2): 274-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568834&dopt=Abstract

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Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer's disease. Author(s): Fagan AM, Watson M, Parsadanian M, Bales KR, Paul SM, Holtzman DM. Source: Neurobiology of Disease. 2002 April; 9(3): 305-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950276&dopt=Abstract

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Human antibodies against amyloid beta peptide: a potential treatment for Alzheimer's disease. Author(s): Dodel R, Hampel H, Depboylu C, Lin S, Gao F, Schock S, Jackel S, Wei X, Buerger K, Hoft C, Hemmer B, Moller HJ, Farlow M, Oertel WH, Sommer N, Du Y. Source: Annals of Neurology. 2002 August; 52(2): 253-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210803&dopt=Abstract

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Human brain nucleoside diphosphate kinase activity is decreased in Alzheimer's disease and Down syndrome. Author(s): Kim SH, Fountoulakis M, Cairns NJ, Lubec G. Source: Biochemical and Biophysical Research Communications. 2002 August 30; 296(4): 970-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200143&dopt=Abstract

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Hydrogen magnetic resonance spectroscopy in Alzheimer's disease. Author(s): Rapoport SI. Source: Lancet. Neurology. 2002 June; 1(2): 82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849509&dopt=Abstract

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Hypertension and hypercholesterolaemia as risk factors for Alzheimer's disease: potential for pharmacological intervention. Author(s): Kivipelto M, Laakso MP, Tuomilehto J, Nissinen A, Soininen H. Source: Cns Drugs. 2002; 16(7): 435-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12056919&dopt=Abstract

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Hypertension and related factors in the etiology of Alzheimer's disease. Author(s): Skoog I, Gustafson D. Source: Annals of the New York Academy of Sciences. 2002 November; 977: 29-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480731&dopt=Abstract

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Hypothalamic digoxin, hemispheric chemical dominance, and Alzheimer's disease. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 March; 113(3): 361-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803139&dopt=Abstract

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Hypothesis for a common basis for neuroprotection in glaucoma and Alzheimer's disease: anti-apoptosis by alpha-2-adrenergic receptor activation. Author(s): Tatton W, Chen D, Chalmers-Redman R, Wheeler L, Nixon R, Tatton N. Source: Survey of Ophthalmology. 2003 April; 48 Suppl 1: S25-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852432&dopt=Abstract

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Hypoxia signaling to genes: significance in Alzheimer's disease. Author(s): Bazan NG, Palacios-Pelaez R, Lukiw WJ. Source: Molecular Neurobiology. 2002 October-December; 26(2-3): 283-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428761&dopt=Abstract

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Ibuprofen for Alzheimer's disease. Author(s): Tabet N, Feldmand H. Source: Cochrane Database Syst Rev. 2003; (2): Cd004031. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804498&dopt=Abstract

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Identification of a single nucleotide polymorphism in the choline acetyltransferase gene associated with Alzheimer's disease. Author(s): Mubumbila V, Sutter A, Ptok U, Heun R, Quirin-Stricker C. Source: Neuroscience Letters. 2002 November 15; 333(1): 9-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401548&dopt=Abstract

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Identification of peptides that specifically bind Abeta1-40 amyloid in vitro and amyloid plaques in Alzheimer's disease brain using phage display. Author(s): Kang CK, Jayasinha V, Martin PT. Source: Neurobiology of Disease. 2003 October; 14(1): 146-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678675&dopt=Abstract

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Identifying severely atrophic cortical subregions in Alzheimer's disease. Author(s): Halliday GM, Double KL, Macdonald V, Kril JJ. Source: Neurobiology of Aging. 2003 October; 24(6): 797-806. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927762&dopt=Abstract

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Imaging of Alzheimer's disease. Author(s): Lee BC, Mintun M, Buckner RL, Morris JC. Source: Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging. 2003 July; 13(3): 199-214. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889165&dopt=Abstract

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Imaging of the 5-HT2A system: age-, gender-, and Alzheimer's disease-related findings. Author(s): Versijpt J, Van Laere KJ, Dumont F, Decoo D, Vandecapelle M, Santens P, Goethals I, Audenaert K, Slegers G, Dierckx RA, Korf J. Source: Neurobiology of Aging. 2003 July-August; 24(4): 553-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714112&dopt=Abstract

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Immunotherapy for Alzheimer's disease. Author(s): Dodel RC, Hampel H, Du Y. Source: Lancet. Neurology. 2003 April; 2(4): 215-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849209&dopt=Abstract

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Impaired modulation of GABAergic transmission by muscarinic receptors in a mouse transgenic model of Alzheimer's disease. Author(s): Zhong P, Gu Z, Wang X, Jiang H, Feng J, Yan Z. Source: The Journal of Biological Chemistry. 2003 July 18; 278(29): 26888-96. Epub 2003 May 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746438&dopt=Abstract

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Implicit and explicit measures of memory for perceptual information in young adults, healthy older adults, and patients with Alzheimer's disease. Author(s): Pilotti M, Meade ML, Gallo DA. Source: Experimental Aging Research. 2003 January-March; 29(1): 15-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735079&dopt=Abstract

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Increased frequency of a new polymorphism in the cell division cycle 2 (cdc2) gene in patients with Alzheimer's disease and frontotemporal dementia. Author(s): Johansson A, Hampel H, Faltraco F, Buerger K, Minthon L, Bogdanovic N, Sjogren M, Zetterberg H, Forsell L, Lilius L, Wahlund LO, Rymo L, Prince JA, Blennow K. Source: Neuroscience Letters. 2003 April 3; 340(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648761&dopt=Abstract

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Increased neuronal metabolic activity and estrogen receptors in the vertical limb of the diagonal band of Broca in Alzheimer's disease: relation to sex and aging. Author(s): Ishunina TA, Swaab DF. Source: Experimental Neurology. 2003 September; 183(1): 159-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957499&dopt=Abstract

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Increased p27, an essential component of cell cycle control, in Alzheimer's disease. Author(s): Ogawa O, Lee HG, Zhu X, Raina A, Harris PL, Castellani RJ, Perry G, Smith MA. Source: Aging Cell. 2003 April; 2(2): 105-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882323&dopt=Abstract

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Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer's disease. Author(s): Lorenzl S, Albers DS, Relkin N, Ngyuen T, Hilgenberg SL, Chirichigno J, Cudkowicz ME, Beal MF. Source: Neurochemistry International. 2003 August; 43(3): 191-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12689599&dopt=Abstract

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Inflammation and Alzheimer's disease. Author(s): Gupta A, Pansari K. Source: Int J Clin Pract. 2003 January-February; 57(1): 36-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587940&dopt=Abstract

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Inflammatory markers in matched plasma and cerebrospinal fluid from patients with Alzheimer's disease. Author(s): Sun YX, Minthon L, Wallmark A, Warkentin S, Blennow K, Janciauskiene S. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(3): 136-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826739&dopt=Abstract

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Inflammatory processes in Alzheimer's disease. Author(s): McGeer EG, McGeer PL. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 August; 27(5): 741-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921904&dopt=Abstract

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Influence of the apolipoprotein E type 4 allele on cerebral glucose metabolism in Alzheimer's disease patients. Author(s): Lee KU, Lee JS, Kim KW, Jhoo JH, Lee DY, Yoon JC, Lee JH, Lee DS, Lee MC, Woo JI. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Winter; 15(1): 78-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556576&dopt=Abstract

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Informed consent for Alzheimer's disease clinical trials: a survey of clinical investigators. Author(s): Karlawish JH, Knopman D, Clark CM, Morris JC, Marson D, Whitehouse PJ, Kawas CH. Source: Irb. 2002 September-October; 24(5): 1-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737167&dopt=Abstract

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Initial findings from the evaluation of the Alzheimer's Disease Demonstration Grants to States Program. Author(s): Montgomery RJ, Kosloski K, Karner TX, Schaefer JP. Source: Home Health Care Services Quarterly. 2002; 21(3-4): 5-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665070&dopt=Abstract

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Inpatient length of stay and atypical antipsychotic use among elderly patients with psychiatric disorders and Alzheimer's disease. Author(s): Edell WS, Rupnow MF. Source: Manag Care Interface. 2003 May; 16(5): 64-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789866&dopt=Abstract

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Instrumental activities of daily living: a stepping-stone towards Alzheimer's disease diagnosis in subjects with mild cognitive impairment? Author(s): Nygard L. Source: Acta Neurologica Scandinavica. Supplementum. 2003; 179: 42-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603250&dopt=Abstract

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Insulin degrading enzyme (IDE) genetic variants and risk of Alzheimer's disease: evidence of effect modification by apolipoprotein E (APOE). Author(s): Edland SD, Wavrant-De Vriese F, Compton D, Smith GE, Ivnik R, Boeve BF, Tangalos EG, Petersen RC. Source: Neuroscience Letters. 2003 July 10; 345(1): 21-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809979&dopt=Abstract

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Insulin dose-response effects on memory and plasma amyloid precursor protein in Alzheimer's disease: interactions with apolipoprotein E genotype. Author(s): Craft S, Asthana S, Cook DG, Baker LD, Cherrier M, Purganan K, Wait C, Petrova A, Latendresse S, Watson GS, Newcomer JW, Schellenberg GD, Krohn AJ. Source: Psychoneuroendocrinology. 2003 August; 28(6): 809-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812866&dopt=Abstract

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Intentional and automatic measures of specific-category effect in the semantic impairment of patients with Alzheimer's disease. Author(s): Perri R, Carlesimo GA, Zannino GD, Mauri M, Muolo B, Pettenati C, Caltagirone C. Source: Neuropsychologia. 2003; 41(11): 1509-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849769&dopt=Abstract

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Interaction of the H63D mutation in the hemochromatosis gene with the apolipoprotein E epsilon 4 allele modulates age at onset of Alzheimer's disease. Author(s): Combarros O, Garcia-Roman M, Fontalba A, Fernandez-Luna JL, Llorca J, Infante J, Berciano J. Source: Dementia and Geriatric Cognitive Disorders. 2003; 15(3): 151-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584430&dopt=Abstract

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Interactive computer-training as a therapeutic tool in Alzheimer's disease. Author(s): Hofmann M, Rosler A, Schwarz W, Muller-Spahn F, Krauchi K, Hock C, Seifritz E. Source: Comprehensive Psychiatry. 2003 May-June; 44(3): 213-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764709&dopt=Abstract

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Interleukin-6-174 G/C promoter gene polymorphism C allele reduces Alzheimer's disease risk. Author(s): Faltraco F, Burger K, Zill P, Teipel SJ, Moller HJ, Hampel H, Bondy B, Ackenheil M. Source: Journal of the American Geriatrics Society. 2003 April; 51(4): 578-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657090&dopt=Abstract

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Intermetamorphosis in a patient with Alzheimer's disease. Author(s): Assal F, Mendez MF. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Spring; 15(2): 246-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724474&dopt=Abstract

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Intrathecal inflammation precedes development of Alzheimer's disease. Author(s): Tarkowski E, Andreasen N, Tarkowski A, Blennow K. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 September; 74(9): 1200-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933918&dopt=Abstract

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Is Alzheimer's disease a vascular disorder? Author(s): Jellinger KA. Source: Journal of Alzheimer's Disease : Jad. 2003 June; 5(3): 247-50; Discussion 251-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897409&dopt=Abstract

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JKK1, an upstream activator of JNK/SAPK, is activated in Alzheimer's disease. Author(s): Zhu X, Ogawa O, Wang Y, Perry G, Smith MA. Source: Journal of Neurochemistry. 2003 April; 85(1): 87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641730&dopt=Abstract

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Kinematic analysis of handwriting movements in patients with Alzheimer's disease, mild cognitive impairment, depression and healthy subjects. Author(s): Schroter A, Mergl R, Burger K, Hampel H, Moller HJ, Hegerl U. Source: Dementia and Geriatric Cognitive Disorders. 2003; 15(3): 132-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584428&dopt=Abstract

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Lack of association between a single nucleotide polymorphism within the choline acetyltransferase gene and patients with Alzheimer's disease. Author(s): Schwarz S, Eisele T, Diehl J, Muller U, Forstl H, Kurz A, Riemenschneider M. Source: Neuroscience Letters. 2003 June 12; 343(3): 167-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12770689&dopt=Abstract

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Lack of association between Alzheimer's disease and Gln-Arg 192 Q/R polymorphism of the PON-1 gene in an Italian population. Author(s): Pola R, Gaetani E, Flex A, Gerardino L, Aloi F, Flore R, Serricchio M, Pola P, Bernabei R. Source: Dementia and Geriatric Cognitive Disorders. 2003; 15(2): 88-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566597&dopt=Abstract

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Lack of association between angiotensin converting enzyme polymorphism and sporadic Alzheimer's disease. Author(s): Monastero R, Caldarella R, Mannino M, Cefalu AB, Lopez G, Noto D, Camarda C, Camarda LK, Notarbartolo A, Averna MR, Camarda R. Source: Neuroscience Letters. 2002 December 25; 335(2): 147-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459519&dopt=Abstract

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Lack of association between the interleukin-1alpha gene C(-889)T polymorphism and Alzheimer's disease in a Chinese population. Author(s): Tsai SJ, Liu HC, Liu TY, Wang KY, Hong CJ. Source: Neuroscience Letters. 2003 June 5; 343(2): 93-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759172&dopt=Abstract

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Lack of association between thyroid disorders and Alzheimer's disease in older persons: a cross-sectional observational study in a geriatric outpatient population. Author(s): van der Cammen TJ, Raso FM, van Harskamp F, de Jager MC. Source: Journal of the American Geriatrics Society. 2003 June; 51(6): 884. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757585&dopt=Abstract

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Lack of association of interleukin-10 promoter region polymorphisms with Alzheimer's disease. Author(s): Depboylu C, Du Y, Muller U, Kurz A, Zimmer R, Riemenschneider M, Gasser T, Oertelf WH, Klockgether T, Dodel RC. Source: Neuroscience Letters. 2003 May 15; 342(1-2): 132-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727335&dopt=Abstract

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Lack of association of the interleukin-1beta gene polymorphism with Alzheimer's disease in a Chinese population. Author(s): Ma SL, Tang NL, Lam LC, Chiu HF. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(4): 265-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512722&dopt=Abstract

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Left hippocampal volume loss in Alzheimer's disease is reflected in performance on odor identification: a structural MRI study. Author(s): Murphy C, Jernigan TL, Fennema-Notestine C. Source: Journal of the International Neuropsychological Society : Jins. 2003 March; 9(3): 459-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12666770&dopt=Abstract

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Levels of total tau and tau protein phosphorylated at threonine 181 in patients with incipient and manifest Alzheimer's disease. Author(s): Schonknecht P, Pantel J, Hunt A, Volkmann M, Buerger K, Hampel H, Schroder J. Source: Neuroscience Letters. 2003 March 20; 339(2): 172-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614922&dopt=Abstract

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Lewy body pathology is a frequent co-pathology in familial Alzheimer's disease. Author(s): Trembath Y, Rosenberg C, Ervin JF, Schmechel DE, Gaskell P, Pericak-Vance M, Vance J, Hulette CM. Source: Acta Neuropathologica. 2003 May; 105(5): 484-8. Epub 2003 February 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677449&dopt=Abstract

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Life situation, coping and quality of life in people with high and low risk of developing Alzheimer's disease. Author(s): Axelman K, Lannfelt L, Almkvist O, Carlsson M. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(4): 220-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512717&dopt=Abstract

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Lifetime principal occupation and risk of Alzheimer's disease in the Kungsholmen project. Author(s): Qiu C, Karp A, von Strauss E, Winblad B, Fratiglioni L, Bellander T. Source: American Journal of Industrial Medicine. 2003 February; 43(2): 204-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12541276&dopt=Abstract

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Lifetime symptoms of depression in Alzheimer's disease. Author(s): Heun R, Kockler M, Ptok U. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2003 March; 18(2): 63-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711401&dopt=Abstract

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Limbic hypometabolism in Alzheimer's disease and mild cognitive impairment. Author(s): Nestor PJ, Fryer TD, Smielewski P, Hodges JR. Source: Annals of Neurology. 2003 September; 54(3): 343-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953266&dopt=Abstract

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Limbic system perfusion in Alzheimer's disease measured by MRI-coregistered HMPAO SPET. Author(s): Callen DJ, Black SE, Caldwell CB. Source: European Journal of Nuclear Medicine and Molecular Imaging. 2002 July; 29(7): 899-906. Epub 2002 April 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111130&dopt=Abstract

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Linkage of Parkinsonism and Alzheimer's disease with Lewy body pathology to chromosome 12. Author(s): Scott WK, Vance JM, Haines JL, Pericak-Vance MA. Source: Annals of Neurology. 2002 October; 52(4): 524; Author Reply 524. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12325086&dopt=Abstract

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Lipid metabolism, epidemiology, and the mechanisms of Alzheimer's disease. Author(s): Friedland RP. Source: Annals of the New York Academy of Sciences. 2002 November; 977: 387-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480777&dopt=Abstract

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Lipid peroxidation in aging brain and Alzheimer's disease. Author(s): Montine TJ, Neely MD, Quinn JF, Beal MF, Markesbery WR, Roberts LJ, Morrow JD. Source: Free Radical Biology & Medicine. 2002 September 1; 33(5): 620-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208348&dopt=Abstract

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Lipoproteins and lipid peroxidation in Alzheimer's disease. Author(s): Bassett CN, Montine TJ. Source: J Nutr Health Aging. 2003; 7(1): 24-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679837&dopt=Abstract

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Local neuroinflammation and the progression of Alzheimer's disease. Author(s): McGeer PL, McGeer EG. Source: Journal of Neurovirology. 2002 December; 8(6): 529-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476347&dopt=Abstract

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Loneliness and depression in spousal caregivers of those with Alzheimer's disease versus non-caregiving spouses. Author(s): Beeson RA. Source: Archives of Psychiatric Nursing. 2003 June; 17(3): 135-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840806&dopt=Abstract

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Long term safety and efficacy of donepezil in the treatment of dementia in Alzheimer's disease in adults with Down syndrome: open label study. Author(s): Prasher VP, Adams C, Holder R; Down Syndrome Research Group. Source: International Journal of Geriatric Psychiatry. 2003 June; 18(6): 549-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789681&dopt=Abstract

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Longitudinal quantitative proton magnetic resonance spectroscopy of the hippocampus in Alzheimer's disease. Author(s): Dixon RM, Bradley KM, Budge MM, Styles P, Smith AD. Source: Brain; a Journal of Neurology. 2002 October; 125(Pt 10): 2332-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12244089&dopt=Abstract

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Long-term cholinesterase inhibitor therapy for Alzheimer's disease: implications for long-term care. Author(s): Brangman SA. Source: Am J Alzheimers Dis Other Demen. 2003 March-April; 18(2): 79-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708222&dopt=Abstract

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Long-term cognitive and functional decline in late onset Alzheimer's disease: therapeutic implications. Author(s): Holmes C, Lovestone S. Source: Age and Ageing. 2003 March; 32(2): 200-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615565&dopt=Abstract

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Long-term effects of donepezil on P300 auditory event-related potentials in patients with Alzheimer's disease. Author(s): Katada E, Sato K, Sawaki A, Dohi Y, Ueda R, Ojika K. Source: Journal of Geriatric Psychiatry and Neurology. 2003 March; 16(1): 39-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641372&dopt=Abstract

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Long-term effects of rivastigmine in moderately severe Alzheimer's disease: does early initiation of therapy offer sustained benefits? Author(s): Doraiswamy PM, Krishnan KR, Anand R, Sohn H, Danyluk J, Hartman RD, Veach J. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 May; 26(4): 705-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188103&dopt=Abstract

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Low vitamin B-12 status in confirmed Alzheimer's disease as revealed by serum holotranscobalamin. Author(s): Refsum H, Smith AD. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 July; 74(7): 959-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810791&dopt=Abstract

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Low-density lipoprotein receptor-related protein 8 (apolipoprotein E receptor 2) gene polymorphisms in Alzheimer's disease. Author(s): Ma SL, Ng HK, Baum L, Pang JC, Chiu HF, Woo J, Tang NL, Lam LC. Source: Neuroscience Letters. 2002 November 8; 332(3): 216-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399018&dopt=Abstract

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Magnetic resonance imaging, Down's syndrome and Alzheimer's disease: research and clinical implications. Author(s): Prasher V, Cumella S, Natarajan K, Rolfe E, Shah S, Haque MS. Source: Journal of Intellectual Disability Research : Jidr. 2003 February; 47(Pt 2): 90-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542574&dopt=Abstract

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Managing Alzheimer's disease in the new health care economy. Author(s): Kettl P. Source: Administration and Policy in Mental Health. 2003 January; 30(3): 267-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854681&dopt=Abstract

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Managing threats to self: awareness in early stage Alzheimer's disease. Author(s): Clare L. Source: Social Science & Medicine (1982). 2003 September; 57(6): 1017-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878102&dopt=Abstract

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Measurement of cerebral perfusion volume and 99mTc-HMPAO uptake using SPECT in controls and patients with Alzheimer's disease. Author(s): Fleming JS, Kemp PM, Bolt L, Goatman KA. Source: Nuclear Medicine Communications. 2002 November; 23(11): 1057-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411833&dopt=Abstract

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Measuring serum oestradiol in women with Alzheimer's disease: the importance of the sensitivity of the assay method. Author(s): Hogervorst E, Williams J, Combrinck M, David Smith A. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 January; 148(1): 67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534359&dopt=Abstract

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Mechanisms of peripheral microvascular dysfunction in transgenic mice overexpressing the Alzheimer's disease amyloid Abeta protein. Author(s): Khalil Z, Poliviou H, Maynard CJ, Beyreuther K, Masters CL, Li QX. Source: Journal of Alzheimer's Disease : Jad. 2002 December; 4(6): 467-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515898&dopt=Abstract

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Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease. Author(s): Matsubara E, Bryant-Thomas T, Pacheco Quinto J, Henry TL, Poeggeler B, Herbert D, Cruz-Sanchez F, Chyan YJ, Smith MA, Perry G, Shoji M, Abe K, Leone A, Grundke-Ikbal I, Wilson GL, Ghiso J, Williams C, Refolo LM, Pappolla MA, Chain DG, Neria E. Source: Journal of Neurochemistry. 2003 June; 85(5): 1101-8. Erratum In: J Neurochem. 2003 September; 86(5): 1312. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753069&dopt=Abstract

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Melatonin rhythmicity: effect of age and Alzheimer's disease. Author(s): Skene DJ, Swaab DF. Source: Experimental Gerontology. 2003 January-February; 38(1-2): 199-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543278&dopt=Abstract

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Memantine in moderate-to-severe Alzheimer's disease. Author(s): Bleich S, Wiltfang J, Kornhuber J. Source: The New England Journal of Medicine. 2003 August 7; 349(6): 609-10; Author Reply 609-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904528&dopt=Abstract

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Memantine in moderate-to-severe Alzheimer's disease. Author(s): Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ; Memantine Study Group. Source: The New England Journal of Medicine. 2003 April 3; 348(14): 1333-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672860&dopt=Abstract

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Memory deficits in Alzheimer's disease: the encoding hypothesis and cholinergic function. Author(s): White KG, Ruske AC. Source: Psychonomic Bulletin & Review. 2002 September; 9(3): 426-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412885&dopt=Abstract

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Memory disturbances and temporal lobe epilepsy simulating Alzheimer's disease: a case report. Author(s): Sinforiani E, Manni R, Bernasconi L, Banchieri LM, Zucchella C. Source: Funct Neurol. 2003 January-March; 18(1): 39-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760413&dopt=Abstract

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Memory for new information as a cognitive marker of liability to Alzheimer's disease in a high risk group: a research note. Author(s): Rice F, Abraham R, Rudrasingham V, Owen MJ, Williams J. Source: International Journal of Geriatric Psychiatry. 2003 February; 18(2): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571825&dopt=Abstract

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Meta-analysis of double blind randomized controlled clinical trials of acetyl-Lcarnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Author(s): Montgomery SA, Thal LJ, Amrein R. Source: International Clinical Psychopharmacology. 2003 March; 18(2): 61-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598816&dopt=Abstract

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Microtubule reduction in Alzheimer's disease and aging is independent of tau filament formation. Author(s): Cash AD, Aliev G, Siedlak SL, Nunomura A, Fujioka H, Zhu X, Raina AK, Vinters HV, Tabaton M, Johnson AB, Paula-Barbosa M, Avila J, Jones PK, Castellani RJ, Smith MA, Perry G. Source: American Journal of Pathology. 2003 May; 162(5): 1623-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707046&dopt=Abstract

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MMSE items predict cognitive decline in persons with genetic risk for Alzheimer's disease. Author(s): Ercoli LM, Siddarth P, Dunkin JJ, Bramen J, Small GW. Source: Journal of Geriatric Psychiatry and Neurology. 2003 June; 16(2): 67-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801154&dopt=Abstract

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Molecular genetics of Alzheimer's disease: presenilin 1 gene analysis in a cohort of patients from the Poznan region. Author(s): Kowalska A, Wender M, Florczak J, Pruchnik-Wolinska D, Modestowicz R, Szczech J, Rossa G, Kozubski W. Source: Journal of Applied Genetics. 2003; 44(2): 231-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817569&dopt=Abstract

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Molecular pathogenesis of Alzheimer's disease. Author(s): Iwatsubo T. Source: Intern Med. 2003 March; 42(3): 312. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705809&dopt=Abstract

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Monitoring of disease progression and therapeutic efficacy in Alzheimer's disease by electrophysiological indices. Author(s): Dierks T, Jelic V. Source: Methods Find Exp Clin Pharmacol. 2002; 24 Suppl D: 75. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809081&dopt=Abstract

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Mood, cognition and Alzheimer's disease. Author(s): Compton J, van Amelsvoort T, Murphy D. Source: Best Practice & Research. Clinical Obstetrics & Gynaecology. 2002 June; 16(3): 357-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099667&dopt=Abstract

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Morphological analysis of active microglia--rod and ramified microglia in human brains affected by some neurological diseases (SSPE, Alzheimer's disease and Wilson's disease). Author(s): Wierzba-Bobrowicz T, Gwiazda E, Kosno-Kruszewska E, Lewandowska E, Lechowicz W, Bertrand E, Szpak GM, Schmidt-Sidor B. Source: Folia Neuropathol. 2002; 40(3): 125-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572918&dopt=Abstract

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Mortality in Alzheimer's disease. Author(s): Bonsignore M, Heun R. Source: Dementia and Geriatric Cognitive Disorders. 2003; 15(4): 231-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626857&dopt=Abstract

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Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer's disease: evidence of impaired glutamatergic neurotransmission? Author(s): Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Dileone M, Tonali PA. Source: Annals of Neurology. 2003 June; 53(6): 824; Author Reply 824-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783435&dopt=Abstract

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MR spectroscopy in Alzheimer's disease: gender differences in probabilistic learning capacity. Author(s): Colla M, Ende G, Bohrer M, Deuschle M, Kronenberg G, Henn F, Heuser I. Source: Neurobiology of Aging. 2003 July-August; 24(4): 545-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714111&dopt=Abstract

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MRI study of caudate nucleus volume in Parkinson's disease with and without dementia with Lewy bodies and Alzheimer's disease. Author(s): Almeida OP, Burton EJ, McKeith I, Gholkar A, Burn D, O'Brien JT. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(2): 57-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784028&dopt=Abstract

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Multiple-peptide conjugates for binding beta-amyloid plaques of Alzheimer's disease. Author(s): Zhang G, Leibowitz MJ, Sinko PJ, Stein S. Source: Bioconjugate Chemistry. 2003 January-February; 14(1): 86-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12526697&dopt=Abstract

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Muscarinic receptors in basal ganglia in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease. Author(s): Piggott MA, Owens J, O'Brien J, Colloby S, Fenwick J, Wyper D, Jaros E, Johnson M, Perry RH, Perry EK. Source: Journal of Chemical Neuroanatomy. 2003 March; 25(3): 161-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706204&dopt=Abstract

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Myeloperoxidase G-463A polymorphism and Alzheimer's disease in the ApoEurope study. Author(s): Leininger-Muller B, Hoy A, Herbeth B, Pfister M, Serot JM, StavljenicRukavina M, Massana L, Passmore P, Siest G, Visvikis S. Source: Neuroscience Letters. 2003 October 2; 349(2): 95-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946561&dopt=Abstract

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Nature of personal semantic memory: evidence from Alzheimer's disease. Author(s): Kazui H, Hashimoto M, Hirono N, Mori E. Source: Neuropsychologia. 2003; 41(8): 981-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667533&dopt=Abstract

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Negative symptoms in Alzheimer's disease: a confirmatory factor analysis. Author(s): de Jonghe JF, Goedhart AW, Ooms ME, Kat MG, Kalisvaart KJ, van Ewijk WM, Ribbe MW. Source: International Journal of Geriatric Psychiatry. 2003 August; 18(8): 748-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891644&dopt=Abstract

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Neocortical glial cell numbers in Alzheimer's disease. A stereological study. Author(s): Pelvig DP, Pakkenberg H, Regeur L, Oster S, Pakkenberg B. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(4): 212-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512716&dopt=Abstract

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Neural basis for semantic memory difficulty in Alzheimer's disease: an fMRI study. Author(s): Grossman M, Koenig P, Glosser G, DeVita C, Moore P, Rhee J, Detre J, Alsop D, Gee J; fMRI study. Functional magnetic resonance imaging. Source: Brain; a Journal of Neurology. 2003 February; 126(Pt 2): 292-311. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538399&dopt=Abstract

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Neuroimaging to predict preclinical Alzheimer's disease. Author(s): Kumari V, Mitterschiffthaler MT, Sharma T. Source: Hosp Med. 2002 June; 63(6): 341-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096663&dopt=Abstract

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Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer's disease. Author(s): Yang Y, Mufson EJ, Herrup K. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 April 1; 23(7): 2557-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684440&dopt=Abstract

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Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. Author(s): Palop JJ, Jones B, Kekonius L, Chin J, Yu GQ, Raber J, Masliah E, Mucke L. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 August 5; 100(16): 9572-7. Epub 2003 July 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881482&dopt=Abstract

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Neuropathologic changes in Alzheimer's disease. Author(s): Wenk GL. Source: The Journal of Clinical Psychiatry. 2003; 64 Suppl 9: 7-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934968&dopt=Abstract

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Neuroprotection: promise and pitfalls in anti-inflammatory treatment of Alzheimer's disease. Author(s): Memo M, Blandini F, Nappi G, Spano P. Source: Funct Neurol. 2002 October-December; 17(4): 175-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675259&dopt=Abstract

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Neuroprotective strategies in Alzheimer's disease. Author(s): Behl C. Source: Advances in Experimental Medicine and Biology. 2002; 513: 475-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12575833&dopt=Abstract

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Neuropsychological deficits associated with Alzheimer's disease in the very-old: discrepancies in raw vs. standardized scores. Author(s): Bondi MW, Houston WS, Salmon DP, Corey-Bloom J, Katzman R, Thal LJ, Delis DC. Source: Journal of the International Neuropsychological Society : Jins. 2003 July; 9(5): 783-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901784&dopt=Abstract

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Neuropsychological differentiation of small vessel disease, Alzheimer's disease and mixed dementia. Author(s): Schmidtke K, Hull M. Source: Journal of the Neurological Sciences. 2002 November 15; 203-204: 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417351&dopt=Abstract

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Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease. Author(s): Arnaiz E, Almkvist O. Source: Acta Neurologica Scandinavica. Supplementum. 2003; 179: 34-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603249&dopt=Abstract

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Neuropsychological performance in Alzheimer's disease and vascular dementia: comparisons in a memory clinic population. Author(s): Baillon S, Muhommad S, Marudkar M, Suribhatla S, Dennis M, Spreadbury C, Munro D, Lindesay J. Source: International Journal of Geriatric Psychiatry. 2003 July; 18(7): 602-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833304&dopt=Abstract

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Neuropsychological predictors of everyday memory and everyday functioning in patients with mild Alzheimer's disease. Author(s): Cahn-Weiner DA, Ready RE, Malloy PF. Source: Journal of Geriatric Psychiatry and Neurology. 2003 June; 16(2): 84-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801157&dopt=Abstract

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Neuropsychological study of familial Alzheimer's disease caused by mutation E280A in the presenilin 1 gene. Author(s): Arango Lasprilla JC, Iglesias J, Lopera F. Source: Am J Alzheimers Dis Other Demen. 2003 May-June; 18(3): 137-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811988&dopt=Abstract

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Neuroscience. Insulin insults may spur Alzheimer's disease. Author(s): Taubes G. Source: Science. 2003 July 4; 301(5629): 40-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843374&dopt=Abstract

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Neurotoxic effects of aluminium among foundry workers and Alzheimer's disease. Author(s): Polizzi S, Pira E, Ferrara M, Bugiani M, Papaleo A, Albera R, Palmi S. Source: Neurotoxicology. 2002 December; 23(6): 761-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520766&dopt=Abstract

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Neurotoxic mechanisms caused by the Alzheimer's disease-linked Swedish amyloid precursor protein mutation: oxidative stress, caspases, and the JNK pathway. Author(s): Marques CA, Keil U, Bonert A, Steiner B, Haass C, Muller WE, Eckert A. Source: The Journal of Biological Chemistry. 2003 July 25; 278(30): 28294-302. Epub 2003 May 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730216&dopt=Abstract

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New website for Alzheimer's disease launched in Spain. Author(s): Bosch X. Source: Lancet. Neurology. 2003 January; 2(1): 3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849280&dopt=Abstract

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Nicotinic receptors and Alzheimer's disease. Author(s): Bourion M, Ripoll N, Dailly E. Source: Current Medical Research and Opinion. 2003; 19(3): 169-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814128&dopt=Abstract

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No association between Glu298Asp endothelial nitric oxide synthase polymorphism and Italian sporadic Alzheimer's disease. Author(s): Monastero R, Cefalu AB, Camarda C, Buglino CM, Mannino M, Barbagallo CM, Lopez G, Camarda LK, Travali S, Camarda R, Averna MR. Source: Neuroscience Letters. 2003 May 8; 341(3): 229-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697290&dopt=Abstract

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No association between polymorphisms in the neprilysin promoter region and Swedish Alzheimer's disease patients. Author(s): Lilius L, Forsell C, Axelman K, Winblad B, Graff C, Tjernberg L. Source: Neuroscience Letters. 2003 February 6; 337(2): 111-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527400&dopt=Abstract

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No evidence for an association between Saitohin Q7R polymorphism and Alzheimer's disease. Author(s): Cook L, Brayne CE, Easton D, Evans JG, Xuereb J, Cairns NJ, Rubinsztein DC. Source: Annals of Neurology. 2002 November; 52(5): 690-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12402275&dopt=Abstract

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Noncholinergic treatment options for Alzheimer's disease. Author(s): Sano M. Source: The Journal of Clinical Psychiatry. 2003; 64 Suppl 9: 23-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934971&dopt=Abstract

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Nonsteroidal anti-inflammatory drug use and the risk for Alzheimer's disease: dissecting the epidemiological evidence. Author(s): Launer L. Source: Drugs. 2003; 63(8): 731-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662122&dopt=Abstract

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Non-steroidal anti-inflammatory drug users possibly have a decreased risk of Alzheimer's disease. Author(s): Naccari C. Source: Cns Spectr. 2003 May; 8(5): 336. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778901&dopt=Abstract

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Non-steroidal anti-inflammatory drugs and cyclooxygenase in Alzheimer's disease. Author(s): Hoozemans JJ, Veerhuis R, Rozemuller AJ, Eikelenboom P. Source: Current Drug Targets. 2003 August; 4(6): 461-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866660&dopt=Abstract

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NSAID and Alzheimer's disease; possible answers and new questions. Author(s): Davis KL. Source: Molecular Psychiatry. 2002; 7(9): 925-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399941&dopt=Abstract

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NSAIDs and Alzheimer's disease: how far to generalise from trials? Author(s): Breitner JC. Source: Lancet. Neurology. 2003 September; 2(9): 527. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941571&dopt=Abstract

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Object recognition and object orientation in Alzheimer's disease. Author(s): Caterini F, Della Sala S, Spinnler H, Stangalino C, Tumbull OH. Source: Neuropsychology. 2002 April; 16(2): 146-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949706&dopt=Abstract

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Occurrence of T cells in the brain of Alzheimer's disease and other neurological diseases. Author(s): Togo T, Akiyama H, Iseki E, Kondo H, Ikeda K, Kato M, Oda T, Tsuchiya K, Kosaka K. Source: Journal of Neuroimmunology. 2002 March; 124(1-2): 83-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11958825&dopt=Abstract

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Of mice and men: The relevance of transgenic mice Abeta immunizations to Alzheimer's disease. Author(s): Roher AE, Kokjohn TA. Source: Journal of Alzheimer's Disease : Jad. 2002 October; 4(5): 431-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446974&dopt=Abstract

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Of replications and refutations: the status of Alzheimer's disease genetic research. Author(s): Bertram L, Tanzi RE. Source: Curr Neurol Neurosci Rep. 2001 September; 1(5): 442-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898555&dopt=Abstract

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Olanzapine as a treatment of neuropsychiatric disorders of Alzheimer's disease and other dementias: a 24-month follow-up of 68 patients. Author(s): Moretti R, Torre P, Antonello RM, Cazzato G, Griggio S, Bava A. Source: Am J Alzheimers Dis Other Demen. 2003 July-August; 18(4): 205-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955785&dopt=Abstract

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Older women caring for spouses with Alzheimer's disease at home: making sense of the situation. Author(s): Paun O. Source: Health Care for Women International. 2003 April; 24(4): 292-312. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746002&dopt=Abstract

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Olfactory event-related potentials in Alzheimer's disease. Author(s): Morgan CD, Murphy C. Source: Journal of the International Neuropsychological Society : Jins. 2002 September; 8(6): 753-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12240739&dopt=Abstract

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On disentangling states versus traits: demonstration of a new technique using the Alzheimer's disease assessment scale. Author(s): Taylor JL, Kraemer HC, Noda A, Friedman L, Zarcone V, Tinklenberg JR, Yesavage JA. Source: Alzheimer Disease and Associated Disorders. 2002 October-December; 16(4): 254-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468900&dopt=Abstract

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On the structural form of iron in ferritin cores associated with progressive supranuclear palsy and Alzheimer's disease. Author(s): Dobson J. Source: Cell Mol Biol (Noisy-Le-Grand). 2001; 47 Online Pub: Ol49-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936873&dopt=Abstract

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Optimizing coding and reimbursement to improve management of Alzheimer's disease and related dementias. Author(s): Fillit H, Geldmacher DS, Welter RT, Maslow K, Fraser M. Source: Journal of the American Geriatrics Society. 2002 November; 50(11): 1871-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410910&dopt=Abstract

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Outcomes of Alzheimer's disease treatment: the Italian CRONOS project. Author(s): Bianchetti A, Padovani A, Trabucchi M. Source: International Journal of Geriatric Psychiatry. 2003 January; 18(1): 87-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12497562&dopt=Abstract

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Overexpression of Alzheimer's disease amyloid-beta opposes the age-dependent elevations of brain copper and iron. Author(s): Maynard CJ, Cappai R, Volitakis I, Cherny RA, White AR, Beyreuther K, Masters CL, Bush AI, Li QX. Source: The Journal of Biological Chemistry. 2002 November 22; 277(47): 44670-6. Epub 2002 September 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215434&dopt=Abstract

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Overexpression of hAPPswe impairs rewarded alternation and contextual fear conditioning in a transgenic mouse model of Alzheimer's disease. Author(s): Corcoran KA, Lu Y, Turner RS, Maren S. Source: Learning & Memory (Cold Spring Harbor, N.Y.). 2002 September-October; 9(5): 243-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359834&dopt=Abstract

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Overexpression of semicarbazide sensitive amine oxidase in the cerebral blood vessels in patients with Alzheimer's disease and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Author(s): Ferrer I, Lizcano JM, Hernandez M, Unzeta M. Source: Neuroscience Letters. 2002 March 15; 321(1-2): 21-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11872247&dopt=Abstract

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Overexpression of wild-type presenilin 2 or its familial Alzheimer's diseaseassociated mutant does not induce or increase susceptibility to apoptosis in different cell lines. Author(s): Gamliel A, Teicher C, Hartmann T, Beyreuther K, Stein R. Source: Neuroscience. 2003; 117(1): 19-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605888&dopt=Abstract

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Oxidative nerve cell death in Alzheimer's disease and stroke: antioxidants as neuroprotective compounds. Author(s): Behl C, Moosmann B. Source: Biological Chemistry. 2002 March-April; 383(3-4): 521-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12033440&dopt=Abstract

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Oxidative processes in the brain and non-neuronal tissues as biomarkers of Alzheimer's disease. Author(s): Gibson GE, Huang HM. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2002 April 1; 7: D1007-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11897553&dopt=Abstract

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Oxidative stress, perturbed calcium homeostasis, and immune dysfunction in Alzheimer's disease. Author(s): Mattson MP. Source: Journal of Neurovirology. 2002 December; 8(6): 539-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476348&dopt=Abstract

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Oxidative stress-mediated DHEA formation in Alzheimer's disease pathology. Author(s): Brown RC, Han Z, Cascio C, Papadopoulos V. Source: Neurobiology of Aging. 2003 January-February; 24(1): 57-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493551&dopt=Abstract

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P2X7 mediates superoxide production in primary microglia and is up-regulated in a transgenic mouse model of Alzheimer's disease. Author(s): Parvathenani LK, Tertyshnikova S, Greco CR, Roberts SB, Robertson B, Posmantur R. Source: The Journal of Biological Chemistry. 2003 April 11; 278(15): 13309-17. Epub 2003 January 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12551918&dopt=Abstract

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P38 MAP kinase is activated at early stages in Alzheimer's disease brain. Author(s): Sun A, Liu M, Nguyen XV, Bing G. Source: Experimental Neurology. 2003 October; 183(2): 394-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14552880&dopt=Abstract

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Pathological determinants of dementia in Alzheimer's disease (AD). Author(s): Royall DR, Roman GC, Delacourte A. Source: Experimental Aging Research. 2003 January-March; 29(1): 107-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735084&dopt=Abstract

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Pathology and pathways of Alzheimer's disease with an update on new developments in treatment. Author(s): DeKosky ST. Source: Journal of the American Geriatrics Society. 2003 May; 51(5 Suppl Dementia): S314-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801388&dopt=Abstract

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Patterns of change in the treatment of psychiatric symptoms in patients with probable Alzheimer's disease from 1983 to 2000. Author(s): Lopez OL, Becker JT, Sweet RA, Klunk W, Kaufer DI, Saxton J, DeKosky ST. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Winter; 15(1): 67-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556574&dopt=Abstract

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Perceptual organization based upon spatial relationships in Alzheimer's disease. Author(s): Kurylo DD, Allan WC, Collins TE, Baron J. Source: Behavioural Neurology. 2003; 14(1-2): 19-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719635&dopt=Abstract

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Performance on the dementia rating scale in Parkinson's disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer's disease. Author(s): Aarsland D, Litvan I, Salmon D, Galasko D, Wentzel-Larsen T, Larsen JP. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 September; 74(9): 1215-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933921&dopt=Abstract

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Person recognition and approach behaviors among individuals with probable Alzheimer's disease. Author(s): Sotnak DL, Seifert LS. Source: Experimental Aging Research. 2003 January-March; 29(1): 67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735082&dopt=Abstract

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Pharmacologic agents associated with a preventive effect on Alzheimer's disease: a review of the epidemiologic evidence. Author(s): in 't Veld BA, Launer LJ, Breteler MM, Hofman A, Stricker BH. Source: Epidemiologic Reviews. 2002; 24(2): 248-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762096&dopt=Abstract

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Pharmacotherapy for Alzheimer's disease: 2002. Author(s): Knopman D. Source: Clinical Neuropharmacology. 2003 March-April; 26(2): 93-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671529&dopt=Abstract

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Physiopathological modulators of amyloid aggregation and novel pharmacological approaches in Alzheimer's disease. Author(s): Defelice FG, Ferreira ST. Source: Anais Da Academia Brasileira De Ciencias. 2002 June; 74(2): 265-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098753&dopt=Abstract

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Polymorphism at codon 174 of the prion-like protein gene is not associated with sporadic Alzheimer's disease. Author(s): Infante J, Llorca J, Rodero L, Palacio E, Berciano J, Combarros O. Source: Neuroscience Letters. 2002 November 8; 332(3): 213-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399017&dopt=Abstract

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Polymorphism in the BACE gene influences the risk for Alzheimer's disease. Author(s): Kirschling CM, Kolsch H, Frahnert C, Rao ML, Maier W, Heun R. Source: Neuroreport. 2003 July 1; 14(9): 1243-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824768&dopt=Abstract

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Polymorphisms of the gene encoding the inflammatory cytokine interleukin-6 determine the magnitude of the increase in soluble interleukin-6 receptor levels in Alzheimer's disease. Results of a pilot study. Author(s): Bagli M, Papassotiropoulos A, Hampel H, Becker K, Jessen F, Burger K, Ptok U, Rao ML, Moller HJ, Maier W, Heun R. Source: European Archives of Psychiatry and Clinical Neuroscience. 2003 February; 253(1): 44-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664314&dopt=Abstract

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Possible increased risk for Alzheimer's disease associated with neprilysin gene. Author(s): Clarimon J, Munoz FJ, Boada M, Tarraga L, Sunyer J, Bertranpetit J, Comas D. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2003 June; 110(6): 651-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768360&dopt=Abstract

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Possible involvement of Wiskott-Aldrich syndrome protein family in aberrant neuronal sprouting in Alzheimer's disease. Author(s): Kitamura Y, Tsuchiya D, Takata K, Shibagaki K, Taniguchi T, Smith MA, Perry G, Miki H, Takenawa T, Shimohama S. Source: Neuroscience Letters. 2003 August 7; 346(3): 149-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853106&dopt=Abstract

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Possible mechanisms of APP-mediated oxidative stress in Alzheimer's disease. Author(s): Multhaup G, Scheuermann S, Schlicksupp A, Simons A, Strauss M, Kemmling A, Oehler C, Cappai R, Pipkorn R, Bayer TA. Source: Free Radical Biology & Medicine. 2002 July 1; 33(1): 45-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086681&dopt=Abstract

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Potential roles of insulin and IGF-1 in Alzheimer's disease. Author(s): Gasparini L, Xu H. Source: Trends in Neurosciences. 2003 August; 26(8): 404-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900169&dopt=Abstract

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Prediction of the rate of decline in cognitive function in Alzheimer's disease: a model based on simple demographic data and widely used rating scales. Author(s): Johnsen S, Hughes S, Bullock R, Hindmarch I. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(4): 276-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512724&dopt=Abstract

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Preliminary evaluation of nanoscale biogenic magnetite in Alzheimer's disease brain tissue. Author(s): Hautot D, Pankhurst QA, Khan N, Dobson J. Source: Proceedings of the Royal Society of London. Series B. Biological Sciences. 2003 August 7; 270 Suppl 1: S62-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952638&dopt=Abstract

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Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer's disease. Author(s): Michalski B, Fahnestock M. Source: Brain Research. Molecular Brain Research. 2003 March 17; 111(1-2): 148-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654514&dopt=Abstract

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Progressive degeneration of nonphosphorylated neurofilament protein-enriched pyramidal neurons predicts cognitive impairment in Alzheimer's disease: stereologic analysis of prefrontal cortex area 9. Author(s): Bussiere T, Giannakopoulos P, Bouras C, Perl DP, Morrison JH, Hof PR. Source: The Journal of Comparative Neurology. 2003 August 25; 463(3): 281-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820162&dopt=Abstract

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Proteomic identification of nitrated proteins in Alzheimer's disease brain. Author(s): Castegna A, Thongboonkerd V, Klein JB, Lynn B, Markesbery WR, Butterfield DA. Source: Journal of Neurochemistry. 2003 June; 85(6): 1394-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787059&dopt=Abstract

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Proteomics in Alzheimer's disease: insights into potential mechanisms of neurodegeneration. Author(s): Butterfield DA, Boyd-Kimball D, Castegna A. Source: Journal of Neurochemistry. 2003 September; 86(6): 1313-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950441&dopt=Abstract

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Psychiatric disorders in relatives of subjects with Alzheimer's disease. No evidence for common genetic risk factors. Author(s): Heun R, Kockler M, Ptok U. Source: European Archives of Psychiatry and Clinical Neuroscience. 2002 April; 252(2): 93-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111343&dopt=Abstract

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Psychiatric symptoms vary with the severity of dementia in probable Alzheimer's disease. Author(s): Lopez OL, Becker JT, Sweet RA, Klunk W, Kaufer DI, Saxton J, Habeych M, DeKosky ST. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Summer; 15(3): 346-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928511&dopt=Abstract

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Psychopathological features in Alzheimer's disease: course and relationship with cognitive status. Author(s): Holtzer R, Tang MX, Devanand DP, Albert SM, Wegesin DJ, Marder K, Bell K, Albert M, Brandt J, Stern Y. Source: Journal of the American Geriatrics Society. 2003 July; 51(7): 953-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834515&dopt=Abstract

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Qualitative performance characteristics differentiate dementia with Lewy bodies and Alzheimer's disease. Author(s): Doubleday EK, Snowden JS, Varma AR, Neary D. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 May; 72(5): 602-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11971046&dopt=Abstract

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Qualitative performance characteristics differentiate dementia with Lewy bodies and Alzheimer's disease. Author(s): Ballard C, O'Brien J, Tovee M. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 May; 72(5): 565-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11971037&dopt=Abstract

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Quantification of regional glial fibrillary acidic protein levels in Alzheimer's disease. Author(s): Ross GW, O'Callaghan JP, Sharp DS, Petrovitch H, Miller DB, Abbott RD, Nelson J, Launer LJ, Foley DJ, Burchfiel CM, Hardman J, White LR. Source: Acta Neurologica Scandinavica. 2003 May; 107(5): 318-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12713522&dopt=Abstract

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Quantitative assessment of DNA fragmentation and beta-amyloid deposition in insular cortex and midfrontal gyrus from patients with Alzheimer's disease. Author(s): Colurso GJ, Nilson JE, Vervoort LG. Source: Life Sciences. 2003 August 22; 73(14): 1795-803. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888118&dopt=Abstract

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Quantitative EEG abnormalities and cognitive dysfunctions in frontotemporal dementia and Alzheimer's disease. Author(s): Lindau M, Jelic V, Johansson SE, Andersen C, Wahlund LO, Almkvist O. Source: Dementia and Geriatric Cognitive Disorders. 2003; 15(2): 106-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566600&dopt=Abstract

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Quantitative EEG and dynamic susceptibility contrast MRI in Alzheimer's disease: a correlative study. Author(s): Mattia D, Babiloni F, Romigi A, Cincotti F, Bianchi L, Sperli F, Placidi F, Bozzao A, Giacomini P, Floris R, Grazia Marciani M. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 July; 114(7): 1210-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842717&dopt=Abstract

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Rate of cognitive decline in preclinical Alzheimer's disease: the role of comorbidity. Author(s): Backman L, Jones S, Small BJ, Aguero-Torres H, Fratiglioni L. Source: The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences. 2003 July; 58(4): P228-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878651&dopt=Abstract

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Rates of cognitive decline in Alzheimer's disease and dementia with Lewy bodies. Author(s): Helmes E, Bowler JV, Merskey H, Munoz DG, Hachinski VC. Source: Dementia and Geriatric Cognitive Disorders. 2003; 15(2): 67-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566594&dopt=Abstract

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Reduced glutamate neurotransmission in patients with Alzheimer's disease -- an in vivo (13)C magnetic resonance spectroscopy study. Author(s): Lin AP, Shic F, Enriquez C, Ross BD. Source: Magma (New York, N.Y.). 2003 February; 16(1): 29-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695884&dopt=Abstract

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Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer's disease is associated with the apolipoprotein E-epsilon4 allele. Author(s): Cook DG, Leverenz JB, McMillan PJ, Kulstad JJ, Ericksen S, Roth RA, Schellenberg GD, Jin LW, Kovacina KS, Craft S. Source: American Journal of Pathology. 2003 January; 162(1): 313-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507914&dopt=Abstract

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Reduction of beta-amyloid plaques in brain of transgenic mouse model of Alzheimer's disease by EFRH-phage immunization. Author(s): Frenkel D, Dewachter I, Van Leuven F, Solomon B. Source: Vaccine. 2003 March 7; 21(11-12): 1060-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559780&dopt=Abstract

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Re-evaluation of tropicamide in the pupillary response test for Alzheimer's disease. Author(s): Iijima A, Haida M, Ishikawa N, Ueno A, Minamitani H, Shinohara Y. Source: Neurobiology of Aging. 2003 October; 24(6): 789-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927761&dopt=Abstract

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Regional brain atrophy in patients with mild Alzheimer's disease and delusions. Author(s): Geroldi C, Bresciani L, Zanetti O, Frisoni GB. Source: Int Psychogeriatr. 2002 December; 14(4): 365-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670058&dopt=Abstract

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Regional cerebral blood flow and EEG in clinically diagnosed dementia with Lewy bodies and Alzheimer's disease. Author(s): Londos E, Passant U, Brun A, Rosen I, Risberg J, Gustafson L. Source: Archives of Gerontology and Geriatrics. 2003 May-June; 36(3): 231-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849079&dopt=Abstract

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Regional cerebral glucose metabolism in monozygotic twins discordant for Alzheimer's disease. Author(s): Jarvenpaa T, Raiha I, Kaprio J, Koskenvuo M, Laine M, Kurki T, Vahlberg T, Viljanen T, Ahonen K, Rinne JO. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(4): 245-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512720&dopt=Abstract

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Regional pattern of hippocampus and corpus callosum atrophy in Alzheimer's disease in relation to dementia severity: evidence for early neocortical degeneration. Author(s): Teipel SJ, Bayer W, Alexander GE, Bokde AL, Zebuhr Y, Teichberg D, MullerSpahn F, Schapiro MB, Moller HJ, Rapoport SI, Hampel H. Source: Neurobiology of Aging. 2003 January-February; 24(1): 85-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493554&dopt=Abstract

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Regional quantitative study of formation process of neurofibrillary tangles in the hippocampus of non-demented elderly brains: comparison with late-onset Alzheimer's disease brains. Author(s): Takayama N, Iseki E, Yamamoto T, Kosaka K. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. 2002 September; 22(3): 147-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416553&dopt=Abstract

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Regulation of promoter activity of the APP gene by cytokines and growth factors: implications in Alzheimer's disease. Author(s): Ge YW, Lahiri DK. Source: Annals of the New York Academy of Sciences. 2002 November; 973: 463-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485912&dopt=Abstract

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Regulation of the frontocortical sodium pump by Na+ in Alzheimer's disease: difference from the age-matched control but similarity to the rat model. Author(s): Kairane C, Roots K, Uusma T, Bogdanovic N, Karelson E, Koks S, Zilmer M. Source: Febs Letters. 2002 November 6; 531(2): 241-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417319&dopt=Abstract

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Relation between medial temporal atrophy and functional brain activity during memory processing in Alzheimer's disease: a combined MRI and SPECT study. Author(s): Garrido GE, Furuie SS, Buchpiguel CA, Bottino CM, Almeida OP, Cid CG, Camargo CH, Castro CC, Glabus MF, Busatto GF. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 November; 73(5): 508-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397142&dopt=Abstract

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Relationship between blood pressure and Alzheimer's disease in Linxian County, China. Author(s): Wu C, Zhou D, Wen C, Zhang L, Como P, Qiao Y. Source: Life Sciences. 2003 January 24; 72(10): 1125-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505543&dopt=Abstract

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Relationship between positive and negative symptoms and neuropsychological scores in frontotemporal dementia and Alzheimer's disease. Author(s): Boone KB, Miller BL, Swartz R, Lu P, Lee A. Source: Journal of the International Neuropsychological Society : Jins. 2003 July; 9(5): 698-709. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901776&dopt=Abstract

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Relatives' attitudes towards informing patients about the diagnosis of Alzheimer's disease. Author(s): Pucci E, Belardinelli N, Borsetti G, Giuliani G. Source: Journal of Medical Ethics. 2003 February; 29(1): 51-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569197&dopt=Abstract

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Report of three cases of Alzheimer's disease with focal motor symptoms: clinical correlates of neuroimaging findings. Author(s): Kobayashi K, Shimoda K, Higashima M, Nakano H, Miyazu K, Hayashi M, Tabata O, Koshino Y. Source: World J Biol Psychiatry. 2000 July; 1(3): 164-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607227&dopt=Abstract

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Resource utilisation and cost analysis of memantine in patients with moderate to severe Alzheimer's disease. Author(s): Wimo A, Winblad B, Stoffler A, Wirth Y, Mobius HJ. Source: Pharmacoeconomics. 2003; 21(5): 327-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627986&dopt=Abstract

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Response-monitoring dysfunction in aging and Alzheimer's disease: an event-related potential study. Author(s): Mathalon DH, Bennett A, Askari N, Gray EM, Rosenbloom MJ, Ford JM. Source: Neurobiology of Aging. 2003 September; 24(5): 675-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885575&dopt=Abstract

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Results of a high-resolution genome screen of 437 Alzheimer's disease families. Author(s): Blacker D, Bertram L, Saunders AJ, Moscarillo TJ, Albert MS, Wiener H, Perry RT, Collins JS, Harrell LE, Go RC, Mahoney A, Beaty T, Fallin MD, Avramopoulos D, Chase GA, Folstein MF, McInnis MG, Bassett SS, Doheny KJ, Pugh EW, Tanzi RE; NIMH Genetics Initiative Alzheimer's Disease Study Group. Source: Human Molecular Genetics. 2003 January 1; 12(1): 23-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490529&dopt=Abstract

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Risk factors for Alzheimer's disease: role of multiple antioxidants, non-steroidal antiinflammatory and cholinergic agents alone or in combination in prevention and treatment. Author(s): Prasad KN, Cole WC, Prasad KC. Source: Journal of the American College of Nutrition. 2002 December; 21(6): 506-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480796&dopt=Abstract

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Rivastigmine in patients with Alzheimer's disease and concurrent hypertension. Author(s): Erkinjuntti T, Skoog I, Lane R, Andrews C. Source: Int J Clin Pract. 2002 December; 56(10): 791-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510954&dopt=Abstract

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Rivastigmine: an update on therapeutic efficacy in Alzheimer's disease and other conditions. Author(s): Gabelli C. Source: Current Medical Research and Opinion. 2003; 19(2): 69-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740150&dopt=Abstract

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Role of cytokines in the gene expression of amyloid beta-protein precursor: identification of a 5'-UTR-binding nuclear factor and its implications in Alzheimer's disease. Author(s): Lahiri DK, Chen D, Vivien D, Ge YW, Greig NH, Rogers JT. Source: Journal of Alzheimer's Disease : Jad. 2003 April; 5(2): 81-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719626&dopt=Abstract

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Role of serine/threonine protein phosphatase in Alzheimer's disease. Author(s): Tian Q, Wang J. Source: Neuro-Signals. 2002 September-October; 11(5): 262-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566927&dopt=Abstract

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Role of the immune system in the pathogenesis, prevention and treatment of Alzheimer's disease. Author(s): Blasko I, Grubeck-Loebenstein B. Source: Drugs & Aging. 2003; 20(2): 101-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534311&dopt=Abstract

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RT and non-RT methodology for semantic priming research with Alzheimer's disease patients: a critical review. Author(s): Ober BA. Source: J Clin Exp Neuropsychol. 2002 October; 24(7): 883-911. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647767&dopt=Abstract

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Screening for Alzheimer's disease with the short cognitive evaluation battery. Author(s): Robert PH, Schuck S, Dubois B, Olie JP, Lepine JP, Gallarda T, Goni S, Troy S; Investigators' Group. Source: Dementia and Geriatric Cognitive Disorders. 2003; 15(2): 92-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566598&dopt=Abstract

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Screening for Alzheimer's disease: the memory impairment screen versus the conventional three-word memory test. Author(s): Kuslansky G, Buschke H, Katz M, Sliwinski M, Lipton RB. Source: Journal of the American Geriatrics Society. 2002 June; 50(6): 1086-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110070&dopt=Abstract

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Secretases as targets for the treatment of Alzheimer's disease: the prospects. Author(s): Dewachter I, Van Leuven F. Source: Lancet. Neurology. 2002 November; 1(7): 409-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849363&dopt=Abstract

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Selective attention skills in differentiating between Alzheimer's disease and normal aging. Author(s): Solfrizzi V, Panza F, Torres F, Capurso C, D'Introno A, Colacicco AM, Capurso A. Source: Journal of Geriatric Psychiatry and Neurology. 2002 Summer; 15(2): 99-109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083601&dopt=Abstract

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Self-reported memory compensation: similar patterns in Alzheimer's disease and very old adult samples. Author(s): Dixon RA, Hopp GA, Cohen AL, de Frias CM, Backman L. Source: J Clin Exp Neuropsychol. 2003 May; 25(3): 382-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916651&dopt=Abstract

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Semantic versus phonological false recognition in aging and Alzheimer's disease. Author(s): Budson AE, Sullivan AL, Daffner KR, Schacter DL. Source: Brain and Cognition. 2003 April; 51(3): 251-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727179&dopt=Abstract

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Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease. Author(s): Harold D, Peirce T, Moskvina V, Myers A, Jones S, Hollingworth P, Moore P, Lovestone S, Powell J, Foy C, Archer N, Walter S, Edmonson A, McIlroy S, Craig D, Passmore PA, Goate A, Hardy J, O'Donovan M, Williams J, Liddell M, Owen MJ, Jones L. Source: Human Genetics. 2003 August; 113(3): 258-67. Epub 2003 May 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759818&dopt=Abstract

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Serotonin transporters are preserved in the neocortex of anxious Alzheimer's disease patients. Author(s): Tsang SW, Lai MK, Francis PT, Wong PT, Spence I, Esiri MM, Keene J, Hope T, Chen CP. Source: Neuroreport. 2003 July 18; 14(10): 1297-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876460&dopt=Abstract

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Serum paraoxonase activity changes in patients with Alzheimer's disease and vascular dementia. Author(s): Paragh G, Balla P, Katona E, Seres I, Egerhazi A, Degrell I. Source: European Archives of Psychiatry and Clinical Neuroscience. 2002 April; 252(2): 63-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111338&dopt=Abstract

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Shifts in angiotensin I converting enzyme insertion allele frequency across Europe: implications for Alzheimer's disease risk. Author(s): Panza F, Solfrizzi V, D'Introno A, Colacicco AM, Capurso C, Capurso A, Kehoe PG. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 August; 74(8): 115961. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876265&dopt=Abstract

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Short-term longitudinal evaluation of cerebral blood flow in mild Alzheimer's disease. Author(s): Tonini G, Shanks MF, Venneri A. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2003 April; 24(1): 24-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754653&dopt=Abstract

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Should home screening tests for Alzheimer's disease be regulated? Author(s): Kapp MB. Source: The Gerontologist. 2003 June; 43(3): 292-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810891&dopt=Abstract

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Signal transduction through tyrosine-phosphorylated C-terminal fragments of amyloid precursor protein via an enhanced interaction with Shc/Grb2 adaptor proteins in reactive astrocytes of Alzheimer's disease brain. Author(s): Russo C, Dolcini V, Salis S, Venezia V, Zambrano N, Russo T, Schettini G. Source: The Journal of Biological Chemistry. 2002 September 20; 277(38): 35282-8. Epub 2002 June 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084708&dopt=Abstract

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Similarities between Alzheimer's disease and vascular dementia. Author(s): Kalaria R. Source: Journal of the Neurological Sciences. 2002 November 15; 203-204: 29-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417353&dopt=Abstract

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Simultaneous analysis of five genetic risk factors in Polish patients with Alzheimer's disease. Author(s): Styczynska M, Religa D, Pfeffer A, Luczywek E, Wasiak B, Styczynski G, Peplonska B, Gabryelewicz T, Golebiowski M, Kobrys M, Barcikowska M. Source: Neuroscience Letters. 2003 June 26; 344(2): 99-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782337&dopt=Abstract

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Sleep/wake cycle disturbance in Alzheimer's disease: how much is due to an inherent trait? Author(s): Yesavage JA, Taylor JL, Kraemer H, Noda A, Friedman L, Tinklenberg JR. Source: Int Psychogeriatr. 2002 March; 14(1): 73-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094910&dopt=Abstract

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Spatial and temporal distribution of intracellular free cholesterol in brains of a Niemann-Pick type C mouse model showing hyperphosphorylated tau protein. Implications for Alzheimer's disease. Author(s): Treiber-Held S, Distl R, Meske V, Albert F, Ohm TG. Source: The Journal of Pathology. 2003 May; 200(1): 95-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692847&dopt=Abstract

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Spatial patterns of mammalian brain aging: distribution of cathepsin Dimmunoreactive cell bodies and dystrophic dendrites in aging dogs resembles that in Alzheimer's disease. Author(s): Bi X, Head E, Cotman CW, Lynch G. Source: The Journal of Comparative Neurology. 2003 September 22; 464(3): 371-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900930&dopt=Abstract

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Special care for persons with Alzheimer's disease and related dementias in Virginia adult care residences. Author(s): Cotter JJ, Leon J, Akers AJ, Smith WR. Source: Am J Alzheimers Dis Other Demen. 2003 March-April; 18(2): 105-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708226&dopt=Abstract

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Statistical parametric mapping of (99m)Tc-HMPAO-SPECT images for the diagnosis of Alzheimer's disease: normalizing to cerebellar tracer uptake. Author(s): Soonawala D, Amin T, Ebmeier KP, Steele JD, Dougall NJ, Best J, Migneco O, Nobili F, Scheidhauer K. Source: Neuroimage. 2002 November; 17(3): 1193-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414259&dopt=Abstract

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Statistical parametric mapping of brain SPECT perfusion abnormalities in patients with Alzheimer's disease. Author(s): Lee YC, Liu RS, Liao YC, Sun CM, Wang PS, Wang PN, Liu HC. Source: European Neurology. 2003; 49(3): 142-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646756&dopt=Abstract

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Stereologic analysis of neurofibrillary tangle formation in prefrontal cortex area 9 in aging and Alzheimer's disease. Author(s): Bussiere T, Gold G, Kovari E, Giannakopoulos P, Bouras C, Perl DP, Morrison JH, Hof PR. Source: Neuroscience. 2003; 117(3): 577-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617964&dopt=Abstract

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Structure of the Alzheimer's disease amyloid precursor protein copper binding domain. A regulator of neuronal copper homeostasis. Author(s): Barnham KJ, McKinstry WJ, Multhaup G, Galatis D, Morton CJ, Curtain CC, Williamson NA, White AR, Hinds MG, Norton RS, Beyreuther K, Masters CL, Parker MW, Cappai R. Source: The Journal of Biological Chemistry. 2003 May 9; 278(19): 17401-7. Epub 2003 February 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611883&dopt=Abstract

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Structure versus processing deficits in Alzheimer's disease, a matter of degree: a comment on Storms et al. (2003). Author(s): Hutchison KA, Balota DA. Source: Neuropsychology. 2003 April; 17(2): 306-9; Discussion 323-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803437&dopt=Abstract

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Subicular dendritic arborization in Alzheimer's disease correlates with neurofibrillary tangle density. Author(s): Falke E, Nissanov J, Mitchell TW, Bennett DA, Trojanowski JQ, Arnold SE. Source: American Journal of Pathology. 2003 October; 163(4): 1615-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14507668&dopt=Abstract

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Subjective memory complaints of family members of patients with Alzheimer's disease and depression. Author(s): Heun R, Kockler M, Ptok U. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(2): 78-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784031&dopt=Abstract

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Susceptibility testing for Alzheimer's disease: race for the future. Author(s): Barber M, Whitehouse PJ. Source: Lancet. Neurology. 2002 May; 1(1): 10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849539&dopt=Abstract

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Synaptic plasticity in animal models of early Alzheimer's disease. Author(s): Rowan MJ, Klyubin I, Cullen WK, Anwyl R. Source: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 2003 April 29; 358(1432): 821-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740129&dopt=Abstract

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Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease. Author(s): Holmes C, El-Okl M, Williams AL, Cunningham C, Wilcockson D, Perry VH. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 June; 74(6): 788-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754353&dopt=Abstract

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Taking the thumbs off the multidimensional scales in the debate on semantic memory and Alzheimer's disease: a comment on Storms et al. (2003). Author(s): Milberg W, McGlinchey R. Source: Neuropsychology. 2003 April; 17(2): 312-4; Discussion 323-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803439&dopt=Abstract

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The 4,752 C/T polymorphism in the presenilin 1 gene increases the risk of Alzheimer's disease in apolipoprotein E4 carriers. Author(s): Matsubara-Tsutsui M, Yamagata H, Morishima A, Nakura J, Mitsuda N, Kamino K, Kondo I, Miki T. Source: Intern Med. 2002 October; 41(10): 823-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413003&dopt=Abstract

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The amygdala and Alzheimer's disease: positron emission tomographic study of the cholinergic system. Author(s): Shinotoh H, Fukushi K, Nagatsuka S, Tanaka N, Aotsuka A, Ota T, Namba H, Tanada S, Irie T. Source: Annals of the New York Academy of Sciences. 2003 April; 985: 411-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724174&dopt=Abstract

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The amyloid-beta (Abeta) peptide pattern in cerebrospinal fluid in Alzheimer's disease: evidence of a novel carboxyterminally elongated Abeta peptide. Author(s): Lewczuk P, Esselmann H, Meyer M, Wollscheid V, Neumann M, Otto M, Maler JM, Ruther E, Kornhuber J, Wiltfang J. Source: Rapid Communications in Mass Spectrometry : Rcm. 2003; 17(12): 1291-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811752&dopt=Abstract

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The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. Author(s): Terry AV Jr, Buccafusco JJ. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 September; 306(3): 821-7. Epub 2003 June 12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12805474&dopt=Abstract

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The costs of vascular dementia: a comparison with Alzheimer's disease. Author(s): Fillit H, Hill J. Source: Journal of the Neurological Sciences. 2002 November 15; 203-204: 35-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417354&dopt=Abstract

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The identification and characterization of oxidized RNAs in Alzheimer's disease. Author(s): Shan X, Tashiro H, Lin CL. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 June 15; 23(12): 4913-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832513&dopt=Abstract

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The metallobiology of Alzheimer's disease. Author(s): Bush AI. Source: Trends in Neurosciences. 2003 April; 26(4): 207-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12689772&dopt=Abstract

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The neural basis of intrusions in free recall and cued recall: a PET study in Alzheimer's disease. Author(s): Desgranges B, Baron JC, Giffard B, Chetelat G, Lalevee C, Viader F, de la Sayette V, Eustache F. Source: Neuroimage. 2002 November; 17(3): 1658-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414304&dopt=Abstract

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The neuropsychological profiles of mild Alzheimer's disease and questionable dementia as compared to age-related cognitive decline. Author(s): Vliet EC, Manly J, Tang MX, Marder K, Bell K, Stern Y. Source: Journal of the International Neuropsychological Society : Jins. 2003 July; 9(5): 720-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901778&dopt=Abstract

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The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidence. Author(s): Danysz W, Parsons CG. Source: International Journal of Geriatric Psychiatry. 2003 September; 18(Suppl 1): S2332. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12973747&dopt=Abstract

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The p38 MAP kinase signaling pathway in Alzheimer's disease. Author(s): Johnson GV, Bailey CD. Source: Experimental Neurology. 2003 October; 183(2): 263-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14552867&dopt=Abstract

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The potential of anti-inflammatory drugs for the treatment of Alzheimer's disease. Author(s): Aisen PS. Source: Lancet. Neurology. 2002 September; 1(5): 279-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849425&dopt=Abstract

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The REAL.FR research program on Alzheimer's disease and its management: methods and preliminary results. Author(s): Gillette-Guyonnet S, Nourhashemi F, Andrieu S, Cantet C, Micas M, Ousset PJ, Vellas B; REAL.FR Group. Source: J Nutr Health Aging. 2003; 7(2): 91-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679828&dopt=Abstract

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The reduced release of GH by GHRH in 8 subjects aged 65-69 years is augmented considerably by rivastigmine, a drug for Alzheimer's disease. Author(s): Obermayr RP, Mayerhofer L, Knechtelsdorfer M, Tragl KH, Geyer G. Source: Gerontology. 2003 May-June; 49(3): 191-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679611&dopt=Abstract

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The relationship between Lewy body disease, Parkinson's disease, and Alzheimer's disease. Author(s): Hardy J. Source: Annals of the New York Academy of Sciences. 2003 June; 991: 167-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846985&dopt=Abstract

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The role of 24S-hydroxycholesterol in Alzheimer's disease. Author(s): Kolsch H, Lutjohann D, von Bergmann K, Heun R. Source: J Nutr Health Aging. 2003; 7(1): 37-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679839&dopt=Abstract

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The search for better noncholinergic treatment options for Alzheimer's disease. Author(s): Mintzer JE. Source: The Journal of Clinical Psychiatry. 2003; 64 Suppl 9: 18-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934970&dopt=Abstract

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The temporal localization of frame-shift ubiquitin-B and amyloid precursor protein, and complement proteins in the brain of non-demented control patients with increasing Alzheimer's disease pathology. Author(s): Konishi Y, Beach T, Sue LI, Hampel H, Lindholm K, Shen Y. Source: Neuroscience Letters. 2003 September 4; 348(1): 46-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893422&dopt=Abstract

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The treatment of Alzheimer's disease: success short of cure. Author(s): Rockwood K, Wallack M, Tallis R. Source: Lancet. Neurology. 2003 October; 2(10): 630-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505585&dopt=Abstract

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The use of formic acid to embellish amyloid plaque detection in Alzheimer's disease tissues misguides key observations. Author(s): D'Andrea MR, Reiser PA, Polkovitch DA, Gumula NA, Branchide B, Hertzog BM, Schmidheiser D, Belkowski S, Gastard MC, Andrade-Gordon P. Source: Neuroscience Letters. 2003 May 15; 342(1-2): 114-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727331&dopt=Abstract

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The validity and reliability of 6 sets of clinical criteria to classify Alzheimer's disease and vascular dementia in cases confirmed post-mortem: added value of a decision tree approach. Author(s): Hogervorst E, Bandelow S, Combrinck M, Irani S, Smith AD. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(3): 170-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826744&dopt=Abstract

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The Wnt pathway, cell-cycle activation and beta-amyloid: novel therapeutic strategies in Alzheimer's disease? Author(s): Caricasole A, Copani A, Caruso A, Caraci F, Iacovelli L, Sortino MA, Terstappen GC, Nicoletti F. Source: Trends in Pharmacological Sciences. 2003 May; 24(5): 233-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767722&dopt=Abstract

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Therapeutic strategies for Alzheimer's disease. Author(s): Wolfe MS. Source: Nature Reviews. Drug Discovery. 2002 November; 1(11): 859-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415246&dopt=Abstract

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Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Author(s): Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM. Source: Neuron. 2003 July 31; 39(3): 409-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12895417&dopt=Abstract

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Truncated beta-amyloid peptide species in pre-clinical Alzheimer's disease as new targets for the vaccination approach. Author(s): Sergeant N, Bombois S, Ghestem A, Drobecq H, Kostanjevecki V, Missiaen C, Wattez A, David JP, Vanmechelen E, Sergheraert C, Delacourte A. Source: Journal of Neurochemistry. 2003 June; 85(6): 1581-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787077&dopt=Abstract

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Tumor necrosis factor alpha polymorphism C-850T is not associated with Alzheimer's disease and vascular dementia in an Italian population. Author(s): Terreni L, Fogliarino S, Quadri P, Ruggieri RM, Piccoli F, Tettamanti M, Lucca U, Forloni G. Source: Neuroscience Letters. 2003 June 26; 344(2): 135-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782345&dopt=Abstract

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Two novel presenilin-1 mutations (Y256S and Q222H) are associated with early-onset Alzheimer's disease. Author(s): Miklossy J, Taddei K, Suva D, Verdile G, Fonte J, Fisher C, Gnjec A, Ghika J, Suard F, Mehta PD, McLean CA, Masters CL, Brooks WS, Martins RN. Source: Neurobiology of Aging. 2003 September; 24(5): 655-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885573&dopt=Abstract

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Unaltered brain levels of 1,N2-propanodeoxyguanosine adducts of trans-4-hydroxy-2nonenal in Alzheimer's disease. Author(s): Gotz ME, Wacker M, Luckhaus C, Wanek P, Tatschner T, Jellinger K, Leblhuber F, Ransmayr G, Riederer P, Eder E. Source: Neuroscience Letters. 2002 May 10; 324(1): 49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983292&dopt=Abstract

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Unbiased morphological measurements show no neuronal loss in the substantia nigra in Alzheimer's disease. Author(s): Kemppainen N, Roytta M, Collan Y, Ma SY, Hinkka S, Rinne JO. Source: Acta Neuropathologica. 2002 January; 103(1): 43-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11837746&dopt=Abstract

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Understanding and managing behavioural symptoms in Alzheimer's disease and related dementias: focus on rivastigmine. Author(s): Robert P. Source: Current Medical Research and Opinion. 2002; 18(3): 156-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094826&dopt=Abstract

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Upper and lower face and ideomotor apraxia in patients with Alzheimer's disease. Author(s): Capone JG, Della Sala S, Spinnler H, Venneri A. Source: Behavioural Neurology. 2003; 14(1-2): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719633&dopt=Abstract

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Up-regulation of cell division cycle (cdc) 2 kinase in neurons with early stage Alzheimer's disease neurofibrillary degeneration. Author(s): Pei JJ, Braak H, Gong CX, Grundke-Iqbal I, Iqbal K, Winblad B, Cowburn RF. Source: Acta Neuropathologica. 2002 October; 104(4): 369-76. Epub 2002 May 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200623&dopt=Abstract

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Up-regulation of glycohydrolases in Alzheimer's Disease fibroblasts correlates with Ras activation. Author(s): Emiliani C, Urbanelli L, Racanicchi L, Orlacchio A, Pelicci G, Sorbi S, Bernardi G, Orlacchio A. Source: The Journal of Biological Chemistry. 2003 October 3; 278(40): 38453-60. Epub 2003 July 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878600&dopt=Abstract

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Up-regulation of mitogen-activated protein kinases ERK1/2 and MEK1/2 is associated with the progression of neurofibrillary degeneration in Alzheimer's disease. Author(s): Pei JJ, Braak H, An WL, Winblad B, Cowburn RF, Iqbal K, Grundke-Iqbal I. Source: Brain Research. Molecular Brain Research. 2002 December 30; 109(1-2): 45-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531514&dopt=Abstract

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Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer's disease. Author(s): An WL, Cowburn RF, Li L, Braak H, Alafuzoff I, Iqbal K, Iqbal IG, Winblad B, Pei JJ. Source: American Journal of Pathology. 2003 August; 163(2): 591-607. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875979&dopt=Abstract

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US Alzheimer's disease prevention study under attack. Author(s): Larkin M. Source: Lancet. Neurology. 2002 November; 1(7): 397. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849347&dopt=Abstract

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Use of a false recognition paradigm in an Alzheimer's disease clinical trial: a pilot study. Author(s): Budson AE, Michalska KJ, Rentz DM, Joubert CC, Daffner KR, Schacter DL, Sperling RA. Source: Am J Alzheimers Dis Other Demen. 2002 March-April; 17(2): 93-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954675&dopt=Abstract

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Use of artificial networks in clinical trials: a pilot study to predict responsiveness to donepezil in Alzheimer's disease. Author(s): Mecocci P, Grossi E, Buscema M, Intraligi M, Savare R, Rinaldi P, Cherubini A, Senin U. Source: Journal of the American Geriatrics Society. 2002 November; 50(11): 1857-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410907&dopt=Abstract

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Use of cholinesterase inhibitors in Alzheimer's disease. Author(s): Slawson D. Source: American Family Physician. 2003 May 15; 67(10): 2203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776972&dopt=Abstract

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Use of in vivo models to study the role of cholesterol in the etiology of Alzheimer's disease. Author(s): Burns M, Duff K. Source: Neurochemical Research. 2003 July; 28(7): 979-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737522&dopt=Abstract

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Use of surrogate respondents in a case control study of dietary risk factors for Alzheimer's disease. Author(s): Petot GJ, Debanne SM, Riedel TM, Smyth KA, Koss E, Lerner AJ, Friedland RP. Source: Journal of the American Dietetic Association. 2002 June; 102(6): 848-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067055&dopt=Abstract

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Utility and limits of the mini mental state examination in evaluating consent capacity in Alzheimer's disease. Author(s): Kim SY, Caine ED. Source: Psychiatric Services (Washington, D.C.). 2002 October; 53(10): 1322-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364686&dopt=Abstract

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Utility of olfactory identification test for diagnosing Chinese patients with Alzheimer's disease. Author(s): Chan A, Tam J, Murphy C, Chiu H, Lam L. Source: J Clin Exp Neuropsychol. 2002 April; 24(2): 251-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992207&dopt=Abstract

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Vaccines for Alzheimer's disease: how close are we? Author(s): Janus C. Source: Cns Drugs. 2003; 17(7): 457-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751917&dopt=Abstract

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Value of event-related P300 subcomponents in the clinical diagnosis of mild cognitive impairment and Alzheimer's Disease. Author(s): Frodl T, Hampel H, Juckel G, Burger K, Padberg F, Engel RR, Moller HJ, Hegerl U. Source: Psychophysiology. 2002 March; 39(2): 175-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12212666&dopt=Abstract

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Variation in the DCP1 gene, encoding the angiotensin converting enzyme ACE, is not associated with increased susceptibility to Alzheimer's disease. Author(s): Carbonell J, Allen R, Kalsi G, McQuillin A, Livingston G, Katona C, Walker Z, Katz A, Rands G, Stevens T, Crossan I, Curtis D, Gurling H. Source: Psychiatric Genetics. 2003 March; 13(1): 47-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605101&dopt=Abstract

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Vascular disorder in Alzheimer's disease: role in pathogenesis of dementia and therapeutic targets. Author(s): Zlokovic BV. Source: Advanced Drug Delivery Reviews. 2002 December 7; 54(12): 1553-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453672&dopt=Abstract

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Vascular pathology in Alzheimer's disease. Author(s): Miyakawa T. Source: Annals of the New York Academy of Sciences. 2002 November; 977: 303-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480765&dopt=Abstract

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Very early-onset familial Alzheimer's disease: a novel presenilin 1 mutation. Author(s): Goldman JS, Reed B, Gearhart R, Kramer JH, Miller BL. Source: International Journal of Geriatric Psychiatry. 2002 July; 17(7): 649-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112163&dopt=Abstract

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Vigilance. Evolution and definition for caregivers of family members with Alzheimer's disease. Author(s): Mahoney DF. Source: Journal of Gerontological Nursing. 2003 August; 29(8): 24-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677157&dopt=Abstract

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Visual field loss and Alzheimer's disease. Author(s): Whittaker KW, Burdon MA, Shah P. Source: Eye (London, England). 2002 March; 16(2): 206-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11988830&dopt=Abstract

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Visual identification and spatial location in Alzheimer's disease. Author(s): Stehli Nguyen A, Chubb C, Jacob Huff F. Source: Brain and Cognition. 2003 July; 52(2): 155-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821097&dopt=Abstract

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Visual memory predicts Alzheimer's disease more than a decade before diagnosis. Author(s): Kawas CH, Corrada MM, Brookmeyer R, Morrison A, Resnick SM, Zonderman AB, Arenberg D. Source: Neurology. 2003 April 8; 60(7): 1089-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682311&dopt=Abstract

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Visual object recognition in early Alzheimer's disease: deficits in semantic processing. Author(s): Laatu S, Revonsuo A, Jaykka H, Portin R, Rinne JO. Source: Acta Neurologica Scandinavica. 2003 August; 108(2): 82-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859283&dopt=Abstract

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Visual search in Alzheimer's disease: a deficiency in processing conjunctions of features. Author(s): Tales A, Butler SR, Fossey J, Gilchrist ID, Jones RW, Troscianko T. Source: Neuropsychologia. 2002; 40(12): 1849-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12207983&dopt=Abstract

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Visuospatial impairment in dementia with Lewy bodies and Alzheimer's disease: a process analysis approach. Author(s): Simard M, van Reekum R, Myran D. Source: International Journal of Geriatric Psychiatry. 2003 May; 18(5): 387-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766913&dopt=Abstract

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Volume reduction in cerebral blood flow in patients with Alzheimer's disease: a sonographic study. Author(s): Maalikjy Akkawi N, Borroni B, Agosti C, Pezzini A, Magoni M, Rozzini L, Prometti P, Romanelli G, Vignolo LA, Padovani A. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(3): 163-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826743&dopt=Abstract

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Volumetric MRI measurements can differentiate Alzheimer's disease, mild cognitive impairment, and normal aging. Author(s): Bottino CM, Castro CC, Gomes RL, Buchpiguel CA, Marchetti RL, Neto MR. Source: Int Psychogeriatr. 2002 March; 14(1): 59-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094908&dopt=Abstract

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Volumetric MRI study of the caudate nucleus in patients with dementia with Lewy bodies, Alzheimer's disease, and vascular dementia. Author(s): Barber R, McKeith I, Ballard C, O'Brien J. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 March; 72(3): 406-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11861709&dopt=Abstract

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Voxel-based comparison of rCBF SPET images in frontotemporal dementia and Alzheimer's disease highlights the involvement of different cortical networks. Author(s): Varrone A, Pappata S, Caraco C, Soricelli A, Milan G, Quarantelli M, Alfano B, Postiglione A, Salvatore M. Source: European Journal of Nuclear Medicine and Molecular Imaging. 2002 November; 29(11): 1447-54. Epub 2002 August 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397463&dopt=Abstract

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We'll fight it as long as we can: coping with the onset of Alzheimer's disease. Author(s): Clare L. Source: Aging & Mental Health. 2002 May; 6(2): 139-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028882&dopt=Abstract

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What can our nose tell us about possible treatments for Alzheimer's disease? Author(s): Weiss S. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2003 February; 30(1): 3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619775&dopt=Abstract

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What can rodent models tell us about cognitive decline in Alzheimer's disease? Author(s): Davis S, Laroche S. Source: Molecular Neurobiology. 2003 June; 27(3): 249-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845151&dopt=Abstract

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What do Alzheimer's disease patients know about animals? It depends on task structure and presentation format. Author(s): Rich JB, Park NW, Dopkins S, Brandt J. Source: Journal of the International Neuropsychological Society : Jins. 2002 January; 8(1): 83-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843077&dopt=Abstract

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What evidence would prove the amyloid hypothesis? Towards rational drug treatments for Alzheimer's disease. Author(s): Morgan D, Keller RK. Source: Journal of Alzheimer's Disease : Jad. 2002 June; 4(3): 257-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226546&dopt=Abstract

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When parsimony backfires: neglecting DNA repair may doom neurons in Alzheimer's disease. Author(s): Nouspikel T, Hanawalt PC. Source: Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology. 2003 February; 25(2): 168-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12539243&dopt=Abstract

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White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging. Author(s): Bozzali M, Falini A, Franceschi M, Cercignani M, Zuffi M, Scotti G, Comi G, Filippi M. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 June; 72(6): 742-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12023417&dopt=Abstract

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Why the preeminent risk factor in sporadic Alzheimer's disease cannot be genetic. Author(s): Foster HD. Source: Medical Hypotheses. 2002 July; 59(1): 57-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160681&dopt=Abstract

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Will a healthy lifestyle help prevent Alzheimer's disease? Author(s): Pope SK, Shue VM, Beck C. Source: Annual Review of Public Health. 2003; 24: 111-32. Epub 2001 November 06. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415146&dopt=Abstract

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Wives giving care to husbands with Alzheimer's disease: a process of interpretive caring. Author(s): Perry J. Source: Research in Nursing & Health. 2002 August; 25(4): 307-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124724&dopt=Abstract

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Wives' struggle in living through treatment decisions for husbands with advanced Alzheimer's disease. Author(s): Robinson EM. Source: J Nurs Law. 2000 May; 7(1): 21-39. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12545984&dopt=Abstract

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Working memory and online syntactic processing in Alzheimer's disease: studies with auditory moving window presentation. Author(s): Waters G, Caplan D. Source: The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences. 2002 July; 57(4): P298-311. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084781&dopt=Abstract

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Working memory in mild Alzheimer's disease and early Parkinson's disease. Author(s): Kensinger EA, Shearer DK, Locascio JJ, Growdon JH, Corkin S. Source: Neuropsychology. 2003 April; 17(2): 230-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803428&dopt=Abstract

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Zinc takes the center stage: its paradoxical role in Alzheimer's disease. Author(s): Cuajungco MP, Faget KY. Source: Brain Research. Brain Research Reviews. 2003 January; 41(1): 44-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505647&dopt=Abstract

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CHAPTER 2. NUTRITION AND ALZHEIMER’S DISEASE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Alzheimer’s disease.

Finding Nutrition Studies on Alzheimer’s Disease The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “Alzheimer’s disease” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following is a typical result when searching for recently indexed consumer information on Alzheimer’s disease: •

A 28-week, double-blind, placebo-controlled study with Cerebrolysin in patients with mild to moderate Alzheimer's disease. Author(s): Goettingen University Clinic for Psychiatry, Germany. Source: Ruether, E Husmann, R Kinzler, E Diabl, E Klingler, D Spatt, J Ritter, R Schmidt, R Taneri, Z Winterer, W Koper, D Kasper, S Rainer, M Moessler, H Int-ClinPsychopharmacol. 2001 September; 16(5): 253-63 0268-1315

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A review of epidemiologic studies on aluminum and silica in relation to Alzheimer's disease and associated disorders. Author(s): INSERM U330, Bordeaux. [email protected] Source: Rondeau, V Rev-Environ-Health. 2002 Apr-June; 17(2): 107-21 0048-7554

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A role for estrogen in the primary prevention of Alzheimer's disease. Source: Thomas, T Climacteric. 2001 June; 4(2): 102-9 1369-7137

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Accumulation of calbindin in cortical pyramidal cells with ageing; a putative protective mechanism which fails in Alzheimer's disease. Author(s): Department of Biomedical Science, University of Sheffield, Sheffield, UK. [email protected] Source: Greene, J R Radenahmad, N Wilcock, G K Neal, J W Pearson, R C NeuropatholAppl-Neurobiol. 2001 October; 27(5): 339-42 0305-1846

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Acetylcholinesterase inhibitors for vascular dementia and Alzheimer's disease combined with cerebrovascular disease. Author(s): Department of Neurology, Royal Free Hospital, London, UK. [email protected] Source: Bowler, J V Stroke. 2003 February; 34(2): 584-6 1524-4628

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Actigraphic sleep-wake patterns and urinary 6-sulfatoxymelatonin excretion in patients with Alzheimer's disease. Author(s): Endocrine Institute, Haemek Medical Center, Afula, Israel. Source: Luboshitzky, R Shen Orr, Z Tzischichinsky, O Maldonado, M Herer, P Lavie, P Chronobiol-Int. 2001 May; 18(3): 513-24 0742-0528

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Action-based memory in Alzheimer's disease: a longitudinal look at tea making. Author(s): Laboratory of Experimental Psychology, University of Sussex, Brighton BN1 9QG, UK. [email protected] Source: Rusted, Jennifer Sheppard, Linda Neurocase. 2002; 8(1-2): 111-26 1355-4794

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Activated microglia in Alzheimer's disease and stroke. Author(s): Cell Signalling Laboratory, Institute of Neurology, University College, 1 Wakefield Street, London WC1NPJ, UK. [email protected] Source: Pocock, J M Liddle, A C Hooper, C Taylor, D L Davenport, C M Morgan, S C Ernst-Schering-Res-Found-Workshopage 2002; (39): 105-32 0947-6075

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Advances in Alzheimer's disease. Author(s): Florida Gulf Coast University, Fort Myers, USA. Source: Gray Vickrey, P Nursing. 2002 November; 32(11 Pt 1): 64 0360-4039

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Alzheimer's disease is not associated with altered concentrations of the nitric oxide synthase inhibitor asymmetric dimethylarginine in cerebrospinal fluid. Author(s): Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands, Sweden. Source: Mulder, C Wahlund, L O Blomberg, M de Jong, S van Kamp, G J Scheltens, P Teerlink, T J-Neural-Transm. 2002 September; 109(9): 1203-8 0300-9564

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Cerebrolysin in Alzheimer's disease: a randomized, double-blind, placebo-controlled trial with a neurotrophic agent. Author(s): McGill Centre for Studies in Ageing, Montreal, Quebec, Canada. Source: Panisset, M Gauthier, S Moessler, H Windisch, M J-Neural-Transm. 2002 July; 109(7-8): 1089-104 0300-9564

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Cerebrospinal fluid levels of thiamine in patients with Alzheimer's disease. Author(s): Department of Neurology, Hospital Universitario Doce de Octubre, E-28030 Madrid, Spain. Source: Molina, J A Jimenez Jimenez, F J Hernanz, A Fernandez Vivancos, E Medina, S de Bustos, F Gomez Escalonilla, C Sayed, Y J-Neural-Transm. 2002 July; 109(7-8): 1035-44 0300-9564

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Clinical and cost-effectiveness of donepezil, rivastigmine, and galantamine for Alzheimer's disease. A systematic review. Author(s): University of Southampton. Source: Clegg, A Bryant, J Nicholson, T McIntyre, L De Broe, S Gerard, K Waugh, N IntJ-Technol-Assess-Health-Care. 2002 Summer; 18(3): 497-507 0266-4623

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Contrasting, species-dependent modulation of copper-mediated neurotoxicity by the Alzheimer's disease amyloid precursor protein. Author(s): Department of Pathology, The University of Melbourne, Victoria 3010, Australia. Source: White, Anthony R Multhaup, Gerd Galatis, Denise McKinstry, William J Parker, Michael W Pipkorn, Rudiger Beyreuther, Konrad Masters, Colin L Cappai, Roberto JNeurosci. 2002 January 15; 22(2): 365-76 1529-2401

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Contributions of mitochondrial alterations, resulting from bad genes and a hostile environment, to the pathogenesis of Alzheimer's disease. Author(s): Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [email protected]/gov Source: Mattson, M P Int-Rev-Neurobiol. 2002; 53: 387-409 0074-7742

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Current status and new developments with galantamine in the treatment of Alzheimer's disease. Author(s): Univeristy of Rochester Medical Center, Rochester, NY, USA. Source: Tariot, P Expert-Opin-Pharmacother. 2001 December; 2(12): 2027-49 1465-6566

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D-cycloserine for Alzheimer's disease. Author(s): Department of Geriatric Medicine, Ullevaal Hospital, Kirkevn. 166, Oslo, Norway. [email protected] Source: Laake, K Oeksengaard, A R Cochrane-Database-Syst-Revolume 2002; (2): CD003153 1469-493X

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Development of indole-3-propionic acid (OXIGON) for Alzheimer's disease. Author(s): Minden BioPharmaceuticals, Ltd, Jerusalem, Israel. [email protected] Source: Bendheim, P E Poeggeler, B Neria, E Ziv, V Pappolla, M A Chain, D G J-MolNeurosci. 2002 Aug-October; 19(1-2): 213-7 0895-8696

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Diet-related prevention of Alzheimer's disease: different hypotheses. Source: Nicolas, A S Vellas, B Nestle-Nutr-Workshop-Ser-Clin-Perform-Programme. 2001; (5): 219-27; discussion 228-30 1422-7584

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Differences in the fatty acid composition of the grey and white matter of different regions of the brains of patients with Alzheimer's disease and control subjects. Author(s): Department of Molecular and Cell Biology, University of Aberdeen, Scotland.

162 Alzheimer’s Disease

Source: Skinner, E R Watt, C Besson, J A Best, P V Brain. 1993 June; 116 ( Pt 3): 717-25 0006-8950 •

Do cholinesterase inhibitors have disease-modifying effects in Alzheimer's disease? Author(s): University Hospitals of Geneva, Department of Geriatrics, University of Geneva Medical School, Thonex, Switzerland. [email protected] Source: Giacobini, E CNS-Drugs. 2001; 15(2): 85-91 1172-7047

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Does caffeine intake protect from Alzheimer's disease? Author(s): Dementia Clinics, Hospital of Santa Maria and Laboratory of Neurosciences, Faculty of Medicine of Lisbon, Portugal. Source: Maia, L de Mendonca, A Eur-J-Neurol. 2002 July; 9(4): 377-82 1351-5101

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Dysregulation of cellular calcium homeostasis in Alzheimer's disease: bad genes and bad habits. Author(s): Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, MD 21224, USA. [email protected] Source: Mattson, M P Chan, S L J-Mol-Neurosci. 2001 October; 17(2): 205-24 0895-8696

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Effects of Cerebrolysin on amyloid-beta deposition in a transgenic model of Alzheimer's disease. Author(s): Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA 92093-0624, USA. Source: Rockenstein, E Mallory, M Mante, M Alford, M Windisch, M Moessler, H Masliah, E J-Neural-Transm-Suppl. 2002; (62): 327-36 0303-6995

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Effects of rapid tryptophan depletion on salivary and plasma cortisol in Alzheimer's disease and the healthy elderly. Author(s): Department of Psychological Medicine, Christchurch School of Medicine, University of Otago, New Zealand. Source: Porter, R J Marshall, E F O'Brien, J T J-Psychopharmacol. 2002 Mar; 16(1): 73-8 0269-8811

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Efficacy and safety of nicotine on Alzheimer's disease patients. Author(s): Hospital de Cantoblanco, Consejeria de Sanidad, Carretera de Colmenar km 14.500, Madrid, Madrid, Spain, 28049. [email protected] Source: Lopez Arrieta, J M Rodriguez, J L Sanz, F Cochrane-Database-Syst-Revolume 2001; (2): CD001749 1469-493X

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Efficacy of metrifonate in improving the psychiatric and behavioral disturbances of patients with Alzheimer's disease. Author(s): Reed Neurological Research Center, University of California at Los Angeles, 90095-1769, USA. Source: Cummings, J L Nadel, A Masterman, D Cyrus, P A J-Geriatr-Psychiatry-Neurol. 2001 Summer; 14(2): 101-8 0891-9887

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Estrogen and Alzheimer's disease. Author(s): The Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, Montreal, Quebec, Canada. [email protected] Source: LeBlanc, A Curr-Opin-Investig-Drugs. 2002 May; 3(5): 768-73 1472-4472

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Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. Author(s): Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland 21224, USA.

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Source: Kruman, Inna I Kumaravel, T S Lohani, Althaf Pedersen, Ward A Cutler, Roy G Kruman, Yuri Haughey, Norman Lee, Jaewon Evans, Michele Mattson, Mark P JNeurosci. 2002 Mar 1; 22(5): 1752-62 1529-2401 •

Galantamine for Alzheimer's disease. Author(s): Adult and Geriatric Treatment and Preventative Interventions Branch, National Institute of Mental Health, NIMH, Room 7160, MSC 9635, 6001 Executive Blvd., Bethesda, Maryland 20892-9635, USA. [email protected] Source: Olin, J Schneider, L Cochrane-Database-Syst-Revolume 2001; 1: CD001747 1469493X

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Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. Author(s): Janssen Pharmaceutical Inc., Janssen Research Foundation, Division of Janssen Pharmaceutica Ltd., 1125 Trenton Harbourton Road, Titusville, NJ 08560, USA. [email protected]. Source: Lilienfeld, S CNS-Drug-Revolume 2002 Summer; 8(2): 159-76 1080-563X

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Genetic and environmental risk factors for Alzheimer's disease in Israeli Arabs. Author(s): Department of Neurology, Case Western Reserve University School of Medicine, Cleveland OH 44106, USA. Source: Bowirrat, A Friedland, R P Farrer, L Baldwin, C Korczyn, A J-Mol-Neurosci. 2002 Aug-October; 19(1-2): 239-45 0895-8696

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Implications of the kynurenine pathway and quinolinic acid in Alzheimer's disease. Author(s): Centre for Immunology and Department of Neurology, St Vincent's Hospital and University of New South Wales, Sydney, Australia. [email protected] Source: Guillemin, G J Brew, B J Redox-Repage 2002; 7(4): 199-206 1351-0002

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Increased oxidative stress in Alzheimer's disease as assessed with 4-hydroxynonenal but not malondialdehyde. Author(s): Department of Geriatric Medicine, Queens University of Belfast, Belfast, UK. Source: McGrath, L T McGleenon, B M Brennan, S McColl, D McILroy, S Passmore, A P QJM. 2001 September; 94(9): 485-90 1460-2725

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In-vitro activity of S. lavandulaefolia (Spanish sage) relevant to treatment of Alzheimer's disease. Author(s): Pharmacognosy Research Laboratories, Department of Pharmacy, King's College London, UK. Source: Perry, N S Houghton, P J Sampson, J Theobald, A E Hart, S Lis Balchin, M Hoult, J R Evans, P Jenner, P Milligan, S Perry, E K J-Pharm-Pharmacol. 2001 October; 53(10): 1347-56 0022-3573

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Is vitamin E the magic bullet for the treatment of Alzheimer's disease (AD)? Author(s): Mount Sinai Hospital, Toronto. Source: Woo, K Perspectives. 2000 Spring; 24(1): 7-10 0831-7445

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Lipid peroxidation and advanced glycation end products in the brain in normal aging and in Alzheimer's disease. Author(s): Department of Neurology, Nagoya University School of Medicine, Tsurumai 65, Showa, Nagoya 466-8550, Japan. Source: Dei, R Takeda, A Niwa, H Li, M Nakagomi, Y Watanabe, M Inagaki, T Washimi, Y Yasuda, Y Horie, K Miyata, T Sobue, G Acta-Neuropathol-(Berl). 2002 August; 104(2): 113-22 0001-6322

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Lipid peroxidation in neurodegeneration: new insights into Alzheimer's disease. Author(s): Department of Molecular Cell Biology, Institute for Medical Biochemistry and Molecular Biology, University Hospital Hamburg-Eppendorf, Germany. [email protected] Source: Arlt, S Beisiegel, U Kontush, A Curr-Opin-Lipidol. 2002 June; 13(3): 289-94 09579672

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Locally reduced levels of acidic FGF lead to decreased expression of 28-kda calbindin and contribute to the selective vulnerability of the neurons in the entorhinal cortex in Alzheimer's disease. Author(s): Institute of Neuropathology, Medical School of Hannover, Germany. [email protected] Source: Thorns, V Licastro, F Masliah, E Neuropathology. 2001 September; 21(3): 203-11 0919-6544

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Medical treatment of Alzheimer's disease: past, present, and future. Author(s): Memorial Hospital Alzheimer's Disease and Memory Disorders Center, Pawtucket, RI, USA. [email protected] Source: Ott, B R Med-Health-R-I. 2002 July; 85(7): 210-2 1086-5462

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Medications for the treatment of Alzheimer's disease. Author(s): Donald W. Reynolds Department of Geriatric Medicine, 921 NE 13th Street, VA Medical Center, #11G-Geriatrics, Oklahoma City, OK 73104-5028, USA. Source: Lampley Dallas, V T J-Okla-State-Med-Assoc. 2001 August; 94(8): 347-9 00301876

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Melatonin acts as antioxidant and pro-oxidant in an organotypic slice culture model of Alzheimer's disease. Author(s): Institute of Arctic Biology and Department of Chemistry, University of Alaska Fairbanks, Fairbanks, AK 99775, USA. Source: Clapp Lilly, K L Smith, M A Perry, G Harris, P L Zhu, X Duffy, L K Neuroreport. 2001 May 8; 12(6): 1277-80 0959-4965

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Mitochondrial abnormalities in Alzheimer's disease. Author(s): Institute of Pathology, Department of Neurology, Case Western Reserve University, Cleveland, Ohio 44106, USA. Source: Hirai, K Aliev, G Nunomura, A Fujioka, H Russell, R L Atwood, C S Johnson, A B Kress, Y Vinters, H V Tabaton, M Shimohama, S Cash, A D Siedlak, S L Harris, P L Jones, P K Petersen, R B Perry, G Smith, M A J-Neurosci. 2001 May 1; 21(9): 3017-23 1529-2401

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Nicotinic receptor modulation: advantages for successful Alzheimer's disease therapy. Source:

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No long-term effect of behavioral treatment on psychotropic drug use for agitation in Alzheimer's disease patients. Author(s): Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, USA. Source: Weiner, M F Tractenberg, R E Sano, M Logsdon, R Teri, L Galasko, D Gamst, A Thomas, R Thal, L J J-Geriatr-Psychiatry-Neurol. 2002 Summer; 15(2): 95-8 0891-9887

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Novel excitatory actions of galanin on rat cholinergic basal forebrain neurons: implications for its role in Alzheimer's disease. Author(s): Division of Neurology, Department of Medicine, University of Alberta, 530 Heritage Medical Research Centre, Edmonton, Alberta T6G 2S2, Canada. [email protected] Source: Jhamandas, Jack H Harris, Kim H MacTavish, David Jassar, Balvinder S JNeurophysiol. 2002 February; 87(2): 696-704 0022-3077

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Nutritional factors and Alzheimer's disease. Author(s): Department of Clinical Gerontology and Internal Medicine, University Hospital of Toulouse, France. Source: Reynish, W Andrieu, S Nourhashemi, F Vellas, B J-Gerontol-A-Biol-Sci-Med-Sci. 2001 November; 56(11): M675-80 1079-5006

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Oxidative nerve cell death in Alzheimer's disease and stroke: antioxidants as neuroprotective compounds. Source: Behl, C. Moosmann, B. Biol-Chem. Berlin; New York : W. de Gruyter, c1996-. Mar/April 2002. volume 383 (3/4) page 521-536. 1431-6730

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Pharmacodynamic-tolerability relationships of cholinesterase inhibitors for Alzheimer's disease. Author(s): Research & Development Department, Chiesi Farmaceutici, Parma, Italy. [email protected] Source: Imbimbo, B P CNS-Drugs. 2001; 15(5): 375-90 1172-7047

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Physostigmine for Alzheimer's disease. Author(s): Departamento de Medicina Clinica, Universidade Federal do Ceara, Fortaleza, Ceara, Brazil. [email protected] Source: Coelho, F Birks, J Cochrane-Database-Syst-Revolume 2001; (2): CD001499 1469493X

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Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. Author(s): Department of Neurology, Boston University School of Medicine, MA 021182526, USA. Source: Seshadri, Sudha Beiser, Alexa Selhub, Jacob Jacques, Paul F Rosenberg, Irwin H D'Agostino, Ralph B Wilson, Peter W F Wolf, Philip A N-Engl-J-Med. 2002 February 14; 346(7): 476-83 1533-4406

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Plasma membrane cholesterol controls the cytotoxicity of Alzheimer's disease AbetaP (1-40) and (1-42) peptides. Author(s): Department of Anatomy, Physiology and Genetics, and Institute for Molecular Medicine, Uniformed Services University School of Medicine, USUHS, Bethesda, Maryland 20814, USA. [email protected] Source: Arispe, N Doh, M FASEB-J. 2002 October; 16(12): 1526-36 1530-6860

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Prevention of Alzheimer's disease. Author(s): McGill Centre for Studies in Aging, 6825 Boul. LaSalle, Verdun, Quebec, Canada H4H 1R3. Source: Gauthier, S Ann-Med-Interne-(Paris). 1998 June; 149(4): 228-30 0003-410X

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Prevention of Alzheimer's disease: where we stand. Author(s): Department of Neurology, College of Physicians and Surgeons of Columbia University, 630 W. 168th Street, Box 16, New York, NY 10032, USA. [email protected] Source: Sano, M Curr-Neurol-Neurosci-Repage 2002 September; 2(5): 392-9 1528-4042

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Protein phosphatase 2A methylation: a link between elevated plasma homocysteine and Alzheimer's Disease. Author(s): Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. [email protected] Source: Vafai, Scott B Stock, Jeffry B FEBS-Lett. 2002 May 8; 518(1-3): 1-4 0014-5793

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Proton MR spectroscopic study at 3 Tesla on glutamate/glutamine in Alzheimer's disease. Author(s): BF Research Institute, Inc, National Cardiovascular Center, Suita, Osaka, Japan. Source: Hattori, Noriaki Abe, Kazuo Sakoda, Saburo Sawada, Tohru Neuroreport. 2002 January 21; 13(1): 183-6 0959-4965

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Regulation of the frontocortical sodium pump by Na+ in Alzheimer's disease: difference from the age-matched control but similarity to the rat model. Author(s): Department of Biochemistry, Tartu University, Ravila 19, Tartu, Estonia. Source: Kairane, C Roots, K Uusma, T Bogdanovic, N Karelson, E Koks, S Zilmer, M FEBS-Lett. 2002 Nov 6; 531(2): 241-4 0014-5793

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Relationship of calbindin D28K-immunoreactive cells and neuropathological changes in the hippocampal formation of Alzheimer's disease. Author(s): Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Setagaya, Japan. [email protected] Source: Iritani, S Niizato, K Emson, P C Neuropathology. 2001 September; 21(3): 162-7 0919-6544

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Safety and efficacy of idebenone versus tacrine in patients with Alzheimer's disease: results of a randomized, double-blind, parallel-group multicenter study. Author(s): Wilhelm Griesinger Hospital, Department of Gerontopsychiatry, Retzdorffpromenade 3, 12161 Berlin, Germany. [email protected] Source: Gutzmann, H Kuhl, K P Hadler, D Rapp, M A Pharmacopsychiatry. 2002 January; 35(1): 12-8 0176-3679

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Serum pentosidine as an indicator of Alzheimer's disease. Author(s): Service de Biochimie, Hopital Nord, CHU Saint-Etienne, Saint-Etienne, France. Source: Meli, M Perier, C Ferron, C Parssegny, F Denis, C Gonthier, R Laurent, B Reynaud, E Frey, J Chamson, A J-Alzheimers-Dis. 2002 April; 4(2): 93-6 1387-2877

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Sustained improvement of cognition and global function in patients with moderately severe Alzheimer's disease: a double-blind, placebo-controlled study with the neurotrophic agent Cerebrolysin. Author(s): Gottingen University Clinic for Psychiatry, Gottingen, Federal Republic of Germany. Source: Ruether, E Alvarez, X A Rainer, M Moessler, H J-Neural-Transm-Suppl. 2002; (62): 265-75 0303-6995

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Tacrine-huperzine A hybrids (huprines): a new class of highly potent and selective acetylcholinesterase inhibitors of interest for the treatment of Alzheimer's disease. Author(s): Laboratori de Quimica Farmaceutica, Facultat de Farmacia, Universitat de Barcelona, Av Diagonal 643, E-08028, Barcelona, Spain. [email protected] Source: Camps, P Munoz Torrero, D Mini-Rev-Med-Chem. 2001 July; 1(2): 163-74 13895575

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Tau-mediated cytotoxicity in a pseudohyperphosphorylation model of Alzheimer's disease. Author(s): Department of Neurobiology, University of Osnabruck, 49076 Osnabruck, Germany. Source: Fath, T Eidenmuller, J Brandt, R J-Neurosci. 2002 November 15; 22(22): 9733-41 1529-2401

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The interaction of serum folate and estradiol levels in Alzheimer's disease. Author(s): Oxford Project To Investigate Memory and Ageing, University Department of Pharmacology, Radcliffe Infirmary, Oxford, United Kingdom. [email protected] Source: Hogervorst, E Smith, A D Neuroendocrinol-Lett. 2002 April; 23(2): 155-60 0172780X

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The neuronal calcium sensor protein VILIP-1 is associated with amyloid plaques and extracellular tangles in Alzheimer's disease and promotes cell death and tau phosphorylation in vitro: a link between calcium sensors and Alzheimer's disease? Author(s): Research Institute for Applied Neuroscience, FAN GmbH, Magdeburg, Germany. Source: Schnurra, I Bernstein, H G Riederer, P Braunewell, K H Neurobiol-Dis. 2001 October; 8(5): 900-9 0969-9961

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The role of tau in Alzheimer's disease. Author(s): Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Maloney Building, 3rd Floor, HUP, Philadelphia, PA 19104, USA. [email protected] Source: Trojanowski, John Q Lee, Virginia M Y Med-Clin-North-Am. 2002 May; 86(3): 615-27 0025-7125

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The significance of environmental factors in the etiology of Alzheimer's disease. Author(s): 12 Sir Francis Wyatt Place, Newport News, VA 23606-3660, USA. [email protected] Source: Grant, W B Campbell, A Itzhaki, R F Savory, J J-Alzheimers-Dis. 2002 June; 4(3): 179-89 1387-2877

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The treatment of Alzheimer's disease: the approach from a clinical specialist in the trenches. Author(s): Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA. Source: Hake, A M Semin-Neurol. 2002 March; 22(1): 71-4 0271-8235

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The use of melatonin in Alzheimer's disease. Author(s): Departament of Physiology, Faculty of Medicine, University of Buenos Aires, Argentina. [email protected] Source: Cardinali, D P Brusco, L I Liberczuk, C Furio, A M Neuroendocrinol-Lett. 2002 April; 23 Suppl 1: 20-3 0172-780X

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The utility of muscarinic agonists in the treatment of Alzheimer's disease. Author(s): Department of Pharmacology, College of Pharmacy, The University of Toledo, OH 43606, USA. [email protected] Source: Messer, W S Jr J-Mol-Neurosci. 2002 Aug-October; 19(1-2): 187-93 0895-8696

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Treatment of Alzheimer's disease. New developments. Author(s): Department of Geriatrics, University Hospitals of Geneva, Geneva Medical School, Route de Mon-Idee, CH-1226 Thonex, Geneva.

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Source: Giacobini, E Michel, J P Ann-Med-Interne-(Paris). 1998 June; 149(4): 231-7 0003410X •

What evidence would prove the amyloid hypothesis? Towards rational drug treatments for Alzheimer's disease. Author(s): Department of Pharmacology and Biochemistry, University of South Florida College of Medicine, Tampa FL 33612-4799, USA. [email protected] Source: Morgan, D Keller, R K J-Alzheimers-Dis. 2002 June; 4(3): 257-60 1387-2877

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What's new in Alzheimer's disease? Author(s): The Capstone Group, 3416 E. Winona Street, Phoenix, AZ 85044, USA. [email protected] Source: Long, C O Dougherty, J Home-Healthc-Nurse. 2003 January; 21(1): 8-14; quiz 15 0884-741X

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Your best bets for preventing Alzheimer's disease. Source: Anonymous Harv-Health-Lett. 2002 August; 27(10): 6 1052-1577

The following information is typical of that found when using the “Full IBIDS Database” to search for “Alzheimer’s disease” (or a synonym): •

A 28-week, double-blind, placebo-controlled study with Cerebrolysin in patients with mild to moderate Alzheimer's disease. Author(s): Goettingen University Clinic for Psychiatry, Germany. Source: Ruether, E Husmann, R Kinzler, E Diabl, E Klingler, D Spatt, J Ritter, R Schmidt, R Taneri, Z Winterer, W Koper, D Kasper, S Rainer, M Moessler, H Int-ClinPsychopharmacol. 2001 September; 16(5): 253-63 0268-1315

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A review of epidemiologic studies on aluminum and silica in relation to Alzheimer's disease and associated disorders. Author(s): INSERM U330, Bordeaux. [email protected] Source: Rondeau, V Rev-Environ-Health. 2002 Apr-June; 17(2): 107-21 0048-7554

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A role for estrogen in the primary prevention of Alzheimer's disease. Source: Thomas, T Climacteric. 2001 June; 4(2): 102-9 1369-7137

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Accumulation of calbindin in cortical pyramidal cells with ageing; a putative protective mechanism which fails in Alzheimer's disease. Author(s): Department of Biomedical Science, University of Sheffield, Sheffield, UK. [email protected] Source: Greene, J R Radenahmad, N Wilcock, G K Neal, J W Pearson, R C NeuropatholAppl-Neurobiol. 2001 October; 27(5): 339-42 0305-1846

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Acetylcholinesterase inhibitors for vascular dementia and Alzheimer's disease combined with cerebrovascular disease. Author(s): Department of Neurology, Royal Free Hospital, London, UK. [email protected] Source: Bowler, J V Stroke. 2003 February; 34(2): 584-6 1524-4628

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Actigraphic sleep-wake patterns and urinary 6-sulfatoxymelatonin excretion in patients with Alzheimer's disease. Author(s): Endocrine Institute, Haemek Medical Center, Afula, Israel. Source: Luboshitzky, R Shen Orr, Z Tzischichinsky, O Maldonado, M Herer, P Lavie, P Chronobiol-Int. 2001 May; 18(3): 513-24 0742-0528

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Action-based memory in Alzheimer's disease: a longitudinal look at tea making. Author(s): Laboratory of Experimental Psychology, University of Sussex, Brighton BN1 9QG, UK. [email protected]

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Source: Rusted, Jennifer Sheppard, Linda Neurocase. 2002; 8(1-2): 111-26 1355-4794 •

Activated microglia in Alzheimer's disease and stroke. Author(s): Cell Signalling Laboratory, Institute of Neurology, University College, 1 Wakefield Street, London WC1NPJ, UK. [email protected] Source: Pocock, J M Liddle, A C Hooper, C Taylor, D L Davenport, C M Morgan, S C Ernst-Schering-Res-Found-Workshopage 2002; (39): 105-32 0947-6075

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Advances in Alzheimer's disease. Author(s): Florida Gulf Coast University, Fort Myers, USA. Source: Gray Vickrey, P Nursing. 2002 November; 32(11 Pt 1): 64 0360-4039

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Alzheimer's disease is not associated with altered concentrations of the nitric oxide synthase inhibitor asymmetric dimethylarginine in cerebrospinal fluid. Author(s): Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands, Sweden. Source: Mulder, C Wahlund, L O Blomberg, M de Jong, S van Kamp, G J Scheltens, P Teerlink, T J-Neural-Transm. 2002 September; 109(9): 1203-8 0300-9564

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Cerebrolysin in Alzheimer's disease: a randomized, double-blind, placebo-controlled trial with a neurotrophic agent. Author(s): McGill Centre for Studies in Ageing, Montreal, Quebec, Canada. Source: Panisset, M Gauthier, S Moessler, H Windisch, M J-Neural-Transm. 2002 July; 109(7-8): 1089-104 0300-9564

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Cerebrospinal fluid levels of thiamine in patients with Alzheimer's disease. Author(s): Department of Neurology, Hospital Universitario Doce de Octubre, E-28030 Madrid, Spain. Source: Molina, J A Jimenez Jimenez, F J Hernanz, A Fernandez Vivancos, E Medina, S de Bustos, F Gomez Escalonilla, C Sayed, Y J-Neural-Transm. 2002 July; 109(7-8): 1035-44 0300-9564

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Clinical and cost-effectiveness of donepezil, rivastigmine, and galantamine for Alzheimer's disease. A systematic review. Author(s): University of Southampton. Source: Clegg, A Bryant, J Nicholson, T McIntyre, L De Broe, S Gerard, K Waugh, N IntJ-Technol-Assess-Health-Care. 2002 Summer; 18(3): 497-507 0266-4623

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Contrasting, species-dependent modulation of copper-mediated neurotoxicity by the Alzheimer's disease amyloid precursor protein. Author(s): Department of Pathology, The University of Melbourne, Victoria 3010, Australia. Source: White, Anthony R Multhaup, Gerd Galatis, Denise McKinstry, William J Parker, Michael W Pipkorn, Rudiger Beyreuther, Konrad Masters, Colin L Cappai, Roberto JNeurosci. 2002 January 15; 22(2): 365-76 1529-2401

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Contributions of mitochondrial alterations, resulting from bad genes and a hostile environment, to the pathogenesis of Alzheimer's disease. Author(s): Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [email protected]/gov Source: Mattson, M P Int-Rev-Neurobiol. 2002; 53: 387-409 0074-7742

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Current status and new developments with galantamine in the treatment of Alzheimer's disease. Author(s): Univeristy of Rochester Medical Center, Rochester, NY, USA. Source: Tariot, P Expert-Opin-Pharmacother. 2001 December; 2(12): 2027-49 1465-6566

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D-cycloserine for Alzheimer's disease. Author(s): Department of Geriatric Medicine, Ullevaal Hospital, Kirkevn. 166, Oslo, Norway. [email protected] Source: Laake, K Oeksengaard, A R Cochrane-Database-Syst-Revolume 2002; (2): CD003153 1469-493X

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Development of indole-3-propionic acid (OXIGON) for Alzheimer's disease. Author(s): Minden BioPharmaceuticals, Ltd, Jerusalem, Israel. [email protected] Source: Bendheim, P E Poeggeler, B Neria, E Ziv, V Pappolla, M A Chain, D G J-MolNeurosci. 2002 Aug-October; 19(1-2): 213-7 0895-8696

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Diet-related prevention of Alzheimer's disease: different hypotheses. Source: Nicolas, A S Vellas, B Nestle-Nutr-Workshop-Ser-Clin-Perform-Programme. 2001; (5): 219-27; discussion 228-30 1422-7584

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Differences in the fatty acid composition of the grey and white matter of different regions of the brains of patients with Alzheimer's disease and control subjects. Author(s): Department of Molecular and Cell Biology, University of Aberdeen, Scotland. Source: Skinner, E R Watt, C Besson, J A Best, P V Brain. 1993 June; 116 ( Pt 3): 717-25 0006-8950

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Do cholinesterase inhibitors have disease-modifying effects in Alzheimer's disease? Author(s): University Hospitals of Geneva, Department of Geriatrics, University of Geneva Medical School, Thonex, Switzerland. [email protected] Source: Giacobini, E CNS-Drugs. 2001; 15(2): 85-91 1172-7047

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Does caffeine intake protect from Alzheimer's disease? Author(s): Dementia Clinics, Hospital of Santa Maria and Laboratory of Neurosciences, Faculty of Medicine of Lisbon, Portugal. Source: Maia, L de Mendonca, A Eur-J-Neurol. 2002 July; 9(4): 377-82 1351-5101

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Dysregulation of cellular calcium homeostasis in Alzheimer's disease: bad genes and bad habits. Author(s): Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, MD 21224, USA. [email protected] Source: Mattson, M P Chan, S L J-Mol-Neurosci. 2001 October; 17(2): 205-24 0895-8696

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Effects of Cerebrolysin on amyloid-beta deposition in a transgenic model of Alzheimer's disease. Author(s): Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA 92093-0624, USA. Source: Rockenstein, E Mallory, M Mante, M Alford, M Windisch, M Moessler, H Masliah, E J-Neural-Transm-Suppl. 2002; (62): 327-36 0303-6995

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Effects of rapid tryptophan depletion on salivary and plasma cortisol in Alzheimer's disease and the healthy elderly. Author(s): Department of Psychological Medicine, Christchurch School of Medicine, University of Otago, New Zealand. Source: Porter, R J Marshall, E F O'Brien, J T J-Psychopharmacol. 2002 Mar; 16(1): 73-8 0269-8811

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Efficacy and safety of nicotine on Alzheimer's disease patients. Author(s): Hospital de Cantoblanco, Consejeria de Sanidad, Carretera de Colmenar km 14.500, Madrid, Madrid, Spain, 28049. [email protected] Source: Lopez Arrieta, J M Rodriguez, J L Sanz, F Cochrane-Database-Syst-Revolume 2001; (2): CD001749 1469-493X

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Efficacy of metrifonate in improving the psychiatric and behavioral disturbances of patients with Alzheimer's disease. Author(s): Reed Neurological Research Center, University of California at Los Angeles, 90095-1769, USA. Source: Cummings, J L Nadel, A Masterman, D Cyrus, P A J-Geriatr-Psychiatry-Neurol. 2001 Summer; 14(2): 101-8 0891-9887

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Estrogen and Alzheimer's disease. Author(s): The Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, Montreal, Quebec, Canada. [email protected] Source: LeBlanc, A Curr-Opin-Investig-Drugs. 2002 May; 3(5): 768-73 1472-4472

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Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. Author(s): Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland 21224, USA. Source: Kruman, Inna I Kumaravel, T S Lohani, Althaf Pedersen, Ward A Cutler, Roy G Kruman, Yuri Haughey, Norman Lee, Jaewon Evans, Michele Mattson, Mark P JNeurosci. 2002 Mar 1; 22(5): 1752-62 1529-2401

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Galantamine for Alzheimer's disease. Author(s): Adult and Geriatric Treatment and Preventative Interventions Branch, National Institute of Mental Health, NIMH, Room 7160, MSC 9635, 6001 Executive Blvd., Bethesda, Maryland 20892-9635, USA. [email protected] Source: Olin, J Schneider, L Cochrane-Database-Syst-Revolume 2001; 1: CD001747 1469493X

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Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. Author(s): Janssen Pharmaceutical Inc., Janssen Research Foundation, Division of Janssen Pharmaceutica Ltd., 1125 Trenton Harbourton Road, Titusville, NJ 08560, USA. [email protected]. Source: Lilienfeld, S CNS-Drug-Revolume 2002 Summer; 8(2): 159-76 1080-563X

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Genetic and environmental risk factors for Alzheimer's disease in Israeli Arabs. Author(s): Department of Neurology, Case Western Reserve University School of Medicine, Cleveland OH 44106, USA. Source: Bowirrat, A Friedland, R P Farrer, L Baldwin, C Korczyn, A J-Mol-Neurosci. 2002 Aug-October; 19(1-2): 239-45 0895-8696

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Implications of the kynurenine pathway and quinolinic acid in Alzheimer's disease. Author(s): Centre for Immunology and Department of Neurology, St Vincent's Hospital and University of New South Wales, Sydney, Australia. [email protected] Source: Guillemin, G J Brew, B J Redox-Repage 2002; 7(4): 199-206 1351-0002

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Increased oxidative stress in Alzheimer's disease as assessed with 4-hydroxynonenal but not malondialdehyde. Author(s): Department of Geriatric Medicine, Queens University of Belfast, Belfast, UK. Source: McGrath, L T McGleenon, B M Brennan, S McColl, D McILroy, S Passmore, A P QJM. 2001 September; 94(9): 485-90 1460-2725

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In-vitro activity of S. lavandulaefolia (Spanish sage) relevant to treatment of Alzheimer's disease. Author(s): Pharmacognosy Research Laboratories, Department of Pharmacy, King's College London, UK.

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Source: Perry, N S Houghton, P J Sampson, J Theobald, A E Hart, S Lis Balchin, M Hoult, J R Evans, P Jenner, P Milligan, S Perry, E K J-Pharm-Pharmacol. 2001 October; 53(10): 1347-56 0022-3573 •

Is vitamin E the magic bullet for the treatment of Alzheimer's disease (AD)? Author(s): Mount Sinai Hospital, Toronto. Source: Woo, K Perspectives. 2000 Spring; 24(1): 7-10 0831-7445

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Lipid peroxidation and advanced glycation end products in the brain in normal aging and in Alzheimer's disease. Author(s): Department of Neurology, Nagoya University School of Medicine, Tsurumai 65, Showa, Nagoya 466-8550, Japan. Source: Dei, R Takeda, A Niwa, H Li, M Nakagomi, Y Watanabe, M Inagaki, T Washimi, Y Yasuda, Y Horie, K Miyata, T Sobue, G Acta-Neuropathol-(Berl). 2002 August; 104(2): 113-22 0001-6322

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Lipid peroxidation in neurodegeneration: new insights into Alzheimer's disease. Author(s): Department of Molecular Cell Biology, Institute for Medical Biochemistry and Molecular Biology, University Hospital Hamburg-Eppendorf, Germany. [email protected] Source: Arlt, S Beisiegel, U Kontush, A Curr-Opin-Lipidol. 2002 June; 13(3): 289-94 09579672

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Locally reduced levels of acidic FGF lead to decreased expression of 28-kda calbindin and contribute to the selective vulnerability of the neurons in the entorhinal cortex in Alzheimer's disease. Author(s): Institute of Neuropathology, Medical School of Hannover, Germany. [email protected] Source: Thorns, V Licastro, F Masliah, E Neuropathology. 2001 September; 21(3): 203-11 0919-6544

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Medical treatment of Alzheimer's disease: past, present, and future. Author(s): Memorial Hospital Alzheimer's Disease and Memory Disorders Center, Pawtucket, RI, USA. [email protected] Source: Ott, B R Med-Health-R-I. 2002 July; 85(7): 210-2 1086-5462

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Medications for the treatment of Alzheimer's disease. Author(s): Donald W. Reynolds Department of Geriatric Medicine, 921 NE 13th Street, VA Medical Center, #11G-Geriatrics, Oklahoma City, OK 73104-5028, USA. Source: Lampley Dallas, V T J-Okla-State-Med-Assoc. 2001 August; 94(8): 347-9 00301876

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Melatonin acts as antioxidant and pro-oxidant in an organotypic slice culture model of Alzheimer's disease. Author(s): Institute of Arctic Biology and Department of Chemistry, University of Alaska Fairbanks, Fairbanks, AK 99775, USA. Source: Clapp Lilly, K L Smith, M A Perry, G Harris, P L Zhu, X Duffy, L K Neuroreport. 2001 May 8; 12(6): 1277-80 0959-4965

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Mitochondrial abnormalities in Alzheimer's disease. Author(s): Institute of Pathology, Department of Neurology, Case Western Reserve University, Cleveland, Ohio 44106, USA. Source: Hirai, K Aliev, G Nunomura, A Fujioka, H Russell, R L Atwood, C S Johnson, A B Kress, Y Vinters, H V Tabaton, M Shimohama, S Cash, A D Siedlak, S L Harris, P L Jones, P K Petersen, R B Perry, G Smith, M A J-Neurosci. 2001 May 1; 21(9): 3017-23 1529-2401

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Nicotinic receptor modulation: advantages for successful Alzheimer's disease therapy. Source:

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No long-term effect of behavioral treatment on psychotropic drug use for agitation in Alzheimer's disease patients. Author(s): Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, USA. Source: Weiner, M F Tractenberg, R E Sano, M Logsdon, R Teri, L Galasko, D Gamst, A Thomas, R Thal, L J J-Geriatr-Psychiatry-Neurol. 2002 Summer; 15(2): 95-8 0891-9887

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Novel excitatory actions of galanin on rat cholinergic basal forebrain neurons: implications for its role in Alzheimer's disease. Author(s): Division of Neurology, Department of Medicine, University of Alberta, 530 Heritage Medical Research Centre, Edmonton, Alberta T6G 2S2, Canada. [email protected] Source: Jhamandas, Jack H Harris, Kim H MacTavish, David Jassar, Balvinder S JNeurophysiol. 2002 February; 87(2): 696-704 0022-3077

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Nutritional factors and Alzheimer's disease. Author(s): Department of Clinical Gerontology and Internal Medicine, University Hospital of Toulouse, France. Source: Reynish, W Andrieu, S Nourhashemi, F Vellas, B J-Gerontol-A-Biol-Sci-Med-Sci. 2001 November; 56(11): M675-80 1079-5006

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Oxidative nerve cell death in Alzheimer's disease and stroke: antioxidants as neuroprotective compounds. Source: Behl, C. Moosmann, B. Biol-Chem. Berlin; New York : W. de Gruyter, c1996-. Mar/April 2002. volume 383 (3/4) page 521-536. 1431-6730

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Pharmacodynamic-tolerability relationships of cholinesterase inhibitors for Alzheimer's disease. Author(s): Research & Development Department, Chiesi Farmaceutici, Parma, Italy. [email protected] Source: Imbimbo, B P CNS-Drugs. 2001; 15(5): 375-90 1172-7047

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Physostigmine for Alzheimer's disease. Author(s): Departamento de Medicina Clinica, Universidade Federal do Ceara, Fortaleza, Ceara, Brazil. [email protected] Source: Coelho, F Birks, J Cochrane-Database-Syst-Revolume 2001; (2): CD001499 1469493X

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Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. Author(s): Department of Neurology, Boston University School of Medicine, MA 021182526, USA. Source: Seshadri, Sudha Beiser, Alexa Selhub, Jacob Jacques, Paul F Rosenberg, Irwin H D'Agostino, Ralph B Wilson, Peter W F Wolf, Philip A N-Engl-J-Med. 2002 February 14; 346(7): 476-83 1533-4406

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Plasma membrane cholesterol controls the cytotoxicity of Alzheimer's disease AbetaP (1-40) and (1-42) peptides. Author(s): Department of Anatomy, Physiology and Genetics, and Institute for Molecular Medicine, Uniformed Services University School of Medicine, USUHS, Bethesda, Maryland 20814, USA. [email protected] Source: Arispe, N Doh, M FASEB-J. 2002 October; 16(12): 1526-36 1530-6860

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Prevention of Alzheimer's disease. Author(s): McGill Centre for Studies in Aging, 6825 Boul. LaSalle, Verdun, Quebec, Canada H4H 1R3. Source: Gauthier, S Ann-Med-Interne-(Paris). 1998 June; 149(4): 228-30 0003-410X

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Protein phosphatase 2A methylation: a link between elevated plasma homocysteine and Alzheimer's Disease. Author(s): Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. [email protected] Source: Vafai, Scott B Stock, Jeffry B FEBS-Lett. 2002 May 8; 518(1-3): 1-4 0014-5793

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Proton MR spectroscopic study at 3 Tesla on glutamate/glutamine in Alzheimer's disease. Author(s): BF Research Institute, Inc, National Cardiovascular Center, Suita, Osaka, Japan. Source: Hattori, Noriaki Abe, Kazuo Sakoda, Saburo Sawada, Tohru Neuroreport. 2002 January 21; 13(1): 183-6 0959-4965

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Regulation of the frontocortical sodium pump by Na+ in Alzheimer's disease: difference from the age-matched control but similarity to the rat model. Author(s): Department of Biochemistry, Tartu University, Ravila 19, Tartu, Estonia. Source: Kairane, C Roots, K Uusma, T Bogdanovic, N Karelson, E Koks, S Zilmer, M FEBS-Lett. 2002 Nov 6; 531(2): 241-4 0014-5793

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Relationship of calbindin D28K-immunoreactive cells and neuropathological changes in the hippocampal formation of Alzheimer's disease. Author(s): Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Setagaya, Japan. [email protected] Source: Iritani, S Niizato, K Emson, P C Neuropathology. 2001 September; 21(3): 162-7 0919-6544

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Safety and efficacy of idebenone versus tacrine in patients with Alzheimer's disease: results of a randomized, double-blind, parallel-group multicenter study. Author(s): Wilhelm Griesinger Hospital, Department of Gerontopsychiatry, Retzdorffpromenade 3, 12161 Berlin, Germany. [email protected] Source: Gutzmann, H Kuhl, K P Hadler, D Rapp, M A Pharmacopsychiatry. 2002 January; 35(1): 12-8 0176-3679

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Serum pentosidine as an indicator of Alzheimer's disease. Author(s): Service de Biochimie, Hopital Nord, CHU Saint-Etienne, Saint-Etienne, France. Source: Meli, M Perier, C Ferron, C Parssegny, F Denis, C Gonthier, R Laurent, B Reynaud, E Frey, J Chamson, A J-Alzheimers-Dis. 2002 April; 4(2): 93-6 1387-2877

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Sustained improvement of cognition and global function in patients with moderately severe Alzheimer's disease: a double-blind, placebo-controlled study with the neurotrophic agent Cerebrolysin. Author(s): Gottingen University Clinic for Psychiatry, Gottingen, Federal Republic of Germany. Source: Ruether, E Alvarez, X A Rainer, M Moessler, H J-Neural-Transm-Suppl. 2002; (62): 265-75 0303-6995

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Tacrine-huperzine A hybrids (huprines): a new class of highly potent and selective acetylcholinesterase inhibitors of interest for the treatment of Alzheimer's disease. Author(s): Laboratori de Quimica Farmaceutica, Facultat de Farmacia, Universitat de Barcelona, Av Diagonal 643, E-08028, Barcelona, Spain. [email protected]

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Source: Camps, P Munoz Torrero, D Mini-Rev-Med-Chem. 2001 July; 1(2): 163-74 13895575 •

Tau-mediated cytotoxicity in a pseudohyperphosphorylation model of Alzheimer's disease. Author(s): Department of Neurobiology, University of Osnabruck, 49076 Osnabruck, Germany. Source: Fath, T Eidenmuller, J Brandt, R J-Neurosci. 2002 November 15; 22(22): 9733-41 1529-2401

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The interaction of serum folate and estradiol levels in Alzheimer's disease. Author(s): Oxford Project To Investigate Memory and Ageing, University Department of Pharmacology, Radcliffe Infirmary, Oxford, United Kingdom. [email protected] Source: Hogervorst, E Smith, A D Neuroendocrinol-Lett. 2002 April; 23(2): 155-60 0172780X

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The neuronal calcium sensor protein VILIP-1 is associated with amyloid plaques and extracellular tangles in Alzheimer's disease and promotes cell death and tau phosphorylation in vitro: a link between calcium sensors and Alzheimer's disease? Author(s): Research Institute for Applied Neuroscience, FAN GmbH, Magdeburg, Germany. Source: Schnurra, I Bernstein, H G Riederer, P Braunewell, K H Neurobiol-Dis. 2001 October; 8(5): 900-9 0969-9961

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The role of tau in Alzheimer's disease. Author(s): Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Maloney Building, 3rd Floor, HUP, Philadelphia, PA 19104, USA. [email protected] Source: Trojanowski, John Q Lee, Virginia M Y Med-Clin-North-Am. 2002 May; 86(3): 615-27 0025-7125

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The significance of environmental factors in the etiology of Alzheimer's disease. Author(s): 12 Sir Francis Wyatt Place, Newport News, VA 23606-3660, USA. [email protected] Source: Grant, W B Campbell, A Itzhaki, R F Savory, J J-Alzheimers-Dis. 2002 June; 4(3): 179-89 1387-2877

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The treatment of Alzheimer's disease: the approach from a clinical specialist in the trenches. Author(s): Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA. Source: Hake, A M Semin-Neurol. 2002 March; 22(1): 71-4 0271-8235

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The use of melatonin in Alzheimer's disease. Author(s): Departament of Physiology, Faculty of Medicine, University of Buenos Aires, Argentina. [email protected] Source: Cardinali, D P Brusco, L I Liberczuk, C Furio, A M Neuroendocrinol-Lett. 2002 April; 23 Suppl 1: 20-3 0172-780X

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The utility of muscarinic agonists in the treatment of Alzheimer's disease. Author(s): Department of Pharmacology, College of Pharmacy, The University of Toledo, OH 43606, USA. [email protected] Source: Messer, W S Jr J-Mol-Neurosci. 2002 Aug-October; 19(1-2): 187-93 0895-8696

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Treatment of Alzheimer's disease. New developments. Author(s): Department of Geriatrics, University Hospitals of Geneva, Geneva Medical School, Route de Mon-Idee, CH-1226 Thonex, Geneva. Source: Giacobini, E Michel, J P Ann-Med-Interne-(Paris). 1998 June; 149(4): 231-7 0003410X

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What evidence would prove the amyloid hypothesis? Towards rational drug treatments for Alzheimer's disease. Author(s): Department of Pharmacology and Biochemistry, University of South Florida College of Medicine, Tampa FL 33612-4799, USA. [email protected] Source: Morgan, D Keller, R K J-Alzheimers-Dis. 2002 June; 4(3): 257-60 1387-2877

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What's new in Alzheimer's disease? Author(s): The Capstone Group, 3416 E. Winona Street, Phoenix, AZ 85044, USA. [email protected] Source: Long, C O Dougherty, J Home-Healthc-Nurse. 2003 January; 21(1): 8-14; quiz 15 0884-741X

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Your best bets for preventing Alzheimer's disease. Source: Anonymous Harv-Health-Lett. 2002 August; 27(10): 6 1052-1577

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to Alzheimer’s disease; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Folic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,887,00.html Vitamin B Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10067,00.html Vitamin B Complex Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,962,00.html Vitamin B1 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B1 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B12 Source: Healthnotes, Inc.; www.healthnotes.com

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Vitamin B12 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B6 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Alternative names: Alpha-Tocopherol, Beta-Tocopherol, D-Alpha-Tocopherol, Delta-Tocopherol, Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Source: Prima Communications, Inc.www.personalhealthzone.com •

Minerals Acetyl-l-carnitine Source: Healthnotes, Inc.; www.healthnotes.com Alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Beta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Carnitine Source: Prima Communications, Inc.www.personalhealthzone.com Carnitine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10012,00.html Carnitine (l-carnitine) Source: Integrative Medicine Communications; www.drkoop.com D-alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Delta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Gamma-tocopherol Source: Integrative Medicine Communications; www.drkoop.com

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Iron Source: Healthnotes, Inc.; www.healthnotes.com L-carnitine Source: Integrative Medicine Communications; www.drkoop.com Lecithin/phosphatidylcholine/choline Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Prima Communications, Inc.www.personalhealthzone.com Vinpocetine Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com •

Food and Diet American Cheese Source: Healthnotes, Inc.; www.healthnotes.com Chocolate Source: Healthnotes, Inc.; www.healthnotes.com Water Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND ALZHEIMER’S DISEASE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Alzheimer’s disease. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to Alzheimer’s disease and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “Alzheimer’s disease” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to Alzheimer’s disease: •

A novel treatment for patients with Alzheimer's disease and with vascular dementia. Author(s): Kurz A. Source: Annals of the New York Academy of Sciences. 2002 November; 977: 476-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480788&dopt=Abstract

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A novel trivalent cation chelator Feralex dissociates binding of aluminum and iron associated with hyperphosphorylated tau of Alzheimer's disease. Author(s): Shin RW, Kruck TP, Murayama H, Kitamoto T. Source: Brain Research. 2003 January 24; 961(1): 139-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535786&dopt=Abstract

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A psychoeducational model for Hispanic Alzheimer's disease caregivers. Author(s): Morano CL, Bravo M. Source: The Gerontologist. 2002 February; 42(1): 122-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815707&dopt=Abstract

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A single-photon emission computed tomography imaging study of driving impairment in patients with Alzheimer's disease. Author(s): Ott BR, Heindel WC, Whelihan WM, Caron MD, Piatt AL, Noto RB. Source: Dementia and Geriatric Cognitive Disorders. 2000 May-June; 11(3): 153-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10765046&dopt=Abstract

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A study on the rehabilitation of cognitive function and short-term memory in patients with Alzheimer's disease using transcutaneous electrical nerve stimulation. Author(s): Guo Y, Shi X, Uchiyama H, Hasegawa A, Nakagawa Y, Tanaka M, Fukumoto I. Source: Frontiers of Medical and Biological Engineering : the International Journal of the Japan Society of Medical Electronics and Biological Engineering. 2002; 11(4): 237-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735425&dopt=Abstract

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Acute nicotine effects on auditory sensory memory in tacrine-treated and nontreated patients with Alzheimer's disease: an event-related potential study. Author(s): Engeland C, Mahoney C, Mohr E, Ilivitsky V, Knott VJ. Source: Pharmacology, Biochemistry, and Behavior. 2002 May; 72(1-2): 457-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900820&dopt=Abstract

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Advances in Alzheimer's disease. Author(s): Gray-Vickrey P. Source: Nursing. 2002 November; 32(11 Pt 1): 64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441861&dopt=Abstract

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An event-related potential examination of masked and unmasked repetition priming in Alzheimer's disease: implications for theories of implicit memory. Author(s): Schnyer DM, Allen JJ, Kaszniak AW, Forster KI. Source: Neuropsychology. 1999 July; 13(3): 323-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10447295&dopt=Abstract

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Animal-assisted therapy and Nutrition in Alzheimer's disease. Author(s): Edwards NE, Beck AM. Source: Western Journal of Nursing Research. 2002 October; 24(6): 697-712. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12365769&dopt=Abstract

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Antioxidant strategies for Alzheimer's disease. Author(s): Grundman M, Grundman M, Delaney P.

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Source: The Proceedings of the Nutrition Society. 2002 May; 61(2): 191-202. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133201&dopt=Abstract •

APP transgenic mice Tg2576 accumulate Abeta peptides that are distinct from the chemically modified and insoluble peptides deposited in Alzheimer's disease senile plaques. Author(s): Kalback W, Watson MD, Kokjohn TA, Kuo YM, Weiss N, Luehrs DC, Lopez J, Brune D, Sisodia SS, Staufenbiel M, Emmerling M, Roher AE. Source: Biochemistry. 2002 January 22; 41(3): 922-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11790115&dopt=Abstract

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Association of Alzheimer's disease onset with ginkgo biloba and other symptomatic cognitive treatments in a population of women aged 75 years and older from the EPIDOS study. Author(s): Andrieu S, Gillette S, Amouyal K, Nourhashemi F, Reynish E, Ousset PJ, Albarede JL, Vellas B, Grandjean H; EPIDOS study. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 April; 58(4): 372-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663701&dopt=Abstract

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Beta-amyloid plaques induce neuritic dystrophy of nitric oxide-producing neurons in a transgenic mouse model of Alzheimer's disease. Author(s): Quinn J, Davis F, Woodward WR, Eckenstein F. Source: Experimental Neurology. 2001 April; 168(2): 203-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11259108&dopt=Abstract

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Brain metabolic and clinical effects of rivastigmine in Alzheimer's disease. Author(s): Potkin SG, Anand R, Fleming K, Alva G, Keator D, Carreon D, Messina J, Wu JC, Hartman R, Fallon JH. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2001 September; 4(3): 223-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11602028&dopt=Abstract

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Brain metabolic effects of Neotrofin in patients with Alzheimer's disease. Author(s): Potkin SG, Alva G, Keator D, Carreon D, Fleming K, Fallon JH. Source: Brain Research. 2002 September 27; 951(1): 87-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12231461&dopt=Abstract

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Brain perfusion in Alzheimer's disease with and without apathy: a SPECT study with statistical parametric mapping analysis. Author(s): Benoit M, Koulibaly PM, Migneco O, Darcourt J, Pringuey DJ, Robert PH.

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Source: Psychiatry Research. 2002 June 15; 114(2): 103-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036510&dopt=Abstract •

Brain regional quantification of F-ring and D-/E-ring isoprostanes and neuroprostanes in Alzheimer's disease. Author(s): Reich EE, Markesbery WR, Roberts LJ 2nd, Swift LL, Morrow JD, Montine TJ. Source: American Journal of Pathology. 2001 January; 158(1): 293-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11141503&dopt=Abstract

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Broad therapeutic benefits in patients with probable vascular dementia or Alzheimer's disease with cerebrovascular disease treated with galantamine. Author(s): Lilienfeld S, Kurz A. Source: Annals of the New York Academy of Sciences. 2002 November; 977: 487-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480790&dopt=Abstract

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Cerebral blood flow and cognitive responses to rivastigmine treatment in Alzheimer's disease. Author(s): Vennerica A, Shanks MF, Staff RT, Pestell SJ, Forbes KE, Gemmell HG, Murray AD. Source: Neuroreport. 2002 January 21; 13(1): 83-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11924899&dopt=Abstract

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Cerebral blood flow and metabolic abnormalities in Alzheimer's disease. Author(s): Matsuda H. Source: Ann Nucl Med. 2001 April; 15(2): 85-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448080&dopt=Abstract

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Cerebral metabolic response to passive audiovisual stimulation in patients with Alzheimer's disease and healthy volunteers assessed by PET. Author(s): Pietrini P, Alexander GE, Furey ML, Dani A, Mentis MJ, Horwitz B, Guazzelli M, Shapiro MB, Rapoport SI. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2000 April; 41(4): 575-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10768555&dopt=Abstract

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Changes in the rCBF images of patients with Alzheimer's disease receiving Donepezil therapy. Author(s): Staff RT, Gemmell HG, Shanks MF, Murray AD, Venneri A. Source: Nuclear Medicine Communications. 2000 January; 21(1): 37-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10717900&dopt=Abstract

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Clinical Value of Neuroimaging in the Diagnosis of Dementia. Sensitivity and Specificity of Regional Cerebral Metabolic and Other Parameters for Early

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Identification of Alzheimer's Disease. Author(s): Silverman DH, Small GW, Phelps ME. Source: Clinical Positron Imaging : Official Journal of the Institute for Clinical P.E.T. 1999 May; 2(3): 119-130. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516535&dopt=Abstract •

Coma in a patient with Alzheimer's disease taking low dose trazodone and gingko biloba. Author(s): Galluzzi S, Zanetti O, Binetti G, Trabucchi M, Frisoni GB. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2000 May; 68(5): 679-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10836866&dopt=Abstract

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Combination of serum markers related to several mechanisms in Alzheimer's disease. Author(s): Teunissen CE, Lutjohann D, von Bergmann K, Verhey F, Vreeling F, Wauters A, Bosmans E, Bosma H, van Boxtel MP, Maes M, Delanghe J, Blom HJ, Verbeek MM, Rieckmann P, De Bruijn C, Steinbusch HW, de Vente J. Source: Neurobiology of Aging. 2003 November; 24(7): 893-902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928047&dopt=Abstract

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Cortical and leptomeningeal cerebrovascular amyloid and white matter pathology in Alzheimer's disease. Author(s): Roher AE, Kuo YM, Esh C, Knebel C, Weiss N, Kalback W, Luehrs DC, Childress JL, Beach TG, Weller RO, Kokjohn TA. Source: Molecular Medicine (Cambridge, Mass.). 2003 March-April; 9(3-4): 112-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865947&dopt=Abstract

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Cranial electrostimulation (CES) in patients with probable Alzheimer's disease. Author(s): Scherder EJ, Deijen JB, Vreeswijk SH, Sergeant JA, Swaab DF. Source: Behavioural Brain Research. 2002 January 22; 128(2): 215-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796166&dopt=Abstract

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Current status of metals as therapeutic targets in Alzheimer's disease. Author(s): Finefrock AE, Bush AI, Doraiswamy PM. Source: Journal of the American Geriatrics Society. 2003 August; 51(8): 1143-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890080&dopt=Abstract

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Deficit in sensory motor processing in depression and Alzheimer's disease: a study with EMG and event related potentials. Author(s): Ortiz Alonso T, Lopez-Ibor MI, Martinez Castillo E, Fernandez Lucas A, Maestu Unturbe F, Lopez-Ibor JJ. Source: Electromyogr Clin Neurophysiol. 2000 September; 40(6): 357-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11039120&dopt=Abstract

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Dietary lipids in the aetiology of Alzheimer's disease: implications for therapy. Author(s): Cooper JL. Source: Drugs & Aging. 2003; 20(6): 399-418. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710861&dopt=Abstract

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Differentiating frontal and temporal variant frontotemporal dementia from Alzheimer's disease. Author(s): Perry RJ, Hodges JR. Source: Neurology. 2000 June 27; 54(12): 2277-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10881252&dopt=Abstract

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Diminished neuronal metabolic activity in Alzheimer's disease. Review article. Author(s): Salehi A, Swaab DF. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 1999; 106(9-10): 955-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599878&dopt=Abstract

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Discovery of natural products from Curcuma longa that protect cells from betaamyloid insult: a drug discovery effort against Alzheimer's disease. Author(s): Park SY, Kim DS. Source: Journal of Natural Products. 2002 September; 65(9): 1227-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12350137&dopt=Abstract

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Discussion of the role of the extracellular signal-regulated kinase-phospholipase A2 pathway in production of reactive oxygen species in Alzheimer's disease. Author(s): Andersen JM, Myhre O, Fonnum F. Source: Neurochemical Research. 2003 February; 28(2): 319-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608704&dopt=Abstract

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Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats. Author(s): Hashimoto M, Hossain S, Shimada T, Sugioka K, Yamasaki H, Fujii Y, Ishibashi Y, Oka J, Shido O. Source: Journal of Neurochemistry. 2002 June; 81(5): 1084-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065621&dopt=Abstract

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Effects of individualized versus classical “relaxation” music on the frequency of agitation in elderly persons with Alzheimer's disease and related disorders. Author(s): Gerdner LA. Source: Int Psychogeriatr. 2000 March; 12(1): 49-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10798453&dopt=Abstract

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Effects of low-frequency cranial electrostimulation on the rest-activity rhythm and salivary cortisol in Alzheimer's disease. Author(s): Scherder E, Knol D, van Someren E, Deijen JB, Binnekade R, Tilders F, Sergeant J. Source: Neurorehabilitation and Neural Repair. 2003 June; 17(2): 101-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814055&dopt=Abstract

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Effects of low-level lead on glycolytic enzymes and pyruvate dehydrogenase of rat brain in vitro: relevance to sporadic Alzheimer's disease? Author(s): Yun SW, Hoyer S. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2000; 107(3): 355-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10821444&dopt=Abstract

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Effects of stimulus sequence on event-related potentials and reaction time during target detection in Alzheimer's disease. Author(s): Golob EJ, Starr A. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2000 August; 111(8): 1438-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10904226&dopt=Abstract

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Emerging neuroprotective strategies for Alzheimer's disease: dietary restriction, telomerase activation, and stem cell therapy. Author(s): Mattson MP. Source: Experimental Gerontology. 2000 July; 35(4): 489-502. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10959037&dopt=Abstract

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Estrogen and cerebral blood flow: a mechanism to explain the impact of estrogen on the incidence and treatment of Alzheimer's disease. Author(s): Greene RA. Source: Int J Fertil Womens Med. 2000 July-August; 45(4): 253-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997480&dopt=Abstract

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Ethical, and practical issues in applying functional imaging to the clinical management of Alzheimer's disease. Author(s): Rosen AC, Bokde AL, Pearl A, Yesavage JA. Source: Brain and Cognition. 2002 December; 50(3): 498-519. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480493&dopt=Abstract

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EUROCARE: a cross-national study of co-resident spouse carers for people with Alzheimer's disease: I--Factors associated with carer burden. Author(s): Schneider J, Murray J, Banerjee S, Mann A.

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Source: International Journal of Geriatric Psychiatry. 1999 August; 14(8): 651-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10489656&dopt=Abstract •

Expression of melanotransferrin isoforms in human serum: relevance to Alzheimer's disease. Author(s): Desrosiers RR, Bertrand Y, Nguyen QT, Demeule M, Gabathuler R, Kennard ML, Gauthier S, Beliveau R. Source: The Biochemical Journal. 2003 September 1; 374(Pt 2): 463-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809550&dopt=Abstract

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Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment. Author(s): Conquer JA, Tierney MC, Zecevic J, Bettger WJ, Fisher RH. Source: Lipids. 2000 December; 35(12): 1305-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11201991&dopt=Abstract

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Ginkgo biloba neuroprotection: Therapeutic implications in Alzheimer's disease. Author(s): Luo Y. Source: Journal of Alzheimer's Disease : Jad. 2001 August; 3(4): 401-407. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12214044&dopt=Abstract

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Health professionals' views on standards for decision-making capacity regarding refusal of medical treatment in mild Alzheimer's disease. Author(s): Volicer L, Ganzini L. Source: Journal of the American Geriatrics Society. 2003 September; 51(9): 1270-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919240&dopt=Abstract

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Homocysteine and Alzheimer's disease. Author(s): Leboeuf R. Source: Journal of the American Dietetic Association. 2003 March; 103(3): 304-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616250&dopt=Abstract

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How physicians approach advance care planning in patients with mild to moderate Alzheimer's disease. Author(s): Cavalieri TA, Latif W, Ciesielski J, Ciervo CA Jr, Forman LJ. Source: J Am Osteopath Assoc. 2002 October; 102(10): 541-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401040&dopt=Abstract

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Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease. Author(s): Bai DL, Tang XC, He XC.

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Source: Current Medicinal Chemistry. 2000 March; 7(3): 355-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10637369&dopt=Abstract •

Huprine X is a novel high-affinity inhibitor of acetylcholinesterase that is of interest for treatment of Alzheimer's disease. Author(s): Camps P, Cusack B, Mallender WD, El Achab RE, Morral J, Munoz-Torrero D, Rosenberry TL. Source: Molecular Pharmacology. 2000 February; 57(2): 409-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10648652&dopt=Abstract

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In vivo imaging of region and cell type specific neocortical neurodegeneration in Alzheimer's disease. Perspectives of MRI derived corpus callosum measurement for mapping disease progression and effects of therapy. Evidence from studies with MRI, EEG and PET. Author(s): Hampel H, Teipel SJ, Alexander GE, Pogarell O, Rapoport SI, Moller HJ. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2002 May; 109(5-6): 83755. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111472&dopt=Abstract

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Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease. A property common to most cyclin-dependent kinase inhibitors? Author(s): Leclerc S, Garnier M, Hoessel R, Marko D, Bibb JA, Snyder GL, Greengard P, Biernat J, Wu YZ, Mandelkow EM, Eisenbrand G, Meijer L. Source: The Journal of Biological Chemistry. 2001 January 5; 276(1): 251-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11013232&dopt=Abstract

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Inflammation and cerebral amyloidosis are disconnected in an animal model of Alzheimer's disease. Author(s): Quinn J, Montine T, Morrow J, Woodward WR, Kulhanek D, Eckenstein F. Source: Journal of Neuroimmunology. 2003 April; 137(1-2): 32-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667645&dopt=Abstract

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Influence of the severity of cognitive impairment on the effect of the Gnkgo biloba extract EGb 761 in Alzheimer's disease. Author(s): Le Bars PL, Velasco FM, Ferguson JM, Dessain EC, Kieser M, Hoerr R. Source: Neuropsychobiology. 2002; 45(1): 19-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11803237&dopt=Abstract

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Influence of vitamin E and C supplementation on lipoprotein oxidation in patients with Alzheimer's disease. Author(s): Kontush A, Mann U, Arlt S, Ujeyl A, Luhrs C, Muller-Thomsen T, Beisiegel U.

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Source: Free Radical Biology & Medicine. 2001 August 1; 31(3): 345-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11461772&dopt=Abstract •

In-vitro activity of S. lavandulaefolia (Spanish sage) relevant to treatment of Alzheimer's disease. Author(s): Perry NS, Houghton PJ, Sampson J, Theobald AE, Hart S, Lis-Balchin M, Hoult JR, Evans P, Jenner P, Milligan S, Perry EK. Source: The Journal of Pharmacy and Pharmacology. 2001 October; 53(10): 1347-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11697542&dopt=Abstract

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Is vitamin E the magic bullet for the treatment of Alzheimer's disease (AD)? Author(s): Woo K. Source: Perspectives. 2000 Spring; 24(1): 7-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026332&dopt=Abstract

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Lateralized cortical perfusion in women with Alzheimer's disease. Author(s): Ott BR, Heindel WC, Tan Z, Noto RB. Source: J Gend Specif Med. 2000 September-October; 3(6): 29-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11253380&dopt=Abstract

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Longitudinal PET Evaluation of Cerebral Metabolic Decline in Dementia: A Potential Outcome Measure in Alzheimer's Disease Treatment Studies. Author(s): Alexander GE, Chen K, Pietrini P, Rapoport SI, Reiman EM. Source: The American Journal of Psychiatry. 2002 May; 159(5): 738-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986126&dopt=Abstract

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Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case-control study. Author(s): Tully AM, Roche HM, Doyle R, Fallon C, Bruce I, Lawlor B, Coakley D, Gibney MJ. Source: The British Journal of Nutrition. 2003 April; 89(4): 483-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654166&dopt=Abstract

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Management of Alzheimer's disease. Author(s): Grossberg GT, Desai AK. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 April; 58(4): 331-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663697&dopt=Abstract

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Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. Author(s): Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M.

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Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 July; 74(7): 863-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810768&dopt=Abstract •

More than memory. The ancient art of storytelling can liberate the voices and imaginations of those with Alzheimer's disease. Author(s): Maher L. Source: Contemporary Longterm Care. 2002 July; 25(7): 16-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154617&dopt=Abstract

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Music therapy increases serum melatonin levels in patients with Alzheimer's disease. Author(s): Kumar AM, Tims F, Cruess DG, Mintzer MJ, Ironson G, Loewenstein D, Cattan R, Fernandez JB, Eisdorfer C, Kumar M. Source: Alternative Therapies in Health and Medicine. 1999 November; 5(6): 49-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10550905&dopt=Abstract

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Neuroimaging in Alzheimer's disease: relevance for treatment. Author(s): van Dyck CH. Source: Current Psychiatry Reports. 2001 February; 3(1): 13-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11177754&dopt=Abstract

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Nicotinic receptor abnormalities of Alzheimer's disease: therapeutic implications. Author(s): Nordberg A. Source: Biological Psychiatry. 2001 February 1; 49(3): 200-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11230871&dopt=Abstract

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Non-cholinergic strategies for treating and preventing Alzheimer's disease. Author(s): Doraiswamy PM. Source: Cns Drugs. 2002; 16(12): 811-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421115&dopt=Abstract

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Oxidative damage and protection by antioxidants in the frontal cortex of Alzheimer's disease is related to the apolipoprotein E genotype. Author(s): Ramassamy C, Averill D, Beffert U, Bastianetto S, Theroux L, Lussier-Cacan S, Cohn JS, Christen Y, Davignon J, Quirion R, Poirier J. Source: Free Radical Biology & Medicine. 1999 September; 27(5-6): 544-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10490274&dopt=Abstract

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Oxidative injury in diseases of the central nervous system: focus on Alzheimer's disease. Author(s): Pratico D, Delanty N.

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Source: The American Journal of Medicine. 2000 November; 109(7): 577-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063960&dopt=Abstract •

Part VI. Primary drug therapies for Alzheimer's disease. Author(s): Knopman DS. Source: Disease-A-Month : Dm. 2000 November; 46(11): 745-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11130325&dopt=Abstract

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PET studies and cholinergic therapy in Alzheimer's disease. Author(s): Nordberg A. Source: Revue Neurologique. 1999; 155 Suppl 4: S53-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10637939&dopt=Abstract

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Pharmacologic treatment of Alzheimer's disease: an update. Author(s): DeLaGarza VW. Source: American Family Physician. 2003 October 1; 68(7): 1365-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567491&dopt=Abstract

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Pharmacological studies supporting the therapeutic use of Ginkgo biloba extract for Alzheimer's disease. Author(s): Ahlemeyer B, Krieglstein J. Source: Pharmacopsychiatry. 2003 June; 36 Suppl 1: S8-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130383&dopt=Abstract

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Plants with traditional uses and activities, relevant to the management of Alzheimer's disease and other cognitive disorders. Author(s): Howes MJ, Perry NS, Houghton PJ. Source: Phytotherapy Research : Ptr. 2003 January; 17(1): 1-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12557240&dopt=Abstract

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Practice guidelines for the diagnosis and treatment of Alzheimer's disease in a managed care setting: Part II--Pharmacologic therapy. Alzheimer's Disease (AD) Managed Care Advisory Council. Author(s): Fillit H, Cummings J. Source: Manag Care Interface. 2000 January; 13(1): 51-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10747691&dopt=Abstract

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Preserved stimulus deviance detection in Alzheimer's disease. Author(s): Pekkonen E, Jaaskelainen LP, Erkinjuntti T, Hietanen M, Huotilainen M, Ilmoniemi RJ, Naatanen R.

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Source: Neuroreport. 2001 June 13; 12(8): 1649-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11409733&dopt=Abstract •

Prevention of Alzheimer's disease: where we stand. Author(s): Sano M. Source: Curr Neurol Neurosci Rep. 2002 September; 2(5): 392-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169218&dopt=Abstract

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Progress in clinical, pharmacological, chemical and structural biological studies of huperzine A: a drug of traditional chinese medicine origin for the treatment of Alzheimer's disease. Author(s): Jiang H, Luo X, Bai D. Source: Current Medicinal Chemistry. 2003 November; 10(21): 2231-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529340&dopt=Abstract

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Quantification of F-ring and D-/E-ring isoprostanes and neuroprostanes in Alzheimer's disease. Author(s): Reich EE, Markesbery WR, Roberts LJ 2nd, Swift LL, Morrow JD, Montine TJ. Source: Advances in Experimental Medicine and Biology. 2001; 500: 253-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11764949&dopt=Abstract

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Reduced high-affinity agonist binding at the M(1) muscarinic receptor in Alzheimer's disease brain: differential sensitivity to agonists and divalent cations. Author(s): Ladner CJ, Lee JM. Source: Experimental Neurology. 1999 August; 158(2): 451-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10415152&dopt=Abstract

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Regional cerebral blood flow and prognostic evaluation in Alzheimer's disease. Author(s): Nobili F, Copello F, Buffoni F, Vitali P, Girtler N, Bordoni C, Safaie-Semnani E, Mariani G, Rodriguez G. Source: Dementia and Geriatric Cognitive Disorders. 2001 March-April; 12(2): 89-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11173880&dopt=Abstract

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Regional cerebral blood flow patterns and response to donepezil treatment in patients with Alzheimer's disease. Author(s): Hanyu H, Shimizu T, Tanaka Y, Takasaki M, Koizumi K, Abe K. Source: Dementia and Geriatric Cognitive Disorders. 2003; 15(4): 177-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626849&dopt=Abstract

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Regional effects of donepezil and rivastigmine on cortical acetylcholinesterase activity in Alzheimer's disease. Author(s): Kaasinen V, Nagren K, Jarvenpaa T, Roivainen A, Yu M, Oikonen V, Kurki T, Rinne JO.

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Source: Journal of Clinical Psychopharmacology. 2002 December; 22(6): 615-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454562&dopt=Abstract •

Reminiscence group activities and discourse interaction in Alzheimer's disease. Author(s): Moss SE, Polignano E, White CL, Minichiello MD, Sunderland T. Source: Journal of Gerontological Nursing. 2002 August; 28(8): 36-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12219552&dopt=Abstract

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Response patterns of EGb 761 in Alzheimer's disease: influence of neuropsychological profiles. Author(s): Le Bars PL. Source: Pharmacopsychiatry. 2003 June; 36 Suppl 1: S50-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130389&dopt=Abstract

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Responses to donepezil in Alzheimer's disease and Parkinson's disease. Author(s): Mori S. Source: Annals of the New York Academy of Sciences. 2002 November; 977: 493-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480791&dopt=Abstract

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Review of the next generation of Alzheimer's disease therapeutics: challenges for drug development. Author(s): Cutler NR, Sramek JJ. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2001 January; 25(1): 27-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11263756&dopt=Abstract

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Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized and placebo-controlled trial. Author(s): Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. Source: Journal of Clinical Pharmacy and Therapeutics. 2003 February; 28(1): 53-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605619&dopt=Abstract

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Sensory cortical interactions in aging, mild cognitive impairment, and Alzheimer's disease. Author(s): Golob EJ, Miranda GG, Johnson JK, Starr A. Source: Neurobiology of Aging. 2001 September-October; 22(5): 755-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11705635&dopt=Abstract

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Sensory gating deficit expressed by a disturbed suppression of the P50 event-related potential in patients with Alzheimer's disease. Author(s): Jessen F, Kucharski C, Fries T, Papassotiropoulos A, Hoenig K, Maier W, Heun R.

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Source: The American Journal of Psychiatry. 2001 August; 158(8): 1319-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11481170&dopt=Abstract •

Should we encourage the use of high-dose vitamin E in persons with memory complaints as a preventive strategy against Alzheimer's disease? Author(s): Gauthier S. Source: Journal of Psychiatry & Neuroscience : Jpn. 2000 September; 25(4): 394. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11022404&dopt=Abstract

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Skill learning in patients with moderate Alzheimer's disease: a prospective pilotstudy of waltz-lessons. Author(s): Rosler A, Seifritz E, Krauchi K, Spoerl D, Brokuslaus I, Proserpi SM, Gendre A, Savaskan E, Hofmann M. Source: International Journal of Geriatric Psychiatry. 2002 December; 17(12): 1155-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12461765&dopt=Abstract

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Spelling via semantics and phonology: exploring the effects of age, Alzheimer's disease, and primary semantic impairment. Author(s): Cortese MJ, Balota DA, Sergent-Marshall SD, Buckner RL. Source: Neuropsychologia. 2003; 41(8): 952-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667531&dopt=Abstract

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The brain alpha7 nicotinic receptor may be an important therapeutic target for the treatment of Alzheimer's disease: studies with DMXBA (GTS-21). Author(s): Kem WR. Source: Behavioural Brain Research. 2000 August; 113(1-2): 169-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942043&dopt=Abstract

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The dentate gyrus neurogenesis: a therapeutic target for Alzheimer's disease. Author(s): Tatebayashi Y, Lee MH, Li L, Iqbal K, Grundke-Iqbal I. Source: Acta Neuropathologica. 2003 March; 105(3): 225-32. Epub 2002 November 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12557008&dopt=Abstract

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The development of an Alzheimer's disease channel for the Michigan Interactive Health Kiosk Project. Author(s): Connell CM, Shaw BA, Holmes SB, Hudson ML, Derry HA, Strecher VJ. Source: Journal of Health Communication. 2003 January-February; 8(1): 11-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635808&dopt=Abstract

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The effect of therapeutic touch on agitated behavior and cortisol in persons with Alzheimer's disease. Author(s): Woods DL, Dimond M.

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Source: Biological Research for Nursing. 2002 October; 4(2): 104-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12408216&dopt=Abstract •

The Effect of Therapist and Activity Characteristics on the Purposeful Responses of Probable Alzheimer's Disease Participants. Author(s): Groene II R. Source: J Music Ther. 1999; 35(2): 119-136. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10519832&dopt=Abstract

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The effectiveness of slow-stroke massage in diffusing agitated behaviors in individuals with Alzheimer's disease. Author(s): Rowe M, Alfred D. Source: Journal of Gerontological Nursing. 1999 June; 25(6): 22-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10603811&dopt=Abstract

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The 'hidden' victims of Alzheimer's disease. Author(s): Ullman T. Source: Fda Consumer. 2003 July-August; 37(4): 40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971350&dopt=Abstract

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The importance of awareness: An experience of small support groups for the caregivers of Alzheimer's disease patients. Author(s): Monini P, Tognetti A, Cinque R, Di Franco F, Bartorelli L. Source: Archives of Gerontology and Geriatrics. 2001 January; 33 Suppl 1: 267-271. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11431073&dopt=Abstract

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Theory of mind in patients with frontal variant frontotemporal dementia and Alzheimer's disease: theoretical and practical implications. Author(s): Gregory C, Lough S, Stone V, Erzinclioglu S, Martin L, Baron-Cohen S, Hodges JR. Source: Brain; a Journal of Neurology. 2002 April; 125(Pt 4): 752-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912109&dopt=Abstract

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Thiamine for Alzheimer's disease. Author(s): Rodriguez-Martin JL, Qizilbash N, Lopez-Arrieta JM. Source: Cochrane Database Syst Rev. 2001; (2): Cd001498. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11405995&dopt=Abstract

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Thiamine for Alzheimer's disease. Author(s): Rodriguez-Martin JL, Lopez-Arrieta JM, Qizilbash N.

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Source: Cochrane Database Syst Rev. 2000; (2): Cd001498. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796655&dopt=Abstract •

Treatment of Alzheimer's disease by transposition of the omentum. Author(s): Goldsmith HS. Source: Annals of the New York Academy of Sciences. 2002 November; 977: 454-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480786&dopt=Abstract

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Treatment of Alzheimer's disease with clioquinol. Author(s): Regland B, Lehmann W, Abedini I, Blennow K, Jonsson M, Karlsson I, Sjogren M, Wallin A, Xilinas M, Gottfries CG. Source: Dementia and Geriatric Cognitive Disorders. 2001 November-December; 12(6): 408-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11598313&dopt=Abstract

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Treatment of Alzheimer's disease: current status and new perspectives. Author(s): Scarpini E, Scheltens P, Feldman H. Source: Lancet. Neurology. 2003 September; 2(9): 539-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941576&dopt=Abstract

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Treatment options for Alzheimer's disease. Author(s): Dinsmore ST. Source: J Am Osteopath Assoc. 1999 September; 99(9 Suppl): S6-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10730506&dopt=Abstract

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Use of neuroimaging to detect early brain changes in people at genetic risk for Alzheimer's disease. Author(s): Small GW. Source: Advanced Drug Delivery Reviews. 2002 December 7; 54(12): 1561-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453673&dopt=Abstract

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Using complementary and alternative approaches for residents with Alzheimer's disease. Author(s): Eliopoulos C. Source: Director. 2000 Winter; 8(1): 16. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11081017&dopt=Abstract

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Using music therapy to help a client with Alzheimer's disease adapt to long-term care. Author(s): Kydd P. Source: Am J Alzheimers Dis Other Demen. 2001 March-April; 16(2): 103-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11302070&dopt=Abstract

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Utilization of Alzheimer's disease community resources by Asian-Americans in California. Author(s): Chow TW, Ross L, Fox P, Cummings JL, Lin KM. Source: International Journal of Geriatric Psychiatry. 2000 September; 15(9): 838-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984731&dopt=Abstract

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Validity of direct assessment of functional status as a tool for measuring Alzheimer's disease severity. Author(s): Zanetti O, Frisoni GB, Rozzini L, Bianchetti A, Trabucchi M. Source: Age and Ageing. 1998 September; 27(5): 615-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675100&dopt=Abstract

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Visual object and face processing in mild-to-moderate Alzheimer's disease: from segmentation to imagination. Author(s): Tippett LJ, Blackwood K, Farah MJ. Source: Neuropsychologia. 2003; 41(4): 453-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559162&dopt=Abstract

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Weight loss in cancer and Alzheimer's disease is mediated by a similar pathway. Author(s): Knittweis J. Source: Medical Hypotheses. 1999 August; 53(2): 172-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10532714&dopt=Abstract

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What's new in Alzheimer's disease? Author(s): Long CO, Dougherty J. Source: Home Healthcare Nurse. 2003 January; 21(1): 8-14; Quiz 15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544456&dopt=Abstract

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Yellow glasses improve contrast sensitivity of a patient with a visual variant of Alzheimer's disease. Author(s): Sakai S, Hirayama K, Iwasaki S, Fujii T, Hashimoto R, Yamadori A. Source: European Neurology. 2002; 48(4): 224-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422073&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to Alzheimer’s disease; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Age-related Cognitive Decline Source: Healthnotes, Inc.; www.healthnotes.com Alzheimer's Disease Source: Healthnotes, Inc.; www.healthnotes.com Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com Cyclic Mastalgia Alternative names: Cyclic Mastitis, Fibrocystic Breast Disease Source: Prima Communications, Inc.www.personalhealthzone.com Dementia Source: Integrative Medicine Communications; www.drkoop.com Depression (mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com High Homocysteine Source: Healthnotes, Inc.; www.healthnotes.com Menopause Source: Integrative Medicine Communications; www.drkoop.com

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Senile Dementia Source: Integrative Medicine Communications; www.drkoop.com •

Alternative Therapy Art Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,671,00.html Music Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,719,00.html

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Herbs and Supplements Amino Acids Overview Source: Healthnotes, Inc.; www.healthnotes.com Antioxidants Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10004,00.html Ashwagandha Alternative names: Withania somniferum Source: Healthnotes, Inc.; www.healthnotes.com Beta-carotene Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10103,00.html Carotenoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,763,00.html Coenzyme Q Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,768,00.html Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com Dehydroepiandrosterone (dhea) Source: Healthnotes, Inc.; www.healthnotes.com

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Dha Source: Integrative Medicine Communications; www.drkoop.com Dhea (dehydroepiandrosterone) Source: Prima Communications, Inc.www.personalhealthzone.com Dmae Source: Healthnotes, Inc.; www.healthnotes.com Dmae Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10023,00.html Docosahexaenoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Docosahexaenoic Acid (dha) Source: Integrative Medicine Communications; www.drkoop.com Donepezil Source: Healthnotes, Inc.; www.healthnotes.com Edta Source: Integrative Medicine Communications; www.drkoop.com Ethylenediaminetetraacetic Acid (edta) Source: Integrative Medicine Communications; www.drkoop.com Ginkgo Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Ginkgo Biloba Source: Healthnotes, Inc.; www.healthnotes.com Ginkgo Biloba Source: Integrative Medicine Communications; www.drkoop.com Ginkgo Biloba Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,788,00.html Gotu Kola Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10031,00.html

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Huperzia Source: Healthnotes, Inc.; www.healthnotes.com Huperzine a Source: Prima Communications, Inc.www.personalhealthzone.com Huperzine a Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10038,00.html Inositol Source: Prima Communications, Inc.www.personalhealthzone.com Lecithin Source: Prima Communications, Inc.www.personalhealthzone.com Lemon Balm Alternative names: Melissa officinalis, Melissa Source: Integrative Medicine Communications; www.drkoop.com L-tyrosine Source: Healthnotes, Inc.; www.healthnotes.com Maidenhair Tree Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,804,00.html Melissa Source: Integrative Medicine Communications; www.drkoop.com Melissa Officinalis Source: Integrative Medicine Communications; www.drkoop.com Milk Thistle Alternative names: Silybum marianum, Carduus marianus Source: Healthnotes, Inc.; www.healthnotes.com Milk Thistle Source: Prima Communications, Inc.www.personalhealthzone.com Nadh Source: Healthnotes, Inc.; www.healthnotes.com Nadh Source: Prima Communications, Inc.www.personalhealthzone.com

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Nadh Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10047,00.html Phosphatidylserine Source: Healthnotes, Inc.; www.healthnotes.com Phosphatidylserine Source: Prima Communications, Inc.www.personalhealthzone.com Phosphatidylserine (ps) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,813,00.html Pregnenolone Source: Prima Communications, Inc.www.personalhealthzone.com S-adenosylmethionine (same) Source: Integrative Medicine Communications; www.drkoop.com Same Source: Healthnotes, Inc.; www.healthnotes.com Same Source: Integrative Medicine Communications; www.drkoop.com Siberian Ginseng Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,821,00.html Tacrine Source: Healthnotes, Inc.; www.healthnotes.com Trazodone Source: Healthnotes, Inc.; www.healthnotes.com Willow Bark Alternative names: There are several species of willow includingSalix alba, Salix nigra, Salix fragilis, Salix purpurea, Salix babylonica, White Willow, European Willow, Black Willow, Pussy Willow, Crack Willow, Purple Willow, Weeping Willow, Liu-zhi Source: Integrative Medicine Communications; www.drkoop.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the

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MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON ALZHEIMER’S DISEASE Overview In this chapter, we will give you a bibliography on recent dissertations relating to Alzheimer’s disease. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “Alzheimer’s disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Alzheimer’s disease, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Alzheimer’s Disease ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to Alzheimer’s disease. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

A Comparison of Actual Food Consumption to Estimated Needs of Individuals with Alzheimer's Disease in a Long-term Care Facility by Heidemann, Regina Anne; Ms from D'youville College, 2002, 72 pages http://wwwlib.umi.com/dissertations/fullcit/1413007

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A Field Assessment of the Relationships among Interpersonal Communication Competence, Social Support, and Depression among Caregivers for Individuals with Alzheimer's Disease by Query, Jim L., Jr., Phd from Ohio University, 1990, 245 pages http://wwwlib.umi.com/dissertations/fullcit/9030057

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A Financial Impact Scale for Long-term Caregivers: Application to Alzheimer Family Caregivers (Alzheimer's Disease) by Todtman, Kathee L., Phd from Texas Tech University, 1989, 142 pages http://wwwlib.umi.com/dissertations/fullcit/9104755

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A Formative Evaluation of Adapted Work Services for Alzheimer's Disease Victims: a Framework for Practical Evaluation in Health Care (sheltered Workplaces) by Quinn, Doris Claire, Phd from Vanderbilt University, 1996, 227 pages http://wwwlib.umi.com/dissertations/fullcit/9626286

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A Functional Characterization of the Alzheimer's Disease Beta-secretase by Huse, Jason Thomas; Phd from University of Pennsylvania, 2002, 157 pages http://wwwlib.umi.com/dissertations/fullcit/3043890

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A Meta-analysis of the Effects of Exercise Training and Physical Activity on Healthrelated Physical Fitness, Cognitive and Physical Functioning, and Behavior of Individuals with Alzheimer's Disease and Related Cognitive Disorders by Heyn, Patricia; Phd from University of Central Florida, 2002, 243 pages http://wwwlib.umi.com/dissertations/fullcit/3069447

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A Microeconomic Analysis of California's Alzheimer's Disease Diagnostic and Treatment Program: the Production of Care and Implications for California Policy (social Services) by Ginther, Shawn Damon, Phd from University of California, Berkeley, 1991, 189 pages http://wwwlib.umi.com/dissertations/fullcit/9203571

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A Naturalistic Study of the Well-being of Caregivers to Family Members with Alzheimer's Disease (family Caregivers, Caregiver Well-being) by Jivanjee, Pauline Raye, Phd from University of Kansas, 1992, 369 pages http://wwwlib.umi.com/dissertations/fullcit/9323024

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A Study of Animal-assisted Therapy and Weekday Placement of a Social Therapy Dog in an Alzheimer's Disease Unit by Martin, Daun Adair, Edd from Washington State University, 1998, 160 pages http://wwwlib.umi.com/dissertations/fullcit/9917440

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A Study of Caregiver Burden For: Spouse Caregivers of Persons with Organic Mental Disorders of the Alzheimer's Type or Related Disorders (alzheimer's Disease) by Hale, Mary Anne, Dsw from Tulane University, School of Social Work, 1994, 248 pages http://wwwlib.umi.com/dissertations/fullcit/9523265

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A Study of the Relationship between a Home Based Therapeutic Recreation Program As Implemented by a Certified Therapeutic Recreation Specialist and the Reduction of Excess Disability in Persons with Early to Mid-stage Alzheimer's Disease by Stavola Daly, Frances A.; Edd from Temple University, 2002, 417 pages http://wwwlib.umi.com/dissertations/fullcit/3057115

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Agenda Building on Health Issues: a Focus on Alzheimer's Disease by Steckenrider, Janie S., Phd from University of Southern California, 1988 http://wwwlib.umi.com/dissertations/fullcit/f4136324

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Alzheimer Caregivers' Guilt Reactions to Institutionalization and Religiosity (alzheimer's Disease) by Biner, Barbara Kathryn, Phd from University of Colorado at Boulder, 1991, 373 pages http://wwwlib.umi.com/dissertations/fullcit/9220394

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Alzheimer's Disease As Developmental Asynchrony: a Dialectical Paradigm of the Marital Relationship of Older Couples by Wright, Lore Kathe, Phd from University of Georgia, 1988, 319 pages http://wwwlib.umi.com/dissertations/fullcit/8903537

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Alzheimer's Disease Caregivers: the Transition from Home Care to Formal Care by Duncan, Marie Theresa, Phd from Portland State University, 1992, 174 pages http://wwwlib.umi.com/dissertations/fullcit/9305303

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Alzheimer's Disease Family Caregiver Well-being a General Model by Guerriero Austrom, Mary; Phd from York University (canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL51429

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Alzheimer's Disease Neuropathology in Aging and Mild Cognitive Impairment by Guillozet, Angela Lorene; Phd from Northwestern University, 2002, 222 pages http://wwwlib.umi.com/dissertations/fullcit/3071647

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Alzheimer's Disease Special Care Units: a Comparative Study of the Retrofit Design (nursing Home Design) by Debauge, Lucia K., Phd from Texas A&m University, 1990, 342 pages http://wwwlib.umi.com/dissertations/fullcit/9118215

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Alzheimer's Disease: the Nature and Chronology of the Spouse Caregiving Experience. a Retrospective Multiple-case Study Approach by Assam, Kay Swenson, Edd from University of South Dakota, 1988, 520 pages http://wwwlib.umi.com/dissertations/fullcit/8911462

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Alzheimer's Disease: the Relationship between Selected Wallcovering Patterns and Resident Behaviors in a Special Care Unit by Dobbs, Margaret Carol Nagy, Phd from Texas Tech University, 1990, 157 pages http://wwwlib.umi.com/dissertations/fullcit/9104762

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Alzheimer's Disease: the Social Construction of Senile Dementia by Fox, Patrick John, Phd from University of California, San Francisco, 1988, 293 pages http://wwwlib.umi.com/dissertations/fullcit/8809497

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An Examination of Reinforcer Identification and Stimulus Discrimination in Elderly Individuals with Alzheimer's Disease by Smith, Wanda L; Phd from The University of Manitoba (canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL14750

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An Examination of the Family Leisure Experiences and Leisure Adjustments Made with a Relative Diagnosed with Alzheimer's Disease in a Long-term Care Facility by Martin, Penny-lynne; Ma from Dalhousie University (canada), 2002, 121 pages http://wwwlib.umi.com/dissertations/fullcit/MQ75519

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An Exploratory Study of the Effects of a Training Program on the Ability to Prepare a Breakfast Meal by Clients with Mild Alzheimer's Disease by Curtin, Alicia J.; Phd from University of Rhode Island, 2002, 326 pages http://wwwlib.umi.com/dissertations/fullcit/3053101

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Anti-amyloid Protein Monoclonal Antibodies for Diagnostics and Theraputics of Alzheimer's Disease by Li, Ge; Msc from University of Alberta (canada), 2002, 130 pages http://wwwlib.umi.com/dissertations/fullcit/MQ69727

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Application of Chemotactic Models to Alzheimer's Disease by Luca, Magdalena; Phd from The University of British Columbia (canada), 2002, 163 pages http://wwwlib.umi.com/dissertations/fullcit/NQ73199

208 Alzheimer’s Disease

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Art Preference in Alzheimer's Disease: Does It Remain Stable over Time? by Hickory, Meredith Ann; Psyd from Massachusetts School of Professional Psychology, 2003, 76 pages http://wwwlib.umi.com/dissertations/fullcit/3088235

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Aspects of Perceived Competency: a Study of Husbands and Wives As Caregivers for Confused and Not Confused Spouses (alzheimer's Disease) by Wilken, Carolyn Russell, Phd from Purdue University, 1988, 228 pages http://wwwlib.umi.com/dissertations/fullcit/8912019

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Association between Apathy and Executive Dysfunction in Alzheimer's Disease by Arnold, Ginger Leigh Demolar; Phd from Fuller Theological Seminary, School of Psychology, 2002, 180 pages http://wwwlib.umi.com/dissertations/fullcit/3046361

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Becoming a Caregiver: Processes in the Career of Caring for a Family Member with Alzheimer's Disease (family Caregivers) by Blum, Nancy Sue, Phd from University of California, Los Angeles, 1992, 354 pages http://wwwlib.umi.com/dissertations/fullcit/9224123

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Biochemical Investigation of Tau and Map2 Polymerization: Implications for Neuropathic Filament Assembly in Alzheimer's Disease by Di Noto, Luca; Phd from University of Florida, 2002, 162 pages http://wwwlib.umi.com/dissertations/fullcit/3052345

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Biophysical Studies on the Met35 Oxidation of Alzheimer's Disease Amyloid Betapeptides by Hou, Liming; Phd from Case Western Reserve University, 2003, 222 pages http://wwwlib.umi.com/dissertations/fullcit/3092011

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Caregiver Coping with Dementia: Relationships among Patient Characteristics, Caregiver Coping Styles, and Consequences of Caregiving (alzheimer's Disease) by Ramsey, Nina Sharp, Phd from University of Washington, 1990, 270 pages http://wwwlib.umi.com/dissertations/fullcit/9109822

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Caregivers for Alzheimer's Disease Patients; a Study of Religiosity and Burden by Bacik, Patricia Lee, Phd from The University of Toledo, 1990, 164 pages http://wwwlib.umi.com/dissertations/fullcit/9104078

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Cellular Trafficking and Metabolism of the Alzheimer's Disease Amyloid Precursor Protein (app) in the Secretory and Endocytic Pathways by Steinhilb, Michelle Leigh; Phd from University of Michigan, 2002, 195 pages http://wwwlib.umi.com/dissertations/fullcit/3042175

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Characteristics and Stress Levels of Hispanic and Non-hispanic Caregivers of Alzheimer's Disease Patients by Gonzalez-lima, Erika Musiol, Phd from Texas A&m University, 1989, 205 pages http://wwwlib.umi.com/dissertations/fullcit/9015504

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Chlamydia Pneumoniae Infection in Human Monocytes and Brain Endothelial Cells: Initiating Factors in the Development of Alzheimer's Disease by Macintyre, Angela; Phd from Mcp Hahnemann University, 2002, 147 pages http://wwwlib.umi.com/dissertations/fullcit/3051098

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Choices and Tradeoffs in Advanced Alzheimer's Disease: Balancing Survival, Health, Comfort, and Cost by Fabiszewski, Kathy Jean; Phd from University of Massachusetts Boston, 1999, 236 pages http://wwwlib.umi.com/dissertations/fullcit/9951870

Dissertations 209

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Cognitive Coping Strategies of Older Spouse Caring for One with Alzheimer's Disease (caregivers, Spouse Caregivers, Stress) by Tebb, Susan Carol Steiger, Phd from University of Kansas, 1992, 215 pages http://wwwlib.umi.com/dissertations/fullcit/9313182

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Cognitive Training of the Cognitively-impaired Elderly (memory, Alzheimer's Disease) by Maaser, Bruce Wayne, Phd from The University of Wisconsin - Madison, 1988, 400 pages http://wwwlib.umi.com/dissertations/fullcit/8822256

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Comparative Analysis of a Moderating and Mediating Model of Stress, Appraisal, and Coping in Hispanic and Non-hispanic Alzheimer's Disease Caregivers by Morano, Carmen Louis; Phd from Florida International University, 1999, 214 pages http://wwwlib.umi.com/dissertations/fullcit/9949326

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Comparisons of Marital Relationship Measures among Elderly Wives of Alzheimer's, Chronically Ill, and Healthy Spouses (alzheimer's Disease) by Rubin, Judith A., Phd from The University of Wisconsin - Madison, 1991, 434 pages http://wwwlib.umi.com/dissertations/fullcit/9133413

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Conducting Differential Diagnosis of Alzheimer's Disease Utilizing Neuropsychological Assessments by Cisneros, Wendy L.; Psyd from Carlos Albizu University, 2002, 86 pages http://wwwlib.umi.com/dissertations/fullcit/3054216

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Confidence-based Calibration and the Detection of Early Cognitive Loss in Probable and Possible Alzheimer's Disease Sufferers by Minns, Joanne E.; Ma from Carleton University (canada), 2002, 73 pages http://wwwlib.umi.com/dissertations/fullcit/MQ72052

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Constructing the Dementia Process: the Identification, Definition and Management of Alzheimer's Disease (caregiving) by Manuel, Lisa Kimberley Catherine, Phd from University of Toronto (canada), 1995, 312 pages http://wwwlib.umi.com/dissertations/fullcit/NN02808

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Coping with Memory Problems in Normal Aging and Alzheimer's Disease: an Exploratory Field Study by Brustrom, Jennifer Elizabeth, Phd from University of California, Davis, 1996, 184 pages http://wwwlib.umi.com/dissertations/fullcit/9721020

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Correlates of Demoralization in a Cohort of Spousal Caregivers of Alzheimer's Victims (alzheimer's Disease, Caregivers) by Yatzkan, Elaine S., Phd from New York University, 1990, 190 pages http://wwwlib.umi.com/dissertations/fullcit/9023057

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Development and Evaluation of a Scale to Assess the Stress of Caring for an Older Adult with Alzheimer's Disease by Kinney, Jennifer Martin, Phd from Kent State University, 1987, 188 pages http://wwwlib.umi.com/dissertations/fullcit/8726977

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Development of Novel Bivalent 1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole Derivatives As Selective, Potent, and Efficacious Human M1 Muscarinic Agonists for the Treatment of Alzheimer's Disease by Cao, Yang; , Phd from The University of Toledo, 2002, 165 pages http://wwwlib.umi.com/dissertations/fullcit/3045999

210 Alzheimer’s Disease

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Diagnostic Assessment and Treatment Service Utilization among Alzheimer's Disease Clients in California by Douglass, Carolinda, Phd from The Rand Graduate Institute, 1994, 237 pages http://wwwlib.umi.com/dissertations/fullcit/9510322

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Distress and Coping among Caregivers of Victims of Alzheimer's Disease and Related Disorders (new York) by Dundon, Margaret M., Phd from State University of New York at Buffalo, 1987, 129 pages http://wwwlib.umi.com/dissertations/fullcit/8710702

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Dyspragmia in Wernicke's Aphasia and Alzheimer's Disease: an Investigation in Clinical Pragmatics by Beach, Woodford Ascher; Phd from The University of Chicago, 2002, 416 pages http://wwwlib.umi.com/dissertations/fullcit/3070156

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Effect of a Rational-emotive Therapy-based Counseling Group on the Psychological Distress of Caregivers of Alzheimer's Disease Patients by Thompson, John Michael, Phd from University of Georgia, 1987, 195 pages http://wwwlib.umi.com/dissertations/fullcit/8800306

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Effectiveness of Music Therapy Intervention with Individuals Having Senile Dementia of the Alzheimer's Type (alzheimer's Disease) by Groene, Robert William, Ii, Phd from University of Minnesota, 1992, 205 pages http://wwwlib.umi.com/dissertations/fullcit/9306504

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Effects of an Exercise Program on Mentally Impaired Older Adults in a Long-term Care Facility (alzheimer's Disease, Dementia) by Frizzell, Linda D. Bane, Phd from The University of North Dakota, 1991, 182 pages http://wwwlib.umi.com/dissertations/fullcit/9220363

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Effects of Informational Support and Emotional Support on Morale of Nursing Home Staff Providing Care to Alzheimer's Disease Patients by Kline, Priscilla Mackenzie, Edd from Clemson University, 1987, 179 pages http://wwwlib.umi.com/dissertations/fullcit/8803904

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Effects of Working Memory and Semantic Impairments on Speech in Alzheimer's Disease by Altmann, Lori Jean, Phd from University of Southern California, 1998, 198 pages http://wwwlib.umi.com/dissertations/fullcit/9919007

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Emotional Experience, Facial Expression, and Startle Reflex Modulation in Young Adults, Healthy Older Adults, and Alzheimer's Disease by Burton, Keith Wayne; Phd from The University of Arizona, 2003, 93 pages http://wwwlib.umi.com/dissertations/fullcit/3089918

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Etude Geographique De La Maladie D'alzheimer Au Saguenay-lac-saint-jean (quebec) (french Text, Alzheimer's Disease) by Emard, Jean-francois, Phd from Universite De Montreal (canada), 1992, 280 pages http://wwwlib.umi.com/dissertations/fullcit/NN88880

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Expression and Localization of Alzheimer's Disease (ad)-related Proteins in Senescence-accelerated Mouse (sam) and Normal Mouse by Yao, Hong-bing; Phd from Chinese University of Hong Kong (people's Republic of China), 2002, 152 pages http://wwwlib.umi.com/dissertations/fullcit/3038012

Dissertations 211

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Factors Affecting Social Work Students' Willingness to Work with Elders with Alzheimer's Disease by Kane, Michael N., Phd from Barry University School of Social Work, 1997, 265 pages http://wwwlib.umi.com/dissertations/fullcit/9722252

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Familial Alzheimer's Disease Mutations Decrease Gamma-secretase Processing of Beta Amyloid Precurson Protein by Wiley, Jesse Carey; Phd from University of Washington, 2003, 146 pages http://wwwlib.umi.com/dissertations/fullcit/3091090

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Family Burden and Outpatients with Alzheimer's Disease by Morycz, Richard Karl, Phd from University of Pittsburgh, 1982, 414 pages http://wwwlib.umi.com/dissertations/fullcit/8305584

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Family Caregiving Experiences with Alzheimer's Disease: a Collective Case Study by Agee, Annabel Lee; Phd from The University of Tennessee, 2000, 221 pages http://wwwlib.umi.com/dissertations/fullcit/9973428

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Fighting the Living Death Through the Maintenance of Personhood: a Study on a Support Group for Early-stage Alzheimer's Disease by Adomako, Paul Robert Kwaku, Jr.; Msc from University of Guelph (canada), 2003, 193 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76044

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Formulaic Language in Aging and Alzheimer's Disease by De Santi, Susan M., Phd from City University of New York, 1993, 244 pages http://wwwlib.umi.com/dissertations/fullcit/9315456

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Fostering Effective Interaction between Nursing Home Staff and Residents Experiencing Alzheimer's Related Dementia (alzheimer's Disease, Staff Resident Interactions) by Pray, Jackie E., Phd from University of Kansas, 1993, 203 pages http://wwwlib.umi.com/dissertations/fullcit/9405781

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Functional Regions of the Corpus Callosum: Evidence from Alzheimer's Disease Patients by Hallam, Bradley John; Phd from Fuller Theological Seminary, School of Psychology, 2002, 222 pages http://wwwlib.umi.com/dissertations/fullcit/3046367

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Getting Lost Behavior and Directed Attention Impairments in Taiwanese Patients with Early Alzheimer's Disease by Chiu, Yu-hong; Phd from University of Michigan, 2002, 278 pages http://wwwlib.umi.com/dissertations/fullcit/3057923

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Giving Up and Giving In: Young Adolescents' Dilemmas When Caring for a Grandparent with Alzheimer's Disease by Beach, Diane Lee, Edd from University of San Diego, 1999, 124 pages http://wwwlib.umi.com/dissertations/fullcit/9930613

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Group Counseling Experiences of Clients with Alzheimer's Disease by White, Carolyn Crabtree; Phd from University of New Orleans, 2002, 187 pages http://wwwlib.umi.com/dissertations/fullcit/3051368

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Husbands' Decisions to Institutionalize Wives Afflicted with Alzheimer's Disease: an Empirical Phenomenological Study by Dickerson, Paul Bryant, Phd from Duquesne University, 1999, 359 pages http://wwwlib.umi.com/dissertations/fullcit/9936947

212 Alzheimer’s Disease

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I Know Just When It Happened: a Turning Point Analysis of Communication and Change in Relationships Where One Partner Has Alzheimer's Disease by Karmon, Carolyn Lee, Phd from Ohio University, 1997, 212 pages http://wwwlib.umi.com/dissertations/fullcit/9804588

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Identity Loss, Moral Commitment, and Alzheimer's Disease: an Interactionist Perspective (alzheimer's Disease) by Orona, Celia J., Phd from University of California, San Francisco, 1989, 311 pages http://wwwlib.umi.com/dissertations/fullcit/8926413

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Impact of a Formal Education and Group Support Program on the Subjective Wellbeing and Burden Perceptions of Primary Caregivers for Adults with Progressive Dementia (caregivers, Alzheimer's Disease) by Stanley, Sharon A. R., Phd from The Ohio State University, 1989, 158 pages http://wwwlib.umi.com/dissertations/fullcit/9014492

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Improving the Dressing Skills of Persons with Alzheimer's Disease Using Picture Cues by Talbert-johnson, Carolyn, Phd from The Ohio State University, 1991, 171 pages http://wwwlib.umi.com/dissertations/fullcit/9201761

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Improving Transgenic Mouse Models of Alzheimer's Disease: Attempts to Enhance Acute Phase Reactions to Amyloid Deposition by Boyett, Kristal Wright; Phd from University of South Florida, 2002, 172 pages http://wwwlib.umi.com/dissertations/fullcit/3071291

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In Vivo Molecular Imaging Probes for Alzheimer's Disease: Molecular Requirements for Binding of 2-[1-(6-dialkylamino-2-naphthyl)ethylidene]malononitrile Molecular Imaging Probes to Beta-amyloid Fibrils and Senile Plaques by Agdeppa, Eric Dustin; Phd from University of California, Los Angeles, 2002, 165 pages http://wwwlib.umi.com/dissertations/fullcit/3076589

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Informational Supports for Caregivers Responsible for Spouses with Alzheimer's Disease by Mathews, Janet Lynn, Phd from Portland State University, 1995, 170 pages http://wwwlib.umi.com/dissertations/fullcit/9608482

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Intellectual Deficits Associated with Alzheimer's Disease by Pelletier, Frederick L; Phd from Queen's University at Kingston (canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL50079

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Intergenerational Programming: Yesterday's Memories, Today's Moments, and Tomorrow's Hopes (alzheimer's Disease) by O'rourke, Kathleen Ann; Phd from The University of Tennessee, 1999, 138 pages http://wwwlib.umi.com/dissertations/fullcit/9959308

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Investigation of Cognitive Impairments Using Functional Magnetic Resonance Imaging (fmri) and Positron Emission Tomography (pet) in Patients with Mild Alzheimer's Disease by Stanonik, Mateja De Leonni; Phd from The University of Tennessee, 2002, 369 pages http://wwwlib.umi.com/dissertations/fullcit/3062332

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Is Pharmacological Prevention of Alzheimer's Disease a Realistic Goal? Evidence from the Cache County Study by Zandi, Peter P.; Phd from The Johns Hopkins University, 2002, 135 pages http://wwwlib.umi.com/dissertations/fullcit/3028352

Dissertations 213

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Kinetics of Abeta Peptide Deposition: toward in Vivo Imaging of Alzheimer's Disease Amyloid by Marshall, Jeffrey Richard; Phd from University of Cincinnati, 2002, 266 pages http://wwwlib.umi.com/dissertations/fullcit/3053844

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Life History of Men with Alzheimer's Disease and Their Spousal Caregivers: Relevance for Grounded Theory of Family Care (caregivers) by Flatt, Margaret Mary, Phd from Michigan State University, 1991, 141 pages http://wwwlib.umi.com/dissertations/fullcit/9216304

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Loneliness, Depression, and Social Support among Caregivers of Spouses with Alzheimer's Disease: the Home Versus the Nursing Home Care Experience (home Care, Family Caregivers) by Bergman, Brenda Faith, Phd from University of Nebraska Medical Center, 1992, 169 pages http://wwwlib.umi.com/dissertations/fullcit/9221966

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Mapping Out the Experience of Women Caregivers for Individuals with Alzheimer's Disease by Cassisi, Carmela C.; Mph from Southern Connecticut State University, 2002, 102 pages http://wwwlib.umi.com/dissertations/fullcit/1409790

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Medicalizing Intersubjectivity: Diagnostic Practices and the Self in Alzheimer's Disease by Smith, Andre Philippe; Phd from Mcgill University (canada), 2000, 341 pages http://wwwlib.umi.com/dissertations/fullcit/NQ69933

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Memory Training with Dementia Adults: a Nonpharmacologic Attempt to Improve Memory (alzheimer's Disease) by Winston, Marilynn Rauzin, Phd from Georgia State University, 1989, 107 pages http://wwwlib.umi.com/dissertations/fullcit/9015715

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Mild Cognitive Impairment: a Useful Construct for Predicting Alzheimer's Disease by Geslani, Daphne Melissa; Msc from University of Toronto (canada), 2002, 125 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74106

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Negotiating Disease: Senile Dementia and Alzheimer's Disease, 1900-1980 by Holstein, Martha Beller, Phd from The University of Texas Graduate Sch. of Biomedical Sci. at Galveston, 1996, 352 pages http://wwwlib.umi.com/dissertations/fullcit/9700425

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No Aging in India (dementia, Alzheimer's Disease) by Cohen, Lawrence, Phd from Harvard University, 1992, 467 pages http://wwwlib.umi.com/dissertations/fullcit/9228327

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On the Mechanisms of Semantic Associative Processing in the Perception and Interpretation of Affective Stimuli (alzheimer's Disease) by Bortz, Jennifer Jean, Phd from The University of Arizona, 1992, 170 pages http://wwwlib.umi.com/dissertations/fullcit/9303313

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On-line Sentence Comprehension in Alzheimer's Disease by Small, Jeff Alan, Phd from University of Southern California, 1994 http://wwwlib.umi.com/dissertations/fullcit/f1879875

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Oxidative Stress in Models of Alzheimer's Disease: I. Roles of Peroxynitrite, Amyloid Beta-peptide, and 4-hydroxy-2-nonenal. Ii. Modulation by Gamma-glutamylcysteine Ethyl Ester by Drake, Jennifer Le; Phd from University of Kentucky, 2003, 236 pages http://wwwlib.umi.com/dissertations/fullcit/3092307

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Oxidatively-modified Proteins: I. Proteomic Identification of Specifically-oxidized Proteins in Alzheimer's Disease Brain. Ii. Modulation of Synaptosomal Membrane

214 Alzheimer’s Disease

Lipid Bilayer Asymmetry by 4-hydroxy-2-trans-nonenal by Castegna, Alessandra; Phd from University of Kentucky, 2003, 170 pages http://wwwlib.umi.com/dissertations/fullcit/3092304 •

Perceptual Processing Deficits and Short-term Memory in Persons with Alzheimer's Disease by Rosswurm, Mary Ann Herrity, Edd from University of Cincinnati, 1986, 108 pages http://wwwlib.umi.com/dissertations/fullcit/8612838

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Predicting Hippocampal Atrophy in a Sample of Non-demented Older Adults at Increased Risk for Alzheimer's Disease with Two Novel Memory Transfer Tests by Schnirman, Geoffrey Miles; Phd from Fordham University, 2002, 124 pages http://wwwlib.umi.com/dissertations/fullcit/3037229

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Predicting Lack of Awareness of Cognitive Deficits in Alzheimer's Disease by Muir, James Jeffrey; Phd from Georgia State University, 2002, 170 pages http://wwwlib.umi.com/dissertations/fullcit/3075428

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Predictors of Psychological Symptoms in Spouse Caregivers of Patients with Alzheimer's Disease by Forrest, Nancy Marie, Phd from The Herman M. Finch U. of Health Sciences - the Chicago Medical Sch., 1994, 126 pages http://wwwlib.umi.com/dissertations/fullcit/9507598

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Psychological Stress, Personality Characteristics, Ways of Coping, and Life Satisfaction in Caregivers of Advanced Stage Alzheimer's Disease Victims by O'brien, Marianne Scates, Phd from The University of Tennessee, 1990, 125 pages http://wwwlib.umi.com/dissertations/fullcit/9221789

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Semantic Memory Impairment in Patients with Alzheimer's Disease (memory) by Gresch, Anna Marie, Phd from The University of Wisconsin - Milwaukee, 1992, 118 pages http://wwwlib.umi.com/dissertations/fullcit/9317621

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Senility and Self in Modern America: a Cultural History of Alzheimer's Disease by Ballenger, Jesse Francis; Phd from Case Western Reserve University, 2000, 368 pages http://wwwlib.umi.com/dissertations/fullcit/9968137

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Serotonergic Alterations in Rats with a Cholinergic Hypofunction and in Alzheimer's Disease by Garcia Alloza, Monica; Dr from Universidad De Navarra (spain), 2002, 294 pages http://wwwlib.umi.com/dissertations/fullcit/f364817

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Service Utilization Patterns of Caregivers of People with Alzheimer's Disease by Webber, Pamela Arnsberger, Phd from University of California, Berkeley, 1991, 221 pages http://wwwlib.umi.com/dissertations/fullcit/9228904

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Simulated Design and Analysis of a Cognitive Prosthetic for Alzheimer's Disease by Delnegro, Rina Alice; Ms from San Jose State University, 2002, 124 pages http://wwwlib.umi.com/dissertations/fullcit/1408786

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Social Support and Coping with Spousal Alcoholism and Alzheimer's Disease by Reibstein, Ruth Joy, Edd from Boston University, 1989, 177 pages http://wwwlib.umi.com/dissertations/fullcit/8918515

Dissertations 215

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Social Support and Psychological Distress among Spouse Caregivers of Dementia Patients (alzheimer's Disease) by Fox, Mary Vyn, Phd from The University of Arizona, 1986, 114 pages http://wwwlib.umi.com/dissertations/fullcit/8613815

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Spiritual Well-being and Caregiver Burden in Primary Family Caregivers of Community Dwelling Persons with Alzheimer's Disease and Related Disorders by Spurlock, Wanda Raby; Dns from Louisiana State Univ. Health Sciences Center School of Nursing, 2002, 182 pages http://wwwlib.umi.com/dissertations/fullcit/3049620

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Stress in the Work of Dementia Care: a Comparison of Eight Alzheimer's Day Care Centers (alzheimer's Disease) by Lyman, Karen A., Phd from University of Southern California, 1989 http://wwwlib.umi.com/dissertations/fullcit/f3590612

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Structure and Cytotoxicity of the Beta Amyloid Peptide in Alzheimer's Disease by Demeester, Nathalie; Drsc from Rijksuniversiteit Te Gent (belgium), 2002, 99 pages http://wwwlib.umi.com/dissertations/fullcit/f364545

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Studies on Nitric Oxide Synthases in Age-dependent Cognitive Impairments and Alzheimer's Disease by Law, Andrew C.-k.; Phd from Mcgill University (canada), 2002, 304 pages http://wwwlib.umi.com/dissertations/fullcit/NQ78710

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Syntactic and Symbolic Abilities in Alzheimer's Disease (aphasia, Grammar) by Kempler, Daniel, Phd from University of California, Los Angeles, 1984, 165 pages http://wwwlib.umi.com/dissertations/fullcit/8428531

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Temporal Morphology and Neuropsychological Correlates in Alzheimer's Disease and Normal Aging by Hessel, Cory Dean; Phd from Brigham Young University, 2003, 83 pages http://wwwlib.umi.com/dissertations/fullcit/3077572

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Testing the View That the Semantic Memory Deficit in Alzheimer's Disease Reflects a Loss of Semantic Knowledge by Alathari, Lina; Phd from The George Washington University, 2002, 90 pages http://wwwlib.umi.com/dissertations/fullcit/3045166

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The Appraisal Process in Stress and Coping Models: Fear of Inheritability, Knowledge of Alzheimer's Disease, and Caregiver Burden by Kelly, Timothy Brian, Phd from University of Georgia, 1994, 103 pages http://wwwlib.umi.com/dissertations/fullcit/9507221

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The Caregiving Experience of Spouses of Persons with Alzheimer's Disease by Dolan, Brigit Mary; Msn from Gonzaga University, 2002, 73 pages http://wwwlib.umi.com/dissertations/fullcit/1409466

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The Cd40/cd40l Receptor/ligand Dyad: Role in the Pathogenesis of Alzheimer's Disease by Town, Terrence Christopher; Phd from University of South Florida, 2002, 180 pages http://wwwlib.umi.com/dissertations/fullcit/3071328

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The Contribution of Higher-level Visual Processes to Everyday Functional Activities in Alzheimer's Disease (ad) by Jefferson, Angela Lee; Phd from Drexel University, 2003, 121 pages http://wwwlib.umi.com/dissertations/fullcit/3086402

216 Alzheimer’s Disease

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The Effect of a Leisure Education Program on the Coping Strategies and Leisure Attitudes of Caregivers of Persons with Alzheimer's Disease by Lynch, Susan Elaine, Phd from Texas Woman's University, 1993, 137 pages http://wwwlib.umi.com/dissertations/fullcit/9407749

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The Effects of a Group Support Program on Decreasing Feelings of Burden and Depression in Relatives of Patients with Alzheimer's Disease and Other Dementing Illnesses by Kahan, Jason S., Phd from United States International University, 1984, 149 pages http://wwwlib.umi.com/dissertations/fullcit/8414952

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The Effects of Music Therapy Interventions on Naming and Verbal Fluency in Persons with Probable Alzheimer's Disease by York, Elizabeth Fair, Phd from University of Miami, 1995, 129 pages http://wwwlib.umi.com/dissertations/fullcit/9600365

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The Family Caregivers' Health Decision-making about Early Diagnosis for Alzheimer's Disease Patients by Zhao, Ping Zhong, Phd from Portland State University, 1991, 174 pages http://wwwlib.umi.com/dissertations/fullcit/9202279

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The Grammars of the Old Age Problem: from Activity Theory to Alzheimer's Disease (senility, Gerontology) by Lynott, Robert Joseph, Phd from Loyola University of Chicago, 1987, 275 pages http://wwwlib.umi.com/dissertations/fullcit/8704849

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The Gratifications, Frustrations, and Well-being of Older Women Caring at Home for Husbands with Alzheimer's Disease or a Related Disorder (family Caregivers, Dementia, Caregivers) by Motenko, Aluma K., Phd from Boston University, 1988, 192 pages http://wwwlib.umi.com/dissertations/fullcit/9209493

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The Impact of Alzheimer's Disease on Nursing Care: Implications for Nursing Education by Cullen, Patricia Anne, Edd from Temple University, 1994, 170 pages http://wwwlib.umi.com/dissertations/fullcit/9434661

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The Impact of Anticipatory Grief on Caregivers of Patients with Alzheimer's Disease (grief) by Walker, Rebecca Albritton, Phd from The University of Texas at Austin, 1994, 329 pages http://wwwlib.umi.com/dissertations/fullcit/9506122

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The Impact of Family Environment on Coping with Spouse Impairment in Alcoholism and Alzheimer's Disease (alzheimer Disease) by Golden, Lisa Anne, Edd from Boston University, 1989, 173 pages http://wwwlib.umi.com/dissertations/fullcit/8920097

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The Influence of Autobiographical Significance and Time of Acquisition on Semantic Memory: Evidence from Amnesia, Alzheimer's Disease, Semantic Dementia and Healthy Aging by Westmacott, Robyn Margaret; Phd from University of Toronto (canada), 2002, 341 pages http://wwwlib.umi.com/dissertations/fullcit/NQ74775

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The Influence of Frequency, Concreteness, and Grammatical Category on Semantic Processing and Word Retrieval in Probable Alzheimer's Disease by Granier, Jay Patrick; Phd from The University of Iowa, 2002, 196 pages http://wwwlib.umi.com/dissertations/fullcit/3058405

Dissertations 217

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The Influence of the Environment on Resistiveness to Care and the Effectiveness of an Intervention to Decrease Resistiveness to Care in People with Alzheimer's Disease Residing in Institutions by Bellar, Ann; Phd from Wayne State University, 2002, 275 pages http://wwwlib.umi.com/dissertations/fullcit/3071756

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The Lived Experience of Men and Women Who Have Placed a Spouse with Alzheimer's Disease in a Nursing Home by Browne, Vera Janis; Dnsc from Rush University, 2002, 187 pages http://wwwlib.umi.com/dissertations/fullcit/3042246

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The Medicalization of Alzheimer's Disease: Processes and Consequences for Public Policy by Rotwein, Suzanne, Phd from The University of Texas at Dallas, 1991, 205 pages http://wwwlib.umi.com/dissertations/fullcit/9135740

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The Pathological Role of Alterations in Calcineurin (protein Phosphatase 2b) Phosphatase Activity in Alzheimer's Disease by Lian, Qingyu; Phd from Loyola University of Chicago, 2002, 185 pages http://wwwlib.umi.com/dissertations/fullcit/3039290

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The Phoenix Rising: Self-development in Caregivers for Relatives with Alzheimer's Disease by Bar-david, Geila Naava, Phd from University of Toronto (canada), 1992, 365 pages http://wwwlib.umi.com/dissertations/fullcit/NN92894

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The Role of Cyclin-dependent Kinase 5 in Alzheimer's Disease Pathogenesis by Lee, Ming-sum; Phd from Harvard University, 2002, 267 pages http://wwwlib.umi.com/dissertations/fullcit/3051216

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The Role of Focal Adhesion Signaling in Alzheimer's Disease by Grace, Elizabeth Ann; Phd from The University of Connecticut, 2002, 118 pages http://wwwlib.umi.com/dissertations/fullcit/3062080

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The Role of Human Kallikrein 6 in the Pathogenesis of Alzheimer's Disease by Zarghooni, Maryam; Msc from University of Toronto (canada), 2002, 103 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74047

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The Role of Mapk Pathways in Alzheimer's Disease by Zhu, Xiongwei; Phd from Case Western Reserve University (health Sciences), 2002, 147 pages http://wwwlib.umi.com/dissertations/fullcit/3061319

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The Role of Mononuclear Phagocyte Priming and Activation in Hiv-1-associated Dementia and Alzheimer's Disease by Cotter, Robin L.; Phd from University of Nebraska Medical Center, 2002, 265 pages http://wwwlib.umi.com/dissertations/fullcit/3054198

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The Role of Verb Knowledge in the Sentence Comprehension Deficits of Individuals with Alzheimer's Disease and Frontotemporal Dementia by Price, Catherine E. Crenshaw; Phd from Drexel University, 2002, 201 pages http://wwwlib.umi.com/dissertations/fullcit/3061130

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The Search for Novel Susceptibility Loci Involved in Late Onset Alzheimer's Disease: Significant Findings on Chromosome 10 and a Possible Protective Effect of the Urokinase Plasminogen Activator Gene by Myers, Amanda Jennings; Phd from Washington University, 2002, 245 pages http://wwwlib.umi.com/dissertations/fullcit/3065075

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The Use of Single Photon Emission Computed Tomography (spect) Profiles to Identify Correlates of Behavioural Responses to Donepezil Therapy in Alzheimer's Disease by Lolou, Maysoon Mohamed Nasr; Msc from University of Toronto (canada), 2002, 167 pages http://wwwlib.umi.com/dissertations/fullcit/MQ68808

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The Value of Support Groups for Caregivers of a Patient with Alzheimer's Disease: a Family System's Perspective by Stanley, Renee, Phd from Texas Woman's University, 1987, 115 pages http://wwwlib.umi.com/dissertations/fullcit/8715024

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Theory of Mind, Empathy, and Insight in Alzheimer's Disease by Caoile, Jacqueline Daasch; Phd from Fuller Theological Seminary, School of Psychology, 2002, 108 pages http://wwwlib.umi.com/dissertations/fullcit/3046363

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Using Engineering Tools to Examine the Mechanisms of Alzheimer's Disease by Wang, Sheng-shih; Phd from Texas A&m University, 2002, 207 pages http://wwwlib.umi.com/dissertations/fullcit/3060919

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Visual Selective Attention in Alzheimer's Disease: Effects of Physical Similarity, Density, and Target-to-distractor Ratio in a Cancellation Task by Schaefer, Lynn Anne; Phd from City University of New York, 2002, 258 pages http://wwwlib.umi.com/dissertations/fullcit/3037441

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Wandering, Getting Lost, and Alzheimer's Disease: Influences on Precautions Taken and Levels of Supervision Provided by Caregivers by Salmons, Terri Gail; Phd from University of Massachusetts Boston, 1999, 135 pages http://wwwlib.umi.com/dissertations/fullcit/9951876

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL TRIALS AND ALZHEIMER’S DISEASE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Alzheimer’s disease.

Recent Trials on Alzheimer’s Disease The following is a list of recent trials dedicated to Alzheimer’s disease.8 Further information on a trial is available at the Web site indicated. •

A study of the safety and efficacy of multiple doses of ABT-089 in subjects with Alzheimer's disease Condition(s): Alzheimer's Disease Study Status: This study is currently recruiting patients. Sponsor(s): Abbott Laboratories Purpose - Excerpt: The purpose of this study is to compare the safety and efficacy of 2 mg, 4 mg, and 20 mg of ABT-089 BID to placebo in adults with Alzheimer's disease. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069849

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Alzheimer's Disease and Aging: Therapeutic potential of estrogen Condition(s): Alzheimer's Disease Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: This study is designed to evaluate the potential beneficial effects of estrogen on cognitive function of women with Alzheimer's Disease.

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These are listed at www.ClinicalTrials.gov.

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Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018343 •

Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT) Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Aging (NIA); Veterans Administration (VA) Puget Sound Health Care System,; University of Washington, Seattle; Johns Hopkins University Purpose - Excerpt: The purpose of this trial is to test the ability of the non-steroidal antiinflammatory medications naproxen and celecoxib to delay or prevent the onset of AD and age-related cognitive decline. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007189

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Alzheimer's Disease Genetics Study Condition(s): Alzheimer Disease; Late Onset Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Aging (NIA) Purpose - Excerpt: The purpose of the Alzheimer's Disease Genetics Study is to identify the genes that are responsible for causing Alzheimer's Disease (AD). One of the ways in which the risk factor genes for late onset AD can be investigated is by identifying and collecting genetic material from families with multiple members diagnosed with late onset (over 60 years of age) AD. Families meeting the criteria will have a sibling pair diagnosed with AD with an onset of age 60 or older and at least one other affected or unaffected relative willing to participate. Families will be evaluated for a medical diagnosis and other factors. If eligible, blood samples will be collected to establish cell lines. If one of the identified family members is deceased, DNA will be extracted and stored from autopsy samples. Local sites will collect clinical and demographic data from the families and will send coded data (without identifiers) to the National Cell Repository for Alzheimer's Disease (NCRAD) at Indiana University. Persons interested in registering to participate in this study can call the toll-free NCRAD number 1-800526-2839 for more information. Local study sites are located all over the United States, and arrangements may be made for eligible families who do not live near a participating site Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00064870

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Alzheimer's Disease Treatment and Illness Perceptions Survey (TIPS) II Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): Alzheimer's Association Purpose - Excerpt: The TIPS Study, or Treatment and Illness Perceptions Survey, is a study funded by the national Alzheimer's Association to learn more about differences between African Americans' and Whites' attitudes, beliefs, and experiences related to Alzheimer's disease (AD). The study involves a one-time 30-minute telephone survey in which participants are asked about a range of topics related to AD, including their personal experiences, their beliefs about the disease's symptoms and risk factors, and their attitude toward possible future treatment options. Information from the survey will be used to develop more culturally sensitive health education and healthcare services for persons with AD. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00059410

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Alzheimer's Disease: Therapeutic Potential of Estrogen Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institutes of Health (NIH) Purpose - Excerpt: This is a 15-month study to determine the effectiveness of hormone replacement therapy in improving memory and the ability to live independently in postmenopausal women with Alzheimer's disease. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066157

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Bathing persons with Alzheimer's disease aT Home (The BATH Study) Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Nursing Research (NINR) Purpose - Excerpt: This study will evaluate the effectiveness of a 3-week reminiscence intervention applied during bathing persons with Alzheimer's disease (AD) in decreasing resistiveness to care (RTC), relieving patient discomfort, and improving spouse caregiver appraisals of burden, capabilities and confidence while bathing the patient. Reminiscence provides opportunities for the patient to feel good and recall pleasant memories, easily done by caregivers in a home setting. Home visits and telephone calls from trained nurses provide coaching and practice for caregivers for the preliminary phase of this study. Each couple will be enrolled in the study for approximately 9 weeks. The study will recruit 100 patient/spouse caregiver couples randomly divided into one of two groups: reminiscence with coaching, or bathing support (control). Bathing support will be provided to participants in both conditions

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including: individualized assessment; education regarding bathing techniques for people with dementia; and individualized problem solving. In addition to the bathing support intervention, participants in the experimental group will receive a pleasant memories interview and reminiscence script with coaching for implementation. Caregivers will keep a journal of their experiences in bathing the care recipien Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062569 •

Brain Imaging in Alzheimer's Disease Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to use brain imaging technology to examine the role of certain brain chemicals in individuals with Alzheimer's disease (AD) and in healthy volunteers. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039702

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Brain Imaging in Elderly People and Individuals with Alzheimer's Disease Condition(s): Alzheimer's Disease; Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to use brain imaging technology to study the effects of aging and Alzheimer's Disease (AD) on a specific type of brain receptor. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001917

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Brain Study of Patients with Frontal Lobe Dementia and Parkinsonian Disorders Condition(s): Alzheimer's Disease; Dementia; Down's Syndrome Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The Cognitive Neuroscience Section of the National Institute of Neurological Disorders and Stroke proposes to continue its cross-sectional and longitudinal studies of cerebral metabolism in frontal lobe dementias and atypical basal ganglia disorders. These studies include repeated assessments of neuropsychological and brain anatomical and metabolic function in subjects with these important and possibly related brain disorders. Study Type: Observational Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00001178 •

CATIE-Alzheimer's Disease Trial Condition(s): Alzheimer's Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The CATIE Alzheimer's Disease Trial is part of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Project. The study is for people with Alzheimer's disease who are having trouble with their thinking or behavior. In particular, this study is trying to find out the best treatment for people who have hallucinations (seeing or hearing things that aren't there), delusions (false beliefs), or agitation. The design of the trial helps to increase the chance that participants in the study receive a medication that helps them. The study uses three medications known as atypical antipsychotics (olanzapine, quetiapine, risperidone), which are the newest medications that are currently available for treating these problems. Participants may also receive an antidepressant (citalopram). The trial lasts for 36 weeks. Participants are given a thorough evaluation at no cost to ensure that this study is appropriate. In addition, the caregiver, family member, or friend who comes with the participant will be offered an educational program about Alzheimer's disease. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015548

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Cholesterol Lowering Agent to Slow Progression (CLASP) of Alzheimer's Disease Study Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Aging (NIA) Purpose - Excerpt: CLASP is a research study to investigate the safety and effectiveness of simvastatin (a cholesterol lowering drug or statin) to slow the progression of Alzheimer's disease (AD). Statins are commonly used to treat high cholesterol levels, which increase the risk of heart disease and stroke. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053599

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Clinical and Genetic Studies of Familial Presenile Dementia with Neuronal Inclusion Bodies Condition(s): Familial Dementia with Neuroserpin Inclusion Bodies; Nervous System Heredodegenerative Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Human Genome Research Institute (NHGRI)

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Purpose - Excerpt: The purpose of this study is to learn more about the medical problems and the genetic factors involved in a recently defined form of inherited dementia called "familial dementia with neuroserpin inclusion bodies (FDNIB)." Abnormal substances in nerve cells of patients with this disease affect brain and nervous system function, causing confusion, memory decline and impaired cognition (thinking ability). Patients also develop movement disorders and, possibly, seizures. Symptoms begin in midlife, between 45 and 55 years of age. Patients with FDNIB and family members 18 years of age or older at risk for the disease may be eligible for this 3-year study. Participants will have a medical and family history and review of medical records; interview with a medical geneticist (specialist in genetics); physical, neurological and psychiatric examinations; and the following tests and procedures: 1. Blood tests to assess general health 2. Chest and skull X-rays 3. Electrocardiogram (EKG)-record of the electrical activity of the heart using electrodes placed on the chest 4. Electroencephalogram (EEG)-record of the electrical activity of the brain using electrodes placed on the head 5. Ultrasound of the abdomen-imaging of abdominal organs using sound waves 6. Brain magnetic resonance imaging (MRI)-imaging of the brain using a strong magnetic field and radio waves 7. Hearing evaluation 8. Assessment of performance of daily living activities 9. Single photon emission computed tomography (SPECT)-imaging of brain metabolism and blood flow using a radioactive substance injected into a vein The evaluation will be done over a 3- to 4-day period. At their completion, participants will meet with a physician and a genetics counselor to discuss the clinically significant findings. Participants may be asked to return for followup evaluations every 6 months to a year (depending on the individual's condition) for 3 years. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006176 •

COGNIShunt(r) System for Alzheimer's Disease Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): Eunoe Purpose - Excerpt: This is a study of the effect on the progression of Alzheimer's Disease of a surgically implanted shunt (tube) to increase the flow of cerebrospinal fluid and improve the clearance of potential neurotoxins from the fluid bathing the brain. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056628

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Cognitive and Neurophysiological Effects of Raloxifene in Alzheimer's Disease Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): University of Wisconsin Purpose - Excerpt: The aim of this study is to determine the effectiveness of treatment with raloxifene, an estrogen-like medication approved by the Food and Drug

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Administration for the treatment of osteoporosis, in improving memory and the ability to live independently in postmenopausal women with Alzheimer's disease. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065767 •

Diagnosis and Natural History Study of Patients with Neurological Conditions Condition(s): Alzheimer's Disease; Dementia; Movement Disorder; Multiple System Atrophy; Parkinson's Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The purpose of this study is to improve understanding of neurological conditions. Patients participating in this study will continue receiving medical care, routine laboratory tests, and diagnostics tests (X-rays, CT-scans, and nuclear imaging), from their primary care physician. Doctors at the NIH plan to follow these patients and offer advice and assistance to their primary care physicians. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001549

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Effects of an Anti-Inflammatory Drug in Alzheimer's Disease Condition(s): Alzheimer's Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to evaluate the effects of the drug cyclophosphamine (CY) on inflammation and immune responses in individuals with Alzheimer's Disease (AD). Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00013650

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Effects of Estrogen on Memory in Post-Menopausal Women and Patients With Alzheimer's Disease Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Alzheimer's Association; Pfizer; Eisai Medical Research Inc Purpose - Excerpt: The goal of this study is to examine whether the administration of estrogen to post-menopausal women and women with mild to moderate Alzheimer's disease will enhance their memory and their capacity for learning.

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Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006399 •

Efficacy and Safety of LY451395 in Patients with Probable Alzheimer's Disease Condition(s): Alzheimer's Disease Study Status: This study is currently recruiting patients. Sponsor(s): Eli Lilly and Company Purpose - Excerpt: Study of an investigational medication for the treatment of Alzheimer's Disease in patients who are not taking Aricept, Reminyl, Exelon. Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051909

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Evaluation of Age- and Alzheimer's Disease-Related Memory Disorder Condition(s): Alzheimer Disease; Dementia; Memory Disorder; Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to examine how a part of the brain called the hippocampus contributes to memory changes that occur with aging and Alzheimer's disease (AD). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029120

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Gene-Environment Interactions in Alzheimer's Disease Condition(s): Alzheimer's Disease Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: This study will create Alzheimer 's disease risk profiles for defined combinations of genotypes and environmental exposures. This study will carry out a molecular epidemiologic study to identify genetic and environmental risks factors using state of the art techniques. The following will be done during the course of this study 1) Recruit both Alzheimer's patients and cognitively normal aged veterans. 2) Evaluate gene interaction in Alzheimer's disease. 3) Evaluate gene-environment interactions on the risk of Alzheimer's disease. These procedures should initially address the question as to whether certain genes either independently or synergistically modify the risk of Alzheimer's disease. This study will also determine whether certain environmental factors (smoking, alcohol consumption etc.) can modify the risk of AD and whether this effect is dependent on certain genetic backgrounds. This study will provide information that will be useful in designing therapies, develop risk factor profiles to be further tested in future studies, designating patients for specific therapies based on genetic factors and providing data and genetic material for future studies. This study will also provide a

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cohort of older and well characterized cognitively normal veterans for prospective genetic epidemiological studies on aging. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018473 •

High Intensity Light Therapy in Alzheimer's Disease Condition(s): Alzheimer's Disease; Dementia Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM); National Institute on Aging (NIA) Purpose - Excerpt: The purpose of this study is to determine whether bright light improves the sleep, mood, and behavior of persons with Alzheimer's disease and related dementias (AD) who live in long-term care settings and, if so, to determine the best timing for the light therapy. The light levels being used in the study have been shown to improve depression in persons with seasonal affective disorder (SAD) and to relieve sleep problems in persons with jet lag and other body rhythm disturbances. Because persons with AD often will not remain still in front of a fluorescent panel, this project has involved renovations in the study units that provide for even, regulated, highintensity light in all public areas of the study settings. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065689

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Insulin, Neurogentics and Memory in Alzheimer's Disease Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: This study examines the use of insulin-sensitizing compounds, as therapeutic agents for cognitive impairment in Alzheimer's disease. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018382

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Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADVISE) Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Aging (NIA); National Cancer Institute (NCI) Purpose - Excerpt: The Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADVISE) prevention trial is an important addition to the Selenium and Vitamin E

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Cancer Prevention Trial (SELECT). As a prevention trial, PREADVISE is trying to find out if taking selenium and/or Vitamin E supplements can help to prevent memory loss and dementia such as Alzheimer's disease. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040378 •

Prevention of cognitive decline in Alzheimer's disease by ingested interferon alpha Condition(s): Memory Disorders; Alzheimer's Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Pfizer Purpose - Excerpt: In this phase I-II parallel design, randomized, double-blind clinical trial we will determine if 3,000 or 30,000 units ingested hrIFN-a prevents deterioration of cognitive functioning in patients with dementia of Alzheimer's type (AD) and whether ingested hrIFN-a treatment decreases acute phase reactants and pro-inflammatory cytokine IL-6 in mild to moderate AD. We predict that the novel anti-inflammatory agent ingested human recombinant interferon alpha (hrIFN-a) will modulate inflammation and inhibit the natural history of AD progression. If you are eligible, you will receive Aricept for 5 weeks (donezepil) and thereafter in addition to Aricept either placebo (inactive substance) or interferon alpha at 3,000 or 30,000 units every day for 12 months. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031018

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Safety testing of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Laughter & Crying) Condition(s): Amyotrophic Lateral Sclerosis; Multiple Sclerosis; Alzheimer's Disease; Stroke; Traumatic Brain Injury Study Status: This study is currently recruiting patients. Sponsor(s): Avanir Pharmaceuticals Purpose - Excerpt: The purpose of this study is to evaluate the safety of AVP-923 for the treatment of emotional lability. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056524

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Specific Interventions for Agitation in Alzheimer's Disease Condition(s): Alzheimer's Disease; Dementia Study Status: This study is currently recruiting patients.

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Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: This study is aimed at investigating specific pharmacological interventions in the treatment of the disruptive, agitated behavior associated with Alzheimer's patients. In addition, it is hoped that specific clinical profiles will be found to predict which treatment is most effective for these particular patients. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018291 •

The Effect of Short-Term Statins and NSAIDs on Levels of Beta-Amyloid, a Protein Associated with Alzheimer's Disease Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to determine whether short-term use of the drugs ibuprofen and lovastatin affects levels of a protein called beta-amyloid in people who are at risk for developing Alzheimer's Disease (AD). Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046358

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The Evaluation and Follow-up of Individuals with Memory Disorder Condition(s): Alzheimer's Disease; Dementia; Healthy; Memory Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to evaluate people with mild memory problems, those with dementia, those at risk for developing Alzheimer's disease (AD), and healthy volunteers to identify markers of AD before the changes that occur with the disease begin. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001480

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Treatment of Alzheimer's Disease with CX516 (Ampalex) Condition(s): Alzheimer's Disease; Dementia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: Glutamate is an amino acid released by brain cells that acts to excite other cells. Glutamate attaches to special sites on cells called AMPA (alpha-amino-2,3dihydro-5 methyl 3-oxo-4-isoxazolepropanoic acid) receptors. The brain cells responsible for releasing glutamate are damaged in Alzheimer's disease and other conditions affecting thinking and reasoning. Researchers would like to see if giving

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patients a drug that attaches to AMPA receptors improves the symptoms of Alzheimer's disease. CX516 (Ampalex) is a test drug that affects the AMPA receptors. This study will investigate the effectiveness and safety of CX516 on patients with Alzheimer's disease. Patients will be given capsules of CX516 or placebo (sugar pill that neither harms nor helps) for up to 16 weeks in different amounts. The effectiveness of the drug will be measured by neurological tests. Safety will be monitored by frequent check-ups and lab examinations. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001662 •

Treatment of Behavioral Symptoms in Alzheimer's Disease Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Alzheimer's patients with behavioral problems (e.g., sleep disturbance, agitation) and/or psychosis are commonly treated with antipsychotic medications like haloperidol. This study focuses on the treatment of behavioral symptoms in Alzheimer's disease with haloperidol and whether long term treatment is necessary. The study is conducted in two phases: First, for five months active haloperidol is given, titrating the dose (1-4 mg. daily) for maximum effectiveness while closely monitoring side effects. Second, for those patients who respond and remain stable on the medication, we examine whether continuation medication treatment is necessary. To this end, they are treated for another 24 weeks in a randomized doubleblind placebo-controlled manner. After completing the study, patients are transferred back to their primary physician once the behavioral disturbance and/or psychosis is optimally treated. Drs. D.P. Devanand and G. Pelton are conducting this project. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00009217

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VITAL - VITamins to slow ALzheimer's disease (Homocysteine study) Condition(s): Alzheimer's Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Aging (NIA) Purpose - Excerpt: The purpose of this study is to determine whether reduction of homocysteine levels with high-dose folate (folic acid), B6, and B12 supplementation will slow the rate of cognitive decline in persons with Alzheimer's disease. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056225

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Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “Alzheimer’s disease” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

•

For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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•

For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

•

For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON ALZHEIMER’S DISEASE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “Alzheimer’s disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Alzheimer’s disease, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Alzheimer’s Disease By performing a patent search focusing on Alzheimer’s disease, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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The following is an example of the type of information that you can expect to obtain from a patent search on Alzheimer’s disease: •

4-substituted piperidine analogs and their use as subtype selective NMDA receptor antagonists Inventor(s): Cai; Sui Xiong (Foothill, CA), Wright; Jonathan (Ann Arbor, MI), Bigge; Christopher F. (Ann Arbor, MI), Woodward; Richard (Aliso Viejo, CA), Weber; Eckard (Laguna Beach, CA), Lan; Nancy C. (South Pasadena, CA), Zhou; Zhang-Lin (Irvine, CA), Keana; John F.W. (Eugene, OR) Assignee(s): Warner-Lambert Company (Morris Plains, NJ), Cocensys, Incorporated (Irvine, CA) Patent Number: 6,448,270 Date filed: June 13, 2000 Abstract: Novel 4-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using the 4-substituted piperidine analogs as selectively active antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes for treating conditions such as cerebral ischemia, central nervous system trauma, hypoglycemia, neurodegenerative disorders, anxiety, migraine headaches, convulsions, aminoglycoside antibiotics-induced hearing loss, chronic pain, psychosis, glaucoma, CMV retinitis, opioid tolerance or withdrawal, urinary incontinence and neurodegenerative disorders such as lathyrism, Alzheimers' Disease, Parkinsonism, and Huntington's Disease are described. Also described are novel methods for preparing 4substituted piperidine analogs and novel intermediates of the 4-substituted piperidine analogs. Excerpt(s): This invention is related to 4-substituted piperidine analogs, including hydroxypiperidine and tetrahydropyridine analogs, as well as novel intermediates of the 4-substituted analogs. The analogs are selectively active as antagonists of N-methylD-aspartate (NMDA) receptor subtypes. The invention is also directed to the use of 4substituted piperidine analogs as neuroprotective agents for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headache, chronic pain, glaucoma, CMV retinitis, psychosis, urinary incontinence, opioid tolerance or withdrawal, or neuro-degenerative disorders such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease. Excessive excitation by neurotransmitters can cause the degeneration and death of neurons. It is believed that this degeneration is in part mediated by the excitotoxic actions of the excitatory amino acids (EAA) glutamate and aspartate at the N-methyl-D-Aspartate (NMDA) receptor. This excitotoxic action is considered responsible for the loss of neurons in cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from a range of conditions, such as thromboembolic or hemorrhagic stroke, cerebral vasospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery and cerebral trauma, as well as lathyrism, Alzheimer's Disease, Parkinson's Disease and Huntington's Disease. Ar.sup.1 and Ar.sup.2 are each independently substituted or unsubstituted aryl, a heteroaromatic ring, or a heteroaromatic bicylic ring. The tetrahydropyridines and hydroxypiperidines of this reference are indicated to be useful as central nervous system agents, particularly as dopaminergic, antipsychotic and antihypertensive agents, and for treating central nervous system disorders such as Parkinson Disease, Huntington Disease and depression. The particular 4-substituted piperidines, including the 4-hydroxypiperdines and tetrahydropyridines of this

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invention are not exemplified. In addition, there is no disclosure or suggestion of treating disorders with selective NMDA receptor subtype antagonists and the advantages of such treatment. Web site: http://www.delphion.com/details?pn=US06448270__ •

Chromosome 14 and familial Alzheimers disease genetic markers and assays Inventor(s): Schellenberg; Gerard D. (Seattle, WA), Bird; Thomas D. (Seattle, WA), Wijsman; Ellen M. (Seattle, WA) Assignee(s): University of Washington (Seattle, WA) Patent Number: 5,449,604 Date filed: October 21, 1992 Abstract: Method for isolating a DNA segment indicative of an Alzheimer's disease trait in a family population, wherein said family population consists essentially of a plurality of blood relatives of an individual having a chromosome 14 Alzheimer's disease trait, by: preparing a test sample of immobilized separated genomic DNA fragments from a plurality of the blood relatives, contacting each of the test samples with a test oligonucleotide under conditions permitting hybridization of complementary single stranded DNA molecules, wherein the test oligonucleotide is complementary with at least a portion of a genetic marker located between band q11.2 and band q32.1 in chromosome 14, identifying a plurality of hybridized molecules so formed as alleles of the genetic marker in the family population, identifying one of the genetic marker alleles as indicative of the Alzheimer's disease trait in the family population by either determining by pedigree analysis a segregation value for each of the genetic markers alleles and the Alzheimer's disease trait, and selecting an indicative genetic marker allele that co-segregates with the Alzheimer's disease trait in the family population, or measuring genetic linkage between each of the genetic marker alleles and the Alzheimer's disease trait, and selecting a genetic marker allele as indicative of the Alzheimer's disease trait in the family population if the selected genetic marker allele has a maximal LOD score of at least 3 at a recombination fraction of about 0.0 to about 0.1 for genetic linkage with the Alzheimer's disease trait in the family population, and isolating a chromosome 14 DNA segment containing the indicative genetic marker allele. Excerpt(s): The invention relates to gene probes and molecular genetic assays for early detection of Alzheimer's disease, as well as for identifying individuals who are at an increased relative risk of developing the disease. Alzheimer's disease (AD) is a progressive neurodegenerative disorder which in some (if not all) cases is inherited as an autosomal dominant trait. The first symptoms of AD can occur as early as the fourth to fifth decades of life. Alzheimer's disease is a major disease affecting over 3 million individuals in the U.S. alone at an annual cost of over $30 billion. The role of inheritance in the more common late-onset AD is not presently resolved. Evidence that defective genes may be responsible for some or possibly all late-onset AD has been suggested by clustering of late-onset cases in individual pedigrees (8,14,22), family history data from case-control studies (23-26), and the concordance rates for mono- and di-zygotic twins (27-29). Certain data also suggest the possibility of "sporadic" AD, i.e., where no family history of disease is observed, that could result, for example, from noninherited genetic mechanisms such as somatic recombination or mutation. Web site: http://www.delphion.com/details?pn=US05449604__

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Diagnostic test for alzheimers disease Inventor(s): Favit; Antonelle R. (Bethesda, MD), Grimaldi; Maurizio (Bethesda, MD), Alkon; Daniel L. (Bethesda, MD) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 6,107,050 Date filed: May 11, 1998 Abstract: The present invention provides methods for the diagnosis of Alzheimer's disease using human cells. Specifically, one method detects differences between potassium channels in cells from Alzheimer's patient and normal donors, and differences in intracellular calcium concentrations between Alzheimer's and normal cells in response to chemicals known to increase intracellular calcium levels. Other methods detect differences between the memory associated GTP binding Cp20 protein levels between Alzheimer's and normal cells. Another method utilizes the differential effects of.beta.-amyloid protein on levels of the protein kinase C isoenzymes PKC.alpha. and PKC.gamma. in Alzheimer's and normal cells. Yet another method detects Eu-TTA fluorescence differences between Alzheimer's and normal cells treated with an activator of a receptor-mediated metabolic pathway. In addition a diagnostic index for improved assessment between Alzheimer's and non Alzheimer's cells is provided. Excerpt(s): The present invention relates to methods for diagnosing Alzheimer's disease. The methods utilize newly discovered differences between cells from healthy donors and those with Alzheimer's disease. In one method, differences in the existence of functional potassium channels are assessed. In another method, differences in intracellular calcium levels in response to depolarization by a potassium channel blocker are assessed. In yet another method, differences in intracellular calcium levels in response to a chemical known to increase intracellular calcium levels by releasing calcium from intracellular stores are assessed. In another method, differences in the levels of a memory associated GTP-binding protein (Cp20) between cells from healthy donors and Alzheimer's patients are assessed. This invention also relates to the amino acid sequence for the Cp20 protein. In yet another method, differential effects of.beta.amyloid on levels of the protein kinase C isoenzymes PKC.alpha. and PKC.gamma. in control and Alzheimer's cells are assessed. The invention further relates to another method in which differences in Europium (III) thenoyltrifluoro-acetate (Eu-TAA) fluorescence of cells from healthy donors and Alzheimer's patients are assessed following treatment of the cells with an activator of a receptor-mediated metabolic pathway. In addition, diagnostic indexes that utilize two or more of the above methods to distinguish Alzheimer's patients' cells from control non-AD cells are also provided. Alzheimer's disease is associated with extensive loss of specific neuronal subpopulations in the brain (Sims, N. R., et al. (1987) Annals of Neurology 21:451), with memory loss being the most universal symptom. (Katzman, R. (1986) New England Journal of Medicine 314:964). Alzheimer's disease has been linked to a genetic origin. (Schellenberg, G. D., et al. (1992) Science 258:668; Li, G., et al. (1991) Psychiatric Clinics of North America 14:267; St. George-Hyslop, P. H., et al. (1989) Neurobiology of Aging 10:417; St. George-Hyslop, P. H., et al. (1987) Science 235:885). Early-onset familial forms of the disease exhibit a genetic defect on chromosome 21. (St. George-Hyslop, P. H., et al. (1987)). Cellular changes, leading to neuronal loss and the underlying etiology of the disease, remain unknown. Proposed causes include environmental factors, (Perl, D. P. (1985) Environmental Health Perspective 63:149; Katzman, R. (1986)), including metal toxicity, (Perl, D. P., et al. (1980) Science 208:297), defects in.beta.-amyloid protein

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metabolism, (Shoji, M., et al. (1992) Science 258:126; Joachim, C. L. and Selkoe, D. J. (1992) Alzheimer Disease Assoc. Disord. 6:7; Kosik, K. S. (1992) Science 256:780; Selkoe, D. J. (1991) Neuron 6:487; Hardy, H. and Allsop, D. (1991) Trends in Pharmacological Science 12:383), and abnormal calcium homeostasis and/or calcium activated kinases. (Mattson, M. P., et al. (1992) Journal of Neuroscience 12:376; Borden, L. A., et al. (1991) Neurobiology of Aging 13:33; Peterson, E., et al. (1989) Annals of New York Academy of Science 568:262; Peterson, C., et al. (1988) Neurobiology of Aging 9:261; Peterson, C., et al. (1986) Proceedings of the National Academy of Science 83:7999). Web site: http://www.delphion.com/details?pn=US06107050__ •

Preventive or therapeutic agents for alzheimers disease a screening method of alzheimers disease and tau-protein kinase I originated from human being Inventor(s): Shiratsuchi; Akiko (Sagamihara, JP), Takashima; Akihiko (Machida, JP), Saito; Ken-ichi (Asao-ku, JP), Hoshino; Toshimitsu (Machida, JP), Imahori; Kazutomo (Meguro-ku, JP), Sato; Showbu (Machida, JP) Assignee(s): Mitsubishi Chemical Corporation (Tokyo, JP) Patent Number: 5,837,853 Date filed: February 20, 1996 Abstract: A preventive or therapeutic agent for Alzheimer's disease which comprises a substance exhibiting an inhibitory action to tau-protein kinase I as an effective component is provided. A pharmaceutical composition comprising said agent and a method of inhibiting neuronal cell death in the brain are also provided. Excerpt(s): The present invention relates to a preventive or a therapeutic agent for Alzheimer's disease, a method of screening Alzheimer's disease and tau-protein kinase I which is originated from a human being. More particularly, it relates to a preventive or a therapeutic agent for Alzheimer's disease using a tau-protein kinase I inhibitor; a method of screening for a preventive or a therapeutic agent for Alzheimer's disease utilizing an amyloid beta-protein; a human-originated tau-protein kinase I which phosphorylates tau-protein, partial peptides thereof or peptides similar thereto; a gene which encodes the kinase; and a method of producing the same. Alzheimer's disease is a progressive dementia which develops in late middle ages (45 to 65 years old) and its etiological changes are shrinkage of cerebral cortex due to a neuronal cell loss and degeneration of the neurons while, from the pathological view, many senile plaques and neurofibrillary tangles are noted in the brain. There is no pathologically substantial difference between the disease and senile dementia caused by the so-called natural aging which develops in the senile period of 65 years and older ages and, therefore, this disease is called senile dementia of Alzheimer type. The numbers of the patients having this disease are increasing with an increase in the population of aged people, and so the disease is becoming an increasing health concern of society. There are various theories on the cause of this disease, but the cause is still ambiguous and, accordingly, there has been a demand for more information about the disease. Web site: http://www.delphion.com/details?pn=US05837853__

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Radiopharmaceutical agents for the detection of Alzheimers disease Inventor(s): Efange; Simon Mbua Ngale (Plymouth, MN), Parsons; Stanley M. (Santa Barbara, CA) Assignee(s): Regents of the University of Minnesota (Minneapolis, MN) Patent Number: 5,721,243 Date filed: June 13, 1994 Abstract: Novel anticholinergics which are related to vesamicol are particularly useful when radiolabeled for evaluating cholinergic innervation in the living human brain. The cholinergic deficit in the Alzheimer's brain should be identifiable with these radioligands. Excerpt(s): This invention relates to a chemical compound that is an anticholinergic. This compound may be labeled and used to track brain nerve cell production of acetylcholine as an indicator of Alzheimer's disease. In U.S. Pat. No. 4,522,965 which issued Nov. 12, 1985 to Stanley M. Parsons, a vesamicol derivative is described for use in blocking conduction at the neuromuscular junction in mammals. Parsons notes that it is desirable to produce a more effective compound than vesamicol for blocking presynaptic release of acetylcholine. The hydroxylated phencyclidine (PCP) isomer trans-2-(4phenylpiperidino)cyclohexanol (vesamicol, AH5183) induces respiratory paralysis and death in rodents and other laboratory animals (Brittain et al., 1969). Subsequent investigations have revealed that the biological activity of vesamicol is mediated in part by its ability to inhibit both the uptake of ACh into cholinergic synaptic vesicles and quantal release of this neurotransmitter from cholinergic neuron (for review, see Marshall and Parsons, 1987). Web site: http://www.delphion.com/details?pn=US05721243__

•

Transdermal propentofylline compositions for the treatment of Alzheimers disease Inventor(s): Venkateshwaran; Srinivasan (Salt Lake City, UT) Assignee(s): Theratech, Inc. (Salt Lake City, UT) Patent Number: 5,762,953 Date filed: August 22, 1996 Abstract: Patients suffering from Alzheimer's disease are treated by transdermally administering an effective amount of propentofylline in the form of an occulsive device containing a delivery composition comprising a carrier vehicle having uniformly distributed therein effective amounts of propentofylline and, optionally, a penetration enhancer. The occulsive device may be a matrix type patch in which the carrier vehicle is a pressure sensitive adhesive or a reservoir type patch in which the carrier vehicle is a liquid of controlled viscosity, i.e. a gel, wherein the reservoir system contains means for maintaining it in a propentofylline transferring relationship with the derma when applied. Daily dosages of between about 5 and 49 mg/day are sufficient to maintain adequate plasma propentofylline levels. Excerpt(s): The present invention relates to a method for the delivery of a pharmaceutical agent for the treatment of memory disfunctions. More particularly, this invention relates to non-oral and noninvasive methods of delivery of a therapeutic agent used for the treatment of memory disfunctions. Specifically, this invention relates to a transdermal method of delivery of 1,2,3,6-tetrahydro-3-methyl-1-(3-oxohexyl)-7-

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propylpurine-2,6-dio ne (hereinafter referred to as propentofylline). Various potential routes for the delivery of pharmaceutical agents have been considered: invasive (e.g. direct injection: intravenous, subcutaneous, intramuscular and depot systems) and noninvasive (e.g. pulmonary, oral, nasal, buccal, ocular, rectal, vaginal and transdermal). Administration of drugs by injection is not suitable for ambulatory patients and is not generally acceptable to patients undergoing drug therapy for chronic diseases. Also this route is far from being an ideal route of administration of molecules with short biological half-lives which necessitate repeated injections. The oral delivery route is often proposed as being superior to all others. However, the delivery of some drugs using the oral route is fraught with difficulties which center around low bioavailability. Some of the factors responsible for low bioavailability are chemical and proteolytic degradation in the GI tract, low permeability of the absorbing tissues due to the size, hydrophilicity and charge characteristics of the drugs, and first pass metabolism in the liver. For drugs with short half-lives, multiple daily dosing would be required. Fluctuations in plasma concentrations due to a combination of low bioavailability and frequent dosing regimen cause wide fluctuations in plasma levels that can lead to pharmacological extremes ranging from drug (and metabolite) associated side effects to significant periods of therapeutically inadequate dosing. Web site: http://www.delphion.com/details?pn=US05762953__ •

Use of presenilin-1 for diagnosis of alzheimers disease Inventor(s): Mathews; Paul M. (Irvington, NY), Nixon; Ralph A. (Tarrytown, NY), Kao; Benjamin H. (New York, NY), Cataldo; Anne M. (Nanuet, NY) Assignee(s): The McLean Hospital Corporation (Belmont, MA) Patent Number: 5,985,581 Date filed: July 17, 1997 Abstract: The invention provides a method of diagnosing Alzheimer's disease. The method utilizes presenilin-1, whose level is found to be substantially decreased in Alzheimer's patients. Included in the invention are diagnostic kits for Alzheimer's disease and methods of screening for effective therapeutics for the disease. The invention also provides a method of studying the function and regulation of presenilin-1 in brain by the use of primate retinoblastoma cells. Excerpt(s): This invention relates to diagnosis of Alzheimer's disease. Alzheimer's disease (AD) is a devastating impairment of cognitive function prevalent in individuals generally forty-five or older. The cause of AD is not known, nor is there a treatment for AD. However, AD is the first common disease for which allelic variation or mutations at multiple genetic loci are linked to the development of disease in affected families (Roses, Annu. Rev. Med. 47: 387, 1996; Schellenberg, Proc. Natl. Acad. Sci. USA, 92: 8552, 1995). The majority (70-80%) of heritable, early-onset AD maps to chromosome 14 and appears to result from one of more than 20 different amino-acid substitutions within presenilin-1 (PS1) (Schellenberg et al., Science, 258: 668, 1992; Alzheimer's Disease Collaborative Group, Nature Genet, 11: 219, 1995; Sobi et al., Lancet., 346: 439, 1995; Van Broeckhoven, Nature Genet., 11: 230, 1995; Wasco et al., Nature Med., 1: 848, 1995; Sherrington et al., Nature, 375: 754, 1995), the product of the recently identified S182 gene (Sherrington et al., 1995). A similar, although less common, AD-risk locus on chromosome 1 encodes the highly homologous presenilin-2 (Levy-Lahad et al., Science, 269: 970, 1995; Levy-Lahad et al., Science, 269: 973, 1995; Li et al., Proc. Natl. Acad. Sci. USA, 92: 12180, 1995; Rogaev et al., Nature, 376: 775, 1995). Several amino-acid substitutions have been identified

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within PS2 that appear to be causative for early-onset AD (Levy-Lahad et al., Science, 269: 973, 1995; Li et al., Proc. Natl. Acad. Sci. USA, 92: 12180, 1995; Rogaev et al., Nature, 376: 775, 1995). Based upon mRNA detection, the presenilins appear to be ubiquitously expressed, suggesting that they are housekeeping proteins required by many cell types. The two mammalian presenilins share 67% amino-acid identity and apparently belong to a larger gene-family of multimembrane spanning proteins that includes the C. elegans spe-4 and sel-12 genes. Mutations in the spe-4 gene disrupt the formation of a Golgiderived storage and delivery organelle required for spermatogenesis in the nematode (L'Hernault et al., J. Cell Bio., 119: 55, 1992). SEL-12 has been shown to facilitate signaling by lin-12, a member of the Notch family of transmembrane receptors critical for cell surface to nucleus signaling during development (Levitan et al., Nature, 377: 351, 1995). A possible ER and/or Golgi localization of epitope-tagged constructs overexpressed in cultured cells and a similar immunolabeling pattern reported in mouse pyramidal neurons are consistent with the presenilins being integral membrane proteins found within compartments of the secretory pathway (Kovacs et al., Nature Med., 224: 224, 1996; Moussaoui et al., FEBS Letters, 383: 219, 1996). This, in conjunction with the spe-4 phenotype and the known importance of membrane proteins and their compartmentalization in AD, has led to the conjecture that the presenilins play a role in membrane protein trafficking and/or processing along the secretory pathway (Kovacs et al., Nature Med., 224: 224, 1996; Pellegrew et al., in Alzheimer disease, eds. R. D. Terry, R. Katzman, and K. L. Bick, Raven Press, New York, 1994; Harrison, Lancet, 346: 388, 1995). However, no direct evidence currently exists ascribing such a function to the presenilins, nor is there evidence suggesting any specialized role for presenilins in the brain. Finally, the broad distribution of the identified AD-causing mutations throughout PS1 and PS2 has yet to suggest any clear mechanistic link between these mutations and the disease process (Van Broeckhoven, Nature Genet., 11: 230, 1995). Web site: http://www.delphion.com/details?pn=US05985581__

Patent Applications on Alzheimer’s Disease As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to Alzheimer’s disease: •

Methods for detecting Alzheimers disease Inventor(s): Diamandis, Eleftherios P.; (Toronto, CA) Correspondence: MERCHANT & GOULD PC; P.O. BOX 2903; MINNEAPOLIS; MN; 55402-0903; US Patent Application Number: 20020182644 Date filed: October 26, 2001 Abstract: Methods for diagnosing and monitoring Alzheimer's Disease in a subject comprising measuring hK6 in a sample from the subject. hK6 may be measured using a reagent that detects or binds to hK6, preferably antibodies reactive with hK6.

10

This has been a common practice outside the United States prior to December 2000.

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Excerpt(s): The invention relates to methods for detecting Alzheimer's Disease. Alzheimer's disease (AD) is the major cause of dementia in the elderly. Although rare genetic forms of AD exist, most patients are classified as having sporadic AD, since no family history is usually identified. Pathologically, AD is characterized by neuronal and synaptic degeneration with an increased number of senile plaques and neurofibrillary tangles compared to non-demented individuals of comparable age (1-3). The senile plaques, characteristic of Alzheimer's disease, are composed of a central core of aggregated beta-amyloid, a breakdown product of amyloid precursor protein (APP) (2). The neurofibrillary tangles are insoluble intracellular thread-like structures made up of a hyberphospholated form of a protein called tau, which is associated with microtubles (4). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with Alzheimer’s disease, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “Alzheimer’s disease” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on Alzheimer’s disease. You can also use this procedure to view pending patent applications concerning Alzheimer’s disease. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON ALZHEIMER’S DISEASE Overview This chapter provides bibliographic book references relating to Alzheimer’s disease. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Alzheimer’s disease include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “Alzheimer’s disease” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on Alzheimer’s disease: •

Early Story of Alzheimer's Disease (Translation of the Historical Papers by Alois Alzheimer, Oskar Fischer, Francesco Bonfiglio, Emil Kraepelin, and Gaetano Perusini) Source: Padova, ITALY: Liviana Press. 1987. 147 p. Contact: Available from Raven Press. 1185 Avenue of the Americas, New York, NY 10036. (212) 886-1200. PRICE: $55.00. ISBN: 8876754237. Summary: These translations of the publications on Alzheimer's disease (AD) is the first effort by the World Federation of Neurology Research Group on Dementias and the Italian Study Group on Brain Aging to bring the thinking of the early researchers to current investigators involved in research on AD and related disorders. Following the key paper describing AD by Alois Alzheimer reporting on a characteristic disease of the cerebral cortex, five additional historic research papers are presented. These include:

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special findings in a case of probable cerebral syphilis (by Francesco Bonfiglio); miliary necrosis with nodular proliferation of the neurofibrils as a common change of the cerebral cortex in senile dementia (Oskar Fischer); descriptions of senile and pre-senile dementias (Emil Kraepelin); histology and clinical findings of several psychiatric diseases of older people (Gaetano Perusini); and the nosographic value of some histopathological findings in senility (Gaetano Perusini). •

When Someone You Love Has Alzheimer's Disease: The Caregiver's Journey Source: Boston, MA: Beacon Press. 1996. 163 p. Contact: Available from Houghton Mifflin. 181 Ballardvale Street, Wilmington, MA 01887. (800) 225-3365. FAX: (800) 634-7568. PRICE: $22.00. ISBN: 0807027200. Summary: This book is designed for families and friends of Alzheimer's disease patients. The authors provide insights based on their own experiences. The book reviews the symptoms and diagnosis of Alzheimer' s disease and the range of emotions that families and loved ones may experience. The authors provide guidelines for caring for Alzheimer's disease patients as well as caregiver support strategies; discuss spiritual and emotional issues among patients and caregivers; and respond to frequently asked questions about symptoms, disease progression, patient care, genetic factors, and safety. References included.

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Broken Connections: Alzheimer's Disease: Part II: Practical Guidelines for Caring for the Alzheimer Patient Source: Amsterdam, Netherlands: Swets and Zeitlinger B. V. Lisse. 1994. 325 p. Contact: Available from Taylor and Francis. 1900 Frost Road, Suite 101, Bristol, PA 19007-1598. (215) 785-5800. PRICE: $30.00. ISBN: 9026513712. Summary: This book is the second part of a two-part guide for the daily care and nursing of patients with Alzheimer's disease (AD) (see AZBK04766 for part 1). Six chapters describe concrete tasks that enable caregivers to give AD patients professional and compassionate care as the disease progresses. Using a series of practical guidelines and suggestions, this book shows how caregivers can work constructively with AD patients. With respect to nursing care, AD is divided into four stages: (1) stimulation and encouragement; (2) intervention; (3) partial take-over of the patient's daily activities by the caregiver; and (4) complete take-over of the patient's daily activities by the caregiver. In each chapter, detailed schemes are given for each stage. They deal personal care and hygiene; household, social, and recreational activities; and financial affairs. Chapters describe early symptoms, how to stimulate activity, intervention, partial takeover actions, and how to take over the patient's activities completely. The final chapter describes a test that helps assess AD patients.

•

Successful Communication with Alzheimer's Disease Patients: An In-Service Manual Source: Boston, MA: Butterworth-Heinemann. 1997. 288 p. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801. (800) 366-2665. Fax (800) 446-6520. E-mail: [email protected]. Website: www.bh.com. PRICE: $39.50 plus shipping and handling. ISBN: 0750695641. Summary: This book offers a series of inservice instructional units written for professionals who care for persons with Alzheimer's disease (AD). Every unit focuses on a specific aspect of communication in long term care (LTC) settings, including:

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communication in the nursing home; communication problems and strengths of patients with AD and related disorders; other communication disorders in AD; effects of the physical environment on communication; effects of the psychosocial environment on communication; communication strengths and problems of professionals who care for patients with AD; multicultural issues in nursing homes; verbal abuse and communication neglect; positive techniques for successful conversation with AD patients; positive techniques for handling difficult communication situations; positive techniques for communicating with families of AD patients; and direct intervention programs for AD patients. Each unit recommends effective techniques that show how to become a better communicator, how to support patients' best communication efforts, and how to minimize or avoid disastrous communication breakdowns. Appendices include quizzes on the material in each chapter, and masters for making overheads of the instructional concepts. A subject index concludes the volume. •

Cuando El Dia Tiene 36 Horas: Una Guia Para Cuidar a Enfermos Con Perdida De Memoria Demencia Senil y Alzheimer. [36 Hour Day: A Family Guide to Caring for Persons With Alzheimer's Disease, Related Dementing Source: Mexico, DF, Mexico: Editorial Pax Mexico, Libreria Carlos Cesarman, S.A. 1990. 275 p. Contact: Editorial Pax Mexico, Libreria Carlos Cesarman, S.A. Avenida Cuauhtemoc Number 1430, Colonia Santa Cruz Atoyac, Mexico, DF, CP 03310. 011-525-604-0843. PRICE: Call or write for price information. Summary: This book, written in Spanish, provides guidance to families about the practical aspects of caring for a person with the disease at home. The book includes chapters about diagnosis, symptoms, the distinction between Alzheimer's disease and normal aging, medical diagnostic tests, choosing a team of health professionals to monitor the patient, deciding when the patient is no longer capable of living independently, facilitating the patient's transition from independent to dependent living, understanding the progression of worsening symptoms, and communicating effectively with the patient. The authors suggest ways to adapt the physical surroundings and daily routine to create a safe and comfortable environment and offer guidance on nutrition, exercise, entertainment, personal hygiene, and common medical and behavioral problems. The book discusses support services for caregivers, the family's continued participation in caring for the patient, and caregivers' own health and emotional needs. The final three chapters discuss legal and financial considerations and current research on Alzheimer's disease. This book also is available in a revised edition in English (see AZBK00080).

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Of Two Minds: A Guide to the Care of People With the Dual Diagnosis of Alzheimer's Disease and Mental Retardation Source: Malden, MA: Alzheimer Support Services Cooperative for Human Services, Inc. 1995. 167 p. Contact: Available from Antonangeli, J.M., Director, Alzheimer Support Services Cooperative for Human Services, Inc. 110 Pleasant Street, Malden, MA 02148. (617) 3244303; FAX (617) 397-9411. PRICE: $19.95. Summary: This guidebook offers practical suggestions and techniques for caregivers of people with the dual diagnosis of Alzheimer's disease (AD) and mental retardation. It provides an overview of AD and its manifestations in people with mental retardation and suggests how to structure physical environments in a home and in a day program.

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It also suggests strategies for evaluating and optimizing safety, preventing wandering, and communicating with persons who have impaired memories. Guidelines are detailed for helping these persons with all activities of daily living. Behavior management strategies are given for dealing with such common problems as depression, inappropriate expressions of sexuality, and catastrophic reactions, and so-called nuisance' behaviors such as pacing. Also highlighted are strategies for medical conditions and engaging persons in failure-free activities. A section on caring for the caregiver discusses educational support, helping housemates understand AD, and helping staff cope with grief and loss. Tables, reading list, selected index, and table guide. •

Vivir Con: La Enfermedad De Alzheimer [Living With: Alzheimer's Disease] Source: Madrid, Spain: Meditor, S.L. 1990. 180 p. Contact: Available from Meditor, S.L. Alberto Alcocer 33, 5to. Centro, 28036 Madrid, SPAIN. PRICE: Write for price information. Summary: This illustrated book in Spanish describes the differences between the normal aging process of the brain and the abnormal deterioration caused by Alzheimer's disease. It provides detailed information on caring for the Alzheimer's disease patient at home, including home safety precautions, hygiene, nutrition, feeding, controlling violent behavior, and how to communicate with the patient through the different stages of the illness. The book also presents practical ways in which caregivers can promote their own well being. A brief discussion of early diagnosis and medications also is included, as well as other sources of information.

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Clinical Diagnosis and Management of Alzheimer's Disease Source: Woburn, MA: Butterworth-Heinemann. 1996. 372 p. Contact: Available from Butterworth-Heinemann Fulfillment Center. 225 Wildwood Avenue, Woburn, MA 081801-9606. (617) 928-2500; FAX (617) 933-6333. PRICE: $125.00 ISBN: 0750698454. Summary: This textbook is intended to guide health care professionals in the diagnosis and management of Alzheimer's disease (AD). Section One introduces the disease process, presents definitions and diagnostic criteria, and explains the pathophysiology of the Alzheimer syndrome. Focusing on diagnosis, Section Two reviews typical clinical features, non-Alzheimer dementias, neuropsychological assessment, brain imaging, and electrophysiological tests. Section Three examines the natural evolution of AD, including prognostic factors, global staging, cognition, mood and behavior, and functional autonomy. Section Four explores the medical management of AD, with attention to mood and behavior management, the use of AD symptomatic drugs (including tacrine [cognex]), and AD symptomatic drugs under development. Discussion also focuses on conditions, and quality of life measurements in intervention studies (mainly drug trials). Section Five, on community and institutional management, examines support of families, community-based formal support services, and institutional care. Ethical and legal issues are delineated in Section Six, with attention to determination of competence and genetic counseling. Section Seven on the future diagnosis and treatment of AD, concludes this book. 44 tables, 24 figure, chapter references.

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Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “Alzheimer’s disease” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “Alzheimer’s disease” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “Alzheimer’s disease” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

"Daily Telegraph": Alzheimer's Disease (The "Daily Telegraph") by Paul Caldwell, et al; ISBN: 1841194743; http://www.amazon.com/exec/obidos/ASIN/1841194743/icongroupinterna

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A Guide to the Understanding of Alzheimer's Disease and Related Disorders by Anthony F. Jorm; ISBN: 0814741703; http://www.amazon.com/exec/obidos/ASIN/0814741703/icongroupinterna

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A-Beta Metabolism and Alzheimer's Disease by Takaomi Comings Saido; ISBN: 1587062305; http://www.amazon.com/exec/obidos/ASIN/1587062305/icongroupinterna

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Advancing Frontiers in Alzheimer's Disease Research by George G. Glenner, Richard J. Wurtman (Editor); ISBN: 0292776020; http://www.amazon.com/exec/obidos/ASIN/0292776020/icongroupinterna

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Aging and Alzheimer's Disease: Sensory Systems Neuronal Growth, and Neuronal Metabolism (Annals of the New York Academy of Sciences, Vol 640) by John H. Growdon, Et Al. (Editor) (1991); ISBN: 0897667263; http://www.amazon.com/exec/obidos/ASIN/0897667263/icongroupinterna

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Allie Learns About Alzheimer's Disease: A Family Story About Love, Patience, and Acceptance ("Special Family and Friends" Series) by Kim Gosselin, Tom Dineen (Illustrator) (2002); ISBN: 1891383159; http://www.amazon.com/exec/obidos/ASIN/1891383159/icongroupinterna

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Aluminium and Alzheimer's Disease by Christopher Exley (Editor); ISBN: 0444508112; http://www.amazon.com/exec/obidos/ASIN/0444508112/icongroupinterna

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Alzheimer's Activities: Hundreds of Activities for Men and Women With Alzheimer's Disease and Related Disorders by B. J. Fitzray; ISBN: 1877810800; http://www.amazon.com/exec/obidos/ASIN/1877810800/icongroupinterna

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Alzheimer's Angels: A Compilation of Poetry Honoring Caregivers and Victims of Alzheimer's Disease by Dorothy Womack (2002); ISBN: 0595245501; http://www.amazon.com/exec/obidos/ASIN/0595245501/icongroupinterna

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Alzheimer's Disease by Barry Reisberg (Editor), Barry Reeisberg; ISBN: 0029262305; http://www.amazon.com/exec/obidos/ASIN/0029262305/icongroupinterna

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Alzheimer's Disease by Ralph, W. Richter, Richter & Richter (2002); ISBN: 0723432635; http://www.amazon.com/exec/obidos/ASIN/0723432635/icongroupinterna

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Alzheimer's Disease (1994); ISBN: 0801620260; http://www.amazon.com/exec/obidos/ASIN/0801620260/icongroupinterna

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Alzheimer's Disease by Judah L. Ronch; ISBN: 0826405002; http://www.amazon.com/exec/obidos/ASIN/0826405002/icongroupinterna

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Alzheimer's Disease by Elwood Cohen; ISBN: 0879839643; http://www.amazon.com/exec/obidos/ASIN/0879839643/icongroupinterna

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Alzheimer's Disease by William Molloy (Contributor), Paul Dr. Caldwell (1998); ISBN: 1552092410; http://www.amazon.com/exec/obidos/ASIN/1552092410/icongroupinterna

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Alzheimer's Disease by Michael R. Murphy, et al; ISBN: 1841100064; http://www.amazon.com/exec/obidos/ASIN/1841100064/icongroupinterna

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Alzheimer's Disease - Diagnosis and Management [DOWNLOAD: PDF] by Apollo Managed Care Consultants (Author); ISBN: B000077VDA; http://www.amazon.com/exec/obidos/ASIN/B000077VDA/icongroupinterna

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Alzheimer's Disease "Fighting For Financial Survival" by Edward D. Beasley, et al; ISBN: 1889902152; http://www.amazon.com/exec/obidos/ASIN/1889902152/icongroupinterna

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Alzheimer's Disease (Advances in Neurology, Vol 51) by Richard J. Wurtman (Editor); ISBN: 0881675741; http://www.amazon.com/exec/obidos/ASIN/0881675741/icongroupinterna

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Alzheimer's Disease (Diseases and Disorders) by Linda Jacobs Altman (2000); ISBN: 1560066954; http://www.amazon.com/exec/obidos/ASIN/1560066954/icongroupinterna

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Alzheimer's Disease (Diseases and People) by Edward Willett; ISBN: 0766015963; http://www.amazon.com/exec/obidos/ASIN/0766015963/icongroupinterna

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Alzheimer's Disease (Facts Research and Intervention in Geriatrics) by L. J. Fitten (Editor), et al (1996); ISBN: 0826196225; http://www.amazon.com/exec/obidos/ASIN/0826196225/icongroupinterna

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Alzheimer's Disease (Health Watch) by Susan Dudley Gold, Paul R. Solomon; ISBN: 0766016501; http://www.amazon.com/exec/obidos/ASIN/0766016501/icongroupinterna

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Alzheimer's Disease (The Facts About) by Laurie Beckelman; ISBN: 0896864898; http://www.amazon.com/exec/obidos/ASIN/0896864898/icongroupinterna

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Alzheimer's Disease : Activity-Focused Care, 2nd Ed. by Carly R. Hellen (1998); ISBN: 0750699086; http://www.amazon.com/exec/obidos/ASIN/0750699086/icongroupinterna

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Alzheimer's Disease : Advances in Etiology, Pathogenesis and Therapeutics [DOWNLOAD: ADOBE READER] by Khalid Iqbal (Editor), et al (2001); ISBN: B0000EZPP6; http://www.amazon.com/exec/obidos/ASIN/B0000EZPP6/icongroupinterna

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Alzheimer's Disease : An Eclipse before Sunset by A-M. Ghadirian; ISBN: 1890101192; http://www.amazon.com/exec/obidos/ASIN/1890101192/icongroupinterna

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Alzheimer's Disease : New Medical Therapies by Lisa Henderson; ISBN: 1930624034; http://www.amazon.com/exec/obidos/ASIN/1930624034/icongroupinterna

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Alzheimer's Disease : The Face of Alzheimer's by Diane A. Hawksford; ISBN: 1891421069; http://www.amazon.com/exec/obidos/ASIN/1891421069/icongroupinterna

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Alzheimer's Disease and Marriage by Lore K. Wright (Author) (1993); ISBN: 0803945221; http://www.amazon.com/exec/obidos/ASIN/0803945221/icongroupinterna

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Alzheimer's Disease and Presenile Dementia: Subject Analysis With Reference Bibliography by Michael R. Scarborough (1986); ISBN: 0881644927; http://www.amazon.com/exec/obidos/ASIN/0881644927/icongroupinterna

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Alzheimer's disease and related conditions; a Ciba Foundation symposium; ISBN: 0700014845; http://www.amazon.com/exec/obidos/ASIN/0700014845/icongroupinterna

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Alzheimer's Disease and Related Disorders by M. Nicolini, et al; ISBN: 0080423302; http://www.amazon.com/exec/obidos/ASIN/0080423302/icongroupinterna

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Alzheimer's Disease and Related Disorders Annual, 2004 by Serge Gauthier (Editor), et al (2004); ISBN: 1841843482; http://www.amazon.com/exec/obidos/ASIN/1841843482/icongroupinterna

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Alzheimer's Disease and Related Disorders: Etiology, Pathogenesis and Therapeutics by Khalid Iqbal (Editor), et al; ISBN: 0471986836; http://www.amazon.com/exec/obidos/ASIN/0471986836/icongroupinterna

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Alzheimer's Disease and Related Disorders: Psychosocial Issues for the Patient, Family, Staff and Community by Richard Mayeux; ISBN: 039805469X; http://www.amazon.com/exec/obidos/ASIN/039805469X/icongroupinterna

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Alzheimer's Disease and Related Disorders: Research and Management by William E. Kelly (Editor); ISBN: 0398048959; http://www.amazon.com/exec/obidos/ASIN/0398048959/icongroupinterna

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Alzheimer's Disease Coping With a Living Death by R. Woods (1980); ISBN: 0285650378; http://www.amazon.com/exec/obidos/ASIN/0285650378/icongroupinterna

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Alzheimer's Disease Handbook by Kelly Cornelius, et al; ISBN: 1873413378; http://www.amazon.com/exec/obidos/ASIN/1873413378/icongroupinterna

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Alzheimer's Disease in Primary Care (Medical Pocketbooks) by Serge Gauthier MD; ISBN: 1853174254; http://www.amazon.com/exec/obidos/ASIN/1853174254/icongroupinterna

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Alzheimer's Disease Sourcebook: Basic Consumer Health Information About Alzheimer's Disease, Other Dementias, and Related Disorders (Health Reference Series) by Karen Bellenir (Editor) (2003); ISBN: 0780806662; http://www.amazon.com/exec/obidos/ASIN/0780806662/icongroupinterna

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Alzheimer's Disease Treatment and Family Stress: Directions for Research by Enid Light (Editor), et al (1990); ISBN: 1560321377; http://www.amazon.com/exec/obidos/ASIN/1560321377/icongroupinterna

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Alzheimer's Disease, Down's Syndrome and Aging; ISBN: 0897661826; http://www.amazon.com/exec/obidos/ASIN/0897661826/icongroupinterna

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Alzheimer's Disease, Down's Syndrome and Aging by F. Marott Sinex, Carl R. Merill (Editor); ISBN: 0897661834; http://www.amazon.com/exec/obidos/ASIN/0897661834/icongroupinterna

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Alzheimer's Disease: A Call to Courage for Caregivers by Martha O. Adams; ISBN: 0870292021; http://www.amazon.com/exec/obidos/ASIN/0870292021/icongroupinterna

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Alzheimer's Disease: A Compendium of Current Theories (Annals of the New York Academy of Sciences, Volume 924) by Zaven S. Khachaturian (Editor), M.-Marsel Mesulam (Editor) (2002); ISBN: 0801868343; http://www.amazon.com/exec/obidos/ASIN/0801868343/icongroupinterna

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Alzheimer's Disease: A Guide for Families by Lenore S. Powell, Katie Courtice (Contributor); ISBN: 0201632012; http://www.amazon.com/exec/obidos/ASIN/0201632012/icongroupinterna

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Alzheimer's Disease: A Guide for Families and Caregivers by Lenore Powell (Editor), et al; ISBN: 0738205982; http://www.amazon.com/exec/obidos/ASIN/0738205982/icongroupinterna

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Alzheimer's Disease: A Guide to Diagnosis, Treatment, and Management by James E. Soukup (Author) (1996); ISBN: 0275954609; http://www.amazon.com/exec/obidos/ASIN/0275954609/icongroupinterna

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Alzheimer's Disease: A Handbook for Caregivers by James M. Turnbull, et al; ISBN: 0801672821; http://www.amazon.com/exec/obidos/ASIN/0801672821/icongroupinterna

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Alzheimer's Disease: A Practical Guide for Families and Other Caregivers by Judah L. Ronch; ISBN: 0824512847; http://www.amazon.com/exec/obidos/ASIN/0824512847/icongroupinterna

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Alzheimer's Disease: A Practical Guide for Those Who Help Others (The Continuum Counseling Series) by Judah L. Ronch; ISBN: 0824512839; http://www.amazon.com/exec/obidos/ASIN/0824512839/icongroupinterna

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Alzheimer's Disease: Activities That Work by Catherine A. Abrignani (1991); ISBN: 1877735345; http://www.amazon.com/exec/obidos/ASIN/1877735345/icongroupinterna

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Alzheimer's Disease: Amyloid Precursor Proteins, Signal Transduction, and Neuronal Transplantation (Annals of the New York Academy of Sciences, Vol) by Roger M. Nitsch, et al (1993); ISBN: 0897668545; http://www.amazon.com/exec/obidos/ASIN/0897668545/icongroupinterna

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Alzheimer's Disease: Caregivers Speak Out by Pam Haisman (1998); ISBN: 0966227204; http://www.amazon.com/exec/obidos/ASIN/0966227204/icongroupinterna

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Alzheimer's Disease: Cause(s), Diagnosis, Treatment, and Care by Zaven S. Khachaturian (Editor), et al; ISBN: 0849389976; http://www.amazon.com/exec/obidos/ASIN/0849389976/icongroupinterna

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Alzheimer's Disease: Clinical and Treatment Perspectives by Neal R. Cutler (Editor), et al; ISBN: 0471950394; http://www.amazon.com/exec/obidos/ASIN/0471950394/icongroupinterna

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Alzheimer's Disease: Courage for Those Who Care by Martha O. Adams (1999); ISBN: 0829813047; http://www.amazon.com/exec/obidos/ASIN/0829813047/icongroupinterna

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Alzheimer's Disease: Current Research In Early Diagnosis by Robert E. Becker (Editor), Ezio Giacobini (Editor); ISBN: 0844816590; http://www.amazon.com/exec/obidos/ASIN/0844816590/icongroupinterna

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Alzheimer's Disease: Early Recognition of Potentially Reversible Deficits by Glen; ISBN: 0443020809; http://www.amazon.com/exec/obidos/ASIN/0443020809/icongroupinterna

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Alzheimer's Disease: Everything You Need to Know by Frena Gray-Davidson; ISBN: 0749920416; http://www.amazon.com/exec/obidos/ASIN/0749920416/icongroupinterna

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Alzheimer's Disease: Frequently Asked Questions by Frena Gray-Davidson; ISBN: 0737300795; http://www.amazon.com/exec/obidos/ASIN/0737300795/icongroupinterna

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Alzheimer's Disease: Lessons from Cell Biology (Research and Perspectives in Alzheimer's Disease) by K. S. Kosik (Editor), et al (1995); ISBN: 0387587446; http://www.amazon.com/exec/obidos/ASIN/0387587446/icongroupinterna

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Alzheimer's Disease: New Treatment Strategies (Dementia Reviews Series, No 1) by Zaven S. Khachaturian, John P. Blass (Editor); ISBN: 0824786203; http://www.amazon.com/exec/obidos/ASIN/0824786203/icongroupinterna

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Alzheimer's Disease: Optimizing Drug Development Strategies by Neal R. Cutler, et al; ISBN: 0471951455; http://www.amazon.com/exec/obidos/ASIN/0471951455/icongroupinterna

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Alzheimer's Disease: Overview and Bibliography by Thomas V. Bennington (Editor) (2003); ISBN: 1590335465; http://www.amazon.com/exec/obidos/ASIN/1590335465/icongroupinterna

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Alzheimer's Disease: Problems, Prospects, and Perspectives by Harvey J. Altman (Editor); ISBN: 0306426625; http://www.amazon.com/exec/obidos/ASIN/0306426625/icongroupinterna

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Alzheimer's Disease: Questions and Answers (Questions and Answers Series) by Paul S. Aisen, et al; ISBN: 187341336X; http://www.amazon.com/exec/obidos/ASIN/187341336X/icongroupinterna

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Alzheimer's Disease: Selections from "The World Market for Neurotherapeutic Drugs" [DOWNLOAD: PDF] by Kalorama Information (Author); ISBN: B00006L8C7; http://www.amazon.com/exec/obidos/ASIN/B00006L8C7/icongroupinterna

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Alzheimer's Disease: Senile Dementia and Related Disorders by Robert Katzman (Editor); ISBN: 089004225X; http://www.amazon.com/exec/obidos/ASIN/089004225X/icongroupinterna

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Alzheimer's Disease: The Family Journey by Wayne A. Caron, et al; ISBN: 0962961426; http://www.amazon.com/exec/obidos/ASIN/0962961426/icongroupinterna

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Alzheimer's Disease: The Long Bereavement by Elizabeth Forsythe; ISBN: 0571141102; http://www.amazon.com/exec/obidos/ASIN/0571141102/icongroupinterna

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Alzheimer's Disease: The Physician's Guide to Practical Management by Ralph W. Richter (Editor), et al (2003); ISBN: 0896038912; http://www.amazon.com/exec/obidos/ASIN/0896038912/icongroupinterna

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Alzheimer's Disease: The Silent Epidemic (Discovery) by Julia Frank; ISBN: 0822515784; http://www.amazon.com/exec/obidos/ASIN/0822515784/icongroupinterna

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Alzheimer's Disease: Treatment and Long Term Management (Neurological Disease and Therapy, Vol 4) by Jeffrey L. Cummings, Bruce L. Miller (Editor); ISBN: 0824781775; http://www.amazon.com/exec/obidos/ASIN/0824781775/icongroupinterna

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Alzheimer's Disease: Your Questions Answered by Liz Hodgkinson; ISBN: 0706374010; http://www.amazon.com/exec/obidos/ASIN/0706374010/icongroupinterna

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Amyloid Protein Precursor in Development, Aging and Alzheimer's Disease (Research and Perspectives in Alzheimer's Disease) by K. Beyreuther, et al; ISBN: 0387577882; http://www.amazon.com/exec/obidos/ASIN/0387577882/icongroupinterna

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Annual of Alzheimer's Disease and Related Disorders - 2001 by Serge Gauthier, Jeffrey L. Cummings; ISBN: 184184022X; http://www.amazon.com/exec/obidos/ASIN/184184022X/icongroupinterna

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Apolipoprotein E and Alzheimer's Disease (Research and Perspectives in Alzheimer's Disease) by Allen D. Roses (Editor), et al (1996); ISBN: 3540607986; http://www.amazon.com/exec/obidos/ASIN/3540607986/icongroupinterna

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Apolipoprotein E Genotyping in Alzheimer's Disease (Annals of the New York Academy of Science, Vol 802) by Norman R. Relkin (Editor), et al (1996); ISBN: 1573310484; http://www.amazon.com/exec/obidos/ASIN/1573310484/icongroupinterna

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Assessing Quality of Life in Alzheimer's Disease by Steven M. Albert (Editor), Rebecca G. Logsdon (Editor); ISBN: 0826113338; http://www.amazon.com/exec/obidos/ASIN/0826113338/icongroupinterna

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Behavioral Complications in Alzheimer's Disease (Clinical Practice, No 31) by Brian A. Lawlor (Editor) (1995); ISBN: 0880484772; http://www.amazon.com/exec/obidos/ASIN/0880484772/icongroupinterna

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Beyond Aspirin : Nature's Challenge to Arthritis, Cancer & Alzheimer's Disease by Thomas M. Newmark, et al; ISBN: 0934252823; http://www.amazon.com/exec/obidos/ASIN/0934252823/icongroupinterna

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Biological Aspects of Alzheimer's Disease by Robert Katzman (Editor) (1983); ISBN: 0879692138; http://www.amazon.com/exec/obidos/ASIN/0879692138/icongroupinterna

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Calcium, membranes, aging, and Alzheimer's disease; ISBN: 0897665481; http://www.amazon.com/exec/obidos/ASIN/0897665481/icongroupinterna

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Calcium, Membranes, Aging, and Alzheimer's Disease (Annals of the New York Academy of Sciences, Vol 568) by Zaven S. Khachaturian, et al (1989); ISBN: 0897665473; http://www.amazon.com/exec/obidos/ASIN/0897665473/icongroupinterna

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Can Do Activities for Adults With Alzheimer's Disease: Strength-Based Communication and Programming by Eileen Eisner (2001); ISBN: 0890798621; http://www.amazon.com/exec/obidos/ASIN/0890798621/icongroupinterna

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Candle and Darkness: Current Research in Alzheimer's Disease by Joseph Rogers (1998); ISBN: 1566250951; http://www.amazon.com/exec/obidos/ASIN/1566250951/icongroupinterna

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Caring for a Loved One With Alzheimer's Disease: A Christian Perspective (Haworth Religion and Mental Health.) by Elizabeth T. Hall; ISBN: 0789008726; http://www.amazon.com/exec/obidos/ASIN/0789008726/icongroupinterna

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Caring for Maria: An Experience of Successfully Coping With Alzheimer's Disease by Bernard Heywood; ISBN: 1852305029; http://www.amazon.com/exec/obidos/ASIN/1852305029/icongroupinterna

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Caring for People With Alzheimer's Disease: A Training Manual for Direct Care Providers by Gayle Andresen; ISBN: 187881222X; http://www.amazon.com/exec/obidos/ASIN/187881222X/icongroupinterna

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Cerebrovascular pathology in Alzheimer's disease; ISBN: 1573310875; http://www.amazon.com/exec/obidos/ASIN/1573310875/icongroupinterna

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Cerebrovascular Pathology in Alzheimer's Disease (Annals of the New York Academy of Sciences, Vol 826) by J. C. De LA Torre (Editor), et al (1997); ISBN: 1573310867; http://www.amazon.com/exec/obidos/ASIN/1573310867/icongroupinterna

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Clinical Aspects of Alzheimer's Disease and Senile Dementia by Miller (1980); ISBN: 0890043264; http://www.amazon.com/exec/obidos/ASIN/0890043264/icongroupinterna

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Clinical Diagnosis and Management of Alzheimer's Disease by Serge Gauthier (Editor); ISBN: 1853176559; http://www.amazon.com/exec/obidos/ASIN/1853176559/icongroupinterna

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Clinical Diversity in Late Onset Alzheimer's Disease (Maudsley Monographs, No 34) by Alistair, Md Burns, Raymond, Phd Levy; ISBN: 0192622811; http://www.amazon.com/exec/obidos/ASIN/0192622811/icongroupinterna

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Clinical Management of Alzheimer's Disease by Ladislov Volicer; ISBN: 0871898993; http://www.amazon.com/exec/obidos/ASIN/0871898993/icongroupinterna

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Confronting Alzheimer's Disease by Anne C. Kalicki (Editor) (1987); ISBN: 0932500803; http://www.amazon.com/exec/obidos/ASIN/0932500803/icongroupinterna

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Confronting Alzheimer's Disease and Other Dementias by Office of Technology Assessment Task Force, et al; ISBN: 0397530005; http://www.amazon.com/exec/obidos/ASIN/0397530005/icongroupinterna

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Connections, Cognition and Alzheimer's Disease by B. T. Hyman (Editor), et al; ISBN: 3540622055; http://www.amazon.com/exec/obidos/ASIN/3540622055/icongroupinterna

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Contemporary Diagnosis and Management of Alzheimer's Disease by David S. Geldmacher; ISBN: 1884065392; http://www.amazon.com/exec/obidos/ASIN/1884065392/icongroupinterna

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Controlled Clinical Trials Reports: Alzheimer's Disease by O'Brien, et al (2000); ISBN: 1858733723; http://www.amazon.com/exec/obidos/ASIN/1858733723/icongroupinterna

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Coping When a Grandparent Has Alzheimer's Disease (Coping Series) by Beth Wilkinson (1995); ISBN: 0823919471; http://www.amazon.com/exec/obidos/ASIN/0823919471/icongroupinterna

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Coping With Alzheimer's Disease and Other Dementing Illnesses by Mary Norton Kindig, Molly Carnes (1993); ISBN: 1565930975; http://www.amazon.com/exec/obidos/ASIN/1565930975/icongroupinterna

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Cytochrome Oxidase in Neuronal Metabolism and Alzheimer's Disease by F. Gonzalez-Lima (Editor) (1998); ISBN: 0306460246; http://www.amazon.com/exec/obidos/ASIN/0306460246/icongroupinterna

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Day Care Programs for Alzheimer's Disease and Related Disorders by John Panella; ISBN: 0939957051; http://www.amazon.com/exec/obidos/ASIN/0939957051/icongroupinterna

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Day Is Ending: A Doctor's Love Shattered by Alzheimer's Disease by Richard W., Md Zalar, et al (2003); ISBN: 0974055808; http://www.amazon.com/exec/obidos/ASIN/0974055808/icongroupinterna

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Decoding Darkness: The Search for the Genetic Causes of Alzheimer's Disease by Rudolph E. Tanzi, Ann B. Parson (2001); ISBN: 0738205265; http://www.amazon.com/exec/obidos/ASIN/0738205265/icongroupinterna

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Defense Against Alzheimer's Disease: A Rational Blueprint for Prevention by H. J. Roberts (1995); ISBN: 1884243002; http://www.amazon.com/exec/obidos/ASIN/1884243002/icongroupinterna

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Designing for Alzheimer's Disease : Strategies for Creating Better Care Environments by Elizabeth C. Brawley (Author) (1997); ISBN: 0471139203; http://www.amazon.com/exec/obidos/ASIN/0471139203/icongroupinterna

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Developing Support Groups for Individuals with Early-Stage Alzheimer's Disease: Planning, Implementation, and Evaluation by Robyn Yale (1995); ISBN: 1878812262; http://www.amazon.com/exec/obidos/ASIN/1878812262/icongroupinterna

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Diagnosis and Management of Alzheimer's Disease and Other Dementias by Robert Green; ISBN: 188473541X; http://www.amazon.com/exec/obidos/ASIN/188473541X/icongroupinterna

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Diseases Explained: Alzheimer's Disease Wall Chart by Lexi-Comp; ISBN: 1930598025; http://www.amazon.com/exec/obidos/ASIN/1930598025/icongroupinterna

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Doing Things: A Guide to Programming Activities for Persons With Alzheimer's Disease and Related Disorders by Jitka M. Zgola, Nancy L. Mace (Designer) (1987); ISBN: 0801834678; http://www.amazon.com/exec/obidos/ASIN/0801834678/icongroupinterna

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Drug Discovery and Development for Alzheimer's Disease (2000) by Howard M., Md. Fillit (Editor), et al; ISBN: 082611542X; http://www.amazon.com/exec/obidos/ASIN/082611542X/icongroupinterna

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Early Diagnosis and Treatment of Alzheimer's Disease by Simon Lovestone (1998); ISBN: 1853175803; http://www.amazon.com/exec/obidos/ASIN/1853175803/icongroupinterna

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Early Diagnosis of Alzheimer's Disease by Leonard F. M. Scinto (Editor), et al; ISBN: 0896034526; http://www.amazon.com/exec/obidos/ASIN/0896034526/icongroupinterna

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Encyclopedia of Alzheimer's Disease With Directories of Research, Treatment and Care Facilities: With Directories of Research, Treatment, and Care fa by Elaine A. Moore, et al; ISBN: 0786414383; http://www.amazon.com/exec/obidos/ASIN/0786414383/icongroupinterna

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255

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Everything You Need to Know When Someone You Love Has Alzheimer's Disease (The Need to Know Library) by Joyce Hinnefeld; ISBN: 082391688X; http://www.amazon.com/exec/obidos/ASIN/082391688X/icongroupinterna

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Fatal Attractions: Protein Aggregates in Neurodegenerative Disorders (Research and Perspectives in Alzheimer's Disease) by V. M.-Y Lee (Editor), et al (2000); ISBN: 3540671722; http://www.amazon.com/exec/obidos/ASIN/3540671722/icongroupinterna

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Focus on Alzheimer's Disease Research by Eileen M. Welsh (Editor) (2003); ISBN: 1590337883; http://www.amazon.com/exec/obidos/ASIN/1590337883/icongroupinterna

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Forgetting Whose We Are: Alzheimer's Disease and the Love of God by David Keck (1996); ISBN: 0687020883; http://www.amazon.com/exec/obidos/ASIN/0687020883/icongroupinterna

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Glimmers: A Journey into Alzheimer's Disease by Heidi Hamilton, Marie Foley (2003); ISBN: 188399179X; http://www.amazon.com/exec/obidos/ASIN/188399179X/icongroupinterna

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God Never Forgets: Faith, Hope, and Alzheimer's Disease by Donald K. McKim (Editor) (1998); ISBN: 0664257046; http://www.amazon.com/exec/obidos/ASIN/0664257046/icongroupinterna

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Guide to Alzheimer's Disease by Barry Reisberg (1984); ISBN: 0029263700; http://www.amazon.com/exec/obidos/ASIN/0029263700/icongroupinterna

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Hannah's Heirs: The Quest for the Genetic Origins of Alzheimer's Disease by Daniel A. Pollen (1996); ISBN: 0195106520; http://www.amazon.com/exec/obidos/ASIN/0195106520/icongroupinterna

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He Used to Be Somebody, 1995: A Journey into Alzheimer's Disease Through the Eyes of a Caregiver by Beverly Bigtree Murphy (1996); ISBN: 0943909147; http://www.amazon.com/exec/obidos/ASIN/0943909147/icongroupinterna

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Healing The Wounds of Alzheimer's Disease by Amira Choukar Tame, Amira Choukair Tame; ISBN: 0967218500; http://www.amazon.com/exec/obidos/ASIN/0967218500/icongroupinterna

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Heterogeneity of Alzheimer's Disease (Research and Perspectives in Alzheimer's Disease) by R. Boller, et al; ISBN: 0387559183; http://www.amazon.com/exec/obidos/ASIN/0387559183/icongroupinterna

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Home Care for People With Alzheimer's Disease (Aspen Patient Education Video Series) by Aspen Reference Group, et al (1998); ISBN: 0834207184; http://www.amazon.com/exec/obidos/ASIN/0834207184/icongroupinterna

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I Can't Remember: Family Stories of Alzheimer's Disease by Esther Strauss Smoller, Kathleen O'Brien (1997); ISBN: 1566395550; http://www.amazon.com/exec/obidos/ASIN/1566395550/icongroupinterna

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I'm Just Not Myself Anymore: A Family Guide to Alzheimer's Disease by Charles C. Entwistle; ISBN: 1880416727; http://www.amazon.com/exec/obidos/ASIN/1880416727/icongroupinterna

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Immunization Against Alzheimer's Disease and Other Neurodegenerative Disorders (Research and Perspectives in Alzheimer's Disease) by Yves Christen, Dennis J. Selkoe (2003); ISBN: 3540007075; http://www.amazon.com/exec/obidos/ASIN/3540007075/icongroupinterna

256 Alzheimer’s Disease

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Interventions for Alzheimer's Disease: A Caregiver's Complete Reference by Ruth M. Tappen (1997); ISBN: 1878812394; http://www.amazon.com/exec/obidos/ASIN/1878812394/icongroupinterna

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Journey With Grandpa: Our Family's Struggle With Alzheimer's Disease by Rosalie Walsh Honel (1988); ISBN: 0801837219; http://www.amazon.com/exec/obidos/ASIN/0801837219/icongroupinterna

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Keys to Understanding Alzheimer's Disease (Keys to Retirement Planning) by Gisele Wolf-Klein, Arnold Levy; ISBN: 0812047583; http://www.amazon.com/exec/obidos/ASIN/0812047583/icongroupinterna

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Life Out of Focus: Alzheimer's Disease and Related Disorders (Encyclopedia of Psychological Disorders) by Dan Harmon, Carol C. Nadelson (Editor); ISBN: 0791048969; http://www.amazon.com/exec/obidos/ASIN/0791048969/icongroupinterna

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Living With Alzheimer's Disease: One Couple's Journey by Frances Siegel (2000); ISBN: 1889059811; http://www.amazon.com/exec/obidos/ASIN/1889059811/icongroupinterna

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Living With John: Caring for a Loved One With Alzheimer's Disease by Nellie KiddMadison (2000); ISBN: 1587410613; http://www.amazon.com/exec/obidos/ASIN/1587410613/icongroupinterna

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Losing a Million Minds: Confronting the Tragedy of Alzheimer's Disease and Other Dementias by Office of Technology Assessment (2002); ISBN: 1410202399; http://www.amazon.com/exec/obidos/ASIN/1410202399/icongroupinterna

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Love Is Ageless: Stories About Alzheimer's Disease (2nd Edition) by Jessica Bryan (Editor) (2002); ISBN: 0961931116; http://www.amazon.com/exec/obidos/ASIN/0961931116/icongroupinterna

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Managing Alzheimer's Disease in Primary Care by Brodaty, H. Brodaty (1999); ISBN: 1858733588; http://www.amazon.com/exec/obidos/ASIN/1858733588/icongroupinterna

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Mayo Clinic on Alzheimer's Disease by Ronald C., M.D. Petersen (Editor), Mayo Clinic (2002); ISBN: 1893005224; http://www.amazon.com/exec/obidos/ASIN/1893005224/icongroupinterna

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Mild Cognitive Impairment: Aging to Alzheimer's Disease by Ronald C., Ph.D., M.D. Petersen (Editor), et al (2003); ISBN: 0195123425; http://www.amazon.com/exec/obidos/ASIN/0195123425/icongroupinterna

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Molecular and Cellular Mechanisms of Neuronal Plasticity in Normal Aging and Alzheimer's Disease (Progress in Brain Research, Vol 86) by Paul D. Coleman, et al; ISBN: 0444811214; http://www.amazon.com/exec/obidos/ASIN/0444811214/icongroupinterna

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Molecular Biology and Genetics of Alzheimer's Disease: Proceedings of the International Symposium on Dementia: Molecular Biology and Genetics of Al (International Congress Series, No. 884) by International Symposium on Dementia: Molecular Biology and Genetics Of, et al; ISBN: 0444811125; http://www.amazon.com/exec/obidos/ASIN/0444811125/icongroupinterna

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Molecular Biology of Alzheimer's Disease: Genes and Mechanisms Involved in Amyloid Generation by Christian Haass (Editor); ISBN: 9057023814; http://www.amazon.com/exec/obidos/ASIN/9057023814/icongroupinterna

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257

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Muscarinic Agonists and the Treatment of Alzheimer's Disease (Neuroscience Intelligence Unit) by Abraham Fisher (Editor) (1996); ISBN: 0412103311; http://www.amazon.com/exec/obidos/ASIN/0412103311/icongroupinterna

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My Journey into Alzheimer's Disease by Robert Davis (1989); ISBN: 0842346457; http://www.amazon.com/exec/obidos/ASIN/0842346457/icongroupinterna

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Neurobiology of Alzheimer's Disease (Molecular and Cellular Neurobiology Series) by David Dawbarn (Editor), et al; ISBN: 1872748147; http://www.amazon.com/exec/obidos/ASIN/1872748147/icongroupinterna

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Neurochemistry of Alzheimer's Disease (Neuroscience Perspectives) by Bowen (2000); ISBN: 0121205401; http://www.amazon.com/exec/obidos/ASIN/0121205401/icongroupinterna

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Neuroinflammatory Mechanisms in Alzheimer's Disease: Basic and Clinical Research by Joseph Rogers; ISBN: 3764360747; http://www.amazon.com/exec/obidos/ASIN/3764360747/icongroupinterna

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Neuropsychology of Alzheimer's Disease and Other Dementias by Randolph W. Parks (Editor), et al (1993); ISBN: 019506612X; http://www.amazon.com/exec/obidos/ASIN/019506612X/icongroupinterna

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New Directions in Understanding Dementia and Alzheimer's Disease (Advances in Experimental Medicine and Biology, 282) by Taher Zandi, Richard J. Ham (Editor) (1991); ISBN: 0306437287; http://www.amazon.com/exec/obidos/ASIN/0306437287/icongroupinterna

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Old Timers: A Son Witnesses His Mother's One-Way Journey into the Darkness of Alzheimer's Disease by Jack Turley (2002); ISBN: 0759674167; http://www.amazon.com/exec/obidos/ASIN/0759674167/icongroupinterna

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One Step at a Time: A Definitive Study of Alzheimer's Disease and a Practical Guide for Caregivers by Lorena Shell Eaker (1996); ISBN: 0965300005; http://www.amazon.com/exec/obidos/ASIN/0965300005/icongroupinterna

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Outcome Measures in Alzheimer's Disease by Ian G. McKeith (Editor), et al (1999); ISBN: 1853177458; http://www.amazon.com/exec/obidos/ASIN/1853177458/icongroupinterna

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Pathobiology of Alzheimer's Disease (Neuroscience Perspectives Series) by Alison M. Goate (Editor), Frank Ashall (Editor) (1995); ISBN: 0122869656; http://www.amazon.com/exec/obidos/ASIN/0122869656/icongroupinterna

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Pharmacoeconomic Evaluations: A review of drug treatments in Alzheimer's disease [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B00008R3N7; http://www.amazon.com/exec/obidos/ASIN/B00008R3N7/icongroupinterna

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Pharmacotherapy of Alzheimer's Disease by Serge Gauthier (1998); ISBN: 1853175838; http://www.amazon.com/exec/obidos/ASIN/1853175838/icongroupinterna

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Practice Guidelines for the Treatment of Patients with Alzheimer's Disease and Other Dementias of Late Life by American Psychiatric Association, APA; ISBN: 0890423105; http://www.amazon.com/exec/obidos/ASIN/0890423105/icongroupinterna

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Progress in Alzheimer's Disease & Similar Conditions by Leonard L. Heston (Editor), American Psychopathological Association; ISBN: 0880487607; http://www.amazon.com/exec/obidos/ASIN/0880487607/icongroupinterna

258 Alzheimer’s Disease

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Proteases and Protease Inhibitors in Alzheimer's Disease Pathogenesis (Annals of the New York Academy of Sciences, Vol 674) by Carl D. B. Banner (Editor), Ralph A. Nixon (Editor) (1992); ISBN: 0897667786; http://www.amazon.com/exec/obidos/ASIN/0897667786/icongroupinterna

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Recipes My Mother Forgot.Family Style Cooking and a Caregiver's Guide to Alzheimer's Disease by Cheryl Rhodes; ISBN: 096864130X; http://www.amazon.com/exec/obidos/ASIN/096864130X/icongroupinterna

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Research Advances in Alzheimer's Disease and Related Disorders by Khalid Iqbal, et al; ISBN: 0471952362; http://www.amazon.com/exec/obidos/ASIN/0471952362/icongroupinterna

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Research and Practice in Alzheimer's Disease (Volume 3) by B., M.D. Vellas (Editor), L. J., MD Fitten (Editor); ISBN: 082611413X; http://www.amazon.com/exec/obidos/ASIN/082611413X/icongroupinterna

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Research and Practice in Alzheimer's Disease, Volume 7 by Bruno J. Vellas (2003); ISBN: 0826117457; http://www.amazon.com/exec/obidos/ASIN/0826117457/icongroupinterna

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Senile dementia of the Alzheimer type : proceedings of the Fifth Tarbox Symposium, the Norman Rockwell Conference on Alzheimer's Disease held in Lubbock, Texas, October 18-20, 1984; ISBN: 0845127209; http://www.amazon.com/exec/obidos/ASIN/0845127209/icongroupinterna

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Social Work and Alzheimer's Disease: Practice Issues With Victims and Their Families (The Journal of Gerontological Social Work Series) by Rose Dobrof (Editor) (1986); ISBN: 0866564020; http://www.amazon.com/exec/obidos/ASIN/0866564020/icongroupinterna

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Stolen Memories: One Family's Experience with Alzheimer's Disease by Marie Cloud, Compagno (2000); ISBN: 0595000754; http://www.amazon.com/exec/obidos/ASIN/0595000754/icongroupinterna

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Successful Communication with Alzheimer's Disease Patients: An In-Service Manual by Mary Jo Santo Pietro, et al; ISBN: 0750695641; http://www.amazon.com/exec/obidos/ASIN/0750695641/icongroupinterna

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Successful Communication with Persons with Alzheimer's Disease by Mary Jo Santo Pietro; ISBN: 0750673834; http://www.amazon.com/exec/obidos/ASIN/0750673834/icongroupinterna

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Taking Care of Caregivers: For Families and Others Who Care for People With Alzheimer's Disease and Other Forms of Dementia by D. Jeanne Roberts (1991); ISBN: 0923521097; http://www.amazon.com/exec/obidos/ASIN/0923521097/icongroupinterna

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Tangled Minds: Understanding Alzheimer's Disease and Other Dementias by Muriel R. Gillick, Muriel Gallick; ISBN: 0452276470; http://www.amazon.com/exec/obidos/ASIN/0452276470/icongroupinterna

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The Alzheimer's Health Care Handbook: How to Get the Best Medical Care for Your Relative with Alzheimer's Disease, in and out of the Hospital by Mary S. Mittelman, Cynthia Epstein (2003); ISBN: 1569244456; http://www.amazon.com/exec/obidos/ASIN/1569244456/icongroupinterna

Books

259

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The Biological Substrates of Alzheimer's Disease (UCLA Forum in Medical Sciences, No 27) by Arnold B. Scheibel, et al; ISBN: 0126231303; http://www.amazon.com/exec/obidos/ASIN/0126231303/icongroupinterna

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The Book---Alzheimer's Disease: Caregiver's Home Management by Robert H. Rogge (1996); ISBN: 1570871825; http://www.amazon.com/exec/obidos/ASIN/1570871825/icongroupinterna

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The Changing Brain: Alzheimer's Disease and Advances in Neuroscience by Ira B. Black (2002); ISBN: 0195156978; http://www.amazon.com/exec/obidos/ASIN/0195156978/icongroupinterna

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The Clinical Management of Early Alzheimer's Disease: A Handbook by Reinhild Mulligan (Editor), et al (2003); ISBN: 0805833706; http://www.amazon.com/exec/obidos/ASIN/0805833706/icongroupinterna

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The Early Story of Alzheimer's Disease by Katherine Bick, et al; ISBN: 0881673684; http://www.amazon.com/exec/obidos/ASIN/0881673684/icongroupinterna

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The Encyclopedia of Alzheimer's Disease (Facts on File Library of Health and Living) by Carol Turkington (2003); ISBN: 0816048185; http://www.amazon.com/exec/obidos/ASIN/0816048185/icongroupinterna

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The Epidemiology of Alzheimer's Disease and Related Disorders by Anthony J. Jorm, Anthony F. Jorm (1991); ISBN: 0412315203; http://www.amazon.com/exec/obidos/ASIN/0412315203/icongroupinterna

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The Experience of Alzheimer's Disease: Life Through a Tangled Veil by Steven R. Sabat (2001); ISBN: 0631216669; http://www.amazon.com/exec/obidos/ASIN/0631216669/icongroupinterna

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The Hidden Victims of Alzheimer's Disease: Families Under Stress by Nancy K. Orr (Photographer), et al (1985); ISBN: 081479663X; http://www.amazon.com/exec/obidos/ASIN/081479663X/icongroupinterna

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The Loss of Self: A Family Resource for the Care of Alzheimer's Disease and Related Disorders by Donna, Phd Cohen, Carl, Phd Eisdorfer (2002); ISBN: 0393323331; http://www.amazon.com/exec/obidos/ASIN/0393323331/icongroupinterna

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The Memory Cure : How to Protect Your Brain Against Memory Loss and Alzheimer's Disease by Majid, M.D.,Ph.D Fotuhi, Peter V. Rabins; ISBN: 0071409246; http://www.amazon.com/exec/obidos/ASIN/0071409246/icongroupinterna

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The Memory Cure: How to Protect Your Brain Against Memory Loss and Alzheimer's Disease [ABRIDGED] by Majid, Md. Fotuhi, Simon Vance (Narrator); ISBN: 0972488960; http://www.amazon.com/exec/obidos/ASIN/0972488960/icongroupinterna

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The Neurobiology of Alzheimer's Disease (Annals of the New York Academy of Sciences, V. 777) by Richard J. Wurtman (Editor), et al; ISBN: 0897669738; http://www.amazon.com/exec/obidos/ASIN/0897669738/icongroupinterna

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The Neuropsychiatry of Alzheimer's Disease and Related Dementias by Jeffrey L. Cummings, et al (2002); ISBN: 1841842192; http://www.amazon.com/exec/obidos/ASIN/1841842192/icongroupinterna

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The Person With Alzheimer's Disease: Pathways to Understanding the Experience by Phyllis Braudy, Phd Harris (Editor) (2002); ISBN: 0801868777; http://www.amazon.com/exec/obidos/ASIN/0801868777/icongroupinterna

260 Alzheimer’s Disease

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The Positive Interactions Program of Activities for People With Alzheimer's Disease by Sylvia Nissenboim, Christine Vroman (1998); ISBN: 1878812408; http://www.amazon.com/exec/obidos/ASIN/1878812408/icongroupinterna

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The Rakhma Story: Unconditional Love and Caring for People With Alzheimer's Disease and Dementia by Shirley Joy Shaw, Lynn Baskfield (1999); ISBN: 188009083X; http://www.amazon.com/exec/obidos/ASIN/188009083X/icongroupinterna

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The Stranger I Call Grandma: A Story About Alzheimer's Disease by Swanee Ballman, Stephanie Brunson (Illustrator) (2002); ISBN: 0970295944; http://www.amazon.com/exec/obidos/ASIN/0970295944/icongroupinterna

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Therapeutic Activities With Persons Disabled by Alzheimer's Disease and Related Disorders by Carol Bowlby Sifton (1998); ISBN: 0834211629; http://www.amazon.com/exec/obidos/ASIN/0834211629/icongroupinterna

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Therapeutic Interventions in Alzheimer's Disease: A Program of Functional Skills for Activities of Daily Living and Communication by Joan K. Glickstein; ISBN: 0834209306; http://www.amazon.com/exec/obidos/ASIN/0834209306/icongroupinterna

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Understanding Alzheimer's Disease (Understanding Health and Sickness Series) by Neal R. Cutler, John J. Sramek (Contributor) (1996); ISBN: 0878059105; http://www.amazon.com/exec/obidos/ASIN/0878059105/icongroupinterna

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Understanding Alzheimer's Disease: What It Is How to Cope With It Future Directions by Miriam K. Aronson (Editor), et al; ISBN: 0684184753; http://www.amazon.com/exec/obidos/ASIN/0684184753/icongroupinterna

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Understanding the ABCs of Alzheimer's Disease: A Guide for Caregivers by Frances Oakley; ISBN: 0910317941; http://www.amazon.com/exec/obidos/ASIN/0910317941/icongroupinterna

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Vanishing Mind: A Practical Guide to Alzheimer's Disease and Other Dementias (Series of Books in Psychology) by Leonard L. Heston, June A. White; ISBN: 0716721929; http://www.amazon.com/exec/obidos/ASIN/0716721929/icongroupinterna

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Vascular Factors in Alzheimer's Disease (Annals of the New York Academy of Sciences Vol 903) by Raj N. Kalaria (Editor), Paul Ince (Editor) (2001); ISBN: 0801866952; http://www.amazon.com/exec/obidos/ASIN/0801866952/icongroupinterna

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Waiting for the Morning: A Mother and Daughter's Journey Through Alzheimer's Disease by Brenda Parris Sibley (2001); ISBN: 059518782X; http://www.amazon.com/exec/obidos/ASIN/059518782X/icongroupinterna

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We Never Said Goodbye: The Tragedy of Alzheimer's Disease by Isobelle Gidley, Richard Shears (1986); ISBN: 086861551X; http://www.amazon.com/exec/obidos/ASIN/086861551X/icongroupinterna

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We'll Be Married in Fremantle: Alzheimer's Disease and the Everyday Act of Storying by Julie Goyder (2001); ISBN: 1863683119; http://www.amazon.com/exec/obidos/ASIN/1863683119/icongroupinterna

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When Alzheimer's Disease Strikes by James S. Sapp, Stephen Sapp (1996); ISBN: 0914733125; http://www.amazon.com/exec/obidos/ASIN/0914733125/icongroupinterna

Books

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When I Grow Too Old to Dream: Coping With Alzheimer's Disease by Gerry Naughtin, et al; ISBN: 1863710752; http://www.amazon.com/exec/obidos/ASIN/1863710752/icongroupinterna

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Working with Alzheimer's Disease by David William Sutcliffe; ISBN: 0951461656; http://www.amazon.com/exec/obidos/ASIN/0951461656/icongroupinterna

261

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “Alzheimer’s disease” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Alzheimer's disease: a report of progress in research Author: Corkin, Suzanne.; Year: 1982; New York: Raven Press, c1982; ISBN: 0890046859 http://www.amazon.com/exec/obidos/ASIN/0890046859/icongroupinterna

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Alzheimer's disease: a scientific guide for health practitioners Author: National Institute of Neurological and Communicative Disorders and Stroke. Office of Scientific and Health Reports.; Year: 1982; [Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, [1980]

•

Alzheimer's disease: an information paper Author: United States. Congress. House. Select Committee on Aging. Subcommittee on Health and Long-Term Care.; Year: 1983; Washington: U.S. G.P.O., 1983

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Alzheimer's disease: January 1982 through February 1984: 317 citations Author: Kenton, Charlotte.; Year: 1984; [Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, 1984

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Alzheimer's disease: joint hearing before the Subcommittee on Health and LongTerm Care of the Select Committee on Aging and the Subcommittee on Health and the Environment of the Committee on Energy and Commerce, House of Representatives,Ninety-eighth Congress, first session, Washington, D.C., August 3, 1983. Author: United States. Congress. House. Select Committee on Aging. Subcommittee on Health and Long-Term Care.; Year: 1983; Washington: U.S. G.P.O., 1984

•

Alzheimer's disease: unraveling the mystery Author: National Institute on Aging.; Year: 1970; [Bethesda, Md.]: National Institutes of Health, [2002]

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Alzheimer's disease and related conditions. A Ciba Foundation Symposium. Edited by G. E. W. Wolstenholme and Maeve O'Connor. Author: O'Connor, Maeve.; Year: 1978; London, Churchill, 1970; ISBN: 700014845

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

262 Alzheimer’s Disease

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Alzheimer's disease handbook Author: Lindeman, David A.; Year: 1986; Washington, D.C.: U.S. Dept. of Health and Human Services, Office of Human Development Services, Administration on Aging, [1984]

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Alzheimer's Disease Society day care: projects funded by the Ladbroke Group plc Author: Brownfoot, Jan.; Year: 1995; London: The Society, [1993]

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Alzheimer's disease, advances in basic research and therapies: proceedings of the Third Meeting of the International Study Group on the Treatment of Memory Disorders Associated with Aging, Zurich, Switzerland, January 13-15, 1984 Author: International Study Group on the Treatment of Memory Disorders Associated with Aging. Meeting; Year: 1985; [S.l.]: Center for Brain Sciences and Metabolism Charitable Trust, c1984

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Coping and helping with Alzheimer's disease. Author: Lyons, Walter H.; Year: 1984; Ottawa, Ont.: National Advisory Council on Aging, [1984]; ISBN: 0662129687

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Dementia, a practical guide to Alzheimer's disease and related illnesses Author: Heston, Leonard L.; Year: 1984; New York: Freeman, c1983; ISBN: 0716715686 http://www.amazon.com/exec/obidos/ASIN/0716715686/icongroupinterna

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Impact of Alzheimer's disease on the nation's elderly: joint hearing before the Subcommittee on Aging of the Committee on Labor and Human Resources, United States Senate, and the Subcommittee on Labor, Health, Education, and Welfare of the Committee on Appropriations, House of Representatives, Ninety-sixth Congress, second session, on to analyze the impact of Alzheimer's disease and other dimentias [i. e. dementias] of aging on our society, July 15, 1980. Author: United States. Congress. Senate. Committee on Labor and Human Resources. Subcommittee on Aging.; Year: 1983; Washington, D.C.: U.S. G.P.O., 1980

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National Eldercare Institute on Long Term Care and Alzheimer's Disease [microform]: final report Author: Pfeiffer, Eric,; Year: 2002; Tampa, Fla.: University of South Florida, Suncoast Gerontology Center, [1995]

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NIA Alzheimer's Disease Centers (ADC's) program directory [electronic resource]. Author: NIA Alzheimer's Disease Centers.; Year: 2003; [S.l.: s.n., 2002]

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Oversight on treatment of Alzheimer's disease, 1983: hearing before the Subcommittee on Aging of the Committee on Labor and Human Resources, United States Senate, Ninety-eighth Congress first session, to examine the progress made in the treatment of Alzheimer's disease, focusing on federally funded research on the causes, diagnosis, and treatment of the disease, June 28, 1983. Author: United States. Congress. Senate. Committee on Labor and Human Resources. Subcommittee on Aging.; Year: 1984; Washington: U.S. G.P.O., 1983

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State and area agency instructional guide for Alzheimer's disease family support groups Author: United States. Administration on Aging.; Year: 2002; San Francisco, CA: Aging Health Policy Center, University of California, San Francisco; Washington, D.C.: U.S. Dept. of Health and Human Services, Office of Human Development Services, Administration on Aging, [1984]

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The 36-hour day: a family guide to caring for persons with Alzheimer's disease, related dementing illnesses, and memory loss in later life Author: Mace, Nancy L.; Year: 1984; Baltimore: Johns Hopkins University Press, c1981; ISBN: 0801826594 http://www.amazon.com/exec/obidos/ASIN/0801826594/icongroupinterna

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Chapters on Alzheimer’s Disease In order to find chapters that specifically relate to Alzheimer’s disease, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Alzheimer’s disease using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “Alzheimer’s disease” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on Alzheimer’s disease: •

Genetic Epidemiology of Alzheimer's Disease Source: in Battistin, L.; Gerstenbrand, F., eds. Aging Brain and Dementia: New Trends in Diagnosis and Therapy. Proceedings of A Symposium held in Padova, Italy, September 22-24, 1988. New York, NY: Alan R. Liss, Inc. 1990. p. 57-78. Contact: Available from Alan R. Liss, Inc. 41 East 11th Street, New York, NY 10003. (212) 741-2515. ISBN: 0471562114. Summary: Alzheimer's disease (AD) is the most common cause of old age associated dementia, accounting for as much as 50 to 80 percent of the total dementia population. Genetic factors appear to play a significant role in determining risk for AD. This paper discusses theories of genetic transmission and heterogeneity based on a review of studies of: (1) multi-generational families with many affected members studied by pedigree analysis; (2) smaller families with several affected members; (3) twins; and (4) middle-aged and older individuals with Down syndrome, who represent a unique population that invariably develops Alzheimer type neuropathology before they reach 40 years of age. The preponderance of evidence supports a genetic transmission with variability in age of onset and clinical characteristics, but whether this variability reflects a spectrum of expression related to disease severity or represents etiologically distinct subtypes is not yet clear. 86 references.

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Amyloidosis of Alzheimer's Disease Source: in Platt, D., ed. Gerontology, 4th International Symposium: Present State and Research Perspectives in the Experimental and Clinical Gerontology. New York, NY: Springer-Verlag. 1989. p. 159-174. Contact: Available from Springer-Verlag. 44 Hartz Way, Secaucus, NJ 07094. (201) 3484033. PRICE: $70.60. ISBN: 0387515445. Summary: Definitive lesions in Alzheimer's disease (AD) are the senile plaques in the neuropil and the intraneuronal neurofibrillary tangles; both of these have the staining properties of amyloid (including argyrophilia and birefringement congophilia), although the paired helical filaments characteristic of the tangles are morphologically distinct from all other amyloid filaments. This paper presents the morphological information available for each form of cerebral amyloid under separate headings, although the chemical information will draw together the common features of the extracellular amyloid. Topics include: the morphology and protein chemistry of the amyloid in senile plaques and of the cerebrovascular amyloid (CA); the immunochemistry of A4 amyloid deposits; the chemical nature of the A4 amyloid precursor protein; gaps in the protein chemical data; the morphology and chemistry of neurofibrillary tangles; and other syndromes with plaques, tangles, or cerebrovascular

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amyloid. Speculations on the generation of Alzheimer amyloid also are presented. 76 references. •

Psychopathological Perspectives: Differential Diagnosis of Alzheimer's Disease and Related Disorders Source: in Poon, L.W., ed. Handbook for Clinical Memory Assessment of Older Adults. Hyattsville, MD: American Psychological Association. 1986. p. 81-88. Contact: This publication may be available in your local medical library. Call for information. ISBN: 091270442X. Summary: Differential diagnosis of dementias of later life is an interdisciplinary challenge, with cognitive assessment one of several essential evaluations used to distinguish diseases of the Alzheimer type, vascular dementias, and related disorders. Psychological testing also provides the empirical basis to devise a treatment plan for patients with different forms of dementia. However, it is argued that cognitive and behavioral information is underutilized in patient care. This paper discusses specific research priorities, including information needed to develop an adequate classification to overcome limitations of DSM-III, to test the hypothesis of the heterogeneity of dementia, and to improve the ability to care for people, maximizing their functional effectiveness and quality of life. 58 references.

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Chemical Neuroanatomy of Alzheimer's Disease Source: in Iversen, L.L.; Iversen, S.D.; and Snyder, S.H., eds. Psychopharmacology of the Aging Nervous System, Volume 20. New York, NY: Plenum Press. 1988. p. 131-155. Contact: Available from Plenum Press. 233 Spring Street, New York, NY 10013. (800) 221-9369. PRICE: $85.00. ISBN: 0306427443. Summary: During the past few years experimental neuroanatomical studies have shed considerable light on the potential significance of the distribution of degenerative changes in Alzheimer's disease (AD). These studies give some insight into the significance of specific neurotransmitter deficits in AD, both for the pathogenesis of the dementia and for its potential treatment. This review addresses four principal areas: the relationship of neural connections and neurotransmitters with Alzheimer pathology; limbic and cortical connections and neurotransmitters in AD; cortical connections and neurotransmitters in AD with respect to the brain stem and basal forebrain; and implications for the pathogenesis and treatment of AD. 126 references.

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Alzheimer's Disease: Aluminum and Fibrinous Proteins Source: in De Broe, M.E. and Coburn, J.W. Aluminum and Renal Failure. Norwell, MA: Kluwer Academic Publishers. 1990. p. 127-137. Contact: Available from Kluwer Academic Publishers. 101 Philip Drive, Norwell, MA 02061. (617) 871-6600. PRICE: $139.00. ISBN: 0792303474. Summary: This book chapter discusses the controversy concerning the possible role of aluminum in Alzheimer's disease. The controversy has arisen, in part, as a result of the observation that aluminum concentrations in some cerebral cortical regions in tissue affected with Alzheimer's disease approach those found lethal to aluminum sensitive animals. However, no cause and effect relationship between any of the morphological or biochemical changes reported in Alzheimer's disease have been directly attributable to aluminum. There are two known risk factors for Alzheimer's disease: Down's syndrome

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and a family history of the disease. Approximately 10 percent of Alzheimer's disease cases appear to be familial. Topics discussed include research on Alzheimer amyloid in the human brain and aluminum and aluminum's involvement in senile plaques, amyloid proteins, fibrinous proteins of neurofibrillary degeneration, and aluminum accumulation in the brain. Researchers are attempting to discover how aluminum crosses membrane barriers in the brain. 43 references. •

Association Between Clinical and Neuro-Biological Findings in Alzheimer's Disease Source: in Courtois, Y., Faucheux, B., Forette, B., Knook, D.L., and Treton, J.A., eds. Modern Trends in Aging Research. London, England: John Libbey and Company, Limited. 1986. p. 421-434. Contact: Available from John Libbey and Company, Limited. 80/84 Bondway, London SW8 1SF, UNITED KINGDOM. (01) 582-5266. ISBN: 086916103X. Summary: This book chapter presents some neuropathological features of senile dementia of the Alzheimer type (SDAT). Emphasis is placed on cortical atrophy, mainly due to 'shrinkage' of the length of the cortical ribbon, with thickness remaining constant, on the location of senile plaques, mainly in layers II and III of the neocortex, and on recent data concerning the formation of neurofibrillary tangles. This paper does not intend to be a review of the neuropathology of SDAT; rather, its goal is to pinpoint what currently appears to be the most salient features of SDAT. 31 references.

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Colocalisation of Somatostatin, Neuropeptide Y and Neurofibrillary Tangles in Old Age and Alzheimer's Disease: Histological Evidence for the Loss of Peptidergic Neurons Source: in Bes, A., et al. Senile Dementias: Early Detection. London, England: John Libbey and Company Limited. 1986. p. 569-573. Contact: Available from John Libbey and Company Limited. 80/84 Bondway, London SW8 1SF, ENGLAND. (71) 582-5266. ISBN: 0861960947. PRICE: $90.00. Summary: This book chapter reports the results of a study that measured the coexistence of somatostatin (SOM) and neuropeptide Y (NPY) in various cortical regions of the brain of an Alzheimer patient and of a normal elderly control subject. The results suggest an early specific degeneration of those SOM neurons which contain little NPY immunoreactivity and are localized in clusters of perikarya in the superficial layers of the temporal cortex. It was also found that some pepidergic neurons contained neurofibrillary tangles, as demonstrated by consecutive immunohistological stainings. 11 references. (AA-M).

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to Alzheimer’s disease have been published that consolidate information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:12 12

You will need to limit your search to “Directory” and “alzheimer’s disease” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “alzheimer’s disease” (or

266 Alzheimer’s Disease

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Survey of North American and European Dementia Brain Banks: A 1994 Directory Source: Alzheimer Disease and Associated Disorders. 9(4): 193-202. 1995. Summary: This journal article updates a previous list of U.S. Alzheimer's disease brain banks and adds Canadian and European brain banks to the list. Brain banks serve two purposes: providing definitive diagnoses of dementing disorders, and providing brain and related tissues for research. A 1994 survey showed 48 brain banks in the United States, 3 in Canada, 2 in Austria, 3 in France, 1 in Germany, 1 in The Netherlands, 1 in Northern Ireland, 1 in Spain, 1 in Sweden, and 8 in Great Britan. Increased brain banking activity results from growth in the number of State and privately funded banks, funding by the U.S. National Institutes of Health of new Alzheimer's Disease Centers with integral brain banks, and the formation and funding of the European Brain Bank Network and the American Brain Bank Network. The entry for each brain bank includes its address and telephone number and the fax and telephone numbers of principal administrators. 1 table, 21 references.

synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.

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CHAPTER 8. MULTIMEDIA ON ALZHEIMER’S DISEASE Overview In this chapter, we show you how to keep current on multimedia sources of information on Alzheimer’s disease. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on Alzheimer’s disease is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “Alzheimer’s disease” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “Alzheimer’s disease” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on Alzheimer’s disease: •

Solving Bathing Problems in Persons With Alzheimer's Disease and Related Disorders Source: Chapel Hill, NC: Departments of Family Medicine and Psychology University of North Carolina. 1996. (videocassette). Contact: Available from Terra Nova Films. 9848 S. Winchester Avenue, Chicago, IL 60643. (800) 779-8491; (773) 881-8491; FAX (773) 881-3368. PRICE: $ 129.00 (purchase); $45.00 (rental); plus $9.00 shipping and handling. Order number: ED 259Z. Summary: This videotape shows different bathing situations, problems that can arise while bathing someone who has Alzheimer s disease (AD), and how to prevent or solve those problems. It focuses on individualized care. The introduction describes agitation and aggression and how those behaviors differ. The authors encourage caregivers to: learn about the person (level of dementia, physical problems, bathing preferences); learn about the problem behavior (what is triggering or causing the behavior); and develop a

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plan for bathing the individual (focus on the person, be flexible). According to the authors, once a caregiver has learned what an AD patient prefers and what factors reduce problems while bathing, the caregiver should provide that information in the patient s record to inform other staff members who may bathe that patient. •

Alzheimer's Disease: Natural Feeding Techniques Source: Chicago, IL: Terra Nova Films. 1996. (videocassette). Contact: Terra Nova Films. 9848 S. Winchester Avenue, Chicago, IL 60643. (800) 7798491; (773) 881- 8491; FAX (773) 881- 3368. Internet: http://www.terranova.org. PRICE: $105.00 (purchase), $39.00 (rental) plus $9.00 for shipping. Summary: This videotape uses three case studies to show how natural oral feeding, instead of tube feeding, is administered to and may benefit people who are in the later stages of Alzheimer s disease (AD). The introduction describes how AD affects eating behaviors and what can be done to ensure the person still maintains proper nutrition. Suggested changes in feeding techniques include individualizing the meal to the patient s needs, increasing staff size during meal times, making breakfast and lunch the large meals of the day, modifying food consistency and flavor, and providing the AD patient with verbal and physical cues to chew and swallow. The authors have found that when natural oral feeding techniques are used to replace tube feeding, there is a decrease in infection and an increase in patient comfort and quality of life.

Bibliography: Multimedia on Alzheimer’s Disease The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in Alzheimer’s disease (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on Alzheimer’s disease: •

Alzheimer's disease: unraveling the mystery Source: National Institute on Aging, National Institutes of Health; Year: 2002; [Bethesda, Md.]: National Institutes of Health, [2002]

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Alzheimer's disease [electronic resource] Source: written by Jean Wesley; Year: 1986; Format: Electronic resource; Edwardsville, KS: Medi-Sim, c1986

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Alzheimer's disease [videorecording] Source: produced by Delmar Publishers, Inc.; production by Panagraph Incorporated; Year: 1989; Format: Videorecording; [Albany, N.Y]: Delmar, c1989

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Alzheimer's disease [videorecording] Source: presented by the Medical Learning Center Network at Saint Thomas Hospital; Year: 1989; Format: Videorecording; Nashville, TN: The Network, 1989

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Alzheimer's disease [videorecording] Source: presented as an educational service by Allen & Hanburys, division of Glaxo Inc. [and] Glaxo Pharmaceuticals, division of Glaxo Inc.; a Vision Associates/Medical Vision production; Year: 1988; Format: Videorecording; [Research Triangle Park, N.C.]: Glaxo, c1988

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Alzheimer's disease [videorecording] Source: Marshfield Video Network, in cooperation with Marshfield Clinic, St. Joseph's Hospital, and Marshfield Medical

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Research Foundation; Year: 1988; Format: Videorecording; Marshfield, WI: The Network, c1988 •

Alzheimer's disease [videorecording]: clinical recognition, diagnosis, staging, and management Source: Barry Reisberg; Year: 1984; Format: Videorecording; New York: Network for Continuing Medical Education, 1984

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Alzheimer's disease [videorecording]: coping with confusion Source: HSN, Hospital Satellite Network program of continuing education; Year: 1985; Format: Videorecording; [Los Angeles, Calif.]: The Network, c1985

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Alzheimer's disease [videorecording]: effects on communication Source: [presented by] MEES; a Video Services production; Year: 1986; Format: Videorecording; [Los Angeles, Calif.]: Hospital Satellite Network, c1986

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Alzheimer's Disease [videorecording]: is today's science tomorrow's management? Source: Howard A. Crystal, Peter Davies; Year: 1991; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1991

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Alzheimer's disease [videorecording]: is today's science tomorrow's management? Source: Howard A. Crystal, Peter Davies; Year: 1991; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1991

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Alzheimer's disease [videorecording]: managing the later stages in a health care setting Source: produced by Medical Media Production Service, VA Medical Center, Northport, NY, in cooperation with Geriatric Research, Education & Clinical Center, VA Medical Cen; Year: 1989; Format: Videorecording; [Washington, D.C.]: Dept. of Veterans Affairs, 1989

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Alzheimer's disease [videorecording]: pieces of the puzzle Source: produced by Arizona Long Term Care Gerontology Center and Biomedical Communications, Arizona Health Sciences Center, College of Medicine, the University of Arizona; Year: 1990; Format: Videorecording; Tucson, AZ: The University, c1990

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Alzheimer's disease [videorecording]: stolen tomorrows Source: produced by Lincoln General Hospital; Year: 1986; Format: Videorecording; Lincoln, Neb.: The Hospital, c1986

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Alzheimer's disease [videorecording]: the loss of self: a teleconference Source: presented by the Laurence A. Grossman Medical Learning Center at Saint Thomas Hospital; Year: 1988; Format: Videorecording; Nashville, Tenn.: The Center, c1988

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Alzheimer's disease and other memory disorders [videorecording] Source: produced by Macmillan Healthcare Information/Symposiums International and by the Annenberg Center for Health Sciences at Eisenhower Medical Center; Year: 1986; Format: Videorecording; [Florham Park, N.J.: Macmillan], [1986]

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Alzheimer's disease and the family [electronic resource] Source: developed by University of Rochester Medical School, Department of Pediatrics; Year: 1988; Format: Electronic resource; Chapel Hill, NC: Health Sciences Consortium, 1988

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Alzheimer's disease, a clinical update [videorecording] Source: with Barry Reisberg; Year: 1986; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1986

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Alzheimer's disease, discharge planning [videorecording] Source: HSN, Hospital Satellite Network program of continuing education; Year: 1985; Format: Videorecording; [Los Angeles, Calif.]: The Network, c1985

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Dealing with Alzheimer's disease [videorecording]: a common sense approach to communication Source: production/post production facility, Gillette Children's

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Hospital; Year: 1990; Format: Videorecording; [St. Paul, Minn.]: Ramsey Foundation, c1990 •

Diagnosis of Alzheimer's disease [videorecording] Source: [presented by] Marshfield Clinic, Saint Joseph's Hospital, [and] Marshfield Medical Research Foundation; Year: 1992; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, [1992]

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Geriatrics [videorecording]: Alzheimer's disease and other dementias Source: an AREN production; [produced at the facilities of WQED/Pittsburgh by QED Enterprises]; Year: 1986; Format: Videorecording; Pittsburgh, Pa.: AREN, c1986

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Managing and understanding behavior problems in Alzheimer's disease and related disorders [videorecording]: the ABCs of behavior management in dementia Source: training program developed by Linda Teri; produced in the facilities of Instructional Media Service; Year: 1990; Format: Videorecording; Seattle, WA: [University of Washington], c1990

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Molecular, biological, and neurobiologic contributions to our understanding of Alzheimer's disease [videorecording] Source: produced by the Department of Psychiatry and Behavioral Sciences and the Health Communications Network; Year: 1990; Format: Videorecording; Charleston, S.C.: Medical University of South Carolina, c1990

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Mr. Buttons, a gentleman with Alzheimer's disease [electronic resource] Source: by Sharon Gomez; Year: 1989; Format: Electronic resource; Philadelphia, PA: J.B. Lippincott, c1989

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NIA Alzheimer's Disease Centers (ADC's) program directory [electronic resource]. Year: 2002; Format: Electronic resource; [S.l.: s.n., 2002]

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Not alone in the world-- caring for someone with Alzheimer's disease [videorecording] Source: executive producer, Mary Barringer; contributing producer, James Kvale; Year: 1987; Format: Videorecording; [Springfield, Ill.]: Southern Illinois University School of Medicine, c1987

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Nursing care of the client with Alzheimer's disease [electronic resource]. Year: 1986; Format: Electronic resource; Edwardsville, KS: Medi-Sim, c1986

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The Challenge of Alzheimer's disease [videorecording] Source: Geriatric Education Center; Year: 1990; Format: Videorecording; Richmond, VA: Virginia Commonwealth University, c1990

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The early, often missed signs of Alzheimer's disease [videorecording] Source: [HSTN]; Year: 2003; Format: Videorecording; Carrollton, TX: [PRIMEDIA Workplace Learning], c2002

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CHAPTER 9. PERIODICALS AND NEWS ON ALZHEIMER’S DISEASE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Alzheimer’s disease.

News Services and Press Releases One of the simplest ways of tracking press releases on Alzheimer’s disease is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “Alzheimer’s disease” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to Alzheimer’s disease. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “Alzheimer’s disease” (or synonyms). The following was recently listed in this archive for Alzheimer’s disease: •

Memantine approved in U.S. for Alzheimer's disease Source: Reuters Medical News Date: October 17, 2003

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Ebixa, Aricept combo helps in Alzheimer's disease Source: Reuters Industry Breifing Date: September 23, 2003

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Amyloid-binding ligand a potential biomarker for Alzheimer's disease Source: Reuters Medical News Date: September 23, 2003

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Ratio of Alzheimer's disease markers in CSF may be diagnostic Source: Reuters Medical News Date: September 15, 2003

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Alzheimer's disease cases in US expected to top 13 million by 2050 Source: Reuters Medical News Date: August 19, 2003

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Copper may play a role in Alzheimer's disease Source: Reuters Health eLine Date: August 12, 2003

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R-flurbiprofen lowers amyloid involved in Alzheimer's disease in vivo Source: Reuters Industry Breifing Date: August 07, 2003

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Key enzyme protective against Alzheimer's disease Source: Reuters Health eLine Date: July 30, 2003

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Amyloid-beta promotes neurofibrillary tangles seen in Alzheimer's disease Source: Reuters Medical News Date: July 28, 2003

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Fish and n-3 fatty acids in diet may reduce Alzheimer's disease risk Source: Reuters Medical News Date: July 21, 2003

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Painkillers may protect against Alzheimer's disease Source: Reuters Health eLine Date: July 18, 2003

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Subacute meningoencephalitis complicates Alzheimer's disease immunization Source: Reuters Industry Breifing Date: July 17, 2003

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Analysis supports protective effect of NSAID use against Alzheimer's disease Source: Reuters Medical News Date: July 17, 2003

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Melissa officinalis extract benefits patients with mild-to-moderate Alzheimer's disease Source: Reuters Medical News Date: July 04, 2003

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Investigational drug for Alzheimer's disease meets phase II objectives Source: Reuters Medical News Date: June 23, 2003

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Study published showing NSAIDs do not slow Alzheimer's disease progression Source: Reuters Industry Breifing Date: June 04, 2003

Periodicals and News

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Vaccination with beta-amyloid may slow cognitive decline in Alzheimer's disease Source: Reuters Medical News Date: May 21, 2003

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Lithium reduces hallmarks of Alzheimer's disease pathology in mice Source: Reuters Medical News Date: May 21, 2003

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Depression symptoms linked to Alzheimer's disease Source: Reuters Medical News Date: May 19, 2003

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Tetrahydrocannabinol may reduce agitation in Alzheimer's disease patients Source: Reuters Medical News Date: May 16, 2003

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Progression of parkinsonian-like signs associated with Alzheimer's disease risk Source: Reuters Medical News Date: April 24, 2003

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CSF proteins could be useful markers for Alzheimer's disease Source: Reuters Medical News Date: April 22, 2003

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Apoptotic effect of monomeric aluminum may explain link to Alzheimer's disease Source: Reuters Medical News Date: April 15, 2003

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Unusual cataract associated with Alzheimer's disease Source: Reuters Medical News Date: April 11, 2003

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Form of iron raised in Alzheimer's disease: study Source: Reuters Health eLine Date: April 09, 2003

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DHEA fails to benefit patients with Alzheimer's disease Source: Reuters Industry Breifing Date: April 07, 2003

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Pfizer, Eisai say Aricept may work for dementia beyond Alzheimer's disease Source: Reuters Industry Breifing Date: April 04, 2003

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Drug combo improves cognition in patients with advanced Alzheimer's disease Source: Reuters Industry Breifing Date: April 03, 2003

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Memantine slows progression of moderate-to-severe Alzheimer's disease Source: Reuters Industry Breifing Date: April 02, 2003

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Mixed effects of Alzheimer's disease vaccine seen on autopsy of recipient Source: Reuters Industry Breifing Date: March 17, 2003

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HRT may offer effective therapy for Alzheimer's disease Source: Reuters Industry Breifing Date: February 26, 2003

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Merck, Sunesis collaborate on Alzheimer's disease drugs Source: Reuters Industry Breifing Date: February 18, 2003

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High intake of unsaturated fats may protect against Alzheimer's disease Source: Reuters Medical News Date: February 18, 2003 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “Alzheimer’s disease” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “Alzheimer’s disease” (or synonyms). If you know the name of a company that is relevant to Alzheimer’s disease, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “Alzheimer’s disease” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “Alzheimer’s disease” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on Alzheimer’s disease: •

What Can a Pathologist Tell Us About Alzheimer's Disease? Source: Alzheimer's Disease Society Newsletter. p. 5. September 1988. Contact: Available from Alzheimer's Disease Society. Gordon House, 10 Greencoat Place, London SW1P 1PH, ENGLAND. (071) 306-0606. PRICE: Call for price information. Summary: This article reviews some recent areas of investigation into the causes of Alzheimer's disease. Relatively new techniques, such as immunohistology, electron microscopy, and histochemistry, are discussed, along with the older techniques that enabled Alzheimer to discover the disease.

•

Genetic Factors in Alzheimer's Disease Source: Global Perspective. [Newsletter] 2(1): 6-7. April 1991. Contact: Alzheimer's Disease International. 919 North Michigan Avenue, Suite 1000, Chicago, IL 60611-1676. (800) 272-3900; (312) 335-8882 (TDD); (312) 335-1110 (FAX). PRICE: Call for price information. Summary: This newsletter article discusses a genetic theory for Alzheimer's disease, focusing on formal genetics and population genetic studies. Neither epidemiology studies nor small pedigrees support the suggestion that Alzheimer's Disease is inherited. Further, cross-cultural studies of patients from the nineteenth versus the twentieth centuries who lived in Europe or America found no age-related differences in onset of Alzheimer's disease. However, detailed, extensive pedigree studies that have examined at least three generations of affected families indicate that two types of heritable Alzheimer's disease may exist: an early onset, dominant form of the disease, and a late onset, sporadic form also referred to as senile dementia of the Alzheimer type (SDAT). When data from a large pedigree study of more than 6,000 members of a family with a pattern of early onset Alzheimer's disease were adjusted for late-onset disease (i.e., onset at age 80 rather than 42), statistical analysis revealed that most late-onset carriers, about 80 percent, will die before developing the disease. Formal genetic research studies indicate a possible linkage between early onset Alzheimer's disease and some genes on chromosome 21, including one gene defined as the familial Alzheimer's

276 Alzheimer’s Disease

disease (FAD) gene, but no definitive genetic markers of the disease have been found yet. The author of the study concludes that genetically, based on accumulating evidence, Alzheimer's is a disease similar to thalassemia major (Cooley's anemia). The use of formal genetics is considered a futile route to study the late-onset form of the disease, and systemic cross-cultural, or cross-population studies of founder effect and rare alleles (hereditary characteristics) are recommended for understanding the natural history of Alzheimer's disease.

Academic Periodicals covering Alzheimer’s Disease Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Alzheimer’s disease. In addition to these sources, you can search for articles covering Alzheimer’s disease that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for Alzheimer’s disease. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with Alzheimer’s disease. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).

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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to Alzheimer’s disease: Benzodiazepines •

Systemic - U.S. Brands: Alprazolam Intensol; Ativan; Dalmane; Diastat; Diazepam Intensol; Dizac; Doral; Halcion; Klonopin; Librium; Lorazepam Intensol; Paxipam; ProSom; Restoril; Serax; Tranxene T-Tab; Tranxene-SD; Tranxene-SD Half Strength; Valium; Xanax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202084.html

Buspirone •

Systemic - U.S. Brands: BuSpar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202100.html

Corticosteroids •

Dental - U.S. Brands: Kenalog in Orabase; Orabase-HCA; Oracort; Oralone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202010.html

•

Inhalation - U.S. Brands: AeroBid; AeroBid-M; Azmacort; Beclovent; Decadron Respihaler; Pulmicort Respules; Pulmicort Turbuhaler; Vanceril; Vanceril 84 mcg Double Strength http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202011.html

•

Nasal - U.S. Brands: Beconase; Beconase AQ; Dexacort Turbinaire; Flonase; Nasacort; Nasacort AQ; Nasalide; Nasarel; Nasonex; Rhinocort; Vancenase; Vancenase AQ 84 mcg; Vancenase pockethaler http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202012.html

•

Ophthalmic - U.S. Brands: AK-Dex; AK-Pred; AK-Tate; Baldex; Decadron; Dexair; Dexotic; Econopred; Econopred Plus; Eflone; Flarex; Fluor-Op; FML Forte; FML Liquifilm; FML S.O.P.; HMS Liquifilm; Inflamase Forte; Inflamase Mild; I-Pred; Lite Pred; Maxidex; Ocu-Dex; Ocu-Pred; Ocu-Pr http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202013.html

•

Otic - U.S. Brands: Decadron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202014.html

•

Rectal - U.S. Brands: Anucort-HC; Anu-Med HC; Anuprep HC; Anusol-HC; Anutone-HC; Anuzone-HC; Cort-Dome; Cortenema; Cortifoam; Hemorrhoidal HC; Hemril-HC Uniserts; Proctocort; Proctosol-HC; Rectosol-HC http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203366.html

Donepezil •

Systemic - U.S. Brands: Aricept http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203748.html

Ergoloid Mesylates •

Systemic - U.S. Brands: Gerimal; Hydergine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202215.html

Galantamine •

Systemic - U.S. Brands: Reminyl http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500281.html

Researching Medications

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Phenothiazines •

Systemic - U.S. Brands: Chlorpromazine Hydrochloride Intensol; Compazine; Compazine Spansule; Mellaril; Mellaril Concentrate; Mellaril-S; Permitil; Permitil Concentrate; Prolixin; Prolixin Concentrate; Prolixin Decanoate; Prolixin Enanthate; Serentil; Serentil Concentrate; Ste http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202457.html

Risperidone •

Systemic - U.S. Brands: Risperdal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202769.html

Rivastigmine •

Systemic - U.S. Brands: Exelon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500151.html

Selegiline •

Systemic - U.S. Brands: Carbex; Eldepryl http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202519.html

Tacrine •

Systemic - U.S. Brands: Cognex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202722.html

Trazodone •

Systemic - U.S. Brands: Desyrel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202573.html

Valproic Acid •

Systemic - U.S. Brands: Depacon; Depakene; Depakote; Depakote Sprinkle http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202588.html

Vitamin E •

Systemic - U.S. Brands: Amino-Opti-E; E-Complex-600; Liqui-E; Pheryl-E http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202598.html

Zaleplon •

Systemic - U.S. Brands: Sonata http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500042.html

Zolpidem •

Systemic - U.S. Brands: Ambien http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202707.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

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Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

283

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute13: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

13

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.14 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:15 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

14

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 15 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “Alzheimer’s disease” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “Alzheimer’s disease” (or synonyms) into the “For these words:” box. The following is a sample result: •

Ondansetron in the Treatment of Cognitive Decline in Alzheimer Dementia Source: American Journal of Geriatric Psychiatry. 10(2): 212-215. March-April 2002. Summary: This article describes a clinical trial of ondansetron for the treatment of cognitive decline in Alzheimer's disease (AD). The sample consisted of 185 AD patients, aged 50 years and older, with mild to moderate dementia. Participants were randomly assigned to receive either 10 micrograms per day of ondansetron, 20 micrograms per day of ondansetron, or placebo for 24 weeks. The primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive Subscale, completed at baseline and at the ends of weeks 12 and 24, and the Clinician's Interview-Based Impression of Change, completed at the ends of weeks 12 and 24. Ondansetron was well tolerated without any serious side effects. However, there were no significant differences among groups on either the primary outcome measures or secondary measures of cognitive ability, activities of daily living, and relatives' stress. The results suggest that serotonergic agents such as ondansetron are not effective for improving cognition in patients with AD. 2 figures, 2 tables, 15 references.

•

Understanding Medicaid Long Term Care: A Primer for Alzheimer Advocates Source: Washington, DC: Alzheimer's Association. 1997. 30 p. Contact: Alzheimer's Association. Washington Public Policy Office. 1319 F Street, NW, Suite 710, Washington, DC 20004. (202) 393-7737; FAX (202) 393-2109. PRICE: Single copy free. Summary: This booklet is intended to help Alzheimer's disease (AD) advocates understand Medicaid as a potential source of funding for long term care. An introductory section provides background information about the Medicaid program, who it is designed to help, and the types of services it covers. The next three sections discuss key issues that affect the availability of Medicaid long term care services for people with AD. The first section, on financial eligibility, defines the categories of needy people covered by Medicaid and summarizes the rules concerning income and assets, spousal impoverishment, transfers of assets, and recovery of improperly paid benefits. The next section discusses other eligibility factors such as the need for care, age,

Physician Resources 287

disability, residency, and citizenship. The third section, on long term care services, explains Medicaid coverage for nursing home care and home and community care. The booklet includes a checklist for AD advocates and tables showing selected data for the 50 States. •

Alzheimer Drug Trials in Canada: December 1994 Source: Toronto, Ontario: Alzheimer Society of Canada. 1994. 1 page 4 panels. Contact: Alzheimer Society of Canada. 1320 Yonge Street, Suite 201, Toronto, Ontario M4T 1X2, CANADA. (416) 925-3552; FAX (416) 925-1649. PRICE: FREE. Summary: This fact sheet, updated bi-annually, presents information on the status of the drug approval process for Alzheimer's disease (AD) in Canada. These types of fact sheets are issued during the initial recruitment/enrollment stage of the testing process and provide information on participating in trials. The sheet explains how drugs are approved in Canada and the clinical trial phases. It also provides information on how to obtain a drug outside of the approval process through the Health Protection Branch of Health Canada, Emergency Drug Release Program. A list of drugs currently under investigation for use with AD patients is provided.

•

Alzheimer Care Demonstration Evaluation Report: Senior Companion Program InHome Respite Care Source: Chicago, IL: Alzheimer's Association. 1991. 48 p. Contact: Alzheimer's Association. 919 North Michigan Avenue, Suite 1000, Chicago, IL 60611-1676. (800) 272-3900; (312) 335-8700; (312) 335-8882 (TDD); FAX (312) 335-1110. PRICE: Single copy free. Summary: This report describes a respite care demonstration project conducted by the Alzheimer's Association and the Senior Companion Program SCP, a volunteer program of the federal agency ACTION. The purpose of the demonstration was to evaluate the feasibility and benefits of using trained Senior Companion/Alzheimer's Volunteers to provide in home respite care to clients with Alzheimer's disease and their families. Nine Alzheimer's Association Chapters and SCPs participated in the 3 year project. The results demonstrated both a need for respite care services and the feasibility of the Alzheimer's Association/SCP partnership in providing such services. Evaluation responses from the families and the Senior Companion respite workers were overwhelmingly positive. The Alzheimer's Association recommends continued federal funding to take advantage of the SCP's potential as a source of respite care for patients with Alzheimer's disease and their families.

•

Reports From the National Institute on Aging (6 Reports) Source: Aging: Clinical and Experimental Research. 2(3): 297-316. September 1990. Contact: Available from Editrice Kurtis S.R.L. Via Luigi Zoja, 30-20152 Milano, Italy. Telephone: (02) 48202740 or FAX (02) 48201219. Single issues and subscriptions available for purchase. PRICE: Contact publisher for information. Summary: This special section of this journal issue presents the third set of papers which are comprehensive reports from four of the Alzheimer's Disease Patient Registries funded by the National Institute on Aging (NIA), and details their purposes, plans, and progress. Introductory comments to this section note that the NIA commissioned a number of papers to be published in this journal that further examine issues and

288 Alzheimer’s Disease

questions in the development of large-area, large-scale registries for dementing diseases. This section also outlines the focus of each of these four groupings of papers. The papers in the current issue cover: (1) the East Boston Alzheimers' Disease Registry, covering existing studies that supply data to the registry and discussing patient interviews, diagnostic criteria, general diagnostic inferences, and problem areas needing further studies; (2) the University of Pittsburgh Alzheimer's Disease Patient Registry, including the Monongahela Valley Independent Elders Survey (MoVIES), outlining the MoVIES cognitive screening battery and presenting descriptive demographic statistical results; (3) two projects undertaken prior to the establishment of the Iowa Registry, as well as the plans and progress of the University of Iowa Prototype Alzheimer's Disease Registry, outlining and discussing identified tasks and case-finding sources, and presenting data on demographic distributions, cognitive evaluation, etiologic categories, an evaluation of treatable causes; and (4) the Illinois Alzheimer's Patient Registry and the Prototype Alzheimer Collaborative Team (PACT), discussing the flow of case enrollment forms and providing data on selected demographic characteristics of PACT patients. The other three sets of NIA-commissioned papers discuss the development of registries for other diseases and conditions, major conceptual issues in registry development, and additional NIA-funded Alzheimer's Disease Patient Registries.

The NLM Gateway16 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.17 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Alzheimer’s disease” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 38050 965 938 38 32 40023

HSTAT18 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.19 These documents include clinical practice guidelines, quick16

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

17

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 18 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 19

The HSTAT URL is http://hstat.nlm.nih.gov/.

Physician Resources 289

reference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.20 Simply search by “Alzheimer’s disease” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists21 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.22 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.23 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Alzheimer’s Disease In the following section, we will discuss databases and references which relate to the Genome Project and Alzheimer’s disease.

20

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 21 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 22

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 23 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).24 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “Alzheimer’s disease” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for Alzheimer’s disease: •

Alzheimer Disease; AD Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?104300

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Alzheimer Disease, Familial, Type 3; AD3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607822

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Amyloid Beta A4 Precursor Protein; APP Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?104760

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Alzheimer Disease 2, Late-Onset; AD2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?104310

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Dementia, Lewy Body; DLB Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?127750

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Presenilin 2; PSEN2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600759

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Synuclein, ALPHA; SNCA Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?163890

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Alzheimer Disease, Familial, Type 5 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602096

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Alzheimer Disease, Susceptibility To, Mitochondrial Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?502500

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Alzheimer Disease 6 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605526

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Alzheimer Disease 7 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606187

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Alzheimer Disease 8 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607116

Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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Alzheimer Disease Neuronal Thread Protein Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607413

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Alzheimer Disease, Early-Onset Familial, with Coexisting Amyloid and Prion Pathology Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605055

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Alzheimer Disease without Neurofibrillary Tangles Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604154 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner

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syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html •

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “Alzheimer’s disease” (or synonyms) into the search box and click “Go.”

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Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database25 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database26 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “Alzheimer’s disease” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

25 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 26 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on Alzheimer’s disease can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to Alzheimer’s disease. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to Alzheimer’s disease. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “Alzheimer’s disease”:

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Other guides Alzheimer's Caregivers http://www.nlm.nih.gov/medlineplus/alzheimerscaregivers.html Alzheimer's Disease http://www.nlm.nih.gov/medlineplus/alzheimersdisease.html Congenital Heart Disease http://www.nlm.nih.gov/medlineplus/congenitalheartdisease.html Crohn's Disease http://www.nlm.nih.gov/medlineplus/crohnsdisease.html Degenerative Nerve Diseases http://www.nlm.nih.gov/medlineplus/degenerativenervediseases.html Dementia http://www.nlm.nih.gov/medlineplus/dementia.html Gaucher's Disease http://www.nlm.nih.gov/medlineplus/gauchersdisease.html Huntington's Disease http://www.nlm.nih.gov/medlineplus/huntingtonsdisease.html Parkinson's Disease http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html Parkinson's Disease http://www.nlm.nih.gov/medlineplus/tutorials/parkinsonsdiseaseloader.html

Within the health topic page dedicated to Alzheimer’s disease, the following was listed: •

General/Overview Alzheimer's: Searching for a Cure Source: Food and Drug Administration http://www.fda.gov/fdac/features/2003/403_alz.html

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Diagnosis/Symptoms ApoE (Apolipoprotein E) Genotyping Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/apoe/test.html Expanding the Use of Imaging in Alzheimer's Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00914 Memory Loss: Questions to Ask the Doctor Source: Administration on Aging http://www.aoa.gov/alz/public/alzcarefam/disease_info/questions_to_ask.asp Mild Cognitive Impairment: Possible Predictor of Alzheimer's Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AZ00014

Patient Resources

Tau/Amyloid Beta 42 Peptide Test (Alzheimer Biomarkers) Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/tau/test.html Understanding Alzheimer's: Getting a Diagnosis Source: Fisher Center for Alzheimer's Research Foundation http://www.alzinfo.org/understanding/diagnosis/ Understanding Alzheimer's: Warning Signs & Symptoms Source: Fisher Center for Alzheimer's Research Foundation http://www.alzinfo.org/understanding/signssymptoms/ •

Treatment Alzheimer's Disease Medications Source: National Institute on Aging http://www.alzheimers.org/pubs/medications.htm Standard Prescriptions for Alzheimer's Source: Alzheimer's Association http://www.alz.org/AboutAD/Treatment/Standard.htm Treating Behavioral Symptoms in Alzheimer's Source: Alzheimer's Association http://www.alz.org/AboutAD/Treatment/Behavioral.htm

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Alternative Therapy Alternative Treatments in Alzheimer's Source: Alzheimer's Association http://www.alz.org/AboutAD/Treatment/Alternative.htm

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Nutrition Nutritional Challenges of Alzheimer's Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00217

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Coping Coping with Changes in Daily Life Source: Alzheimer's Association http://www.alz.org/IHaveAD/Coping.htm Helping Your Family and Friends Source: Alzheimer's Association http://www.alz.org/IHaveAD/Helping.htm Making Job Decisions Source: Alzheimer's Association http://www.alz.org/IHaveAD/JobDecisions.htm Modifying the Home Source: Fisher Center for Alzheimer's Research Foundation http://www.alzinfo.org/treatment/modifying/default.aspx

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Taking Care of Yourself Source: Alzheimer's Association http://www.alz.org/IHaveAD/Care.htm •

Specific Conditions/Aspects Alzheimer's: When Driving Becomes an Issue Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HO00046 Choosing Health Care Providers and Facilities Source: Alzheimer's Association http://www.alz.org/IHaveAD/Planning/Choosing.htm Facts about Agitation and Alzheimer's Disease http://www.alz.org/ResourceCenter/FactSheets/FSAgitation.pdf Facts about Sleep Changes in Alzheimer's Disease http://www.alz.org/ResourceCenter/FactSheets/FS_Sleep.pdf Financial Matters for Alzheimer's Care Source: Alzheimer's Association http://www.alz.org/IHaveAD/Planning/FinancialMatters.htm Involvement of Aluminum in the Development of Alzheimer's Disease Source: National Institute of Environmental Health Sciences http://www.niehs.nih.gov/external/faq/alum.htm Legal Issues Source: Alzheimer's Association http://www.alz.org/IHaveAD/Planning/LegalIssues.htm Spirituality and Alzheimer's Disease Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AZ00024

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From the National Institutes of Health Alzheimer's Disease: Unraveling the Mystery Source: National Institute on Aging http://www.alzheimers.org/unraveling/index.htm Forgetfulness: It's Not Always What You Think Source: National Institute on Aging http://www.niapublications.org/engagepages/forgetfulness.asp

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Journals/Newsletters Advances Source: Alzheimer's Association http://www.alz.org/ResourceCenter/ByType/AssociationNewsletters.htm

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Latest News Different Genes Play Roles in Alzheimer's Source: 11/04/2003, United Press International http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14513 .html Families Coping with Alzheimer's Do Better with a Support System Source: 11/03/2003, New York Times Syndicate http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14518 .html FDA Approves Memantine (Namenda) for Alzheimer's Disease Source: 10/17/2003, Food and Drug Administration http://www.fda.gov/bbs/topics/NEWS/2003/NEW00961.html Investigators Explore Selective Silencing of Disease Genes Source: 10/15/2003, National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_gene_silencing.htm Leisure Activity May Cut Alzheimer Risk Source: 10/20/2003, United Press International http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14370 .html More News on Alzheimer's Disease http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/alphanews_a.html#Al zheimersDisease National Alzheimer's Disease Month November 2003 Source: 11/05/2003, Center for Mental Health Services http://www.mentalhealth.org/highlights/november2003/alzheimers/

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Organizations Administration on Aging http://www.aoa.gov/ Alzheimer's Association http://www.alz.org/ Alzheimer's Disease Education and Referral (ADEAR) Center Source: National Institute on Aging http://www.alzheimers.org/ Fisher Center for Alzheimer's Research Foundation http://www.alzinfo.org/ National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/ National Institute on Aging http://www.nia.nih.gov/

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Research “Use It Or Lose It?” Study Suggests Mentally Stimulating Activities May Reduce Alzheimer's Risk Source: National Institute on Aging http://www.nih.gov/news/pr/feb2002/nia-12.htm Effects of Alzheimerâ€™s Disease May Be Influenced by Education Source: National Institute on Aging http://www.nia.nih.gov/news/pr/2003/0623.htm Folic Acid Possibly a Key Factor in Alzheimer's Disease Prevention Source: National Institute on Aging http://www.nih.gov/news/pr/mar2002/nia-01.htm High Homocysteine Levels May Double Risk of Dementia, Alzheimer's Disease, New Report Suggests Source: National Institute on Aging http://www.nih.gov/news/pr/feb2002/nia-13.htm Human Gene Affects Memory Source: National Institute of Child Health and Human Development, National Institute of Mental Health http://www.nih.gov/news/pr/jan2003/nimh-23.htm Investigators Explore Selective Silencing of Disease Genes Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_gene_silencing.htm Life and Death of a Neuron Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/pubs/NINDS_Neuron.htm Lithium Shows Promise against Alzheimer's in Mouse Model Source: National Institute of Mental Health, National Institute on Aging http://www.nih.gov/news/pr/may2003/nimh-21.htm New Studies in Mice Suggest Ways to Clear Damaging Alzheimer's Amyloid Plaques Source: National Institute on Aging http://www.alzheimers.org/nianews/nianews53.htm Prevalence, Incidence, and Cumulative Risk of Alzheimer's Disease Reported Higher in African-American Community Source: Alzheimer's Association http://www.alz.org/Media/newsreleases/current/021202aareport.html Research Aimed at Preventing Alzheimer's Disease Source: Fisher Center for Alzheimer's Research Foundation http://www.alzinfo.org/research/prevention/default.aspx Research Brief: Cells That Live and Let Die Source: National Institute of General Medical Sciences http://www.nigms.nih.gov/news/releases/brief_steller.html Research on Causes of Alzheimer's: Risk Factors and Biology Source: Fisher Center for Alzheimer's Research Foundation http://www.alzinfo.org/research/causes/genetic/default.aspx

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Research: Leading the Battle in Cause, Care, Cure Source: Fisher Center for Alzheimer's Research Foundation http://www.alzinfo.org/research/battle/default.aspx Scientists Pinpoint Gene Influencing Age-at-Onset of Alzheimer’s, Parkinson’s Source: National Institute on Aging http://www.nia.nih.gov/news/pr/2003/1021b.htm What's in a Connection? A Look at Protein Patterns within Synapses Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_synapses.htm WHIMS Study on Estrogen/Progestin Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01226.html •

Statistics FASTATS: Alzheimer's Disease Source: National Center for Health Statistics http://www.cdc.gov/nchs/fastats/alzheimr.htm New Prevalence Study Suggests Dramatically Rising Numbers of People with Alzheimer's Disease Source: National Institute on Aging http://www.nih.gov/news/pr/aug2003/nia-18.htm Statistics about Alzheimer's Disease Source: Alzheimer's Association http://www.alz.org/AboutAD/Statistics.htm

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Teenagers Talking to Children and Teens about Alzheimer's Source: Alzheimer's Association http://www.alz.org/Caregivers/Coping/childrenteens.htm

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on Alzheimer’s disease. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive:

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Let Us Help You Cope With Alzheimer's Disease: The Major Cause of Dementia Source: Boca Raton, FL: Alzheimer's Disease and Related Disorders Association, Palm Beach County Chapter. [6 p.]. Contact: Available from Alzheimer's Association, Palm Beach County Chapter. P.O. Box 272147, Boca Raton, FL 33427-2147. (305) 392-1363 (south) or (305) 763-2699 (north). Summary: The Palm Beach County Chapter of the Alzheimer's Association is part of a nationwide organization dedicated to fighting Alzheimer' s disease on several fronts, including family support, public awareness, advocacy of resources and services, and promotion of research. This brochure also lists characteristics of the three stages of Alzheimer's disease.

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Alzheimer's Disease Resource Book Source: Winter Park, FL: Area Agency on Aging. 1988. 61 p. Contact: Available from Area Agency on Aging. 1011 Wymore Road, Suite 105, Winter Park, FL 32789. (407) 645-3339. Summary: This booklet gives information on Alzheimer's disease and its stages of progression. It explains the purpose of local support groups and gives their addresses and telephone numbers. It also describes community services such as respite care, day care, and nursing homes. Helpful hints on dealing with the Alzheimer person are given, along with a list of videos, films, and books on Alzheimer's.

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Alois Alzheimer Center: Dedicated to the Care and Study of Alzheimer's Disease Source: Cincinnati, OH: Alois Alzheimer Center. [4 p.]. Contact: Available from Alois Alzheimer Center. 70 Damon Road, Cincinnati, OH 45218. (513) 825-2255. PRICE: Free. Summary: This brochure defines Alzheimer's disease, describes the philosophy of the Alois Alzheimer Center, and provides a brief summary about the center's staff, facility, and program. The Alzheimer Center is located within a noninstitutional, campus-like setting in residential Cincinnati. It consists of large, open-spaced walking areas that link furnished patient rooms with the dining room. A chapel, beauty shop, activity room, whirlpool area, and separate rooms for family-patient encounter therapy are also included in the center. The center's program involves maintaining the dignity of the patient while integrating the emotional concerns of the family. The program also includes interactive participation between patient and family through social support groups and professional counseling services provided on a permanent basis.

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Alzheimer's Disease: A Mini-Residency for Allied Health Professionals Source: Pittsburgh, PA: University of Pittsburgh Alzheimer Disease Research Center. 199x. 6 p. Contact: University of Pittsburgh Alzheimer Disease Research Center. University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213-2582. (412) 692-2700; FAX (412) 6922710. PRICE: Free. Summary: This brochure describes a two week educational program offered by the University of Pittsburgh Alzheimer Disease Research Center for health and social service professionals and students. The course is designed to teach the principles of working with families facing cognitive impairment, to enhance understanding of

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current research and the clinical and behavioral aspects of Alzheimer's disease, and to improve clinical, research and advisory skills of participants. Session topics include diagnosis and clinical evaluation, etiology, brain/behavior relationships, neurophysiology of memory, physical changes in normal aging, management of behavior problems, research administration, and accessing community resources. Lectures, conferences and working sessions at other institutions are also part of the course. Continuing education credit is available. •

Epidemiology of Alzheimer Disease in Mental Retardation. Results and Recommendations from an International Conference. Report of the AAMR/IASSID Workgroup on Epidemiology and Alzheimer's Disease Source: Albany, NY: New York State Office of Mental Retardation and Development Disabilities Bureau of Aging Services. 1995. 16 p. Contact: New York State Office of Mental Retardation and Development Disabilities Bureau of Aging Services. 144 Holland Avenue, Albany, NY 12229. (518) 473-7855; FAX (518) 473-0775. PRICE: Free. Summary: This report considers the discussions and recommendations of an epidemiology work group, formed at an international conference convened to discuss Alzheimer's disease among people with mental retardation. Topics include the incidence and prevalence of clinical dementia in this population, risk factors for the development of Alzheimer's disease in adults with mental retardation, and a minimum data set that may be of use for future research on Alzheimer's disease in adults with mental retardation. 1 table, 1 chart, 62 references. The National Guideline Clearinghouse™

The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “Alzheimer’s disease” (or synonyms). The following was recently posted: •

Guidelines for Alzheimer's disease management. Source: Alzheimer's Association of Los Angeles, Riverside and San Bernardino Counties - Private Nonprofit Organization; 1999 January 8 (revised 2002 Jan 1); 52 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3157&nbr=2383&a mp;string=Alzheimer''s+AND+disease Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database:

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Alzheimer's Disease Summary: A general overview of Alzheimer's Disease that includes a description and information about treatment, prognosis and research. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=1105

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Alzheimer's Disease - Iowa Geriatric Education Center Summary: The Alzheimer's disease information on this web site was contributed by medical institutions, health practitioners and other sources and peer-reviewed by members of the Iowa Geriatric Education Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4714

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Alzheimer's Disease Fact Sheet Summary: This sheet provides basic information about Alzheimer's disease, symptoms, diagnosis, and treatment. Source: Alzheimer's Disease Education and Referral Center, National Institute on Aging http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6911

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Alzheimer's Disease Genetics Summary: This fact sheet summarizes current research about the role of genetics in Alzheimer's disease. Source: Alzheimer's Disease Education and Referral Center, National Institute on Aging http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6916

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Alzheimer's Disease Information Summary: This fact sheet discusses Alzheimer's disease, its social and economic impact, and the federal programs and services that are available to the public. Source: U.S. Administration on Aging, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3863

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Alzheimer's Disease Medications Fact Sheet Summary: This fact sheet summarizes the four FDA-approved medications for treating Alzheimer's disease--Reminyl, Exelon, Aricept, and Cognex. Source: Alzheimer's Disease Education and Referral Center, National Institute on Aging http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6917

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Alzheimer's Disease Research Summary: Alzheimer's disease is a progressive, irreversible brain disorder with no known cause or cure. It attacks and slowly steals the minds of its victims. Source: American Health Assistance Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6683

•

Caregiver Guide Summary: This guide provides practical tips for daily coping with bathing, dressing, eating, and activities for people with Alzheimer's disease. Source: Alzheimer's Disease Education and Referral Center, National Institute on Aging http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6912

•

Depression and Alzheimer's Disease Summary: A fact sheet that discusses depression and Alzheimer's disease and how a caregiver can recognize depression in a family member or patient with Alzheimer's disease. Source: American Academy of Family Physicians http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6084

•

Ginkgo Biloba Summary: This fact sheet summarizes the research findings to date regarding the effectiveness of this natural extract in treating Alzheimer's disease. Source: Alzheimer's Disease Education and Referral Center, National Institute on Aging http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6920

•

healthfinder® just for you: Caregivers Summary: healthfinder®'s just for you: Caregivers section features topics such as Alzheimer's disease, home health care, and terminal illness. Source: U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7024

•

Home Safety for People with Alzheimer's Disease Summary: This booklet offers tips and guidelines for creating a safe home environment for people with Alzheimer's disease. Source: Alzheimer's Disease Education and Referral Center, National Institute on Aging http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6915

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•

News and Press Releases - Alzheimer's Disease Education and Referral (ADEAR) Center Summary: This page provides the latest press releases and announcements from this U.S. Department of Health and Human Services agency. Source: Alzheimer's Disease Education and Referral Center, National Institute on Aging http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=1506

•

News Page - Alzheimer's Disease Education and Referral (ADEAR) Center Summary: This page provides visitors with current news, events and announcements related to the services of this U.S. Department of Health and Human Services agency. Source: Alzheimer's Disease Education and Referral Center, National Institute on Aging http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=1754

•

NIH Senior Health Summary: This web site is organized by health topic and currently includes information on Alzheimer's Disease, Caring for Someone with Alzheimer's, and Exercise for Older Adults. Source: National Institutes of Health, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7724

•

NIHSeniorHealth: Alzheimer's Disease Summary: Designed especially for seniors, this page defines Alzheimer's Disease and lists its causes and risk factors, symptoms and diagnosis, treatment and research, and frequently asked questions. Source: National Institutes of Health, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7008

•

Occupational Therapy And People With Alzheimer's Disease Summary: Alzheimer's disease, a condition that affects the brain, occurs in middle or late life, striking men and women of all races, cultures, and backgrounds. Source: American Occupational Therapy Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7305 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to Alzheimer’s disease. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide

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307

useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Alzheimer’s disease. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Alzheimer’s disease. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about Alzheimer’s disease. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “Alzheimer’s disease” (or a synonym), and you will receive information on all relevant organizations listed in the database.

308 Alzheimer’s Disease

Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “Alzheimer’s disease”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “Alzheimer’s disease” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “Alzheimer’s disease” (or a synonym) into the search box, and click “Submit Query.”

309

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.27

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

27

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

310 Alzheimer’s Disease

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)28: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

28

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

312 Alzheimer’s Disease

•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

314 Alzheimer’s Disease

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

315

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on Alzheimer’s disease: •

Basic Guidelines for Alzheimer’s Disease Alzheimer's disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000760.htm Chlamydia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001345.htm

•

Signs & Symptoms for Alzheimer’s Disease Agitation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Aphasia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003204.htm

316 Alzheimer’s Disease

Apraxia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003203.htm Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Incontinence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003142.htm Insomnia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Memory loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003257.htm Restlessness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Seizures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm •

Diagnostics and Tests for Alzheimer’s Disease BUN Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003474.htm CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm Computed Tomography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Magnetic resonance imaging Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm Sedimentation rate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003638.htm Serology Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003511.htm Thyroid function tests Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003444.htm Urinalysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003579.htm

Online Glossaries 317

VDRL Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003515.htm •

Background Topics for Alzheimer’s Disease Autosomal dominant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002049.htm Systemic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002294.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

319

ALZHEIMER’S DISEASE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [NIH]

Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH]

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Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic alpha-Antagonists: Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma. [NIH] Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or

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manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU]

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Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminopropionitrile: 3-Aminopropanenitrile. Reagent used as an intermediate in the manufacture of beta-alanine and pantothenic acid. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloid beta-Protein: A 4 kD protein, 39-43 amino acids long, expressed by a gene located on chromosome 21. It is the major protein subunit of the vascular and plaque amyloid filaments in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (Down syndrome). The protein is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. [NIH] Amyloid beta-Protein Precursor: A precursor to the amyloid-beta protein (beta/A4). Alterations in the expression of the amyloid beta-protein precursor (ABPP) gene, located on chromosome 21, plays a role in the development of the neuropathology common to both Alzheimer disease and Down syndrome. ABPP is associated with the extensive extracellular matrix secreted by neuronal cells. Upon cleavage, this precursor produces three proteins of varying amino acid lengths: 695, 751, and 770. The beta/A4 (695 amino acids) or betaamyloid protein is the principal component of the extracellular amyloid in senile plaques found in Alzheimer disease, Down syndrome and, to a limited extent, in normal aging. [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH]

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Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiopathy: Disease of the blood vessels (arteries, veins, and capillaries) that occurs when someone has diabetes for a long time. There are two types of angiopathy: macroangiopathy and microangiopathy. In macroangiopathy, fat and blood clots build up in the large blood vessels, stick to the vessel walls, and block the flow of blood. In microangiopathy, the walls of the smaller blood vessels become so thick and weak that they bleed, leak protein, and slow the flow of blood through the body. Then the cells, for example, the ones in the center of the eye, do not get enough blood and may be damaged. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anoxia: Clinical manifestation of respiratory distress consisting of a relatively complete absence of oxygen. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH]

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Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antidepressive Agents: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several monoamine oxidase inhibitors are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents also appear to act through brain catecholamine systems. A third group (antidepressive agents, secondgeneration) is a diverse group of drugs including some that act specifically on serotonergic systems. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH] Anti-infective: An agent that so acts. [EU]

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Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antispasmodic: An agent that relieves spasm. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Apathy: Lack of feeling or emotion; indifference. [EU] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH]

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Apraxia: Loss of ability to perform purposeful movements, in the absence of paralysis or sensory disturbance, caused by lesions in the cortex. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Athetosis: A derangement marked by ceaseless occurrence of slow, sinuous, writhing movements, especially severe in the hands, and performed involuntarily; it may occur after hemiplegia, and is then known as posthemiplegic chorea. Called also mobile spasm. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU]

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Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]

Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH]

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Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH]

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Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinesia: Abnormal slowness of movement; sluggishness of physical and mental responses. [EU] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Butyrylcholinesterase: An aspect of cholinesterase (EC 3.1.1.8). [NIH]

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Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual

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patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] CDC2: It is crucial for entry into mitosis of eukaryotic cells. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH]

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Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrovascular Disorders: A broad category of disorders characterized by impairment of blood flow in the arteries and veins which supply the brain. These include cerebral infarction; brain ischemia; hypoxia, brain; intracranial embolism and thrombosis; intracranial arteriovenous malformations; and vasculitis, central nervous system. In common usage, the term cerebrovascular disorders is not limited to conditions that affect the cerebrum, but refers to vascular disorders of the entire brain including the diencephalon; brain stem; and cerebellum. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the

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relatively fixed personality traits and habitual modes of response of an individual. [NIH] Check-up: A general physical examination. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlorpyrifos: An organothiophosphate cholinesterase inhibitor that is used as an insecticide and as an acaricide. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinergic Agents: Any drug used for its actions on cholinergic systems. Included here are agonists and antagonists, drugs that affect the life cycle of acetylcholine, and drugs that affect the survival of cholinergic neurons. The term cholinergic agents is sometimes still used in the narrower sense of muscarinic agonists, although most modern texts discourage that usage. [NIH] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH]

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Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]

Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clioquinol: A potentially neurotoxic 8-hydroxyquinoline derivative long used as a topical anti-infective, intestinal antiamebic, and vaginal trichomonacide. The oral preparation has been shown to cause subacute myelo-optic neuropathy and has been banned worldwide. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of

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the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Compacta: Part of substantia nigra. [NIH] Compassionate: A process for providing experimental drugs to very sick patients who have no treatment options. [NIH] Competency: The capacity of the bacterium to take up DNA from its surroundings. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement

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activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH]

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Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast Sensitivity: The ability to detect sharp boundaries (stimuli) and to detect slight changes in luminance at regions without distinct contours. Psychophysical measurements of this visual function are used to evaluate visual acuity and to detect eye disease. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Callosum: Broad plate of dense myelinated fibers that reciprocally interconnect regions of the cortex in all lobes with corresponding regions of the opposite hemisphere. The corpus callosum is located deep in the longitudinal fissure. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Cribriform: Pierced with small holes as in a sieve. Refers to the appearance of a tumor when viewed under a microscope. The tumor appears to have open spaces or small holes inside. [NIH]

Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH]

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Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Cultured cell line: Cells of a single type that have been grown in the laboratory for several generations (cell divisions). [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cycloserine: Antibiotic substance produced by Streptomyces garyphalus. It may be used in the treatment of resistant tuberculosis as part of a multi-drug regimen. It has also been used in urinary tract infections. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of

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data and facts apart from bibliographic references to them. [NIH] Day Care: Institutional health care of patients during the day. The patients return home at night. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] DHEA: Dehydroepiandrosterone. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diazinon: A cholinesterase inhibitor that is used as an organothiophosphorus insecticide.

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[NIH]

Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Donepezil: A drug used in the treatment of Alzheimer's disease. It belongs to the family of drugs called cholinesterase inhibitors. It is being studied as a treatment for side effects caused by radiation therapy to the brain. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of

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dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Down syndrome: A disorder caused by the presence of an extra chromosome 21 and characterized by mental retardation and distinguishing physical features. [NIH] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Approval: Process that is gone through in order for a drug to receive approval by a government regulatory agency. This includes any required pre-clinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance of the drug. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dystonia: Disordered tonicity of muscle. [EU] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures

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that are advantageous to the patient but not urgent. [EU] Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH]

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Enhancer: Transcriptional element in the virus genome. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epistasis: The degree of dominance exerted by one gene on the expression of a non-allelic gene. [NIH] Epithalamus: The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (habenula) and associated fiber bundles, the pineal body, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the thalamic nuclei although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

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Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exons: Coding regions of messenger RNA included in the genetic transcript which survive the processing of RNA in cell nuclei to become part of a spliced messenger of structural RNA in the cytoplasm. They include joining and diversity exons of immunoglobulin genes. [NIH]

Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH]

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Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feasibility Studies: Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Flurbiprofen: An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting carbonic anhydrase. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH]

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Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fornix: A bundle of nerves connected to the hippocampus. [NIH] Founder Effect: The principle that when a small subgroup of a larger population establishes itself as a separate and isolated entity, its gene pool carries only a fraction of the genetic diversity of the parental population. This may result in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]

Gait: Manner or style of walking. [NIH] Galanin: A neurotransmitter. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Dosage: The number of copies of a given gene present in a cell or nucleus. An increase

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in gene dosage can result in the formation of higher levels of gene product, provided that the gene is not subject to autogenous regulation. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glial Fibrillary Acidic Protein: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000. [NIH] Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

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Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Synthase: An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC 2.4.1.11. [NIH] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gyrus Cinguli: One of the convolutions on the medial surface of the cerebral hemisphere. It surrounds the rostral part of the brain and interhemispheric commissure and forms part of the limbic system. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations. [NIH] Haloperidol: Butyrophenone derivative. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Harmine: Alkaloid isolated from seeds of Peganum harmala L., Zygophyllaceae. It is

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identical to banisterine, or telepathine, from Banisteria caapi and is one of the active ingredients of hallucinogenic drinks made in the western Amazon region from related plants. It has no therapeutic use, but (as banisterine) was hailed as a cure for postencephalitic Parkinson disease in the 1920's. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemiplegia: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical spinal cord diseases; peripheral nervous system diseases; and other conditions may manifest as hemiplegia. The term hemiparesis (see paresis) refers to mild to moderate weakness involving one side of the body. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhagic stroke: A disorder involving bleeding within ischemic brain tissue. Hemorrhagic stroke occurs when blood vessels that are damaged or dead from lack of blood supply (infarcted), located within an area of infarcted brain tissue, rupture and transform an

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"ischemic" stroke into a hemorrhagic stroke. Ischemia is inadequate tissue oxygenation caused by reduced blood flow; infarction is tissue death resulting from ischemia. Bleeding irritates the brain tissues, causing swelling (cerebral edema). Blood collects into a mass (hematoma). Both swelling and hematoma will compress and displace brain tissue. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH]

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Host: Any animal that receives a transplanted graft. [NIH] Housekeeping: The care and management of property. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH]

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Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Imagination: A new pattern of perceptual or ideational material derived from past experience. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]

Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It

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includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH]

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Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH]

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Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Embolism: The sudden obstruction of a blood vessel by an embolus. [NIH] Intracranial Embolism and Thrombosis: Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Jet lag: Symptoms produced in human beings by fast travel through large meridian difference. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and

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developmental disorders. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lathyrism: A paralytic condition of the legs caused by ingestion of lathyrogens, especially beta-aminopropionitrile, found in the seeds of plants of the genus Lathyrus. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leisure Activities: Voluntary use of free time for activities outside the daily routine. [NIH] Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]

Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukoencephalopathy: A condition with spongy holes in the brain's white matter. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Light microscope: A microscope (device to magnify small objects) in which objects are lit directly by white light. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH]

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Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Living will: A health care directive that tells others how a person would like to be treated if they lose their capacity to make decisions about health care; it contains instructions about the person's choices of medical treatment and it is prepared in advance. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Lod: The lowest analyte content which, if actually present, will be detected with reasonable statistical certainty and can be identified according to the identification criteria of the method. If both accuracy and precision are constant over a concentration range. [NIH] Lod Score: The total relative probability, expressed on a logarithmic scale, that a linkage relationship exists among selected loci. Lod is an acronym for "logarithmic odds." [NIH]

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Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Magnetoencephalography: The measurement of magnetic fields over the head generated by electric currents in the brain. As in any electrical conductor, electric fields in the brain are accompanied by orthogonal magnetic fields. The measurement of these fields provides information about the localization of brain activity which is complementary to that provided by electroencephalography. Magnetoencephalography may be used alone or together with electroencephalography, for measurement of spontaneous or evoked activity, and for research or clinical purposes. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

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Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Memantine: Amantadine derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Memory Disorders: Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with dementia; craniocerebraltrauma; encephalitis; alcoholism (see also alcohol amnestic disorder); schizophrenia; and other conditions. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH]

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Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Meningoencephalitis: An inflammatory process involving the brain (encephalitis) and meninges (meningitis), most often produced by pathogenic organisms which invade the central nervous system, and occasionally by toxins, autoimmune disorders, and other conditions. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Microwaves: That portion of the electromagnetic spectrum lying between UHF (ultrahigh frequency) radio waves and heat (infrared) waves. Microwaves are used to generate heat,

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especially in some types of diathermy. They may cause heat damage to tissues. [NIH] Minority Groups: A subgroup having special characteristics within a larger group, often bound together by special ties which distinguish it from the larger group. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate mitogen-activated protein kinases and are themselves phosphorylated by MAP kinase kinase kinases. JNK kinases (also known as SAPK kinases) are a subfamily. EC 2.7.10.- [NIH] Mitogen-Activated Protein Kinases: A superfamily of protein-serine-threonine kinases that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP kinase kinase kinases). Families of these mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs) (also known as c-jun terminal kinases (JNKs)), and p38-mitogen-activated protein kinases. EC 2,7,1.- [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer

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detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Muscarinic Agonists: Drugs that bind to and activate muscarinic cholinergic receptors (receptors, muscarinic). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis,

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prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Neprilysin: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA), an important marker in the diagnosis of human acute lymphocytic leukemia. EC 3.4.24.11. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurites: In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell. [NIH] Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]

Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments:

364 Alzheimer’s Disease

medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofibrils: The delicate interlacing threads, formed by aggregations of neurofilaments and neurotubules, coursing through the cytoplasm of the body of a neuron and extending from one dendrite into another or into the axon. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neuroglia: The non-neuronal cells of the nervous system. They are divided into macroglia (astrocytes, oligodendroglia, and schwann cells) and microglia. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain and blood-retina barriers, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologist: A doctor who specializes in the diagnosis and treatment of disorders of the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuromuscular Junction Diseases: Conditions characterized by impaired transmission of impulses at the neuromuscular junction. This may result from disorders that affect receptor function, pre- or postsynaptic membrane function, or acetylcholinesteraseactivity. The majority of diseases in this category are associated with autoimmune, toxic, or inherited conditions. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neuronal atrophy: Nerve cell death and functional loss. [NIH] Neuronal Plasticity: The capacity of the nervous system to change its reactivity as the result of successive activations. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as

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neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuropil: A dense intricate feltwork of interwoven fine glial processes, fibrils, synaptic terminals, axons, and dendrites interspersed among the nerve cells in the gray matter of the central nervous system. [NIH] Neuropil Threads: Abnormal structures located chiefly in distal dendrites and, along with neurofibrillary tangles and senile plaques, constitute the three morphological hallmarks of Alzheimer disease. Neuropil threads are made up of straight and paired helical filaments which consist of abnormally phosphorylated microtubule-associated tau proteins. It has been suggested that the threads have a major role in the cognitive impairment seen in Alzheimer disease. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular

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endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of

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prevalent cases. [NIH] Oestradiol: Growth hormone. [NIH] Olfaction: Function of the olfactory apparatus to perceive and discriminate between the molecules that reach it, in gas form from an external environment, directly or indirectly via the nose. [NIH] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here. [NIH] Omentum: A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen. [NIH] Ondansetron: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and it has reported anxiolytic and neuroleptic properties. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

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Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH]

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Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral vision: Side vision; ability to see objects and movement outside of the direct line of vision. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Perivascular: Situated around a vessel. [EU] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH]

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Phencyclidine: A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (receptors, N-methyl-Daspartate). As a drug of abuse, it is known as PCP and Angel Dust. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Phrenic Nerve: The motor nerve of the diaphragm. The phrenic nerve fibers originate in the cervical spinal column (mostly C4) and travel through the cervical plexus to the diaphragm. [NIH]

Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Pilot Projects: Small-scale tests of methods and procedures to be used on a larger scale if the pilot study demonstrates that these methods and procedures can work. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Piperidines: A family of hexahydropyridines. Piperidine itself is found in the pepper plant as the alkaloid piperine. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other

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nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH]

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Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH]

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Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [NIH] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propoxur: A carbamate insecticide. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins

A:

(13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic

acid

(PGA(1));

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(5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. EC 2.7.10. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus

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of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudogenes: Genes bearing close resemblance to known genes at different loci, but rendered non-functional by additions or deletions in structure that prevent normal transcription or translation. When lacking introns and containing a poly-A segment near the downstream end (as a result of reverse copying from processed nuclear RNA into doublestranded DNA), they are called processed genes. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychophysics: The science dealing with the correlation of the physical characteristics of a stimulus, e.g., frequency or intensity, with the response to the stimulus, in order to assess the psychologic factors involved in the relationship. [NIH] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]

Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Psychotropic Drugs: A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right

376 Alzheimer’s Disease

ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Puromycin: An antibiotic from Streptomyces alboniger that inhibits protein synthesis by binding to RNA. It is a antineoplastic and antitrypanosomal agent and is used in research as an inhibitor of protein synthesis. [NIH] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [NIH] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quinolinic: It is produced by immune cells and slowly infiltrates the brain tissues after an injury. [NIH] Quinolinic Acid: 2,3-Pyridinedicarboxylic acid. A metabolite of tryptophan with a possible role in neurodegenerative disorders. Elevated CSF levels of quinolinic acid are significantly correlated with the severity of neuropsychological deficits in patients who have AIDS. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Raclopride: A substituted benzamide that has antipsychotic properties. It is a dopamine D2 receptor antagonist. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes

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can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Muscarinic: One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for muscarine over nicotine. There are several subtypes (usually M1, M2, M3.) that are characterized by their cellular actions, pharmacology, and molecular biology. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH]

378 Alzheimer’s Disease

Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Paralysis: Complete or severe weakness of the muscles of respiration. This condition may be associated with motor neuron diseases; peripheral nerve disorders; neuromuscular junction diseases; spinal cord diseases; injury to the phrenic nerve; and other disorders. [NIH] Respite Care: Patient care provided in the home or institution intermittently in order to provide temporary relief to the family home care giver. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rhythmicity: Regular periodicity. [NIH]

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Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH]

380 Alzheimer’s Disease

Seasonal Affective Disorder: A syndrome characterized by depressions that recur annually at the same time each year, usually during the winter months. Other symptoms include anxiety, irritability, decreased energy, increased appetite (carbohydrate cravings), increased duration of sleep, and weight gain. SAD (seasonal affective disorder) can be treated by daily exposure to bright artificial lights (phototherapy), during the season of recurrence. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semantics: The relationships between symbols and their meanings. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Senile Plaques: Spherical masses consisting of amyloid fibrils and neuronal processes. [NIH] Senility: Old age; the physical and mental deterioration associated with old age. [EU] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septal Nuclei: Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of forebrain and brainstem areas including the hippocampus, the lateral hypothalamus, the tegmentum, and the amygdala. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis. [NIH]

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Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the

382 Alzheimer’s Disease

brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of

Dictionary 383

bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Diseases: Pathologic conditions which feature spinal cord damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH]

384 Alzheimer’s Disease

Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Students, Medical: Individuals enrolled in a school of medicine or a formal educational program in medicine. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or

Dictionary 385

chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synaptophysin: A 38-kDa integral membrane glycoprotein of the presynaptic vesicles in neuron and neuroendocrine cells. It is expressed by a variety of normal and neoplastic neuroendocrine cells and is therefore used as an immunocytochemical marker for neuroendocrine differentiation in various tumors. In Alzheimer disease and other dementing disorders there is an important synapse loss due in part to a decrease of synaptophysin in the presynaptic vesicles. [NIH] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Tau Proteins: One of the two major classes of microtubule-associated proteins isolated from the brain. The proteins have two domains: one that binds to microtubules and a second that binds to other cell components. By binding to several unpolymerized tubulin molecules simultaneously, tau proteins speed up the nucleation process in tubulin polymerization. Chemically modified tau proteins also appear to be involved in the formation and/or composition of the neurofibrillary tangles and neuropil threads found in Alzheimer disease. [NIH]

Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant

386 Alzheimer’s Disease

transformation. EC 2.7.7.-. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]

hydroxyethyl)-4-

Thiorphan: A potent inhibitor of membrane metalloendopeptidase (enkephalinase). Thiorphan potentiates morphine-induced analgesia and attenuates naloxone-precipitated withdrawal symptoms. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators

Dictionary 387

of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tranquilizing Agents: A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the anti-anxiety agents (minor tranquilizers), antimanic agents, and the antipsychotic agents (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides

388 Alzheimer’s Disease

(ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transcutaneous: Transdermal. [EU] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]

Trivalent: Having a valence of three. [EU] Tropicamide: A muscarinic antagonist with pharmacologic action similar to atropine and used mainly as an ophthalmic parasympatholytic or mydriatic. It may cause closed-angle glaucoma. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It

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has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Unsaturated Fats: A type of fat. [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH]

390 Alzheimer’s Disease

Vasodilator: An agent that widens blood vessels. [NIH] Vasodilator Agents: Drugs used to cause dilation of the blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is

Dictionary 391

dependent mainly on the sharpness of the retinal focus. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vomeronasal Organ: A specialized part of the olfactory system located anteriorly in the nasal cavity within the nasal septum. Chemosensitive cells of the vomeronasal organ project via the vomeronasal nerve to the accessory olfactory bulb. The primary function of this organ appears to be in sensing pheromones which regulate reproductive and other social behaviors. While the structure has been thought absent in higher primate adults, data now suggests it may be present in adult humans. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Wheelchairs: Chairs mounted on wheels and designed to be propelled by the occupant. [NIH]

White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

393

INDEX A Abdomen, 224, 319, 329, 355, 357, 367, 383, 386, 390 Abdominal, 224, 319, 368, 369 Aberrant, 135, 319 Ablation, 60, 319 Acceptor, 319, 357, 368 ACE, 18, 154, 262, 319 Acetylcholine, 27, 50, 65, 238, 319, 333, 366 Acetylcholinesterase, 67, 107, 160, 166, 168, 174, 189, 193, 319 Actin, 319, 364 Activities of Daily Living, 6, 97, 115, 246, 260, 286, 319 Acute lymphoblastic leukemia, 319, 363 Acute lymphocytic leukemia, 319, 363 Adaptability, 319, 331, 332 Adaptation, 6, 10, 31, 319, 371 Adenosine, 319, 330, 370 Adjustment, 5, 54, 319, 320 Adjuvant, 38, 320, 346 Adrenal Cortex, 320, 337, 343 Adrenal Glands, 320, 322 Adrenal Medulla, 320, 331, 343, 366 Adrenergic, 112, 320, 324, 325, 341, 343, 384 Adrenergic alpha-Antagonists, 320, 324 Adrenergic beta-Antagonists, 320, 324 Adverse Effect, 23, 320, 381 Aerobic, 320, 361 Aetiology, 186, 320 Afferent, 320, 372, 380 Affinity, 28, 189, 193, 320, 321, 326, 364, 382 Agar, 320, 371 Age Groups, 14, 320 Age of Onset, 26, 33, 35, 263, 320 Aged, 80 and Over, 320, 321 Ageing, 74, 109, 120, 160, 161, 167, 168, 169, 175, 198, 321 Agonist, 193, 321, 341, 365, 377 Akathisia, 321, 325 Alertness, 321, 330 Algorithms, 321, 328 Alkaline, 321, 322, 330 Alkaloid, 321, 326, 335, 348, 365, 370, 379 Alleles, 20, 35, 40, 46, 55, 62, 235, 276, 321, 350, 357

Allergen, 321, 380 Allylamine, 321 Alternative medicine, 274, 321 Alum, 298, 321 Aluminum, 160, 168, 181, 264, 273, 298, 321 Ameliorated, 60, 321 Ameliorating, 14, 321 Amine, 132, 321, 350 Amino Acid Sequence, 236, 322, 324 Amino Acid Substitution, 56, 322 Amino Acids, 15, 48, 200, 322, 323, 326, 334, 344, 364, 369, 371, 374, 379, 381, 388 Aminopropionitrile, 322, 356 Ammonia, 321, 322, 347 Amnesia, 30, 216, 322 Amnestic, 322, 359 Amplification, 67, 322 Amygdala, 43, 103, 147, 322, 356, 380 Amyloid beta-Protein, 15, 107, 142, 237, 322 Amyloid beta-Protein Precursor, 142, 322 Amyloidosis, 39, 40, 44, 56, 103, 189, 199, 263, 322 Anaesthesia, 323, 353 Anal, 9, 26, 323, 343, 345, 358 Analgesic, 323, 345, 352 Analytes, 296, 297, 323 Anaphylatoxins, 323, 336 Anatomical, 61, 222, 323, 353, 368, 379 Anemia, 276, 323, 346, 386 Angiogenesis, 323, 359 Angiopathy, 21, 40, 55, 57, 59, 323 Angiotensin-Converting Enzyme Inhibitors, 323, 324 Angiotensinogen, 18, 323, 378 Animal model, 20, 21, 23, 35, 36, 43, 51, 60, 62, 63, 75, 147, 189, 323 Anoxia, 234, 323 Antagonism, 323, 330 Anterior Cerebral Artery, 323, 332 Anti-Anxiety Agents, 324, 372, 375, 387 Antibacterial, 324, 383 Antibiotic, 323, 324, 338, 372, 376, 383, 386 Antibodies, 10, 14, 16, 38, 55, 58, 61, 62, 98, 111, 207, 240, 324, 348, 351, 352, 358, 361, 371

394 Alzheimer’s Disease

Antibody, 52, 58, 70, 75, 88, 105, 320, 324, 329, 335, 336, 343, 348, 350, 352, 353, 359, 361, 376, 380, 382 Anticholinergic, 30, 238, 324 Anticoagulant, 324, 374 Antidepressant, 223, 324, 334 Antidepressive Agents, 324, 375 Antiemetic, 324, 325 Antigen, 14, 38, 320, 324, 335, 350, 351, 352, 353, 359, 363, 380 Antigen-Antibody Complex, 324, 335 Antihypertensive, 234, 324 Antihypertensive Agents, 234, 324 Anti-infective, 324, 334, 351 Anti-Inflammatory Agents, 43, 325, 331 Antimicrobial, 325, 341 Antineoplastic, 325, 376 Antioxidant, 164, 172, 182, 325, 367, 368 Antipsychotic, 115, 223, 230, 234, 325, 364, 376, 379, 387 Antipyretic, 325, 345 Antispasmodic, 325, 379 Anus, 323, 325, 329, 377 Anxiety, 102, 234, 315, 320, 321, 324, 325, 380 Anxiolytic, 325, 367 Apathy, 183, 208, 325, 364 Aphasia, 210, 215, 315, 322, 325 Apolipoproteins, 325, 357 Apoptosis, 24, 37, 58, 112, 132, 325, 331 Apraxia, 152, 316, 326 Aqueous, 326, 327, 338, 351, 356 Arachidonic Acid, 43, 326, 356, 373 Arginine, 323, 326, 365, 388 Aromatic, 326, 370 Arterial, 44, 321, 326, 329, 332, 333, 351, 355, 374, 385 Arteries, 323, 326, 328, 329, 332, 337, 358, 360, 386 Arterioles, 326, 329, 330 Arteriovenous, 326, 332 Aspartate, 43, 58, 61, 234, 326, 355, 370 Aspartic, 58, 326, 344 Aspartic Acid, 326 Asphyxia, 234, 326 Assay, 14, 17, 56, 122, 326 Astrocytes, 20, 29, 32, 36, 37, 55, 56, 98, 144, 326, 347, 361, 364 Asymptomatic, 17, 326 Athetosis, 93, 326 Atrophy, 8, 69, 81, 87, 92, 101, 110, 139, 140, 214, 225, 265, 326, 363

Atropine, 326, 379, 388 Attenuation, 37, 326 Atypical, 115, 222, 223, 326, 379 Auditory, 121, 158, 182, 326, 349, 372 Autacoids, 327, 353 Autoimmune disease, 327 Autoimmunity, 98, 327 Autonomic, 319, 325, 327, 346, 366, 369 Autonomic Nervous System, 327, 369 Autopsy, 10, 11, 12, 17, 21, 26, 42, 45, 47, 220, 273, 327 Axonal, 100, 327 Axons, 327, 339, 365, 367, 376 B Bacteria, 324, 327, 342, 360, 377, 383, 388, 389 Bacterial Physiology, 319, 327 Bacteriophage, 327, 371, 388 Bacterium, 327, 335, 349 Basal Ganglia, 125, 222, 325, 327, 333, 351, 356 Base, 33, 41, 44, 327, 339, 355, 376, 386 Behavioral Symptoms, 45, 97, 230, 297, 327 Benign, 327, 349 Beta-pleated, 322, 327 Bewilderment, 327, 336 Bilateral, 327, 378 Bile, 327, 346, 351, 357, 383 Bioavailability, 239, 328 Biochemical, 11, 30, 43, 47, 55, 61, 79, 81, 111, 188, 208, 264, 321, 328, 356, 381 Biological Markers, 80, 328 Biological response modifier, 328, 354 Biological therapy, 328, 348 Biological Transport, 328, 340 Biomarkers, 24, 73, 80, 132, 297, 328 Biopsy, 80, 328 Biosynthesis, 38, 77, 326, 328, 358, 381 Biotechnology, 38, 66, 71, 261, 274, 285, 328 Biotransformation, 328 Bladder, 328, 333, 353, 362, 374, 389 Blood Coagulation, 328, 330, 386 Blood Platelets, 328, 381 Blood pressure, 54, 65, 140, 324, 328, 333, 346, 351, 361, 366, 382 Blood-Brain Barrier, 329, 385 Blot, 329, 352 Blotting, Western, 329, 352 Body Fluids, 45, 328, 329, 341, 382, 389 Bone Marrow, 319, 329, 352, 358, 362

Index 395

Bone Resorption, 329, 345 Bone scan, 329, 379 Bowel, 323, 329, 340, 355, 369, 383 Bowel Movement, 329, 340, 383 Bradykinesia, 4, 30, 329 Bradykinin, 80, 329, 366 Brain Ischemia, 329, 332 Brain Stem, 264, 329, 332, 364 Branch, 163, 171, 287, 313, 329, 338, 342, 365, 368, 375, 382, 384, 386 Breakdown, 241, 329, 340, 346, 381 Buccal, 239, 329 Burns, 153, 253, 329 Burns, Electric, 329 Butyrylcholinesterase, 82, 107, 329 C Caffeine, 92, 162, 170, 330, 376 Calcium channel blocker, 324, 330 Calcium Channel Blockers, 324, 330 Callus, 330, 342 Capillary, 56, 329, 330, 390 Capsules, 230, 330, 346 Carbohydrate, 330, 371, 380, 381 Carcinogenic, 330, 353, 354, 373, 383 Carcinogens, 330, 367 Cardiac, 234, 320, 321, 330, 343, 362, 383 Cardiac arrest, 234, 330 Cardiovascular, 166, 174, 330, 356, 381 Carnitine, 3, 123, 178, 179, 330 Carotene, 200, 330 Case report, 71, 123, 330, 334 Case-Control Studies, 235, 331, 343 Caspase, 13, 37, 54, 58, 83, 331 Cataract, 273, 331 Catecholamine, 324, 331, 340, 369 Cathode, 331, 342 Cations, 193, 331, 355 Caudal, 331, 340, 351, 372 Caudate Nucleus, 125, 156, 323, 331, 363 Causal, 331, 343, 354 Cause of Death, 331 CDC2, 25, 113, 331 Celecoxib, 220, 331 Cell Cycle, 63, 70, 95, 114, 126, 331, 334, 338 Cell Differentiation, 331, 381 Cell Division, 113, 152, 327, 331, 338, 348, 359, 361, 371, 373, 380 Cell membrane, 21, 328, 330, 331, 339, 344, 346, 370, 372 Cell proliferation, 331, 381 Cell Respiration, 332, 361, 378

Cell Survival, 332, 348 Cellulose, 332, 371 Central Nervous System Infections, 332, 349 Cerebellar, 145, 332, 388 Cerebellar Diseases, 332, 388 Cerebellum, 332, 372 Cerebral hemispheres, 327, 329, 332, 385 Cerebral Infarction, 234, 332 Cerebrospinal, 13, 38, 75, 78, 106, 114, 147, 160, 161, 169, 224, 332, 381 Cerebrospinal fluid, 13, 38, 75, 78, 106, 114, 147, 160, 161, 169, 224, 332, 381 Cerebrovascular, 21, 55, 57, 73, 82, 160, 168, 184, 185, 234, 253, 263, 330, 332 Cerebrovascular Disorders, 234, 332 Cerebrum, 332, 385 Character, 11, 332, 339 Check-up, 230, 333 Chemoreceptor, 325, 333 Chemotactic Factors, 333, 336 Chemotherapy, 333, 367 Chlorpyrifos, 23, 333 Cholesterol Esters, 333, 357 Choline, 112, 117, 179, 319, 333 Cholinergic Agents, 141, 333 Cholinesterase Inhibitors, 68, 71, 88, 96, 153, 162, 165, 170, 173, 333, 340 Chorea, 325, 326, 333 Chorioretinitis, 333, 378 Choroid, 333, 378 Chromatin, 325, 333, 383 Chromosomal, 53, 322, 333, 334, 379 Chromosome, 10, 19, 25, 33, 34, 64, 119, 217, 235, 236, 239, 275, 322, 334, 341, 348, 357, 379, 380, 388, 389 Chronic, 20, 23, 29, 36, 37, 55, 56, 110, 234, 239, 324, 334, 340, 353, 358, 384 Chronic Disease, 239, 334 Chylomicrons, 334, 357 Cisplatin, 334, 367 Citalopram, 223, 334 Clinical Medicine, 334, 372 Clinical study, 334, 337 Clinical trial, 8, 9, 16, 18, 83, 85, 115, 153, 219, 228, 231, 285, 286, 287, 334, 337, 362, 374, 377 Clioquinol, 197, 334 Cloning, 19, 328, 334 Clot Retraction, 334, 371 Codon, 15, 72, 134, 334 Coenzyme, 65, 200, 334, 358, 381

396 Alzheimer’s Disease

Cofactor, 334, 374, 386 Cohort Studies, 334, 343 Colchicine, 335, 389 Collagen, 335, 344, 345, 346, 359, 371 Collapse, 329, 335 Colloidal, 335, 342 Communication Disorders, 96, 231, 245, 284, 335 Comorbidity, 10, 86, 89, 138, 335 Compacta, 31, 335 Compassionate, 244, 335 Competency, 4, 208, 335 Complement, 11, 20, 24, 60, 86, 150, 323, 335, 336, 347, 380 Complement Activation, 20, 323, 336 Complementary and alternative medicine, 181, 203, 336 Complementary medicine, 181, 336 Compress, 336, 350 Computational Biology, 285, 336 Computed tomography, 182, 224, 336, 379 Computerized axial tomography, 336, 379 Computerized tomography, 336 Conduction, 238, 336 Confounding, 96, 336 Confusion, 224, 269, 336, 340, 364 Congestion, 325, 336 Conjugated, 336, 338 Consciousness, 323, 324, 336, 339, 340, 383 Constipation, 325, 336 Constitutional, 336, 378 Constriction, 336, 355, 379 Consultation, 12, 21, 337 Consumption, 205, 226, 337, 366, 378 Continuum, 7, 250, 337 Contraindications, ii, 337 Contrast Sensitivity, 198, 337 Control group, 17, 337 Controlled clinical trial, 9, 123, 337 Controlled study, 90, 160, 166, 168, 174, 337 Convulsions, 234, 337, 365 Coronary, 44, 91, 337, 360 Coronary Thrombosis, 337, 360 Corpus, 87, 139, 189, 211, 337, 363 Corpus Callosum, 139, 189, 211, 337 Cortisol, 162, 170, 187, 195, 337 Cranial, 185, 187, 332, 337, 344, 349, 367, 369 Craniocerebral Trauma, 337, 349 Cribriform, 337, 367 Crossing-over, 337, 377

Cross-Sectional Studies, 338, 343 Cues, 15, 212, 268, 338 Cultured cell line, 28, 338 Cultured cells, 16, 240, 338 Curative, 338, 365, 386 Cyclic, 199, 330, 338, 348, 366, 370, 373 Cyclin, 70, 189, 217, 338 Cycloserine, 161, 170, 338 Cytochrome, 52, 59, 254, 338 Cytogenetics, 338, 379 Cytokine, 29, 35, 36, 38, 56, 60, 135, 228, 338 Cytoplasm, 325, 331, 338, 344, 348, 362, 364, 379, 385 Cytoskeleton, 24, 58, 338, 360 Cytotoxic, 338, 367, 381 Cytotoxicity, 21, 165, 167, 173, 175, 215, 321, 334, 338 D Data Collection, 54, 338 Databases, Bibliographic, 285, 338 Day Care, 215, 254, 262, 302, 339 Degenerative, 17, 31, 55, 234, 264, 296, 339, 347, 362 Dehydroepiandrosterone, 200, 201, 339 Deletion, 18, 325, 339 Delirium, 325, 339 Delusions, 89, 139, 223, 339, 375 Dendrites, 145, 339, 363, 364, 365, 367, 376 Dendritic, 146, 339 Density, 18, 24, 65, 146, 218, 339, 357, 367, 382 Dentate Gyrus, 126, 195, 339, 350 Depolarization, 236, 339, 381 Deuterium, 339, 351 DHEA, 90, 133, 200, 273, 339 Diagnostic procedure, 45, 233, 274, 339 Diarrhea, 65, 339 Diastolic, 339, 351 Diazinon, 23, 339 Diencephalon, 332, 340, 343, 351, 364, 372, 385, 386 Diffusion, 91, 157, 328, 340 Digestion, 327, 329, 340, 355, 357, 383, 389 Digestive system, 231, 340 Dihydrotestosterone, 340, 377 Diploid, 340, 371, 388 Disease Progression, 18, 22, 42, 49, 50, 52, 58, 124, 189, 244, 272, 340 Disorientation, 15, 336, 339, 340 Dissection, 61, 340 Dissociation, 320, 340

Index 397

Distal, 327, 340, 365, 375 Diuresis, 330, 340 Diuretics, Thiazide, 324, 340 Dominance, 112, 340, 343 Donepezil, 87, 93, 96, 97, 103, 108, 120, 121, 153, 161, 169, 184, 193, 194, 201, 218, 278, 340 Dopamine, 12, 31, 50, 110, 325, 340, 361, 370, 376, 379 Dorsal, 341, 343, 372, 380, 383 Down syndrome, 10, 76, 111, 120, 263, 322, 341 Doxycycline, 58, 341 Drive, ii, vi, 9, 17, 29, 36, 38, 159, 264, 341 Drug Approval, 277, 287, 341 Drug Interactions, 280, 341 Drug Tolerance, 341, 387 Duct, 341, 379 Dyes, 322, 341 Dyskinesia, 325, 334, 341 Dystonia, 325, 341 Dystrophic, 13, 29, 145, 341 Dystrophy, 46, 57, 183, 341 E Ectopic, 63, 95, 341 Edema, 341, 350 Effector, 20, 29, 319, 335, 341, 365, 370 Effector cell, 341, 365 Elective, 143, 341 Electroencephalography, 342, 358 Electrolysis, 331, 342 Electrolyte, 339, 342, 372, 382 Electrons, 325, 327, 331, 342, 355, 358, 367, 368, 376 Electrophoresis, 53, 342 Electrophysiological, 97, 124, 246, 342 Elementary Particles, 342, 358, 374 Embryo, 331, 342, 353 Embryogenesis, 58, 342 Empirical, 211, 264, 342 Encephalitis, 342, 359, 360 Endemic, 342, 383 Endocytosis, 57, 342 Endothelium, 342, 365, 371 Endothelium-derived, 342, 365 Endotoxic, 342, 357 Endotoxin, 342, 389 Enhancer, 238, 343 Entorhinal Cortex, 58, 59, 164, 172, 343, 350 Environmental Exposure, 23, 52, 226, 328, 343

Environmental Health, 236, 284, 286, 298, 343 Enzymatic, 19, 55, 330, 335, 343, 350 Epidemic, 251, 343, 383 Epidemiologic Studies, 160, 168, 328, 343 Epidemiological, 19, 22, 26, 38, 43, 44, 65, 129, 227, 343 Epinephrine, 320, 340, 343, 366, 389 Epistasis, 53, 343 Epithalamus, 340, 343, 356 Epithelial, 18, 328, 343 Epitope, 88, 98, 240, 343 Erythrocytes, 323, 329, 343, 380 Esophagus, 340, 343, 369, 383 Estradiol, 167, 175, 343 Estrogen, 11, 13, 84, 98, 114, 160, 162, 168, 171, 187, 219, 221, 224, 225, 301, 343, 377, 380 Estrogen receptor, 84, 98, 114, 343 Ethanol, 334, 344 Ethmoid, 344, 367 Ethnic Groups, 35, 344 Eukaryotic Cells, 331, 344, 353, 367, 389 Evoke, 344, 383 Excitation, 44, 234, 333, 344 Excitatory, 43, 165, 173, 234, 344, 347, 365 Excitatory Amino Acids, 234, 344, 365 Excitotoxicity, 43, 61, 344 Exocytosis, 344, 385 Exogenous, 36, 320, 328, 344, 374 Exons, 10, 344 Extracellular, 14, 21, 42, 47, 167, 175, 186, 263, 322, 326, 342, 344, 345, 359, 361, 364, 382 Extracellular Matrix, 322, 344, 345, 359 Extracellular Matrix Proteins, 344, 359 Extrapyramidal, 4, 321, 325, 340, 344 F Family Planning, 285, 344 Fat, 323, 326, 329, 330, 344, 357, 378, 389 Fatty acids, 272, 345, 357, 373, 387 Feasibility Studies, 13, 345 Ferritin, 131, 345 Fetus, 345, 370, 372, 389 Fibril, 15, 345 Fibrin, 64, 328, 334, 345, 371, 386 Fibrinogen, 345, 371, 386 Fibroblasts, 13, 152, 345, 354 Fibrosis, 321, 345, 379 Fissure, 337, 339, 345, 372 Fixation, 345, 380 Fluorescence, 53, 69, 236, 345

398 Alzheimer’s Disease

Flurbiprofen, 272, 345 Folate, 167, 175, 230, 345, 346 Fold, 10, 43, 54, 345, 367 Folic Acid, 177, 230, 300, 345, 346 Forearm, 328, 346 Fornix, 12, 346 Founder Effect, 276, 346 Frontal Lobe, 222, 323, 332, 346, 372 Functional magnetic resonance imaging, 27, 126, 346 G Gait, 30, 332, 346 Galanin, 22, 68, 103, 165, 173, 346 Gallbladder, 319, 340, 346 Ganglia, 319, 346, 363, 369 Ganglionic Blockers, 324, 346 Gap Junctions, 346, 384, 385 Gas, 322, 340, 346, 351, 365, 366, 367, 390 Gastric, 330, 346, 350 Gastrin, 346, 350 Gastrointestinal, 329, 333, 343, 344, 346, 356, 381, 382, 384, 389 Gastrointestinal tract, 333, 344, 346, 356, 381, 382, 389 Gelatin, 346, 348, 386 Gene Dosage, 76, 346 Gene Expression, 31, 33, 142, 347 Genetic Counseling, 246, 347 Genetic Engineering, 328, 334, 347 Genetic Markers, 17, 235, 276, 347 Genetic testing, 33, 347 Genomics, 36, 46, 47, 57, 347 Genotype, 7, 11, 26, 29, 49, 51, 53, 54, 64, 76, 78, 85, 106, 115, 191, 347, 370 Gestation, 347, 369, 371 Ginkgo biloba, 183, 188, 192, 347 Gland, 320, 347, 368, 374, 377, 380, 383, 387 Glial Fibrillary Acidic Protein, 137, 347 Gliosis, 38, 347 Glomeruli, 347, 367 Glucose, 42, 114, 139, 332, 347, 348, 349, 354 Glutamate, 61, 91, 107, 138, 166, 174, 229, 234, 344, 347 Glutamic Acid, 346, 347 Glutamine, 166, 174, 347 Glutathione Peroxidase, 347, 380 Glycine, 348, 381 Glycogen, 37, 70, 101, 107, 189, 348 Glycogen Synthase, 70, 101, 189, 348 Glycols, 348, 351

Glycoprotein, 345, 348, 385, 386, 389 Governing Board, 348, 372 Graft, 348, 351, 353 Graft Rejection, 348, 353 Granule, 339, 348, 379 Granulocytes, 348, 381, 391 Grasses, 346, 348 Growth factors, 139, 348, 363 Guanylate Cyclase, 348, 366 Gyrus Cinguli, 323, 348, 356 H Habitual, 333, 348 Hallucinogen, 348, 370 Haloperidol, 4, 230, 348 Haploid, 348, 371 Haptens, 320, 348 Harmine, 23, 348 Headache, 109, 234, 330, 349 Headache Disorders, 349 Health Education, 221, 349 Hearing Disorders, 335, 349 Hematoma, 349, 350 Heme, 338, 349 Hemiplegia, 326, 349 Hemochromatosis, 116, 349 Hemoglobin, 323, 343, 349, 386 Hemolytic, 349, 386 Hemorrhage, 337, 349, 384 Hemorrhagic stroke, 234, 349 Hemostasis, 350, 381 Hepatic, 339, 350, 381 Hereditary, 276, 350, 362, 363, 378, 386 Heredity, 346, 347, 350 Herpes, 67, 350 Herpes Zoster, 350 Heterogeneity, 35, 40, 89, 255, 263, 264, 320, 350 Heterogenic, 350 Heterogenous, 34, 350 Heterozygotes, 67, 75, 340, 350 Hippocampus, 13, 41, 58, 61, 88, 98, 120, 139, 226, 339, 346, 350, 356, 364, 376, 380, 384 Histamine, 323, 325, 350 Histology, 9, 244, 350, 364 Homeostasis, 19, 132, 146, 162, 170, 237, 350 Homogeneous, 337, 350 Homologous, 10, 16, 60, 239, 321, 337, 350, 380, 384, 385 Homozygotes, 340, 350 Hormonal, 326, 350, 369

Index 399

Hormone, 24, 111, 221, 328, 337, 343, 346, 350, 354, 359, 367, 381, 382, 386, 387 Hormone Replacement Therapy, 221, 350 Host, 327, 345, 351, 352, 356, 389, 390 Housekeeping, 240, 351 Humoral, 14, 348, 351 Humour, 351 Hybrid, 48, 351 Hybridization, 59, 235, 351 Hybridomas, 351, 354 Hydrogen Peroxide, 52, 101, 347, 351, 357 Hydrolysis, 319, 326, 328, 334, 351, 370, 371, 374, 388 Hydrophobic, 351, 357, 363 Hydroxides, 351 Hydroxyl Radical, 101, 351 Hypercholesterolemia, 61, 65, 351 Hypersensitivity, 321, 351, 356, 380 Hypertension, 5, 17, 65, 111, 141, 320, 323, 324, 330, 349, 351 Hypoglycemia, 234, 351 Hypokinesia, 351, 368 Hypotension, 325, 337, 346, 351 Hypothalamus, 327, 340, 351, 356, 380, 382 Hypothermia, 73, 352 Hypoxia, 112, 329, 332, 339, 352 I Ibuprofen, 112, 229, 352 Id, 58, 177, 198, 296, 297, 298, 303, 307, 312, 314, 352 Imagination, 198, 352 Imaging procedures, 352, 387 Immune adjuvant, 321, 352 Immune response, 14, 38, 225, 320, 321, 324, 327, 348, 352, 380, 384, 389, 390 Immune Sera, 352 Immune system, 20, 108, 142, 327, 328, 341, 352, 356, 358, 369, 389, 391 Immunity, 14, 352, 388 Immunization, 75, 138, 255, 272, 352, 353, 373, 380 Immunoblotting, 52, 352 Immunochemistry, 52, 263, 352 Immunogenic, 352, 357 Immunoglobulin, 324, 344, 352, 361 Immunohistochemistry, 46, 59, 352 Immunologic, 333, 352 Immunology, 14, 57, 86, 105, 163, 171, 320, 352 Immunosuppressive, 352, 353 Immunosuppressive therapy, 352, 353 Immunotherapy, 38, 113, 328, 352

In situ, 10, 24, 59, 61, 73, 353 In Situ Hybridization, 10, 24, 59, 61, 73, 353 In vitro, 19, 24, 32, 34, 39, 44, 48, 55, 56, 64, 70, 103, 112, 167, 175, 187, 353, 387 Incision, 353, 355 Incontinence, 234, 316, 353, 379 Indicative, 14, 235, 247, 353, 368, 389 Indomethacin, 43, 353 Induction, 14, 29, 30, 54, 58, 64, 325, 346, 353, 355, 381 Infant, Newborn, 320, 353 Infarction, 329, 332, 337, 350, 353, 360 Infection, 37, 147, 208, 268, 328, 333, 339, 342, 352, 353, 358, 364, 384, 391 Informed Consent, 6, 353 Infusion, 18, 63, 353 Ingestion, 353, 356, 371 Inhalation, 278, 353, 371 Initiation, 37, 53, 58, 121, 353, 388 Initiator, 58, 354 Innervation, 238, 354 Inotropic, 341, 354 Insecticides, 354, 369 Insight, 15, 25, 35, 45, 46, 61, 64, 218, 264, 354 Insulin, 92, 106, 115, 128, 135, 138, 227, 354, 363 Insulin-dependent diabetes mellitus, 354 Interferon, 228, 354 Interferon-alpha, 354 Interleukin-1, 29, 36, 73, 117, 118, 354 Interleukin-10, 118, 354 Interleukin-2, 354 Interleukin-6, 116, 135, 354 Intermediate Filaments, 354, 363 Intermittent, 354, 358 Intervention Studies, 11, 246, 354 Intestinal, 330, 334, 354 Intestine, 329, 355, 356 Intoxication, 339, 355, 391 Intracellular Membranes, 355, 359 Intracranial Embolism, 332, 355 Intracranial Embolism and Thrombosis, 332, 355 Intramuscular, 239, 355 Intravenous, 239, 353, 355 Intrinsic, 320, 355 Introns, 355, 375 Invasive, 45, 50, 80, 239, 352, 355, 358 Ion Channels, 326, 355, 364, 365, 385 Ionizing, 343, 355

400 Alzheimer’s Disease

Ions, 327, 340, 342, 351, 355, 361, 372 Ischemia, 43, 234, 326, 329, 350, 355, 365 J Jet lag, 227, 355 Joint, 21, 47, 261, 262, 355 K Kb, 284, 355 Ketamine, 355, 370 Kinetic, 355 L Labile, 335, 355 Lag, 355 Language Disorders, 335, 355 Large Intestine, 340, 355, 356, 377, 382 Latent, 356, 372 Lathyrism, 234, 356 Lectin, 356, 359 Leisure Activities, 92, 356 Length of Stay, 115, 356 Lens, 331, 356, 391 Lesion, 56, 347, 356, 357, 385 Lethal, 10, 264, 356 Leukocytes, 329, 333, 348, 353, 354, 356, 362, 389 Leukoencephalopathy, 132, 356 Leukotrienes, 326, 356 Library Services, 312, 356 Life Expectancy, 5, 23, 356 Ligaments, 337, 356 Ligands, 27, 35, 60, 356 Light microscope, 44, 356 Limbic, 49, 83, 119, 264, 322, 348, 356, 372 Limbic System, 49, 322, 348, 356, 372 Linkage, 19, 25, 33, 35, 64, 100, 119, 235, 275, 347, 357 Linkage Disequilibrium, 20, 64, 100, 357 Lipid, 24, 32, 39, 44, 52, 65, 119, 120, 163, 164, 172, 214, 325, 333, 354, 357, 368 Lipid A, 32, 357 Lipid Peroxidation, 24, 39, 120, 357, 368 Lipid Peroxides, 52, 357 Lipopolysaccharides, 357 Lipoprotein, 18, 32, 65, 189, 357, 358 Lithium, 273, 300, 325, 357 Liver, 239, 319, 322, 326, 327, 330, 340, 346, 348, 349, 350, 357, 358, 379 Liver scan, 357, 379 Living will, 357 Lobe, 332, 357 Localization, 10, 25, 95, 150, 210, 240, 352, 357, 358

Localized, 25, 265, 322, 329, 345, 349, 353, 357, 371 Locomotion, 357, 371 Lod, 34, 357 Lod Score, 34, 357 Longitudinal Studies, 17, 26, 27, 42, 222, 338, 358 Longitudinal study, 31, 40, 358 Long-Term Care, 93, 120, 197, 227, 261, 358 Lovastatin, 229, 358, 381 Low-density lipoprotein, 65, 77, 121, 357, 358 Lymphatic, 342, 353, 358, 383, 387 Lymphocyte, 324, 358, 359 Lymphoid, 324, 358 M Macrophage, 354, 358 Magnetic Resonance Imaging, 51, 54, 157, 212, 224, 358, 379 Magnetic Resonance Spectroscopy, 111, 120, 138, 358 Magnetoencephalography, 101, 358 Malignant, 325, 358, 385 Malnutrition, 326, 358, 362 Malondialdehyde, 24, 163, 171, 359 Mammary, 359, 377 Manic, 325, 357, 359, 375 Manic-depressive psychosis, 359, 375 Manifest, 54, 118, 327, 349, 359 Matrix metalloproteinase, 114, 359 Medial, 84, 140, 344, 348, 359, 380 Mediate, 19, 43, 57, 341, 359 Mediator, 37, 354, 359, 381 Medical Records, 26, 224, 359 MEDLINE, 285, 359 Megaloblastic, 346, 359 Meiosis, 359, 384, 385, 389 Melanin, 359, 370, 389 Memantine, 122, 123, 141, 148, 271, 273, 299, 359 Membrane Glycoproteins, 359 Membrane Proteins, 42, 240, 359 Memory Disorders, 45, 164, 172, 228, 262, 269, 359 Meninges, 332, 337, 359, 360, 383 Meningitis, 360 Meningoencephalitis, 272, 360 Menopause, 199, 360, 372 Mental Disorders, 206, 232, 351, 360, 373, 375 Mental Retardation, 245, 303, 335, 341, 360

Index 401

Mentors, 16, 18, 360 Mesolimbic, 325, 360 Meta-Analysis, 68, 73, 95, 96, 360 Metabolite, 107, 239, 328, 358, 360, 376 Metastasis, 359, 360 MI, 185, 234, 317, 360 Microbe, 360, 387 Microbiology, 57, 319, 326, 360 Microorganism, 334, 360, 391 Microscopy, 44, 59, 68, 275, 360 Microtubule-Associated Proteins, 360, 364, 385 Microtubules, 354, 360, 363, 385 Microwaves, 360, 376 Minority Groups, 40, 361 Mitochondria, 55, 361, 367 Mitochondrial Swelling, 361, 363 Mitogen-Activated Protein Kinase Kinases, 361 Mitogen-Activated Protein Kinases, 152, 361 Mitosis, 325, 331, 361 Mitotic, 95, 361, 390 Modeling, 28, 61, 73, 104, 361 Modification, 49, 108, 115, 347, 361, 376 Modulator, 16, 37, 361 Molecular Structure, 44, 361, 388 Monitor, 12, 33, 45, 245, 361, 366 Monoamine, 50, 324, 361 Monoclonal, 88, 207, 351, 352, 361, 376 Monoclonal antibodies, 352, 361 Monocytes, 43, 55, 208, 354, 356, 362 Mononuclear, 12, 97, 217, 362, 389 Morphological, 25, 29, 124, 151, 263, 264, 321, 342, 362, 365 Morphology, 59, 215, 263, 331, 362 Motility, 353, 362, 381 Motion Sickness, 362, 379 Motor Activity, 337, 362 Movement Disorders, 224, 325, 362 Multicenter study, 166, 174, 362 Muscarinic Agonists, 27, 65, 167, 175, 209, 257, 333, 362 Muscle Fibers, 362 Muscular Atrophy, 54, 362 Muscular Dystrophies, 341, 362 Mutagenesis, 69, 362 Mutagens, 362 Mydriatic, 362, 379, 388 Myocardium, 360, 362 N Nausea, 324, 325, 362, 367

NCI, 1, 227, 231, 283, 362 Necrosis, 151, 244, 325, 332, 353, 360, 363, 381 Neocortex, 143, 265, 363, 364 Neoplastic, 351, 363, 385 Neostriatum, 331, 363 Neprilysin, 129, 135, 363 Nerve, 12, 25, 41, 132, 165, 173, 182, 224, 238, 296, 320, 327, 339, 354, 359, 363, 364, 365, 367, 370, 372, 378, 379, 383, 388, 391 Nerve Growth Factor, 12, 25, 41, 363 Networks, 70, 153, 156, 363 Neurites, 13, 29, 36, 47, 363 Neuroanatomy, 32, 103, 125, 264, 356, 363 Neurodegenerative Diseases, 10, 20, 23, 33, 38, 41, 43, 363 Neuroendocrine, 363, 385 Neurofibrillary Tangles, 15, 36, 39, 48, 57, 60, 62, 83, 91, 139, 237, 241, 263, 265, 272, 363, 365, 385 Neurofibrils, 244, 364 Neurofilaments, 363, 364 Neuroglia, 347, 364 Neuroleptic, 4, 321, 325, 364, 367 Neurologic, 23, 30, 324, 364 Neurologist, 59, 364 Neuromuscular, 238, 319, 364, 378 Neuromuscular Junction, 238, 319, 364, 378 Neuromuscular Junction Diseases, 364, 378 Neuronal atrophy, 24, 364 Neuronal Plasticity, 13, 32, 256, 364 Neuropathy, 334, 364 Neuropeptide, 47, 265, 364 Neurophysiology, 88, 95, 105, 138, 144, 187, 303, 339, 365 Neuropil, 36, 55, 263, 365, 385 Neuropil Threads, 36, 365, 385 Neuroprotective Agents, 234, 365 Neuropsychological Tests, 365 Neuropsychology, 21, 49, 74, 97, 99, 100, 130, 146, 147, 158, 182, 257, 365 Neuroretinitis, 365, 378 Neurotoxic, 20, 35, 48, 56, 128, 334, 365 Neurotoxicity, 18, 24, 39, 44, 48, 55, 161, 169, 365 Neurotoxins, 224, 365 Neurotransmitters, 11, 50, 234, 264, 344, 365 Niacin, 365, 388

402 Alzheimer’s Disease

Nicotine, 107, 162, 170, 182, 365, 377 Nitric Oxide, 35, 52, 55, 128, 160, 169, 183, 215, 365 Nitrogen, 52, 55, 321, 344, 345, 347, 366, 388 Nonverbal Communication, 335, 366 Norepinephrine, 50, 320, 340, 366 Normotensive, 55, 366 Nuclei, 322, 342, 343, 344, 347, 355, 358, 361, 366, 367, 374, 380 Nucleic acid, 351, 353, 362, 366, 373, 376 Nucleic Acid Hybridization, 351, 366 Nursing Care, 216, 244, 366 Nutritional Status, 6, 366 O Observational study, 117, 366 Ocular, 106, 239, 366 Odds Ratio, 366, 378 Oestradiol, 122, 367 Olfaction, 48, 367 Olfactory Bulb, 48, 367, 391 Omentum, 197, 367 Ondansetron, 286, 367 Opacity, 331, 339, 367 Ophthalmic, 278, 367, 388 Opioid Peptides, 363, 367 Optic Nerve, 365, 367, 378 Organelles, 338, 362, 367 Orthostatic, 325, 367 Osteoporosis, 225, 367, 377 Outpatient, 117, 367 Ovary, 343, 367 Overexpress, 56, 367 Oxidants, 55, 367 Oxidation, 189, 208, 319, 325, 328, 338, 347, 357, 367, 368 Oxidation-Reduction, 328, 367, 368 Oxidative Stress, 10, 14, 24, 39, 58, 84, 87, 128, 135, 163, 171, 213, 368 Oxygenation, 350, 368 P Palliative, 368, 386 Palsy, 91, 107, 131, 134, 368 Pancreas, 319, 328, 340, 349, 354, 368, 382, 388, 389 Pancreatic, 330, 368 Paralysis, 326, 368 Parenchyma, 13, 66, 368 Parietal, 136, 323, 368, 369 Parietal Lobe, 323, 368 Parkinsonism, 4, 23, 25, 119, 234, 325, 368 Particle, 368, 382, 388

Patch, 238, 368, 388 Pathologic, 12, 14, 26, 45, 325, 328, 337, 351, 368, 383 Pathologic Processes, 325, 368 Pathologies, 26, 368 Pathophysiology, 40, 45, 47, 59, 246, 368 Patient Education, 255, 301, 310, 312, 317, 369 Pedigree, 53, 235, 263, 275, 369 Perfusion, 81, 119, 122, 145, 183, 190, 352, 369, 387 Perinatal, 234, 369 Periodicity, 369, 378 Periodontal disease, 345, 369 Peripheral Nervous System, 23, 349, 363, 368, 369, 382, 384 Peripheral vision, 369, 391 Peritoneum, 367, 369 Perivascular, 56, 369 Pesticides, 23, 354, 369 PH, 142, 182, 183, 224, 369 Phagocyte, 217, 367, 369 Pharmacokinetic, 369 Pharmacologic, 50, 90, 134, 192, 327, 369, 387, 388 Pharmacotherapy, 66, 109, 134, 257, 369 Pharynx, 77, 369 Phencyclidine, 238, 370 Phenotype, 10, 26, 30, 43, 46, 54, 60, 240, 328, 370 Phenylalanine, 69, 370, 389 Phosphodiesterase, 73, 370 Phospholipases, 370, 381 Phospholipids, 344, 357, 370, 374 Phosphorus, 330, 370 Phosphorylated, 25, 73, 87, 91, 95, 118, 144, 152, 334, 361, 365, 370 Phosphorylates, 37, 237, 370, 374 Phosphorylation, 25, 65, 70, 167, 175, 189, 361, 370, 374 Phototherapy, 370, 380 Phrenic Nerve, 370, 378 Physical Examination, 333, 370 Physiologic, 64, 321, 328, 351, 370, 373, 377, 388 Physiology, 9, 41, 44, 64, 77, 165, 167, 173, 175, 328, 342, 365, 370 Pigments, 330, 370 Pilot Projects, 12, 63, 370 Pilot study, 100, 135, 153, 370 Piperidines, 234, 370 Placenta, 343, 370

Index 403

Plants, 7, 30, 192, 321, 326, 333, 347, 349, 356, 362, 365, 366, 370, 371, 387 Plaque, 18, 21, 24, 38, 39, 43, 60, 62, 67, 70, 111, 150, 322, 371 Plasma cells, 324, 371 Plasmin, 64, 371 Plasminogen, 64, 217, 371 Plasminogen Activators, 371 Plasticity, 37, 147, 371 Platelet Activation, 371, 381 Platelet Aggregation, 323, 366, 371, 386 Platelets, 68, 78, 366, 371, 386 Poisoning, 339, 355, 362, 371 Polymorphic, 20, 66, 339, 371 Polypeptide, 322, 335, 345, 351, 371, 374, 382, 386, 391 Polysaccharide, 324, 332, 371 Pons, 329, 372 Posterior, 8, 27, 91, 323, 332, 333, 341, 343, 368, 372 Postmenopausal, 111, 221, 225, 367, 372, 377 Postsynaptic, 364, 372, 381, 384, 385 Post-traumatic, 349, 362, 372 Potassium, 236, 340, 372 Potassium Channels, 236, 372 Potentiates, 24, 354, 372, 386 Potentiation, 24, 333, 372, 381 Practicability, 345, 372 Practice Guidelines, 257, 288, 303, 372 Preclinical, 17, 38, 45, 48, 49, 51, 60, 67, 89, 126, 127, 138, 148, 372 Predisposition, 106, 372 Prefrontal Cortex, 76, 94, 136, 146, 372 Premedication, 372, 379 Prenatal, 24, 342, 372 Presynaptic, 42, 50, 238, 372, 384, 385 Prevalence, 10, 19, 33, 34, 44, 45, 54, 59, 300, 301, 303, 366, 372 Primary Prevention, 160, 168, 373 Prion, 72, 134, 332, 373 Problem Solving, 98, 222, 373 Prognostic factor, 246, 373 Projection, 366, 367, 372, 373, 376 Promoter, 19, 29, 86, 99, 116, 118, 129, 139, 373 Prone, 55, 373 Prophase, 373, 384, 385, 389 Prophylaxis, 372, 373, 389 Propoxur, 23, 373 Prospective study, 111, 358, 373 Prostaglandin, 24, 38, 43, 323, 373, 386

Prostaglandins A, 38, 353, 373 Prostaglandins D, 374 Prostate, 328, 374, 389 Protease, 57, 64, 258, 374 Protein Binding, 374, 387 Protein C, 47, 146, 229, 241, 263, 322, 325, 327, 334, 345, 357, 374 Protein Conformation, 322, 374 Protein Kinase C, 361, 374 Protein Kinases, 23, 25, 189, 361, 374 Protein S, 30, 261, 322, 328, 374, 376, 379, 386 Protein-Serine-Threonine Kinases, 361, 374 Proteolytic, 16, 239, 335, 345, 371, 374 Protocol, 12, 18, 26, 374 Protons, 351, 355, 358, 374, 376 Proximal, 340, 372, 375, 380 Pseudogenes, 67, 375 Psychic, 375, 380 Psychology, 22, 25, 160, 168, 208, 211, 218, 260, 267, 340, 365, 375 Psychomotor, 339, 364, 375 Psychopathology, 10, 375 Psychophysics, 16, 49, 375 Psychophysiology, 154, 365, 375 Psychosis, 230, 234, 325, 375 Psychotropic, 6, 164, 173, 375 Psychotropic Drugs, 6, 375 Public Health, 42, 53, 157, 261, 289, 375 Public Policy, 217, 285, 286, 375 Publishing, 66, 375 Pulmonary, 234, 239, 328, 337, 356, 375, 390 Pulmonary Artery, 328, 375, 390 Pulse, 361, 376 Purines, 376, 381 Puromycin, 30, 376 Pyramidal Cells, 160, 168, 339, 376 Pyramidal Tracts, 344, 376 Q Quality of Life, 5, 23, 45, 118, 246, 252, 264, 268, 376 Quaternary, 374, 376, 379 Quinolinic, 163, 171, 376 Quinolinic Acid, 163, 171, 376 R Race, 146, 376 Raclopride, 50, 376 Radiation, 340, 342, 343, 345, 355, 376, 379, 391 Radiation therapy, 340, 376

404 Alzheimer’s Disease

Radio Waves, 224, 360, 376 Radioactive, 224, 329, 351, 357, 362, 366, 376, 377, 379, 385, 389 Radioisotope, 52, 376, 387 Radiolabeled, 238, 329, 376, 377 Raloxifene, 224, 377, 380 Randomized, 9, 90, 111, 123, 161, 166, 169, 174, 194, 228, 230, 341, 377 Reaction Time, 187, 377 Reactive Oxygen Species, 186, 377 Reagent, 240, 322, 377 Reality Testing, 375, 377 Receptors, Muscarinic, 362, 377 Receptors, Serotonin, 377, 381 Recombinant, 105, 228, 377, 390 Recombination, 235, 347, 377 Rectal, 239, 278, 377 Rectum, 325, 329, 340, 346, 353, 356, 374, 377 Recur, 369, 377, 380 Recurrence, 359, 369, 377, 380 Reductase, 65, 110, 358, 377, 381 Refer, 1, 329, 335, 345, 347, 350, 357, 363, 364, 375, 377 Refraction, 377, 382 Regimen, 239, 338, 341, 369, 377 Registries, 287, 378 Relative risk, 235, 378 Reliability, 6, 150, 378 Renin, 323, 378 Research Design, 49, 378 Respiration, 333, 361, 378 Respiratory Paralysis, 238, 378 Respite Care, 287, 302, 378 Retina, 167, 175, 333, 356, 364, 365, 367, 378, 379, 391 Retinitis, 234, 378 Retinoblastoma, 239, 378 Retinoid, 98, 378 Retrograde, 41, 378 Retrospective, 101, 207, 378 Rheumatism, 352, 378 Rheumatoid, 367, 378 Rhythmicity, 122, 378 Ribosome, 379, 388 Rigidity, 4, 30, 368, 371, 379 Risperidone, 223, 279, 379 Rod, 124, 327, 379 Rodenticides, 369, 379 Rural Population, 49, 379 S Saliva, 379

Salivary, 162, 170, 187, 340, 379 Salivary glands, 340, 379 Salivation, 65, 379 Satellite, 21, 42, 63, 269, 379 Scans, 225, 379 Schizoid, 379, 391 Schizophrenia, 74, 359, 379, 391 Schizotypal Personality Disorder, 379, 391 Sclerosis, 12, 79, 110, 228, 379 Scopolamine, 30, 50, 379 Screening, 10, 13, 25, 34, 56, 101, 142, 144, 237, 239, 288, 334, 379 Seasonal Affective Disorder, 227, 380 Secretion, 42, 350, 351, 354, 379, 380, 389 Secretory, 208, 240, 380, 384, 385 Segmental, 76, 380 Segmentation, 198, 380 Segregation, 235, 377, 380 Seizures, 224, 316, 339, 380, 383 Selective estrogen receptor modulator, 377, 380 Selenium, 227, 380 Self Care, 319, 380 Semantics, 195, 380 Senile Plaques, 4, 20, 42, 45, 47, 84, 183, 212, 237, 241, 263, 265, 322, 365, 380 Senility, 214, 216, 244, 380 Sensitization, 30, 380 Sensor, 167, 175, 380 Septal, 323, 356, 380 Septal Nuclei, 323, 356, 380 Sequence Analysis, 20, 381 Sequester, 381, 385 Serine, 142, 361, 374, 381, 388 Serotonin, 50, 143, 325, 334, 367, 369, 377, 379, 381, 388 Shock, 70, 320, 381, 388 Shunt, 224, 381 Side effect, 65, 230, 239, 277, 286, 320, 321, 325, 328, 334, 340, 381, 387 Signal Transduction, 36, 43, 250, 381 Simvastatin, 70, 223, 381 Skeletal, 333, 362, 381, 382 Skeleton, 319, 355, 373, 381 Skull, 224, 337, 381, 386 Small intestine, 334, 350, 355, 382, 388 Smooth muscle, 59, 321, 323, 327, 330, 350, 362, 382, 384 Social Environment, 376, 382 Social Support, 9, 205, 213, 214, 215, 302, 382 Social Work, 21, 76, 97, 206, 211, 258, 382

Index 405

Sodium, 18, 140, 166, 174, 340, 382 Soma, 68, 376, 382 Somatic, 235, 342, 351, 356, 359, 361, 369, 372, 382, 385 Somatostatin, 265, 382 Sound wave, 224, 336, 382 Spasm, 325, 326, 382 Spatial disorientation, 8, 15, 382 Specialist, 167, 175, 206, 224, 307, 382 Specificity, 16, 56, 69, 184, 320, 382, 387 Spectrum, 30, 66, 263, 360, 376, 382 Sperm, 334, 383, 389 Spermatogenesis, 240, 383 Spermatozoa, 383 Spinal cord, 326, 329, 332, 333, 349, 359, 363, 364, 365, 369, 376, 378, 383 Spinal Cord Diseases, 349, 378, 383 Spinal Nerves, 369, 383 Spirochete, 383, 385 Spleen, 322, 358, 383 Sporadic, 30, 34, 73, 83, 91, 106, 117, 128, 134, 157, 187, 235, 241, 275, 363, 378, 383 Staging, 246, 269, 379, 383 Statistically significant, 3, 383 Status Epilepticus, 234, 383 Steroid, 98, 337, 381, 383 Stimulant, 330, 350, 383, 385 Stimulus, 27, 187, 192, 207, 341, 344, 354, 355, 375, 377, 383, 386 Stomach, 319, 340, 343, 346, 350, 362, 367, 369, 382, 383 Stool, 353, 356, 383 Stroma, 368, 384 Students, Medical, 42, 384 Subacute, 272, 334, 353, 384 Subarachnoid, 349, 384 Subclinical, 353, 380, 384 Subcutaneous, 239, 341, 384 Subiculum, 350, 384 Subspecies, 382, 384 Substance P, 338, 360, 380, 384 Substrate, 43, 54, 384 Superoxide, 55, 133, 384 Supplementation, 189, 230, 384 Support group, 196, 262, 302, 384 Suppression, 194, 384 Sympathomimetic, 341, 343, 366, 384 Symptomatic, 21, 27, 56, 183, 246, 324, 384 Symptomatology, 26, 50, 384 Synapses, 11, 54, 60, 301, 333, 365, 367, 384, 385 Synapsis, 384, 385

Synaptic, 11, 36, 43, 59, 60, 88, 147, 151, 238, 241, 365, 381, 384, 385 Synaptic Transmission, 365, 385 Synaptic Vesicles, 238, 384, 385 Synaptophysin, 46, 385 Syphilis, 244, 385 Systemic, 147, 276, 278, 279, 317, 322, 328, 329, 339, 343, 353, 364, 376, 385, 388 Systolic, 351, 385 T Tacrine, 166, 174, 182, 203, 246, 279, 385 Tardive, 325, 334, 385 Tau Proteins, 46, 65, 79, 365, 385 Technetium, 74, 385 Telencephalon, 327, 385 Telomerase, 187, 385 Temporal Lobe, 123, 322, 386 Terminator, 334, 386 Testis, 343, 386 Testosterone, 70, 377, 386 Tetracycline, 58, 341, 386 Thalamus, 340, 343, 356, 372, 386 Thalassemia, 276, 386 Therapeutics, 35, 46, 51, 93, 95, 148, 194, 239, 248, 249, 280, 386 Thiamine, 161, 169, 196, 386 Thiorphan, 363, 386 Thorax, 319, 386 Threonine, 91, 118, 142, 361, 374, 381, 386 Threshold, 26, 351, 386 Thrombin, 345, 371, 374, 386 Thrombocytes, 371, 386 Thrombolytic, 371, 386 Thrombomodulin, 374, 386 Thrombosis, 355, 374, 384, 386 Thromboxanes, 326, 386 Thymus, 352, 358, 387 Thyroid, 23, 117, 316, 387, 389 Thyroxine, 370, 387 Tissue Culture, 363, 387 Tissue Distribution, 23, 387 Tolerance, 234, 319, 387 Tomography, 42, 50, 67, 212, 218, 316, 358, 387 Tooth Preparation, 319, 387 Topical, 334, 344, 351, 387 Toxic, iv, 12, 30, 39, 48, 55, 57, 326, 338, 341, 343, 348, 352, 357, 364, 365, 380, 387 Toxicity, 12, 18, 21, 24, 37, 39, 48, 63, 65, 67, 102, 162, 171, 236, 341, 387 Toxicokinetics, 387 Toxicology, 102, 286, 387

406 Alzheimer’s Disease

Toxins, 11, 30, 324, 342, 353, 360, 362, 387, 390 Tracer, 145, 387 Trachea, 369, 387 Tranquilizing Agents, 375, 387 Transcriptase, 385, 387 Transcription Factors, 37, 43, 388 Transcutaneous, 182, 388 Transdermal, 238, 388 Transduction, 43, 144, 381, 388 Transfection, 328, 388 Transfer Factor, 352, 388 Transgenes, 40, 55, 388 Translation, 10, 51, 243, 375, 388 Transmitter, 319, 326, 340, 344, 355, 359, 364, 366, 384, 385, 388 Transplantation, 250, 352, 388 Trauma, 38, 43, 109, 234, 339, 363, 365, 388 Tremor, 4, 23, 30, 368, 388 Tricyclic, 324, 334, 388 Trigger zone, 325, 388 Trisomy, 76, 322, 388 Trivalent, 181, 388 Tropicamide, 139, 388 Trypsin, 388, 391 Tryptophan, 162, 170, 335, 376, 381, 388 Tuberculosis, 337, 338, 388 Tubulin, 30, 360, 385, 388 Tumor marker, 328, 389 Tumor Necrosis Factor, 35, 389 Tyrosine, 12, 31, 43, 52, 144, 202, 340, 389 U Ubiquitin, 69, 150, 364, 389 Unconscious, 352, 389 Univalent, 351, 368, 389 Unsaturated Fats, 274, 389 Uranium, 385, 389 Urinary, 160, 168, 234, 333, 338, 353, 362, 379, 389 Urinary tract, 338, 389 Urinary tract infection, 338, 389 Urine, 328, 340, 353, 389 Urokinase, 64, 217, 389 Uterus, 337, 389 V Vaccination, 14, 60, 151, 273, 389 Vaccine, 38, 138, 273, 320, 321, 374, 389 Vacuoles, 342, 367, 389 Vagina, 389 Vaginal, 239, 334, 389 Vascular, 17, 53, 54, 56, 59, 63, 65, 69, 82, 90, 103, 104, 105, 116, 127, 143, 144, 148,

150, 151, 154, 156, 160, 168, 181, 184, 260, 264, 320, 321, 322, 330, 332, 333, 342, 349, 353, 365, 370, 371, 383, 389 Vasculitis, 332, 389 Vasodilator, 324, 329, 341, 350, 390 Vasodilator Agents, 324, 390 VE, 83, 88, 226, 390 Vector, 388, 390 Vein, 224, 326, 355, 366, 379, 390 Venereal, 385, 390 Venoms, 365, 390 Venous, 326, 332, 355, 374, 390 Venous blood, 332, 390 Ventral, 31, 351, 372, 383, 390 Ventricle, 322, 331, 343, 350, 351, 376, 385, 386, 390 Ventricular, 51, 390 Venules, 329, 330, 390 Vesicular, 16, 350, 390 Veterinary Medicine, 285, 390 Vinblastine, 389, 390 Vincristine, 389, 390 Viral, 342, 388, 390 Virulence, 387, 390 Virus, 327, 332, 343, 347, 354, 371, 388, 390 Viscera, 382, 390 Visceral, 327, 356, 369, 390 Viscosity, 238, 390 Visual Acuity, 337, 390 Visual field, 15, 155, 391 Vitreous Body, 333, 378, 391 Vivo, 18, 20, 32, 35, 36, 39, 44, 51, 56, 61, 64, 69, 70, 138, 153, 157, 189, 212, 213, 272, 353, 357, 367, 386, 391 Vomeronasal Organ, 367, 391 W Weight Gain, 380, 391 Wheelchairs, 7, 391 White blood cell, 319, 324, 356, 358, 371, 391 Windpipe, 369, 387, 391 Withdrawal, 25, 234, 339, 386, 391 Wound Healing, 359, 391 X Xenograft, 323, 391 X-ray, 224, 225, 331, 336, 345, 366, 376, 379, 391 Y Yeasts, 370, 391 Z Zymogen, 64, 374, 391

407

408 Alzheimer’s Disease

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