Clinical Manual of Geriatric Psychiatry (Concise Guides)

Clinical Manual of Geriatric Psychiatry

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Clinical Manual of Geriatric Psychiatry James E. Spar, M.D. Professor of Clinical Psychiatry Department of Psychiatry & Biobehavioral Sciences Geffen School of Medicine at UCLA Los Angeles, California

Asenath La Rue, Ph.D. Senior Scientist Wisconsin Alzheimer’s Institute University of Wisconsin School of Medicine and Public Health Madison, Wisconsin

Washington, DC London, England

Note: The authors have worked to ensure that all information in this book is accurate at the time of publication and consistent with general psychiatric and medical standards, and that information concerning drug dosages, schedules, and routes of administration is accurate at the time of publication and consistent with standards set by the U.S. Food and Drug Administration and the general medical community. As medical research and practice continue to advance, however, therapeutic standards may change. Moreover, specific situations may require a specific therapeutic response not included in this book. For these reasons and because human and mechanical errors sometimes occur, we recommend that readers follow the advice of physicians directly involved in their care or the care of a member of their family. Books published by American Psychiatric Publishing, Inc., represent the views and opinions of the individual authors and do not necessarily represent the policies and opinions of APPI or the American Psychiatric Association. Copyright © 2006 American Psychiatric Publishing, Inc. ALL RIGHTS RESERVED Manufactured in the United States of America on acid-free paper 10 09 08 07 06 5 4 3 2 1 First Edition Typeset in Adobe’s Formata and AGaramond. American Psychiatric Publishing, Inc. 1000 Wilson Boulevard Arlington, VA 22209-3901 www.appi.org Library of Congress Cataloging-in-Publication Data Spar, James E. Clinical manual of geriatric psychiatry / James E. Spar, Asenath La Rue.—1st ed. p. ; cm. Includes bibliographical references and index. ISBN 1-58562-195-1 (pbk. : alk. paper) 1. Geriatric psychiatry—Handbooks, manuals, etc. 2. Older people—Mental health—Handbooks, manuals, etc. 3. Older people—Psychology—Handbooks, manuals, etc. [DNLM: 1. Aged. 2. Mental Disorders—diagnosis. 3. Mental Disorders—therapy. 4. Age Factors. 5. Aging—psychology. WT 150 S736c 2006] I. La Rue, Asenath, 1948– II. Title. RC451.4.A5S63 2006 618.97'689—dc22 2006005228 British Library Cataloguing in Publication Data A CIP record is available from the British Library.

Contents 1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 An Aging World . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Health and Functioning of Older Adults . . . . . . . . . . . . . . 3 Mental Disorders in Later Life . . . . . . . . . . . . . . . . . . . . . . 6 Barriers to Geriatric Mental Health Care. . . . . . . . . . . . . . 8 Diversity in Patterns of Health and Aging. . . . . . . . . . . .12 Working Effectively With Older Adults. . . . . . . . . . . . . . .15 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16

2

Normal Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Conceptual Issues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21 Cognitive Abilities in Later Life: A Processing Resource Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23 Personality and Emotional Changes . . . . . . . . . . . . . . . .38 Social Context of Aging . . . . . . . . . . . . . . . . . . . . . . . . . .43 Biological Aging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .48 Aging and the Clinical Process. . . . . . . . . . . . . . . . . . . . .50 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .61

3

Mood Disorders—Diagnosis . . . . . . . . . . . . . . . . 67 “Normal” Grief (Bereavement) . . . . . . . . . . . . . . . . . . . .68 Complicated Grief . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .70 Depression Due to a General Medical Condition . . . . .70 Substance-Induced Mood Disorder . . . . . . . . . . . . . . . .76 Major Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .80 Dysthymic Disorder. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .91 Minor Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .92 Depressive Personality Disorder . . . . . . . . . . . . . . . . . . .95 Laboratory Evaluation of Depression . . . . . . . . . . . . . . .95 Psychological Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .96 Symptom Rating Scales and Depression Screening . . .97 Assessing Suicidality in the Elderly . . . . . . . . . . . . . . . .105 Theories of Depression . . . . . . . . . . . . . . . . . . . . . . . . .107

Hypomania and Mania . . . . . . . . . . . . . . . . . . . . . . . . . .110 Mixed Mood Disorder. . . . . . . . . . . . . . . . . . . . . . . . . . .117 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .117

4

Mood Disorders—Treatment . . . . . . . . . . . . . . . 127 Psychotherapy for Geriatric Depression . . . . . . . . . . . .127 New Directions in Psychotherapy Research . . . . . . . . .130 Combined Psychotherapy and Pharmacotherapy . . . .132 Psychopharmacotherapy for Geriatric Depression . . .132 Psychopharmacotherapy for Psychotic Depression. . .156 Psychopharmacotherapy for Bipolar Depression. . . . .157 Electroconvulsive Therapy . . . . . . . . . . . . . . . . . . . . . . .157 Experimental Therapies . . . . . . . . . . . . . . . . . . . . . . . . .159 Complementary and Alternative Approaches . . . . . . .161 Hypomania and Mania . . . . . . . . . . . . . . . . . . . . . . . . . .162 Bipolar Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .162 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .166

5

Dementia and Alzheimer’s Disease. . . . . . . . . . . . . . . . . . . . . . 173 Identifying the Dementia Syndrome. . . . . . . . . . . . . . .173 Common Etiologies of Dementia . . . . . . . . . . . . . . . . .186 Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . .192 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .221 Resources for Dementia Caregivers . . . . . . . . . . . . . . .228

6

Other Dementias and Delirium . . . . . . . . . . . . 229 Frontotemporal Dementia . . . . . . . . . . . . . . . . . . . . . . .229 Dementia With Lewy Bodies . . . . . . . . . . . . . . . . . . . . .235 Vascular Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . .241 Mixed Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .248 Dementia Due to General Medical Conditions . . . . . .249 Substance-Induced Persisting Dementia . . . . . . . . . . .254 Reversible Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . .255 Delirium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .256 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .265

7

Anxiety Disorders and Late-Onset Psychosis. . . . . . . . . . . . . . . . . . . . . 273 Anxiety Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .273 Late-Onset Psychosis . . . . . . . . . . . . . . . . . . . . . . . . . . .293 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .306

8

Other Common Mental Disorders of the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . 313 Insomnia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .313 Alcohol Abuse and Dependency . . . . . . . . . . . . . . . . . .320 Other Psychoactive Substance Abuse and Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . .326 Sexual Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . .329 Psychiatric Illness Related to a General Medical Condition . . . . . . . . . . . . . . . . . . . . . . . . . . . .334 Chronic Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .337 Influence of Aging on Disorders of Early Onset . . . . . .339 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .341

9

Competency and Related Forensic Issues. . . . 347 Decisional Competency . . . . . . . . . . . . . . . . . . . . . . . . .348 Undue Influence: The Question of Voluntariness . . . .358 Competency to Care for Oneself and Manage One’s Finances . . . . . . . . . . . . . . . . . . . . . . . .360 Expert Consultation and Testimony on Competency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .366 Competency to Drive . . . . . . . . . . . . . . . . . . . . . . . . . . .367 Elder Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .371 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .373

Appendix: Clinical Assessment Instruments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379 Geriatric Depression Scale . . . . . . . . . . . . . . . . . . . . . . .380 Six-Item Orientation-Memory-Concentration Test. . . .382 Cognistat profile: Example . . . . . . . . . . . . . . . . . . . . . . .383

Instrumental Activities of Daily Living (IADL) Scale . . .384 Revised Memory and Behavior Problems Checklist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .386 Items Rated on the Neuropsychiatric Inventory. . . . . .388

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389

1 Introduction An Aging World For the first time in history, most people in societies such as our own can plan on growing old. Life expectancy from birth has increased dramatically in the United States, from about 47 years in 1900 to 77.3 years in 2002 (Federal Interagency Forum on Aging-Related Statistics 2004). Even those people who are currently “old” can expect to live for many years. For men at age 65, average life expectancy is more than 16 years, and for women at age 65, it is almost 20 years; at age 85, men can expect to live 6 more years and women 7 years (Federal Interagency Forum on Aging-Related Statistics 2004). More than 20% of the current U.S. population are older than age 55, and more than 12% are 65 or older (Federal Interagency Forum on Aging-Related Statistics 2004). The elderly population is the only age segment of the population that is expected to grow substantially in the next quarter century, so that by the year 2030, one in three Americans will be age 55 or older, and one in five will be at least age 65. Very old people (85 years and older) constitute one of the fastest-growing subgroups of the elderly population (Figure 1–1). In 1900, a little more than 100,000 people were age 85 years or older in the United States, compared with an estimated 4.2 million in 2000 (National Center for Health Statistics 2004). By 2050, there will be 19 million to 24 million people in this 85 and older age group, or nearly 5% of the total population. In 2003, more than 50,000 U.S. residents were 100 years or older, an increase of 36% since 1990 (Administration on Aging 2004).

1

2 Clinical Manual of Geriatric Psychiatry

100

Population (millions)

80 60 65 and older

40

85 and older

20 0 1900

1930

1960

1990

2020

2050

Projected

Figure 1–1. Populations of older adults in the United States (in millions). Source. Adapted from Federal Interagency Forum on Aging-Related Statistics 2004. Worldwide, average life expectancy has increased to about 65 years (Cohen 2003), and by 2050, the number of people age 65 years and older is projected at 2.5 billion worldwide (20% of the total population) (Olshansky et al. 1993). Substantial increases in elderly populations are projected in the next quarter century for North America, Europe, Asia, Latin America, and the Caribbean, with smaller increases expected for areas such as sub-Saharan Africa, where both fertility and mortality rates are high. China alone is expected to have 270 million persons age 65 and older—nearly the total current population of the United States—by the middle of this century. As one demographer recently pointed out, the twentieth century may well be the last in which younger people outnumbered older ones (Cohen 2003). By 2050, there will be more than three adults age 60 years or older for every child age 4 years or younger.

Introduction

3

Health and Functioning of Older Adults Most people age 65 and older have at least one chronic medical illness, and many have multiple conditions. The most common illnesses affecting elderly people in the United States are arthritis, hypertension, and heart conditions (Figure 1–2). Sensory impairments are also prevalent. Of 65- to 74-year-olds, 30% report problems seeing and 18% report problems hearing; these rates are approximately twice as high for persons age 85 and older (Federal Interagency Forum on Aging-Related Statistics 2004). Each of these conditions can limit independent function and detract from quality of life. Being overweight or obese has increased dramatically among older Americans in recent years. The percentage of 65- to 74-year-olds who were overweight rose from 57% to 73% between 1976 and 2002, and the obesity rate increased from 18% to 36% (Federal Interagency Forum on Aging-Related Statistics 2004). By contrast, rates of cigarette smoking declined by 2002 to 10% among older men and have remained steady in recent years at about 9% among older women. Heart disease, cancer, and stroke account for two of every three deaths among the elderly and also account for many doctor visits and days of hospitalization. Death rates due to heart disease and stroke decreased by approximately one-third from 1981 through 2001, whereas death rates due to diabetes and chronic lower respiratory diseases increased by 43% and 62%, respectively (Federal Interagency Forum on Aging-Related Statistics 2004). Alzheimer’s disease ranked sixth, after heart disease, cancer, cerebrovascular diseases, respiratory diseases, and influenza or pneumonia, among causes of death for Americans age 65 years and older in 2002 (National Center for Health Statistics 2004). In 2002, people age 65 and older were hospitalized more than three times as often as those ages 45–64, and they remained in the hospital about a day longer on average than did middle-aged adults (Administration on Aging 2004). Older adults visited their physicians six to seven times per year on average, compared with three to four times for 45- to 64-year-olds. In 1999, about 20% of older adults were chronically disabled as a result of health problems; about 3% had limitations in only higher-order activities of daily living (e.g., financial management, transportation, medication schedules), 6% had impairment in one or two basic activities of daily living (e.g., eating, bathing, toileting), another 6% were impaired in three to six basic activities, and slightly fewer than 5% were institutionalized (Federal Inter-

4 Clinical Manual of Geriatric Psychiatry

100

Americans age ≥65 (%)

80 Men

Women

60 40 20 0

Heart disease

Hypertension

Stroke

Emphysema

Asthma Chronic Cancer Diabetes Arthritic bronchitis symptoms

Figure 1–2. Percentage of people age 65 and older with selected chronic conditions, 2001–2002. Source. Adapted from Federal Interagency Forum on Aging-Related Statistics 2004. agency Forum on Aging-Related Statistics 2004). Of disabled older people living in the community, 66% received informal care only, generally from relatives; 26% received a combination of formal and informal services; and 9% had formal care only (Federal Interagency Forum on Aging-Related Statistics 2004). The proportion receiving paid care has increased since the early 1980s, reflecting improved financial resources of older persons as well as liberalization in coverage rules under Medicare and Medicaid. Figure 1–3 shows age trends in independent and assisted living within the United States. Those with chronic needs that cannot be met at home generally receive care in nursing homes. Although fewer than 5% of elderly Americans are in nursing homes at a given time, the proportion of older persons requiring such care increases quite sharply with age (see Figure 1–3). Among persons who reached their 60th birthday in 1990, more than one-half of the women and one-third of the men are expected to enter a nursing home at some point in the future. However, older black Americans and elders from other minority groups use

Introduction

100

1 5

1

Medicare enrollees (%)

2

5

80 60

3

19 7

93

98

5

Long-termcare facility Community housing with services

92 74

40

Traditional community

20 0

≥65

65–74

75–84

≥85

Age (years)

Figure 1–3. Percentage of Medicare enrollees age 65 and older, by type of residence, 2003. Source. Adapted from Federal Interagency Forum on Aging-Related Statistics 2004. paid in-home services and nursing home care less frequently than do white Americans (National Center for Health Statistics 2004). Between 1985 and 1999, the percentage of older adults residing in nursing homes in the United States declined slightly, from 5.4% to 4.3%, but the total number of older nursing home residents increased from 1.3 million to 1.5 million because of growth in the older population (Federal Interagency Forum on Aging-Related Statistics 2004). Three-fourths of current nursing home residents are women. Health care costs for older Americans increased substantially from 1992 through 2001, after adjustment for inflation. During this time span, the proportion of health care dollars spent on acute hospital care decreased, while the proportion spent on prescription drugs increased. The average cost of providing health care for persons age 65 or older is currently three to five times greater than health care costs for younger persons (Centers for Disease Control and Prevention 2004). Long-term-care costs, including nursing home and home health expenditures, doubled between 1990 and 2001, a trend

6 Clinical Manual of Geriatric Psychiatry

shared by other developed nations. In 2001, the average annual cost for elderly residents of long-term-care facilities in the United States was $46,810, compared with $8,466 for community residents of comparable age (Federal Interagency Forum on Aging-Related Statistics 2004). Total Medicare spending increased from $33.9 billion in 1980 to $252.2 billion in 2002 and is projected to grow to twice that amount by 2012 (Centers for Disease Control and Prevention 2004). These trends present a significant challenge to the health care community. The need to learn about aging and older people extends throughout the medical and mental health professions. Creative approaches are required to stem rising costs while maintaining quality assessment and intervention. Alliances with families and other natural supports must be formed to ensure continuity of care, and the strengths of older patients themselves must be marshaled to cope with illness and to interact effectively within the health care system.

Mental Disorders in Later Life Older people with mental disorders constitute a significant subgroup of the elderly population. The multisite Epidemiologic Catchment Area (ECA) Study conducted in the 1980s (Robins and Regier 1991) found that nearly 20% of Americans age 55 and older had diagnosable mental disorders, including dementia (U.S. Public Health Service 1999). The ECA findings are believed by many experts in the field to be underestimates because of methodological limitations in the ECA assessment procedures. A 1999 consensus conference on geriatric mental health estimated the prevalence of psychiatric disorders in community-residing older adults at 25% or more (Jeste et al. 1999). Rates of mental disorder are much higher among elderly patients seen in primary care or hospitalized for medical conditions, 30%–50% of whom have psychiatric conditions (Borson and Unützer 2000; Rapp et al. 1988); and in long-term-care settings, 68%–94% of residents have been found to have mental disorders (Hybels and Blazer 2003). Table 1–1 compares rates for several different types of mental disorders in the ECA community-based survey (1-month prevalence data) with a survey of hospitalized geriatric patients conducted at about the same time. Overall, it is reasonable to estimate that 15%–25% of Americans who are currently age 65 or older have significant mental health problems.

Introduction

7

Older patients experience the same broad spectrum of mental disorders as do younger adults. However, certain conditions are particularly notable in later life because of either increased prevalence or high morbidity (see Table 1–1). The elderly are at much greater risk for cognitive impairment than are younger adults. In the community, at least 5% of people age 65 years or older have prominent cognitive deficits, compared with fewer than 1% of people ages 18–64 (Regier et al. 1988). A larger proportion of older people have mild cognitive problems, with estimates varying widely depending on the procedures used to assess impairment (see Chapter 2, “Normal Aging”). The numbers in Table 1–1 may underestimate the extent of problems related to cognitive deficits, especially in the oldest age ranges. Recent data from the national Health and Retirement Study showed that among Americans age 85 and older residing in the community, one-third had moderate to severe memory impairment (Administration on Aging 2004), and a widely cited epidemiological survey in the East Boston area reported a prevalence of 47% for Alzheimer’s disease alone among community residents age 85 and older (Evans et al. 1989). Cognitive deficits in older patients have many different possible causes, and in many cases, treatment of underlying problems can substantially alleviate cognitive symptoms or slow the course of further decline (see Chapter 5, “Dementia and Alzheimer’s Disease,” and Chapter 6, “Other Dementias and Delirium”). Even for individuals with dementia of the Alzheimer’s type, gains in functional ability can be obtained by treating coexisting medical or psychiatric illnesses. These small gains can make a great difference to family members caring for these patients, as can support, psychotherapy, and respite provided for caregivers. Depression is an equally important condition in older adults. In the community, the percentage of older people meeting strict diagnostic criteria for major depression is generally estimated at 5% or less (U.S. Public Health Service 1999). However, traditional diagnostic criteria may not do justice to the prevalence of depressive symptoms among older people. Serious depressive symptoms were found in 8%–20% of elderly community residents and in up to 37% of the elderly in primary care settings (U.S. Public Health Service 1999). In acute-care hospitals, as many as 25% of older patients have diagnosable mood disorders (e.g., Rapp et al. 1988), and nearly 50% of the admissions of older adults to psychiatric hospitals are for depressive conditions. The presence of comorbid depression or anxiety greatly increases health care

8 Clinical Manual of Geriatric Psychiatry

costs for patients in primary care (Simon et al. 1995), and over time, depression is associated with decrements in function and well-being that are similar to, or greater than, those associated with chronic medical disease (Hays et al. 1995). Geriatric depression can be treated effectively with standard therapies in 60%–80% of cases (U.S. Public Health Service 1999), but it is unlikely to resolve spontaneously. Depression, anxiety, and alcohol and drug abuse in the elderly today are only about one-quarter to one-third as common as among middle-aged persons, and as the 55 million baby boomers grow old, their mental health needs may prompt a crisis in geriatric care (Jeste et al. 1999). Many older people without major mental disorders experience adjustment reactions to personal stresses, bereavement, pain syndromes, and sleep disturbance. Education and interventions directed at these problems may prevent more serious psychiatric or medical problems from developing. The importance of increasing prevention efforts for older adults as well as other age groups was underscored in the U.S. surgeon general’s report on mental health (U.S. Public Health Service 1999). For psychiatrists, therefore, it is important not only to identify and treat specific psychiatric disorders but also to provide education, support, and preventive interventions to strengthen older people and their families in managing common stresses of aging.

Barriers to Geriatric Mental Health Care Improvements have been made since the early 1990s in the detection and treatment of mental disorders in older adults in the United States. In an analysis of national Medicare fee-for-service data, for example, rates of diagnosed depression in older adults increased from 2.8% in 1992 to 5.8% in 1998, and two-thirds of those diagnosed received treatment of some type (Crystal et al. 2003). Similarly, since passage of the Omnibus Budget Reconciliation Act in 1987, efforts have been made, with varying degrees of success, to recognize and treat mental disorders in patients in skilled nursing facilities. The number of effective antidepressant medications has increased (Chapter 4, “Mood Disorders—Treatment”), and medications to slow the course of common progressive dementias have been introduced (Chapter 5, “Dementia and Alzheimer’s Disease,” and Chapter 6, “Other Dementias and Delirium”). The usefulness of psychotherapeutic interventions for common mental disorders of older

Introduction

9

Table 1–1. Mental disorders among older adults Distribution of psychiatric diagnoses (%) Category of illness Cognitive impairment Affective disorders Anxiety disorders Alcohol abuse or dependence Schizophrenic disorders Somatization Personality disorder Other psychiatric disorder

Community residentsa

Medical-surgical inpatientsb

4.9 2.5 5.5 0.9

30.2 18.5 5.2 2.6

0.1 0.1 0 0

0 0 8.3 7.9

aAdapted

from Regier et al. 1988. Adapted from Rapp et al. 1988.

b

adults has been more thoroughly confirmed (Chapters 4 through 8, “Mood Disorders—Treatment,” “Dementia and Alzheimer’s Disease,” “Other Dementias and Delirium,” “Anxiety Disorders and Late-Onset Psychosis,” and “Other Common Mental Disorders of the Elderly,” respectively), as have the complex relationships between mental disorders and medical illness. Despite these improvements, significant inequities remain in identification and treatment of mental health conditions in older people and in accessibility and use of geriatric mental health services (Areán and Unützer 2003; Charney et al. 2003; Moak and Borson 2000). Adults older than 75, minority group members, and persons with Medicare only were less likely than younger, white, and better-insured patients to have received treatment for depression in recent years (Crystal et al. 2003), and even the most recent studies continue to show that most cases of cognitive impairment without obvious dementia go undetected and untreated in primary care (Chodosh et al. 2004; Ganguli et al. 2004). Less common or less widely publicized conditions are even more likely to remain unrecognized and inadequately treated. In nursing homes, psychiatric services are generally restricted to a consultative, as-requested mode instead of being a consistent and integrated part of care management teams, and in the burgeoning numbers of assisted-

10 Clinical Manual of Geriatric Psychiatry

living and community-based programs for senior care, mental health services are patchy and largely unregulated (Moak and Borson 2000). Contemporary older Americans report less past use of mental health services than do younger adults, and older Americans are less likely to express a need for such services (Klap et al. 2003; Wetherell et al. 2004). Older adults most often turn to primary care providers for help with mental health problems (Kaplan et al. 1999), and typically, only one-half or fewer follow through with referrals to specialty mental health providers. In a recent multisite randomized trial, elderly primary care patients who screened positive for depression, anxiety, or increased risk of alcohol use problems were offered collaborative mental health services within primary care or enhanced referral assistance (e.g., scheduling, transportation, and payment assistance to outside mental health specialists) (Bartels et al. 2004). A significantly higher percentage of the patients followed through on pursuing mental health treatment when it was available within primary care (71% vs. 49%), and they completed more mental health visits overall, than did those referred to mental health clinics or specialists, even with enhanced assistance aimed at increasing the odds of compliance with the referral. As the baby boom generation edges into the geriatric age range, the “stiff upper lip” approach to managing emotional distress (Wetherell et al. 2004) may change, but the desire for proximal, integrated medical and mental health services is likely to continue. Without more effective collaborative care, underrecognition of mental health problems, especially among older patients (Young et al. 2001), is likely to continue for several reasons: •

• •

Multiple medical illnesses in elderly patients may divert physicians’ attention away from psychiatric signs and symptoms, especially within the time-pressured context of the standard brief office visit. Depression, anxiety, or memory problems may be viewed as normal for older people with serious medical illness. Physicians with neither psychiatric nor geriatric training may have difficulty distinguishing normal aging changes from signs of mental disorder or may be reluctant to “open the can of worms” that treatment of emotional or cognitive problems may entail.

A probability survey of primary care providers found that only 6% of general internal medicine physicians and 22% of family practice physicians used

Introduction

11

questionnaires or other structured procedures to screen for depression in their older patients, relying instead on very brief informal interviews (Kaplan et al. 1999). Primary care physicians report that the subtlety of mild dementia makes it difficult to recognize during brief interviews, but many physicians remain reluctant to use formal cognitive screening tests (Boise et al. 1999); many also believe that in the absence of effective treatment, there is little purpose to diagnosing mild dementia, although this attitude may delay arrangements for community support services and increase family strain (see Chapter 5, “Dementia and Alzheimer’s Disease”). Among psychiatrists, attitudes about aging and age-related conditions and limited training in geriatric psychiatry may further restrict the availability and quality of mental health care for older patients. Many psychiatrists and other mental health professionals find it difficult to work with elderly patients. Understandably, they may prefer to work with patients who have less daunting problems with physical illness and personal loss, who remind them less of their own mortality, and who are less likely to die in the course of treatment. Nonetheless, recent research has not found mental health professionals to be strongly or pervasively negative in their attitudes about older patients. Instead, age bias seems to take more specific forms (Gatz and Pearson 1988). American psychiatrists and other mental health professionals tend to refer older patients less often for psychotherapy than comparably ill younger patients, and some of these professionals, in an attempt to avoid discrimination against the elderly, may exaggerate the competencies and excuse the deficits of elderly patients. “Fallacy for good reasons” is a phrase coined to refer to the common situation in which a provider, as well as the patient and family members, attributes the depression or anxiety experienced by the older patient to medical illness, multiple losses, or financial difficulties that many older persons face, especially the very old (Cole et al. 1997). Inadequate insurance coverage for patients and limited reimbursement for providers are ongoing barriers to geriatric mental health care. Because prescription drugs have not been covered under Medicare until very recently, elders who could not afford a coinsurance policy with drug benefits were unable to afford psychiatric medications. The 50% copayment rule for psychotherapy services under most insurance policies makes the decision to engage in therapy costly to the patient, and allowable fees are often inadequate (e.g., under Medicare, the psychotherapy fees allowed for an experienced psy-

12 Clinical Manual of Geriatric Psychiatry

chiatrist are half or less of the typical fee expected for this service). The elderly, who generally have many health care needs, often have trouble coordinating their own care, but there is usually no reimbursement for mental health providers to help with coordination. The need for psychiatrists who are capable and willing to work with elderly patients, both in primary care and in specialty roles, is clear. Effective models for collaborative medical and mental health services recently have been developed for primary care (see Chapter 4, “Mood Disorders—Treatment”), but this approach needs to be extended beyond clinical research, and additional models need to be developed for geropsychiatric services within community mental health settings and the full spectrum of long-term-care services (Moak and Borson 2000). Older adults with medical comorbidity, the oldest old, and those with significant chronic mental illness present particular challenges to existing service models (Borson et al. 2001).

Diversity in Patterns of Health and Aging In 2003, persons of minority descent, including Hispanic whites, accounted for 17.6% of the U.S. population age 65 and older, but by 2050, this percentage is projected to rise to 36%. Hispanic and Asian American groups as a whole are the most rapidly growing minority populations, and these trends are projected to continue (Figure 1–4). Methodological difficulties encountered in the processes of sampling, designing valid interview protocols, achieving subject cooperation, and controlling interviewer and subject bias have hampered attempts to generalize about the health and other characteristics of black, Hispanic, American Indian, and Asian populations in the United States. However, in key areas such as life expectancy, prevalence of chronic health conditions, residential patterns, and education, significant differences have been documented across groups. In the United States in 2001, average life expectancy from birth was 5.5 years longer for white persons than for black Americans (Federal Interagency Forum on Aging-Related Statistics 2004). At age 65, however, the life expectancy gap narrowed to about 2 years, and by age 85, life expectancy was slightly longer for older black persons compared with white persons. In 2000–2001, among people age 65 and older, hypertension and diabetes were more common among black than among non-Hispanic white persons; older Hispanics were

Introduction

13

100 2003

Americans age ≥65 (%)

80

2050–projected

60 40 20 0 Non-Hispanic white alone

Black alone

Asian alone

All other races alone Hispanic or in combination of any race

Figure 1–4. Percentage of population age 65 and older, by race and Hispanic origin. Source. Adapted from Federal Interagency Forum on Aging-Related Statistics 2004. comparable to non-Hispanic white Americans in rates of hypertension but were more likely to have diabetes. By contrast, older white people were more likely to have some form of cancer than were older Hispanic or black people (National Center for Health Statistics 2004). Black and Hispanic elders are less well educated than non-Hispanic white and Asian elders (see Figure 2–1 in Chapter 2, “Normal Aging”), and older black and non-Hispanic white persons are more likely to find themselves living alone in old age than are their Hispanic or Asian peers (see Figure 2–2 in Chapter 2). Reports of prevalence of mental disorders for minority groups must be viewed with caution because language and cultural differences can affect results on tests and interviews assessing depression, dementia, and other psychiatric disorders. However, data are emerging on the relative prevalence of mental health–related problems in various groups and on availability and use of mental health services. A recent supplement (U.S. Public Health Service

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2005) to Mental Health: A Report of the Surgeon General (U.S. Public Health Service 1999) concluded that the prevalence of mental disorders within the most populous racial and ethnic minority groups in the United States (blacks, Hispanics, and Asian Americans and Pacific Islanders) is similar to that of white Americans. Among older adults, however, some important differences in prevalence of mental health–related conditions have been documented for racial/ethnic and gender subgroups. For example, the suicide rate is much higher among non-Hispanic white men than in any other elderly subgroup (National Center for Health Statistics 2004), and rates of alcohol abuse and dependence are higher among elderly black men and women compared with elderly white and Hispanic persons (U.S. Public Health Service 1999). The surgeon general’s recent supplement underscored the pivotal role of culture in maintaining mental health and the continuing, often striking, disparities in availability of and access to mental health services among Americans from minority backgrounds. Although not specific to older adults, the recommendations for reducing barriers are as important for diverse geriatric populations as they are for younger groups. The recommendations include the following: •

•

• •

Continuing research to establish the efficacy of evidence-based treatments for racial and ethnic minorities and to better characterize how factors such as acculturation and ethnic identity affect risk for, and protection from, mental illness Improving access to treatment by improving geographic distribution of services, increasing availability of services in preferred languages, and coordinating care for the most vulnerable, high-need subgroups in which racial and ethnic minorities are overrepresented (e.g., low-income or homeless persons) Delivering effective, evidence-based treatments that are individualized according to age, gender, race, ethnicity, and culture Working toward equitable racial and ethnic representation among mental health providers, administrators, and policy makers

Women constitute the majority of older persons in the United States, outnumbering men by a ratio of nearly 3 to 1 by age 85 and older. Important gender differences have been reported for longevity, prevalence of specific

Introduction

15

Table 1–2. Knowledge needed to work effectively with elderly patients Normal aging: biological, psychological, and social changes Mental disorders predominantly observed in later life, including Alzheimer’s disease, related dementias, late-onset psychoses Effects of age on other psychiatric disorders, including mood and anxiety disorders Adjusting psychiatric treatments for aging changes: dose and schedule of psychoactive medications, drug-drug interactions, format and pace of psychotherapy Managing social and physical problems of later life: bereavement, role loss, pain, sleep disturbance Interactions of psychiatric and medical-surgical illnesses and their treatments

medical or mental conditions (e.g., heart disease, Alzheimer’s disease), and rates of disability. At present, the price that women pay for longer lives appears to be a greater proportion of the late life span compromised by functional disability, limited options for home care, and an increased likelihood of spending their last years in a nursing home. Recent research, prompted by the Women’s Health Initiative, is helping to elucidate whether preventive health care, or more prompt and appropriate diagnosis and treatment of medical conditions, can reduce the functional limitations now experienced disproportionately by women in later years.

Working Effectively With Older Adults Psychiatric care of older patients requires a blending of specialized knowledge with a broadly based, flexible approach to the patient (Table 1–2). In addition to mastering the content areas covered in this Clinical Manual, a psychiatrist treating older patients needs certain personal qualities and professional approaches that are important for effective work in geriatric psychiatry (Table 1–3). Although some older people can manage today’s complex health care system, many more lack the energy, sophistication, cognitive ability, or funds to negotiate a specialty-oriented system successfully. As a result, psychiatrists working with older people must be willing to play a generalist role, combining routine medical management with psychiatric interventions or helping with specific social or situational problems.

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Table 1–3. Personal qualities and professional approaches needed to work effectively with elderly patients Willingness to provide broadly based, flexible management Comfort in working closely with other health care professionals Patience and skill in providing medical information and assisting in medical decision making Willingness to explore one’s own feelings about aging Openness to discuss patients’ concerns about being treated by younger professionals Acceptance of and comfort with limited treatment goals Ability to maintain therapeutic optimism in the context of an ultimately poor prognosis

The psychiatrist also must have patience and skill in explaining diagnoses and treatments and in assisting older people in medical decision making. Elderly patients often defer to physicians without truly comprehending benefits and risks. This deference may increase efficiency of care in the short run, but it may place the older person at risk for iatrogenic illness (e.g., delirium secondary to drug interactions). Finally, it is helpful to have a willingness to explore one’s own feelings about aging, as well as to be open to discussing older patients’ reservations about the wisdom of youth. Elderly patients may be inclined to view younger therapists as similar to their children, and the therapist, in response, may experience the reactivation of unresolved conflicts with parents or grandparents or unresolved issues related to his or her own personal aging (Meador and David 1994).

References Administration on Aging: A Profile of Older Americans: 2004. Washington, DC, Administration on Aging, 2004. Available at: http://www.aoa.gov/prof/Statistics/ profile/2004/profiles2004.asp. Accessed March 9, 2006. Areán PA, Unützer J: Inequities in depression management in low-income, minority, and old-old adults: a matter of access to preferred treatments? J Am Geriatr Soc 51:1808–1809, 2003

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Bartels SJ, Coakley EH, Zubritsky C, et al: Improving access to geriatric mental health services: a randomized trial comparing treatment engagement with integrated versus enhanced referral care for depression, anxiety, and at-risk alcohol use. Am J Psychiatry 161:1455–1462, 2004 Boise L, Camicioli R, Morgan DL, et al: Diagnosing dementia: perspectives of primary care physicians. Gerontologist 39:457–464, 1999 Borson S, Unützer J: Psychiatric problems in the medically ill, in Comprehensive Textbook of Psychiatry/VII. Edited by Kaplan HI, Sadock BJ. Philadelphia, PA, Lippincott Williams & Wilkins, 2000, pp 3045–3053 Borson S, Bartels SJ, Colenda CC, et al: Geriatric mental health services research: strategic plan for an aging population. Am J Geriatr Psychiatry 9:191–204, 2001 Centers for Disease Control and Prevention and Merck Institute of Aging and Health: The State of Aging and Health in America 2004. Available at: http://www.cdc.gov/ aging/pdf/State_of_Aging_and_Health_in_America_2004.pdf or http:// www.miahonline.org/press/content/11.22.04_SOA_Report.pdf. Accessed August 26, 2005. Charney DS, Reynolds CF III, Lewis L, et al: Depression and bipolar support alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in late life. Arch Gen Psychiatry 60:664–672, 2003 Chodosh J, Petitti DB, Elliott M, et al: Physician recognition of cognitive impairment: evaluating the need for improvement. J Am Geriatr Soc 52:1051–1059, 2004 Cohen JE: Human population: the next half century. Science 302:1172–1175, 2003 Cole SA, Christensen JF, Raju M, et al: Depression, in Behavioral Medicine in Primary Care: A Practical Guide. Edited by Feldman MD, Christensen JF. Stamford, CT, Appleton & Lange, 1997, pp 177–192 Crystal S, Sambamoorthi U, Walkup JT, et al: Diagnosis and treatment of depression in the elderly Medicare population: predictors, disparities, and trends. J Am Geriatr Soc 51:1718–1728, 2003 Evans DA, Funkenstein HH, Albert MS, et al: Prevalence of Alzheimer’s disease in a community population of older persons. JAMA 262:2551–2556, 1989 Federal Interagency Forum on Aging-Related Statistics: Older Americans 2004: Key Indicators of Well-Being. Washington, DC, U.S. Government Printing Office, 2004. Available at: http://www.aoa.gov/prof/Statistics/profile/2004/ profiles2004.asp. Accessed March 9, 2006. Ganguli M, Rodriguez E, Mulsant B, et al: Detection and management of cognitive impairment in primary care: the Steel Valley Seniors Survey. J Am Geriatr Soc 52:1668–1675, 2004 Gatz M, Pearson CG: Ageism revisited and the provision of psychological services. Am Psychol 43:184–194, 1988

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Hays RD, Wells KB, Sherbourne CD, et al: Functioning and well-being outcomes of patients with depression compared with chronic general medical illness. Arch Gen Psychiatry 52:11–19, 1995 Hybels CF, Blazer DG: Epidemiology of late-life mental disorders. Clin Geriatr Med 19:663–696, 2003 Jeste DV, Alexopoulos GS, Bartels SJ, et al: Consensus statement on the upcoming crisis in geriatric mental health: research agenda for the next two decades. Arch Gen Psychiatry 56:848–853, 1999 Kaplan MS, Adamek ME, Calderon A: Managing depressed and suicidal geriatric patients: differences among primary care physicians. Gerontologist 39:417–425, 1999 Klap R, Unroe KT, Unützer J: Caring for mental illness in the United States: a focus on older adults. Am J Geriatr Psychiatry 11:517–524, 2003 Meador KB, David CD: Psychotherapy, in The American Psychiatric Press Textbook of Psychiatry, 2nd Edition. Edited by Hales RE, Yudofsky SC, Talbott JA. Washington, DC, American Psychiatric Press, 1994, pp 395–412 Moak G, Borson W: Mental health services in long-term care: still an unmet need. Am J Geriatr Psychiatry 8:96–100, 2000 National Center for Health Statistics: Health, United States, 2004, With Chartbook on Trends in the Health of Americans. Hyattsville, MD, National Center for Health Statistics, 2004 Olshansky SJ, Carnes BA, Cassel CK: The aging of the human species. Sci Am 268:46– 52, 1993 Rapp SR, Parisi SA, Walsh DA: Psychological dysfunction and physical health among elderly medical inpatients. J Consult Clin Psychol 56:851–855, 1988 Regier DA, Boyd JH, Burke JD, et al: One-month prevalence of mental disorders in the United States. Arch Gen Psychiatry 45:977–986, 1988 Robins LN, Regier DA: Psychiatric Disorders in America: The Epidemiologic Catchment Area Study. New York, Free Press, 1991 Simon G, Ormel J, Von Korff M, et al: Health care costs associated with depressive and anxiety disorders in primary care. Am J Psychiatry 152:352–357, 1995 U.S. Public Health Service: Mental Health: A Report of the Surgeon General. Rockville, MD, Office of the Surgeon General, 1999. Available at: http:// www.surgeongeneral.gov/library/mentalhealth. Accessed January 27, 2006. U.S. Public Health Service: Mental Health: Culture, Race, and Ethnicity: A Supplement to Mental Health: A Report of the Surgeon General. Rockville, MD, Office of the Surgeon General, 2005. Available at: http://www.surgeongeneral.gov/library/ mentalhealth. Accessed March 9, 2006.

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Wetherell JL, Kaplan RM, Kallenberg G, et al: Mental health treatment preferences of older and younger primary care patients. Int J Psychiatry Med 34:219–233, 2004 Young AS, Klap R, Sherbourne CD, et al: The quality of care for depressive and anxiety disorders in the United States. Arch Gen Psychiatry 58:55–61, 2001

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2 Normal Aging Conceptual Issues Who Is Old? Biological and psychological aging changes usually occur gradually, over years or decades, and as a result, there is no single age at which people in general can be said to be old. The common practice of designating people older than 65 as “old” began in Germany in the 1880s, when Otto von Bismarck selected 65 as the starting age for certain social welfare benefits. In the United States, the age at which full Social Security benefits can be received has now been raised to 67 years for persons born in 1960 and later. Although this change is primarily a response to fiscal concerns, the upward shift is also indicative of the increasing vitality and productivity of the aging population. According to a recent national survey, 63 years is the average age at which Americans perceive individuals as becoming old, but there was much variation in perceptions (Abramson and Silverstein 2004). More than one-third of the sample named an age greater than 70 as the start of old age, whereas another one-fourth cited ages less than 60 years. Gerontologists often draw finer chronological demarcations within the general group of aging persons. Comparisons may be made between the youngold and the old-old (generally, those younger than and older than age 75, respectively) or between these groups and the oldest old (generally 85 years and older). Although these distinctions are also arbitrary, they can be useful in identifying important differences in levels of functioning and can help to limit overgeneralization about characteristics of older adults. It is also important to keep in 21

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mind that individuals may age faster in some dimensions than others (e.g., being “old” physically but more youthful psychologically or socially).

Cross-Sectional and Longitudinal Views The most common way to study the effects of aging is to compare a group of older people with a separate group of younger adults. Because generational differences in education, health practices, diet, and other important factors are confounded with age differences when young and old subjects are compared, cross-sectional investigations often provide an inflated estimate of the magnitude of aging changes that will occur in individuals. Longitudinal designs also have been used to study normal aging. These investigations track the same individuals over years, or even decades. The least healthy and able subjects are often the first to drop out from these samples, so longitudinal investigations may provide an overly optimistic estimate of the extent of decline with age. The best picture of normative aging trends is obtained from studies in which multiple cohorts are assessed longitudinally or by combining the results of separate cross-sectional and longitudinal studies. The Seattle Longitudinal Study conducted by Werner Schaie (2005) and colleagues provides one of the best examples of a multiple-cohort longitudinal aging study, outcomes of which have helped to shape understanding of cognitive processes that remain stable or reliably decline with age. At least 25 other longitudinal investigations of behavioral aspects of aging are ongoing at this time, and a burgeoning number of cross-sectional studies are being done.

Heterogeneity in Patterns of Aging On many psychological and biological measures, variability is greater in oldage samples than among younger adults. A longitudinal study of 426 elderly community dwellers by Christensen and associates (1999) found increases in interindividual variability with age in memory, spatial functioning, and speed but not in crystallized intelligence. Being female, being more depressed, being more ill, and having weaker muscle strength were associated with greater variability, whereas having a higher level of education was associated with reduced variability. Pronounced variability decreases the sensitivity in upper age ranges of many measures that are used to infer pathological changes and casts doubt on the search for singular normative aging trends. Many different normal ag-

Normal Aging

23

ing trajectories may exist, with varying trends for different genetic and sociocultural subgroups. Intraindividual variability (i.e., fluctuating performance within and across assessments) is also increased in old age, especially for cognitive and physical performance measures. Heightened variability within the individual has been linked to an accelerated rate of cognitive decline over time and may be a marker for neurobiological aging (MacDonald et al. 2003).

Cognitive Abilities in Later Life: A Processing Resource Model Cognitive changes with aging are well documented and affect a broad range of functions (see the subsection “General Aging Trends” later in this section). However, many of the differences in specific abilities can be traced to declines in three fundamental cognitive-processing resources: the speed at which information can be processed, working memory, and sensory and perceptual skill (Park 1999).

Processing Speed Perhaps the most predictable of all cognitive changes is the reduced speed of information processing and response. Slowed execution of component perceptual and mental operations can affect attention, memory, and decision making and can influence performance even on tasks that have no obvious speed requirements (Salthouse 1996).

Working Memory Working memory refers to short-term retention and manipulation of information held in conscious memory, a type of “online” cognitive processing (Baddeley 1986). Examples include consciously recalling a telephone number long enough to write it down, mentally calculating the sale price of an item that is reduced by 15%, and mentally traversing a route that one intends to walk or drive. Information fades from working memory within about 2 seconds, so to keep details “alive” for a longer time requires active rehearsal or continuing refocusing of attention. Aging is associated with a decline in working memory skills, especially when active manipulation of information is required (e.g., repeating numbers

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backward as opposed to forward). Reductions in working memory, in turn, place limits on other complex cognitive skills, including reasoning and other executive processes, and learning and recall of new information.

Sensory and Perceptual Changes Most older adults experience decrements in visual and auditory acuity and other perceptual changes. Some, but not all, of the age-related visual changes can be corrected by glasses, and although hearing aids help with detection of low-frequency tones, they often amplify background noise. In effect, many older adults find it hard to hear or see well, especially with competing background noise and poor lighting conditions. Recent studies suggest a strong correlative link between sensory and perceptual changes and cognitive performance in old age. Younger adults tested with degraded perception (e.g., by background noise or reduced visual contrast) perform much like older adults on measures of learning, memory, and language (Schneider and Pichora-Fuller 2000). The extra time and effort required to process information necessitated by sensory and perceptual problems tax working memory, effectively overloading the system. The combined effects of central nervous system slowing, reduced working memory, and sensory and perceptual changes limit the processing resources that older persons can bring to bear in particular situations. These changes increase the likelihood of processing overload in circumstances that may have once presented little challenge. In advanced old age, even basic activities such as walking or maintaining postural control become less automatic, with the result that older persons must devote more conscious cognitive resources to these activities.

Neuropsychological Explanations of Cognitive Aging Changes Neuropathological and neuroimaging studies have documented widespread changes in the human brain with aging (Raz 2000; Victoroff 2000). There are generalized atrophic and white matter changes as well as region-specific variations in the extent of cell loss. Within the cortex, the prefrontal lobes are disproportionately affected by aging changes, whereas temporoparietal association areas are less affected. Subcortical monoaminergic cell populations, which connect to the frontal lobes by a complex network of projections, are also subject to prominent decline in aging. Data are more conflicting regard-

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ing changes in the hippocampus and entorhinal cortex, with some studies noting minimal cell loss with normal aging in these regions and others showing decremental changes. Areas in which there is relative sparing with age include the globus pallidus, the paleocerebellum, the sensory cortices, and the pons (Raz 2000). Some of the behavioral changes in aging, such as slowed information processing and response, may be related to generalized changes such as decreased brain volume and white matter density. Other changes appear to mirror the selective pattern of differential change in prefrontal cortical structures and striatal dopaminergic nuclei. Decreased working memory, problems with effortful learning and recall, and changes in efficiency of executive functions are some of the findings that suggest a mild degree of frontal or subcortical brain dysfunction in normal aging (Prull et al. 2000). The “frontal lobe hypothesis” is perhaps the most popular neuropsychological model of normal aging at this time. However, hippocampal changes also may play a role in normal aging memory. Hippocampal volume, as measured by magnetic resonance imaging, correlates with memory performance in older adults, and those with smaller hippocampal volumes are at greater risk for developing dementia. What remains to be resolved, however, is whether reduced hippocampal volume is truly within the normal aging spectrum or instead is a preclinical phase of dementia. Functional neuroimaging studies have shown less regional specificity in older adults’ patterns of brain activation to various cognitive tasks compared with the regional specificity in young adults (Prull et al. 2000; Raz 2000). One interpretation of this finding has been that older persons must recruit more neural systems to perform even relatively simple mental operations. This interpretation coincides in a general way with the behavioral model of reduced processing resources and increased susceptibility to overload on complex tasks.

General Aging Trends Table 2–1 summarizes general aging trends for intelligence and specific areas of cognitive function. In this table, mild decline refers to changes that are generally within a standard deviation of the mean for young adults, whereas moderate decline refers to differences on the order of one to two standard deviations below the average for young adults. As the table indicates, cognitive changes associated with normal aging generally fall within the mild to moderate range, and there are some areas in which performance remains stable or improves. The differential pattern

Ability Intelligence Vocabulary, fund of knowledge Perceptual-motor skills Attention Attention span Complex attention Language Communication Syntax, word knowledge Fluency, naming Comprehension Discourse Memory Short-term (immediate)

Direction of aging change

Comment

Stable or increasing

May decline slightly in very old age; most pronounced on novel tasks Decline begins by ages 50–60

Declining Stable to mild decline Mild decline

Problems with dividing attention, filtering out noise, shifting attention

Stable Stable Mild decline Stable to mild decline Variable

In absence of sensory impairment Varies with education Occasional word-finding lapses Some erosion in processing complex messages May be more imprecise, repetitive

Stable to mild decline

Forward digit span intact (7±2 items), but easily disrupted by interference Reduced ability to manipulate information in short-term memory Encoding and retrieval deficits; storage intact

Working

Mild to moderate decline

Secondary (recent)

Moderate decline

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Table 2–1. Aging effects on cognitive performance

Table 2–1. Aging effects on cognitive performance (continued) Ability

Direction of aging change

Comment

Memory (continued) Implicit

Stable to mild decline Variable Variable

May recall incidental features more easily than consciously processed information Intact for major aspects of personal history Mild to moderate decline on laboratory tasks, but older adults often outperform younger people on naturalistic prospective memory tasks

Remote Prospective

Variable Declining

Intact for simple but not complex figures Most noticeable in unfamiliar terrain

Mild to moderate decline

Logical problem solving Practical reasoning

Declining Mild to moderate decline

Slower and less accurate in shifting from one thought or action to another Some redundancy and disorganization Qualitatively intact, but reduced efficiency on complex or novel tasks Slowing of thought and action is the most reliable aging change

Speed

Declining

Normal Aging

Visuospatial Design copying Topographic orientation Executive functions Cognitive flexibility

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of abilities shown in Table 2–1 is less apparent among the oldest-old (e.g., 85 or older), for whom some studies report a generalized pattern of gradual decline. Another important qualification concerns secular trends in levels of performance. Intellectual performance scores have been increasing over the past few decades, and the rate of increase is higher among older, as opposed to younger, adults. For example, vocabulary scores on the commonly used Wechsler Adult Intelligence Scale (Wechsler 1997) have increased nearly 5 IQ points per decade for 65- to 74year-olds, compared with 1.5 points for 18- to 24-year-olds (Uttl and Van Alstine 2003). Higher absolute levels of intellectual ability may benefit contemporary older adults in learning new information and acquiring new skills (see the subsection “Effect of Cognitive Change on Everyday Function” later in this section).

Factors That Influence Cognitive Aging Table 2–2 summarizes characteristics and experiences that influence the degree of cognitive change individuals show as they age. The cumulative effect of these factors, operating over months or years, may be responsible for increasing variability in cognitive performance at older ages. Healthy and stimulating lifestyles, in addition to early life advantages such as adequate education, are hypothesized to strengthen the “cognitive reserve” that individuals have available to cope with neurobiological changes resulting from aging or illness (Scarmeas and Stern 2003). Increasing evidence, for example, indicates that physical and mental exercise, a healthy diet, and strong social supports may serve as protective factors against the development of dementia (e.g., Fratiglioni et al. 2004).

Learning and Memory When older people complain about their cognitive abilities, they usually mention problems with memory. Research substantiates these complaints, but as shown in Table 2–1, some aspects of memory decline more with age than do others (La Rue 1992; Prull et al. 2000). Short-term or immediate memory remains stable or declines to a modest degree in later life. For example, the median forward digit span for healthy persons in their 80s is six items, compared with seven items for persons in their 30s (Wechsler 1997). On more demanding tests of short-term memory, such as recalling information after an interfering message, age differences favoring the young are likely to be observed, which coincides with the declines in working memory discussed earlier.

Table 2–2. Cognition in normal aging: moderating variables Genetic factors Health Education Mental activity Physical activity Expertise Personality and mood Social and cultural milieu Cognitive training Cohort effects Sex differences

Normal Aging

Racial and ethnic differences

About 50% of cognitive variability in old age can be traced to genetic factors. Optimally healthy elderly persons outperform those with medical illnesses on many cognitive tests. Education accounts for up to 30% of cognitive variability in old age. Mentally stimulating activities correlate with higher cognitive performance and reduced longitudinal decline. Aerobic fitness is associated with better cognitive performance in old age. Aging experts may develop compensatory strategies to maintain a high level of performance despite some erosion in underlying cognitive skills. Depression correlates with self-perceived memory failure and with performance impairments if symptoms are severe. Everyday memory lapses may be judged more critically when experienced by older people than by young adults. Cognitively unimpaired older persons benefit from practice and training in specific cognitive skills. Recently born cohorts are outperforming those born near the turn of the century on many cognitive skills. Cognitive aging trends are similar for the two sexes, but women may show decrements on spatial tasks at an earlier age than men, and men may show decrements on verbal tasks at an earlier age than women. Performance differences favoring elderly white persons have been reported on some cognitive tests, but when education is equated across groups, these differences are reduced or eliminated.

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Anecdotally, remote or long-term memory is well maintained in old age. Research results are not so clear, partly because remote memory is difficult to measure because initial or intervening exposure to the material cannot be precisely controlled (La Rue 1992; Prull et al. 2000). Overall, however, older adults’ absolute levels of performance on remote-memory tests are often impressively high; for example, one study found that people recognized names or photographs of more than 70% of high school classmates after an interval of almost 50 years. Another type of memory that shows minimal or modest age change is implicit or incidental recall. Incidental facts or features (e.g., the color of someone’s dress) can be recalled with about equal accuracy by young and old, whereas the old are more prone to forget information that they had explicitly hoped to retain (e.g., the person’s name). Prospective memory (i.e., memory for actions intended in the future) shows divergent age trends, depending on how and where it is measured (Henry et al. 2004). In laboratory settings, older adults typically do less well than younger persons. However, on naturalistic tasks (e.g., remembering to call to make an appointment), older adults often show superior follow-through, mainly because of more reliable use of external aids such as reminder notes. The largest age decrements are observed in recent, episodic memory (La Rue 1992; Prull et al. 2000). Age differences favoring the young have been found on many explicit tests of recent memory, such as remembering items on shopping lists, learning to associate pairs of words, copying designs from memory, and remembering content of stories and conversations. On the average, healthy older individuals make more mistakes than young adults on memory items from mental status examinations, such as 5-minute delayed recall of three or four simple words. On demanding explicit memory tasks, older persons recall less information initially compared with young adults, but their performance improves with repetition, and they retain most of what they learn after delays and distractions. This ability to retain information, once it is acquired, is one of the best ways to distinguish normally aging memory from that of patients with amnestic conditions or Alzheimer’s disease (see Chapter 5, “Dementia and Alzheimer’s Disease”). Some of the problems that older people have with initial learning may be related to strategies used for processing new information (La Rue 1992). Many older people take a more passive approach to learning and remembering than do

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younger adults. For example, elderly people report less spontaneous use of mnemonic strategies than do younger people and do not appear to capitalize as readily on the organization inherent in words or actions as a basis for learning and recall. The shallower memory traces that result are subsequently harder to retrieve, especially without the aid of reminders or cues. If older individuals are explicitly instructed to use mnemonics or organizational strategies, their learning and recall often improve dramatically, at least in the short term. Active encoding and retrieval may require greater expenditure of effort and energy than most older people can afford. Declines in effortful processing may be caused by altered neurotransmitter functions (especially catecholamines). Alternatively, such processing changes may be seen as an adaptive response to the diminished demands of older adults’ everyday lifestyles. Also, it is important to note that some healthy and active elderly people do as well on demanding recent memory tasks as do more average young adults. Older adults (and younger persons, too) often ask about ways to improve their recall of everyday information. Mnemonic training can produce notable gains in troublesome areas, such as recall of names, locations of objects, and lists of things to be purchased or done, for old as well as young adults. Training is most likely to be effective for young-old persons as opposed to the oldest-old and for individuals with no decline on mental status examination (Verhaeghen et al. 1992). Training also works best in an individual or a small-group format and with relatively short (e.g., half-hour) sessions as opposed to longer workshops or lectures. Follow-up studies often show that people discontinue memory techniques they have learned within a few weeks. In some cases, this may simply mean that the training served its intended purpose (i.e., to prove that one can remember more if need be), but it is also likely that the use of mnemonics may be too effortdemanding in the long run. A greater drawback of mnemonic training approaches is that benefits often fail to generalize to everyday tasks not specifically included in training (Ball et al. 2002). Education and counseling about memory improvement is best approached from a broad perspective, in which improving memory is seen as part of an overall wellness plan. Of the many self-help books providing advice on how to maintain memory function into old age, Keep Your Brain Young (McKhann and Albert 2002) is among the best in terms of readability, breadth, and linkage to research. Learning Throughout Life (National Retired Teachers Association et al. 2004) is another good guide for the general reader. In The Memory Prescription, Small (2004) out-

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lines a 2-week program of diet, exercise, stress reduction, and mental exercise designed to boost brain function. The program is derived from an ongoing program of research, but independent studies are needed to assess benefits of this approach.

Executive Function The term executive function refers to cognitive abilities necessary for complex goaldirected behavior and adaptation to change. Some of the skills included in this category are reasoning, planning, anticipating outcomes of behavior, directing attentional resources in a flexible manner, monitoring one’s own behavior, and selfawareness. Performance of such skills requires the coordinated activity of multiple regions of the brain and can be affected by injury to several different areas. However, the prefrontal cortex and frontal-subcortical brain circuits have been shown to play a central role in executive functions. As noted earlier, normal aging has a greater decremental effect on these brain regions than on many other areas, and predictably, age differences are relatively large on executive function tasks (see Table 5–5 in Chapter 5, “Dementia and Alzheimer’s Disease,” for examples of neuropsychological tests of executive function). Performance on executive function tests correlates more closely than scores on many other cognitive tasks with activities of daily living, and changes in executive function may play a role in determining which older people come to clinical attention for mild cognitive changes (Royall et al. 2005). Although research generally shows that older adults do worse than young or middle-aged persons on both laboratory-based and practical reasoning tasks (Thompson and Dumke 2005), not all studies show this trend. For example, one recent investigation found that cognitively healthy 65- to 74-year-olds provided more relevant solutions to problem situations—such as trying to improve the acrimonious tone of a meeting, dealing with excessive demands by one’s sons to babysit their children, or having blood drawn by a physician who is having difficulty with the procedure—than did a comparison group of 20- to 29-year-olds (Artistico et al. 2003). In general, interpersonal problem solving is an area of strength for older people (Thompson and Dumke 2005).

Effect of Cognitive Change on Everyday Function Although normal aging is accompanied by a variety of cognitive changes, most older adults are not impaired in everyday activities, even when relatively complex cognitive processing is required.

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Several factors help to maintain daily function in the face of mild cognitive decline (Park 1999). The very gradual nature of age-related change allows time to adjust to diminished speed and efficiency in cognitive function. The fact that general knowledge is well preserved in later life allows older adults to access a broad base of information that is useful in solving problems and addressing everyday needs. With practice, many tasks become automatic and require little cognitive processing or effort to perform, and maintaining a familiar environment and routine further reduces cognitive load. Also, many older adults make frequent and effective use of external cognitive aids such as writing reminder notes. Some areas, such as driving and monitoring medications, pose particular risks (Park 1999). Older adults are more likely to be involved in accidents while driving than are younger persons, particularly in certain situations (e.g., left turns in intersections). Cognitive research has identified a measure of peripheral vision (so-called useful field of vision) that is more predictive of driving success than are standard visual acuity measures, and this research also has found that older adults can improve driving skill through a combination of perceptual training and traditional drivers’ education classes (see Chapter 9, “Competency and Related Forensic Issues,” for additional information on driving). Regarding medications, it is important to note that some studies show better compliance with medication regimens among older adults than among younger or middleaged persons, particularly if the older adults are taking only a single medication for a long-standing condition (e.g., hypertension or arthritis). When they are taking multiple medications that require dosing several times a day, the risk of errors is increased, and it has been estimated that about 1% of acute hospital admissions for older persons are precipitated by medical errors or medication reactions. In industrialized nations, an overabundance of new information and rapidly changing technologies place a heavy demand on learning skills. Older adults bring to this situation a wealth of accumulated knowledge and experience, which can facilitate learning of new information in areas of prior knowledge. One recent study found, for example, that older age proved to be an advantage in learning new information about cardiovascular disease, presumably because of older adults’ greater baseline knowledge of health-related subjects (Beier and Ackerman 2005). By contrast, younger adults were more adept at learning about a new technology. Research on training methods has shown that older adults learn best with self-paced training or other training environments that allow ample time to

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assimilate the information presented (Callahan et al. 2003). These modes of educating most effectively remediate, or compensate for, reduced speed of processing and working memory or sensory limitations.

Clinical Implications of Cognitive Change Cognitive declines that accompany normal aging complicate detection and diagnosis of organic mental disorders. One common error is overdiagnosis of dementia, particularly in persons with limited education. In one large multicultural study, most old persons without dementia who had less than 5 years of education were rated with standard mental status examinations as impaired (Wilder et al. 1995). Among healthy, well-educated old persons, brief cognitive screening may fail to detect focal brain impairment or dementia in early stages. For example, as many as one in three older patients with mild Alzheimer’s disease who are otherwise healthy and have at least a high school education can be expected to score in the normal range on very brief tests for cognitive screening. Outcomes of cognitive mental status examinations in older people must be interpreted cautiously, and the clinician should follow up with a more thorough diagnostic assessment for those who score in the impaired range or whose adequate performance on a screening examination is inconsistent with lapses in everyday behavior. Paying attention to the pattern and types of errors may also help to distinguish normal from abnormal cognitive changes. Chapter 5 (“Dementia and Alzheimer’s Disease”) provides more specific guidelines for screening for dementia through the use of cognitive mental status examinations, and the following subsection discusses more specific diagnostic issues concerning age-associated cognitive syndromes. Age-related cognitive changes also have implications for the doctor-patient relationship and for selection and monitoring of treatment. Extra care may be required in explaining medical procedures to ensure informed decision making. Asking the patient to repeat the main points and providing written summaries or illustrations may help to make details of procedures clear, although very complicated medication organizers or instructional charts may be counterproductive. In psychotherapy, the reduced pace of new learning and changes in reasoning processes may result in a slower rate of clinical improvement. Often, this can be dealt with effectively by increasing the number of therapy sessions.

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Abrupt changes in cognitive function always warrant medical attention. Even more gradual declines, emerging over a year or two, may be an early warning of occult illness (so-called terminal decline) and should be carefully monitored. According to one recent study, subclinical cognitive decline increases the risk of mortality in older men as much as a history of cancer does.

Diagnosing Age-Related Cognitive Change and Mild Cognitive Impairment In DSM-IV-TR (American Psychiatric Association 2000) nomenclature, the category of age-related cognitive decline (780.9) may be coded to denote functioning of an older person with mild cognitive changes that are within normal limits for age and not attributable to a medical disorder. No guidelines have been developed for identifying age-related cognitive decline. However, diagnostic criteria have been proposed for a related, but narrower, category of age-associated memory impairment (AAMI). Persons with a diagnosis of AAMI must be 50 years or older, have subjective complaints of memory loss affecting routine activities, and perform below the average level of young adults on a standardized memory test; exclusionary criteria include any neurological, psychiatric, or medical disorders that could reasonably be assumed to be producing the memory change. The prevalence of AAMI based on objective assessment has been estimated to range from 40% for persons in their 50s to 85% for those 80 and older (Larrabee and Crook 1994). Thus, five of every six very old, healthy persons can be expected to perform somewhat lower than young or middle-aged adults do on memory tests and possibly to have mild memory lapses in everyday activities. AAMI has been shown to be stable over intervals of at least 4 years; thus, it is presumed to reflect normal aging, as opposed to beginning dementia or other brain disorder. Clinicians are also likely to see older adults whose cognitive skills are somewhat worse than expected for their age but who are still coping well overall and do not appear to have dementia. Much research has been devoted to this gray area of performance, generally referred to as mild cognitive impairment. Diagnostic criteria for this condition are still evolving, and several definitions have been proposed (see Winblad et al. 2004). The skill most commonly affected in mild cognitive impairment is learning and recall of new information, but in some cases, problems are noted in

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other cognitive areas, such as language, visuospatial skills, or reasoning. The term amnestic mild cognitive impairment is used when memory is impaired, and the term nonamnestic mild cognitive impairment is used for other types of mild cognitive deficits. Additional subcategorization has been proposed to distinguish between cases in which a mild deficit is observed in a single domain (e.g., memory) or in multiple domains (e.g., memory and reasoning). In all forms of mild cognitive impairment, there may be subtle difficulty with higher-order activities of daily living such as financial management, but this difficulty is often intermittent and can be dealt with by extra effort or compensatory approaches such as note taking or double-checking one’s work. Table 2–3 compares diagnostic criteria for amnestic mild cognitive impairment with those for AAMI. The very short tests included in mental status examinations are generally not sensitive to mild cognitive impairment, and if this condition is suspected, referral for neuropsychological testing is recommended. To improve screening accuracy for amnestic mild cognitive impairment, a more challenging test of learning and memory should be incorporated into the psychiatric examination (see Table 5–5 in Chapter 5, “Dementia and Alzheimer’s Disease,” for examples of memory tests). DSM-IV-TR research criteria for mild neurocognitive disorder (coded as cognitive disorder not otherwise specified, 294.9) may be appropriate for some cases of mild cognitive impairment (i.e., when there is mild cognitive dysfunction in two or more areas, and when deficits do not meet criteria for dementia, delirium, or other major organic mental disorders; American Psychiatric Association 2000). The syndrome of mild cognitive impairment can have several different underlying causes. In amnestic mild cognitive impairment, neurodegeneration of an Alzheimer’s type is believed to be the most common etiology (Petersen and Morris 2005). However, depression or other psychiatric disorders, metabolic or medical disorders, trauma, substance abuse or medication reactions, and other conditions also may cause mild cognitive impairment of the various types. In evaluating an individual who presents with mild cognitive impairment, it may be helpful to review the full range of potential causes and contributing factors that have been established for dementia (see Chapter 5, “Dementia and Alzheimer’s Disease”). As shown in Table 2–3, a substantial proportion of persons with amnestic mild cognitive impairment eventually develop dementia, and a high pro-

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Table 2–3. Clinical presentations of memory loss in old age Age-associated memory impairment (AAMI)

Mild cognitive impairment— memory type (amnestic MCI)

Clinical presentation

Memory complaint Normal mental status Normal activities of daily living

Memory test results

≥1 SD below the average level for young adults on a standardized memory test Generally stable for periods of at least 4 years

Memory complaint or memory problems noted by an informant Normal mental status Normal activities of daily living or very subtle changes ≥1.5 SDs below the average level for age peers on a standardized memory test Progresses to dementia at the rate of 10%–12% per year, but some remain free of dementia for at least 10 years

Feature

Clinical course

Note. SD= standard deviation. For further information on AAMI, see Larrabee and Crook 1994. For MCI diagnosis and course, see Petersen and Morris 2005 or Winblad et al. 2004.

portion have Alzheimer-type brain changes on autopsy (Morris et al. 2001). Clinical course is not as well established for nonamnestic mild cognitive impairments, and it is important to recognize that mild cognitive impairment in any form is not invariably progressive. Some persons with mild cognitive impairment have a stable mild level of cognitive difficulty over intervals of several years; others (as many as 40% in some studies) revert to normal performance. In general, individuals who seek help from a physician because of memory concerns (i.e., clinic-based populations) are more likely to show a progressive course than are patients with mild cognitive impairment identified through population-based surveys. Early interventions (e.g., with medications to enhance cholinergic system function) could potentially be of benefit in slowing clinical progression of mild cognitive impairment, but the first large-scale clinical trial of this type yielded disappointing results. Older adults with mild cognitive impairment who received donepezil or vitamin E did not differ from control subjects in cognitive course over a 3-year follow-up, although participants with an apolipoprotein ε4 allele did show some benefit from donepezil (Petersen et al. 2005). These particular interventions may not have been optimal for treating prodromal demen-

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tia symptoms or preventing their progression. Also, effective prevention of Alzheimer’s disease and other dementias may require intervention earlier in the life course (i.e., before mild cognitive impairment becomes apparent). A difficulty for clinicians is that it is not yet possible to separate the individuals with mild cognitive impairment who will progress to dementia within a few years from those who will not. When a clinical diagnosis of mild cognitive impairment is combined with other markers of Alzheimer’s disease (see Chapter 5, “Dementia and Alzheimer’s Disease”), the likelihood of dementia is increased. However, in most cases, this additional information is not available, and only follow-up will determine whether the patient has a progressive course. In clinical situations, it is most useful to explain the category of mild cognitive impairment to the patient, discuss the need to track performance over time (as in other chronic medical conditions), and encourage active compensation for functional effect in the form of simplification of schedules, increased use of note taking and organization, and sharing of responsibility for mentally demanding tasks with others.

Personality and Emotional Changes Personality and emotions have not been studied as thoroughly as cognition in old age. Moreover, it is unknown whether observations about personality made within the confines of a particular generation and culture can be generalized to other places and times. The trends summarized in this section are most applicable to currently old persons in Western urban societies.

Coexisting Stability and Change When older adults compare their current and past selves, they usually perceive more growth than decline in personality; that is, desirable traits are perceived as outweighing undesirable traits to an increasing degree through middle age and early old age. Developmental optimism is a term that has been coined to describe this subjective growth in personality (Krueger and Heckhausen 1993). In contrast, descriptive research suggests that basic personality traits such as introversion-extroversion, psychological tempo, assertiveness, and hostility are stable throughout adult life (McCrae et al. 1999). These personality disposi-

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tions are formed early in life and remain fairly constant in their relative prominence in an individual’s makeup, despite variations in life experiences over the years (Roberts and DelVecchio 2000).

Influences on Adult Personality Precise patterns of ebb and flow in personality probably vary with generations, because each cohort encounters a unique set of pressures and opportunities at successive life phases. However, certain causal processes appear to be consistently important. One influential developmental force is the “social clock” (Neugarten 1970). Most societies have rather firm beliefs about age appropriateness of various actions. Some of these beliefs are formalized through minimum-age laws or standards (e.g., for marriage, voting, or retirement), but most are informally imposed. The social clock sets the pace for psychosocial development within a given generation and provides a standard that individuals may internalize as a normal, expectable life cycle. A second important force is the individual’s desire for continuity in personal past and present. Continuity has been described as “a grand adaptive strategy” promoted by individual preference and reinforced by social approval (Atchley 1989). The search for continuity may be at the heart of reminiscence, which occurs at all ages, and of the process of life review that is so common among elderly adults. A third but poorly understood set of influences is genetic factors. A study of elderly twins and multigenerational families found a genetic contribution to negative affect but not to positive affect. Positive affect showed some resemblance across family members, but the resemblance appeared to be attributable to shared environments rather than genetic similarity (Baker et al. 1992). Individual and social influences may combine to produce ordered transitions or stages in adult personality. Erikson’s (1950) widely cited theory depicts development as progressing through eight age-correlated phases. Each stage is associated with primary developmental tasks, and accomplishment of each task has a bearing on subsequent stages. In late adulthood, the primary tasks concern integrity versus despair; that is, each person is faced with making sense of his or her actions over a lifetime and with judging the purpose and effect of these actions. Morale in old age may depend on success in resolving this issue, in addition to those of earlier life phases.

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To the extent that ordered transitions exist, they may differ for women and men. Among middle-class women in the United States, increasing assertiveness and feelings of efficacy are evident, combined with declining dependency, as they approach their 50s. Among men of similar socioeconomic background, an increase in interpersonal orientation and nurturance in later years is seen. Most contemporary developmental theorists do not propose stage theories but instead emphasize the creative effect on personality of assuming and relinquishing adult roles—most importantly, parenting (Gutmann 1987)— or the dynamic interplay of cognitive processing resources and particular social contexts in shaping expressed personality (Staudinger and Pasupathi 2000).

Personality and Perceptions of Health Older adults’ perceptions of their health have been linked to a variety of objective health outcomes, including mortality. Depression affects subjective health concerns, as do certain personality traits. Neuroticism is inversely associated with self-perceptions of good health, whereas extraversion is positively associated; in a recent study, these associations were stronger among persons age 75 and older than among persons in their 60s and early 70s (Duberstein et al. 2003). This same study found that openness to experience correlated with higher functional status throughout the late-life age range.

Emotions, Coping, and Well-Being Research suggests that old age is an emotionally rich and complex phase of life, and the salience of emotion, relative to more neutral knowledge and skills, increases in later years (Carstensen 1992). Mentally normal older people have better control over emotions than do younger adults, they reason more flexibly about emotion-laden dilemmas, and they remember emotionally charged information better than neutral facts (Isaacowitz et al. 2000). This richness of emotional processing in older persons runs counter to the generally declining patterns seen in many cognitive and physical skills. Instead of necessarily being linked to aging, the priority given to emotion among older people has been interpreted by some as a reaction to shortened time left, or “endings.” Some studies have noted that older people tend to cope with stressful events in different ways than do younger adults; older people rely more often

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on emotion-focused forms of coping, as opposed to active, problem-solving approaches. Emotion-focused coping is more passive than confrontational, is more individual than interpersonal, and is oriented toward control of distressing feelings rather than toward alteration of stressful situations. Examples of emotion-focused coping include distancing from the problem, accepting responsibility, and reappraising the problem positively. However, other research has pointed out that the problem situations that older people face are often less changeable than those of younger adults, and when the type of problem is equated across ages, differences in coping styles are reduced or eliminated (Staudinger and Pasupathi 2000). Locus of control is another dimension that affects response to stressful situations. For example, older people who believe that their health is controlled by powerful others adjust better to acute-care hospitals and high-constraint long-term care than do those who consider their physical well-being to be under their own control. In the community, belief in an external locus of control is associated with increased visits to physicians during times of very high stress. However, regardless of preexisting control orientation, studies of longterm care show that sense of well-being tends to increase when residents are given greater opportunities to regulate their own environment. Although old age presents many personal and social obstacles, poor morale has been found to be the exception rather than the rule among older adults. Current cohorts of older adults are not more prone to depression or anxiety disorders than are young or middle-aged persons, and they do not show lowered self-esteem as a general rule. Not surprisingly, older adults with the highest morale tend to have better education and socioeconomic status when compared to those older adults who did not have such advantages. Specific stressful events have less of an effect on subjective well-being in old age than does attainment of personal goals or the onset of physical disability. Older adults maintain a sense of contentment in the face of functional declines through a combination of mobilizing additional resources, “downsizing” performance standards, and reducing the value placed on particular skills or attributes (Rothermund and Brandtstadter 2003). Throughout the adult life span, individuals compare their own performances and experiences with those of others and often come to positive conclusions. This self-enhancing appraisal serves to sustain self-esteem through difficult transitions and is a support for mental health (Kwan et al. 2003).

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An influential model of adult development that has emerged in recent years relates resilience in old age (i.e., maintaining adaptive behavior in the face of stress and recovering from adversity) to a process of selective optimization, in which goals are reshaped to fit current limitations and environments, and resources are spared for personally important activities that sustain self-esteem (Baltes 1997). Elderly persons with the strongest sense of personal efficacy are flexible in prioritizing goals and accommodating to role changes and resource limitations. Those with several self-domains in which they hold themselves in high esteem seem best able to cope with transitions imposed by role losses or poor health (Staudinger and Pasupathi 2000).

Clinical Implications of Personality and Emotional Changes Core features of personality remain stable throughout adulthood, and any marked change in mood or social behavior may indicate a disorder. However, more subtle reordering of personal priorities and shifts in coping styles are common with normal aging. It is particularly important not to measure older people’s coping by youthful standards. Emotion-focused coping may be a sign of personality development rather than regression, particularly if the problem being faced (e.g., bereavement or serious illness) is difficult to resolve through action. In acute-care situations, the clinician must accurately appraise an individual’s beliefs about locus of control. Those individuals with an internal locus of control adjust best if given an opportunity to participate in medical decision making, whereas those individuals with an external locus of control may benefit more from knowing that they are attended by recognized experts. Those individuals who suspect that their fate depends on chance may adjust best if the care environment is consistent and predictable. Other aspects of personality need to be considered as well. The increased vulnerabilities that accompany old age may amplify neurotic traits, increasing susceptible individuals’ worries about health and making it more difficult to provide reassurance based on objective results. By contrast, socially extroverted persons may respond well to encouragement to share their experiences with others (e.g., by participating in health-oriented support groups).

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Increasing salience of emotional matters can influence assessment, especially of cognitive skills. Older patients may not see the relevance of being asked to learn a list of words or may editorialize about emotional themes in stories they have been asked to remember. Varying the instructions of the task (e.g., encouraging the person to try to remember the story as if he or she were going to relate it to a friend or grandchild) can sometimes help to direct attention and effort toward the task requirements to permit a valid assessment. Older people can benefit from the full range of psychotherapies used with younger people (see Chapter 4, “Mood Disorders—Treatment”). Some highly educated and thoughtful elderly people are well suited for long-term therapy addressing intrapsychic tasks of later life. For many others, situational interventions, aimed at modifying real-life problems, may be most appropriate, and in general, there has been a trend toward short-term, problemfocused therapies in recent years. In either case, goal setting for the future should be part of the psychotherapy agenda.

Social Context of Aging Old age is accompanied by role change and, often, role loss. Most people can expect transformations in occupational, family, and community roles, and for many, the number of different roles declines in later life.

Education, Work, and Financial Status The average education level of older Americans has increased in recent decades; in 2003, nearly three-fourths of persons age 65 and older had a high school diploma. Older Asian Americans had the highest percentage of persons (29%) with at least a bachelor’s degree. By contrast, older black and Hispanic Americans remained disadvantaged in terms of education (Figure 2–1). In industrialized countries, participation of older men in the labor force has declined in recent decades. In the United States between 1963 and 2003, the percentage of men ages 62–64 years in the workforce declined from 76% to 50%, and among those 70 and older, from 21% to 12% (Federal Interagency Forum on Aging-Related Statistics 2004). Most of the decline took place before the 1980s, as the youngest age for Social Security eligibility dropped to 62 and older people began to enjoy better incomes. The leveling off of work rates in recent decades has been attributed to elimination of mandatory retirement laws and

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100

High school graduate or higher Bachelor’s degree or higher

Americans age ≥65 (%)

80 60 40 20 0 Total

Figure 2–1. 2003.

Non-Hispanic white alone

Black alone

Asian alone

Hispanic of any race

Educational attainment of Americans age 65 and older,

Source. Adapted from Federal Interagency Forum on Aging-Related Statistics 2004. changes in Social Security policies regarding delayed retirement credits and earned income. Good health, a strong psychological commitment to work, and an active distaste for retirement are among the strongest predictors of continuing to work past traditional retirement ages. Employment trends for women have moved in the opposite direction. Labor force participation rates have increased for older women since the early 1960s, as new cohorts with a history of working outside the home have begun to age. In 2003, 64% of women ages 55–61 years, and 23% of those ages 65–69, were employed. Although people who retire report that they miss the money and opportunities for social contact provided by their everyday work, most take retirement in stride, adopting new routines and activities to take the place of their work. This type of adjustment is particularly likely when retirement is predictable or self-imposed and when postretirement income is adequate. Health problems,

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either physical or mental, usually do not increase in the weeks or months after retirement, and some studies show that retirees have lower stress levels and engage in more healthful behaviors than do similar-age peers who are still employed (Midanik et al. 1995). Because of Social Security and other pension programs, a majority of older people in the United States are financially independent. Persons with medium income now constitute the largest group of older Americans (35%), and 26% have been rated as having high income (Federal Interagency Forum on Aging-Related Statistics 2004). In 2003, Social Security provided 39% of the total income for Americans age 65 and older, with an additional 25% provided by personal earnings, 19% by pensions, and 14% by asset income. The poorest older adults are heavily dependent on Social Security. In 2003, for example, Social Security provided more than 80% of the funds of older Americans in the lowest two-fifths of the income distribution. About 10% of Americans age 65 and older were considered poor by federal guidelines in 2002, compared with 35% in 1959 (Federal Interagency Forum on Aging-Related Statistics 2004). However, elderly women and members of minority groups have more severe financial strain than do older white men. In 2002, 12% of older women lived in poverty, compared with 8% of older men. Twenty-four percent of older black Americans and 21% of older Hispanics had incomes below the poverty line, compared with 8% of older non-Hispanic white Americans.

Marriage and Widowhood The availability of marital relationships in old age differs sharply for women and men. In 2003, 71% of men and 41% of women age 65 and older were married; among those age 85 and older, 59% of men, but only 14% of women, were married (Federal Interagency Forum on Aging-Related Statistics 2004). For those with long-term marriages that continue into old age, satisfaction may increase in later life compared with earlier marital phases, and there may be greater agreement between the partners on important topics such as money management and relationships with children. Many older women live alone in their final years because their husbands have died or because separations are imposed by a spouse’s failing health (Figure 2–2). Because of increased life expectancy, rates of widowhood are

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gradually declining, but this trend is being offset by increasing numbers of divorced and single older persons. Rates of widowhood are similar for Hispanic and non-Hispanic white women but are higher for black women.

Americans age ≥65 (%)

100

With other relatives

Alone

With spouse

With nonrelatives

M W

M W

M W

Total

Non-Hispanic white alone

Black alone

M W

M W

80 60 40 20 0

Asian alone

Hispanic of any race

Figure 2–2. Living arrangements (percentage of population) for men (M) and women (W) age 65 and older, 2003. Source. Adapted from Federal Interagency Forum on Aging-Related Statistics 2004. Older adults respond to bereavement in many different ways. According to a recent prospective study, approximately one-half of new widows or widowers cope with the loss of their spouse with relatively low levels of distress, and what was once considered a typical response to bereavement (i.e., a marked increase in distress following the loss, with abatement over time) is much less common (Bonanno et al. 2004). Normal bereavement generally

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does not produce a loss of self-esteem or inappropriate guilt (see Chapter 3, “Mood Disorders—Diagnosis”), and chronic grief, persisting beyond 1–2 years, is relatively rare. However, men and women with few friends tend to have a harder time adjusting to widowhood.

Extended Families, Friends, and Group Involvement Compared with younger people, elderly individuals tend to have smaller social networks and less frequent interpersonal contacts. However, most older persons are socially active within this smaller arena. Older people rely more heavily than younger adults on family members and long-term friendships for input on important matters. Nearly 80% of older adults have at least one living child, and at least two-thirds report that they have seen their children within the past week (U.S. Senate Special Committee on Aging 1987–1988). Elderly people are also actively involved with their siblings. As individuals realize that they are aging, sibling relationships appear to increase in importance, with sisters playing a particularly active role in maintaining kinship networks. Intimate, confiding relationships may be most valuable to a person’s wellbeing and mental health in old age. About four of five elderly persons report having confidants. When available, spouses are most likely to be listed as confidants, followed by friends, children, and siblings. However, among currently old Americans, women are less likely than men to view their spouse as the main source of social support (Gurung et al. 2003). Among persons age 85 years and older, declining functional ability is the biggest obstacle to continuing old friendships or making new friends. Nonetheless, in one study, more than 50% of the persons at this age reported one or more close friends, and 75% had weekly contact with persons they identified as friends (Johnson and Troll 1994). A recent population-based study in Chicago, Illinois, found smaller social networks and lower levels of social engagement among elderly black persons compared with elderly white persons (Barnes et al. 2004). Being socially involved and depended on by others is important for successful aging. Fulfilling multiple social roles (e.g., worker, spouse, caregiver, and grandparent) has been linked to higher life satisfaction and feelings of self-efficacy for both white and black older Americans. Having a sense of social worth is also important for health and survival. Two recent studies, one in Japan and one in the United States, found reduced rates of death among

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older adults who perceived themselves as useful to others or were involved in giving social support (Brown et al. 2005; Okamato and Tanaka 2004). Increasing numbers of grandparents are now providing custodial care for grandchildren or extensive noncustodial caregiving, especially in black and Hispanic families. About one-half of older Americans attend church regularly, and about one in six are active in volunteering. Religious beliefs may play an especially important role in adaptation for older Americans of African descent, whereas elderly white persons may rely more often on nonreligious social connectedness (Consedine et al. 2004).

Clinical Implications of Social Context Psychiatrists must identify sources of social support for older people, facilitate meaningful contacts for those without social networks, and promote reciprocity in assistance when possible. Intergenerational family therapy can be useful, particularly if it reinforces older patients’ ability to give as well as to receive. Because older women are frequently widowed and may outlive other kin, they are especially likely to find themselves alone in advanced old age. Women may be more adept than men at forming friendships in later life, but this possible strength may be counteracted by physical or sensory disability. For those with very restricted social resources, therapists must sometimes be willing to provide periodic support on a long-term basis. Being needed by others and making contributions to one’s family or society as a whole are important for maintaining a sense of self-worth. Helping older patients to identify meaningful ways to stay involved, despite changes in physical or mental abilities, can be as important as providing opportunities to mourn the loss of past abilities or social roles.

Biological Aging What Is Aging? A useful definition of aging was proposed by Birren and Zarit (1985): “Biological aging, senescing, is the process of change in the organism, which over time lowers the probability of survival and reduces the physiological capacity for self-regulation, repair and adaptation to environmental demands” (p. 9). Modern gerontologists distinguish primary aging, which is postulated to re-

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flect an intrinsic, presumably genetically preprogrammed limit on cellular longevity, from secondary aging, which is due to the accumulated effects of environmental insult, disease, and trauma. Primary aging seems to account for the relatively constant maximum life span observed in almost all animal species studies, whereas secondary aging explains much of the variability among individual members of a species. That primary aging is “built into” the cell was first appreciated by Hayflick and associates (Hayflick 1965; Hayflick and Moorhead 1961) in a series of experiments that established the maximum number of cell divisions (doublings) that would occur in carefully cultured normal human cells at about 50±10. As cultured cells approach this limit, many functional capacities are lost, with the final cessation of cellular reproduction apparently reflecting accumulated functional losses. Evidence that the “Hayflick phenomenon” is under genetic control includes 1) a fair correlation between the doubling limit and the maximum species-specific life span of the cell donor and 2) a reduced doubling limit in cells cultured from patients with genetic diseases of accelerated aging, such as progeria (Hutchinson-Gilford syndrome) and Werner’s syndrome. The observation that cells in culture retain their preprogrammed doubling limit even after being frozen for years suggests that the doubling limit is not related only to total time elapsed. The observed inverse relation between doubling capacity and the age of the cell donor indicates that the limit is not just an in vitro phenomenon; that is, doublings in vivo appear to “count” as well as those that occur in vitro. Similar losses of functional capacity (i.e., cellular aging) have since been observed in all cell types, including those with little or no reproductive capacity, such as neurons. The precise mechanism underlying the observed limits on normal cellular division is not completely known, but several lines of evidence point to telomeric shortening as at least one likely “clock” mechanism. Telomeres are unique protein-DNA structures that make up the terminal region of chromosomes in eukaryotic cells. The telomere section of the chromosome does not contain genetic information; rather, it is composed of repeated stretches of six nucleotides (TTAGGG in vertebrates) that seem to perform a stabilizing or protective function for the end of the chromosome (Hodes 1999). Multiple studies have shown that telomeres shorten with each cell division, and when a certain limit is reached, cellular division no longer occurs and cellular “senescence” has been reached. Evidence that the observed telomeric shortening is a key determi-

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nant of cellular senescence includes 1) the observation that telomerase, a ribonucleoprotein enzyme that mediates RNA-dependent synthesis of telomeric repeats and prevents telomeric shortening, is found in high concentration in germ cells and malignant cells, both of which are “immortal” and do not senesce; and 2) the observation that when the expression of telomerase is induced in normal cells, senescence is delayed significantly. However, telomeric shortening has not been observed in all senescent cell cultures, and “environmental” factors such as oxidative stress, DNA demethylation, and accumulation of DNA cross-links, which can induce “premature senescence” (i.e., failure of cells to divide before the Hayflick limit has been reached), also have been proposed to play a role in normal cellular senescence. Reddel (1998), summarizing this literature, proposed two models of senescence induction that take these and other potential inducers of premature senescence into account. In his models, environmental and intracellular factors operate either on a single clock mechanism, such as telomeric shortening, or on multiple clock mechanisms. In the latter model, senescence is determined by whichever clock mechanism reaches its critical threshold first. Regardless of which model turns out to be best supported by the evidence, it is not at all clear that the failure of cells to continue reproducing can account for all aging changes in the organism per se.

Primary Aging: Structural and Functional Changes The major structural changes in humans that have been attributed to primary aging are listed, by organ system, in Table 2–4, along with the major functional consequences of these changes. Note that cross-sectional studies produced most of the tabulated findings. In addition to the general shortcomings of such studies described earlier, data on the anatomical and physiological effects of age are usually confounded by selection biases (i.e., random samples are rarely used in this type of research) and by the uncontrollable effects of secondary aging.

Aging and the Clinical Process Although psychiatry textbooks and manuals (including this one) are traditionally divided into chapters and sections that cover specific diagnostic entities, a large proportion of elderly patients who present with cognitive, emotional, and behavioral signs and symptoms do not fit cleanly into well-

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defined (DSM-IV-TR) diagnostic categories, and the older the patient, the more this tends to be the case. The ability to initiate treatment on the basis of only provisional diagnostic impressions, to continue to gather information and modify the treatment plan as a clearer picture emerges, and to take agerelated changes in clinical circumstances into account throughout the process is the hallmark of the well-adapted and successful geriatrician. The following case report is typical: Mr. A, an 85-year-old married, retired businessman presenting for an outpatient assessment, tells the clinician, “There’s nothing wrong with me, and I don’t need to be here.” Gentle probing induces Mr. A to admit to mild memory impairment, some loss of appetite and energy, and multiple somatic symptoms, including dry mouth, intermittent urinary retention, chronic pain in several body parts, occasional episodes of dizziness, and occasional constipation. Mr. A’s spouse adds that she has noticed his irritability, chronic worrying, and social withdrawal and an increasing tendency to stay in bed. She goes on to say that he had been working part-time at a company that he started 40 years ago, which is now being run by their son, but was “invited” to stop coming to the office about 6 months ago and has not been back since. Late in the session, she mentions that Mr. A’s brother died a month prior to the clinic visit. Mr. A discounts the importance of both of these events. Mental status examination finds mildly depressed mood, anxiety, shortterm memory impairment that is partially ameliorated by cues, and inconsistent results on assessment of frontal executive functions. Mr. A has chronic moderate hypertension and coronary artery and peptic ulcer disease; he takes daily doses of a statin, two antihypertensive medications (including a βblocker), a proton pump inhibitor, and intermittent hydrocodone bitartrate– acetaminophen preparations, in addition to stool softeners, ginkgo biloba, low-dose aspirin, and vitamin E. By the end of the interaction, it is clear that Mr. A is suffering and that his physical and social functioning have declined, but the clinician’s persistent effort has failed to establish a clear timetable of the onset and progression of any of the symptoms or their temporal relation to losses, other social stressors, or his other illnesses and their treatments. The patient has no history of mental or emotional problems and does not qualify for any DSM-IV-TR diagnosis (outside the not-otherwise-specified categories), and he says, “Doc, if you had my medical problems, if you’d been through what I’ve been through, you wouldn’t be so chipper, either. I don’t need a psychiatrist, and I don’t need treatment for any ‘mental illness.’”

With this “typical” patient in mind, then, a few general principles of diagnosis and treatment are important to keep in mind.

System Cardiovascular Heart

Arteries

Respiratory Lungs Musculoskeletal

Gastrointestinal

Anatomical changes with age

Functional changes with age

Decreased size, flexibility of collagen matrix; Impaired left ventricular diastolic filling, reduced β-adrenergic (i.e., chronotropic and inotropic) lipofuscin and fat deposition in response to catecholamines, leading to decreased peak myocardium; fatty infiltration and exercise cardiac index and ejection fraction (Schulman calcification of aortic and mitral valves 1999) Redistribution and molecular rearrangement Increased systolic blood pressure (cross-linking) of elastin and collagen in arterial walls; calcification Enlarged alveolar ducts and alveoli; loss of Reduced ventilatory capacity, especially during exercise elasticity Same as above Increased chest wall and joint rigidity; increased kyphosis; degeneration and calcification of cartilage Some loss of smooth muscle cells of intestine; Reduced eliminatory efficiency: constipation; reduced metabolism of drugs atrophy of gastric mucosa; increase in gastric pH; some loss of hepatocytes; reduction in hepatic blood flow

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Table 2–4. Primary aging: changes in anatomy and function of major organ systems

Table 2–4. Primary aging: changes in anatomy and function of major organ systems (continued) Anatomical changes with age

Genitourinary

Reduced glomerular filtration rate and renal plasma Loss of renal mass, loss of glomeruli, flow; loss of bladder-emptying capacity thickening of basement membrane of glomeruli and tubules, development of tubular diverticula, intimal thickening of arteries, development of afferent-efferent shunts in juxtamedullary glomeruli, obliteration of arterioles in cortical glomeruli (Davison 1998); reduced bladder elasticity, especially in women; prostate enlargement in men Atrophy and fibrosis; loss of vascularity; General decline in secretory rate, but resting hormone changes may be very minimal blood levels may remain constant as clearance also declines Inconsistent evidence of reduced blood flow; reduced Loss of brain weight and volume in most metabolism of glucose and oxygen; intellectual studies; loss of neurons, depending on changes as described in text (see “Cognitive Abilities brain area studied; loss of dendritic arbor, in Later Life: A Processing Resource Model”) with reduced interneuronal connectivity; interneuronal accumulation of lipofuscin and loss of organelles; neurofibrillary degeneration of neurons; accumulation of senile plaques, especially in hippocampus, amygdala, and frontal cortex

Endocrinological

Nervous

Functional changes with age

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System

Anatomical changes with age

Functional changes with age

Musculoskeletal

Reduced muscle and bone mass; demineralization of bone; increased fat in muscles and calcium in cartilage; degeneration of cartilage; loss of elasticity in joints Involution of thymus; reduced proportion of naïve T cells; increased proportion of activated/memory T cells; decreased expression of interleukin-2 receptors; decreased cellular proliferative response to T-cell receptor stimulation (Ginaldi et al. 1999) Yellowing of lens in eye

Loss of muscular strength and stamina

Immunological

Special senses

Increased susceptibility to cancer

Loss of auditory and visual acuity, especially night vision

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Table 2–4. Primary aging: changes in anatomy and function of major organ systems (continued)

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Diagnostic Process •

•

•

•

Identify “secondary syndromes” first. A growing list of general medical conditions and medications appear to be risk factors for clinically significant depression, and in some cases, appropriate treatment of the general medical condition and/or modification of the medication regimen may be sufficient to ameliorate depressive symptoms. Do not accept bland denial of symptoms. Sometimes the clinician must use several different approaches, with terms that the patient can understand and is comfortable with, before the true picture emerges. Some elderly patients who vehemently deny being depressed will admit to “the dwindles” or will acknowledge loss of interest in usual activities or irritability. Seek information from ancillary sources when possible. Ancillary sources include the spouse, caregiver, board and care home or nursing home sponsor or head nurse, and other physicians. Lack of insight exacerbated by a widespread cultural bias against acknowledging emotional or mental infirmity may render the patient the least reliable informant. Maintain a healthy index of skepticism. If the history does not fit the current clinical picture, the clinician should probe more deeply. Some bipolar patients and their family members “forget” hypomanic episodes, only to “remember” when the patient switches into one: “Oh yes, he was just like this back in 1984!” “Abrupt onset” of significant cognitive impairment sometimes turns out to be merely “abrupt discovery” of a long-developing condition that has been acutely exacerbated by the patient’s anxious response to a relatively minor change in living circumstances.

Therapeutic Process •

•

First, undo harm. Some presenting signs and symptoms may be due to side effects and adverse reactions to over-the-counter and prescription medications used for physical conditions. Replacement with an alternative agent, or dosage adjustment of medications that can provoke, mimic, or exacerbate depressive or anxiety symptoms, may render specific psychopharmacological treatment unnecessary. See Table 2–5 for a list of common offenders. Do not hesitate to treat just because a full syndrome is not present. There is growing recognition of the clinical significance of subsyndromal condi-

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Table 2–5. Medication-induced signs and symptoms of mental disorder Medication

Signs and symptoms

Antihistamines β-Blockers Antiparkinsonian agents Narcotic analgesics Steroids Decongestants, bronchodilators

Sedation, memory impairment Sedation, psychomotor retardation, reduced energy Hallucinations, agitation

•

•

Sedation, impaired attention and concentration Anxiety, emotional lability Sleep disturbance, anxiety

tions in elderly patients, as shown by the emergence of new diagnostic categories such as minor depressive disorder, mild neurocognitive disorder (see Appendix B, “Criteria Sets and Axes Provided for Further Study,” in DSM-IV-TR), and age-associated memory impairment (listed in DSMIV-TR as “780.9 Age-Related Cognitive Decline” in the “Other Conditions That May Be a Focus of Clinical Attention” chapter). Modify psychotherapeutic technique as necessary. Sensory losses may require that the therapist sit closer and speak more loudly and slowly than would be appropriate for middle-aged patients. Amplification devices may be of value; generally, desktop systems offer much greater clarity and resolution than standard hearing aids. Impaired short-term memory may require that the therapist reiterate key points several times and may contribute to learning difficulties that are indistinguishable from resistance and denial. For example, older patients may be more prone to forget appointments and may need reminder calls. Sensory losses and reduced short-term memory also may contribute to a generalized reduction in attention span and decreased capacity for therapeutic work, so sessions may need to be shorter than with younger patients. Musculoskeletal aging may impair mobility and interfere with older patients’ ability to come to appointments, and the role of telephone contact in their care may be expanded. Determine the patient’s baseline physiological and pharmacological status before initiating pharmacotherapy. Usually, the psychiatrist must evaluate hepatic and renal function and the function of any organ or organ system

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that may be adversely affected by medications (e.g., an electrocardiogram should be obtained before initiating therapy with tricyclic antidepressants). A careful review of the list of other medications the patient is taking, or likely to begin taking, is also important because psychotropic medications affect the function of several hepatic microsomal cytochrome P450 enzymes. This effect can cause significant changes in the blood levels of nonpsychotropic and psychotropic medications. Respect age-related pharmacokinetic and pharmacodynamic changes. Of the four major determinants of pharmacokinetics—absorption, distribution, metabolism, and excretion—all but absorption are significantly affected by normal aging changes (Desai 2003). The distribution of drugs in the body is reliably altered by the aging process, primarily as a result of relative loss of body water and lean body mass. Both of these changes result in relatively increased plasma concentrations of drugs that are distributed in body water, such as lithium carbonate, or in lean body mass, such as digoxin (Cusack et al. 1979). Conversely, drugs that deposit in lean body mass and adipose tissue, such as diazepam, are distributed in a larger “apparent volume” (Greenblatt et al. 1980) and will attain somewhat lower plasma concentrations than in a younger patient. Aging is also associated with reduced amounts (in the range of a 20% reduction) of serum albumin, the serum protein most highly “bound” to drugs in plasma. For drugs that are highly albumin bound (i.e., more than 95%), such as furosemide or warfarin, the reduction may free a significantly higher proportion of drug for distribution to its site of action, with resultant greater drug effect. After distribution, most drugs undergo two-phase metabolism in the liver. The first phase is oxidation, reduction, or hydrolysis, reactions catalyzed by enzymes in the microsomal fraction of homogenated liver tissue. The second phase of metabolism is acetylation, or conjugation with glucuronide, sulfate, or glycine; second-phase metabolism usually produces active or inactive water-soluble compounds that are then excreted by the kidney. Although reductions in hepatic blood flow (about 45% between ages 25 and 65), in relative hepatic mass (about one-third), and in hepatic enzyme activity have been seen in elderly individuals, examination of the actual rate of metabolism of drugs in elderly subjects has produced contradictory results, and few generalizations are possible. One

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such generalization is that hepatic conjugation of drugs is relatively spared by age effects; the significance of this sparing with respect to benzodiazepine therapy is shown clearly in Table 7–8 in Chapter 7 (“Anxiety Disorders and Late-Onset Psychosis”). Age effects on renal excretion of drugs have been much more clearly delineated. Reduction in glomerular filtration rate (which generally corresponds to rate of excretion of drugs) of approximately 1% per year between ages 30 and 80 has been documented, as has comparable reduction in renal plasma flow and renal tubular function, including absorption and secretion (Rowe et al. 1976). For drugs that are excreted by the kidney unchanged, such as lithium salts, or that have active water-soluble metabolites, such as desipramine (i.e., 2-OHdesipramine), this reduction may have great clinical significance. For other agents with inactive water-soluble metabolites, this change is less important. When pharmacokinetic factors are constant, increased or decreased effectiveness of drugs can be assumed to reflect pharmacodynamic changes (the actual physiological response produced by a drug at its site of action). Only a few such pharmacodynamic changes have been documented in healthy elderly persons: increased sensitivity to the depressant effects of benzodiazepine anxiolytics and hypnotics on the central nervous system (Greenblatt et al. 1977), increased sensitivity to the effects of warfarin, and decreased sensitivity to the chronotropic effects of isoproterenol. The emerging field of pharmacogenetics, which attempts to understand and predict genetically determined interindividual differences in pharmacokinetic and pharmacodynamic responses to drugs, is likely to produce clinically applicable findings in the near future (Malhotra et al. 2004). The age-related changes in pharmacokinetics and pharmacodynamics cited above are reflected in the following bullet points: •

Respect the treatment setting. Psychopharmacotherapy in the inpatient setting should be conducted much more aggressively than in the outpatient setting. Almost every psychopharmacological agent on the market is most effective at the highest dosage the patient can tolerate, so an approach that reaches that dosage as rapidly as is safe is most appropriate in the inpatient setting, where side effects and adverse reactions can be monitored and managed. In the outpatient setting, the principle of start low, go slow is more appropriate. The clinician should begin with relatively small

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•

•

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doses—for example, one-third to one-half of the usual adult dose. The clinician should proceed slowly when dosage increase is indicated and remain alert for the development of adverse reactions, side effects, and drug interactions. Choose appropriate target symptoms. Failure to identify appropriate target symptoms is a common cause of unsuccessful treatment. Target symptoms may be absolutely inappropriate (e.g., social withdrawal in a depressed patient who is characterologically antisocial, or unhappiness and dissatisfaction in a patient who feels stuck in a bad marriage) or temporally inappropriate (e.g., adjusting antipsychotic therapy to eliminate delusional content while failing to appreciate improved behavior and reduced agitation; the latter are appropriate early indicators of adequate treatment, whereas the former may require months of therapy). Similarly, typical early indicators of response to antidepressants are improvement in sleep, appetite, and anxiety; subjective improvement in mood usually appears later in the course of therapy. In general, global improvement is a suboptimal target of therapy because it is relatively more sensitive to the vicissitudes of daily life, is subject to more interrater variability, and is more influenced by the mood and expectations of a single rater than are more concrete targets such as appetite, sleep, and specific psychological states such as hopelessness, helplessness, and anhedonia. Keep it simple. The apparently widespread practice of “mixing and matching” antidepressants, antipsychotics, and anticonvulsants to achieve just the “right balance” of neurotransmitter activation and inhibition is inadvisable on several counts. First, because these combinations have had essentially no systematic study, every instance of their use is an “n of 1” clinical trial in which the patient is an unwitting subject; and second, such polypharmacy renders the clinical picture unnecessarily complex, making the task of sorting out which symptoms are “primary” and which are side effects or adverse reactions a matter of guesswork. When possible, change one thing at a time. One goal of psychopharmacotherapy is to identify ineffective approaches. Only if treatment is conducted systematically, adequate dosages are prescribed, adequate amounts of time are allowed, and changes are made one at a time is it possible to determine which treatments are ineffective or unnecessary and need no further exploration. For example, in a patient whose symptoms are unre-

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•

•

sponsive to a tricyclic antidepressant, the dose is increased and lithium is added; rapid response follows. Which maneuver is responsible? Is the lithium necessary? Would a higher dose alone have sufficed? Do not use medications only for their side effects. Common violations of this principle include prescribing increasing amounts of neuroleptic medications when sedation is desired, prescribing antihistamines for their hypnotic or anticholinergic side effects, or prescribing antidepressants as hypnotics for nondepressed patients. (A possible exception is the use of trazodone in subantidepressant dosages as a hypnotic. Trazodone is difficult to use as an antidepressant in the elderly because of its sedative effects and its tendency to provoke orthostatic hypotension in antidepressant dosages, but in low [i.e., 50–100 mg] dosages, it is safe and effective as a hypnotic.) Failure to follow this principle with elderly patients increases the risk of adverse reactions caused by overtreatment (e.g., neuroleptic malignant syndrome or anticholinergic delirium). This principle does not discourage selection of an agent when its therapeutic effects and its side effects are both desirable, such as the use of a sedating antidepressant for a depressed patient with sleep disturbance. Beware of undertreatment. The geriatric literature appropriately emphasizes the side effects and adverse reactions that all psychotropic medications can cause. However, most elderly patients are quite sensitive to medication side effects, so a clear signal usually alerts the clinician when the dosage is reaching its ceiling. Such is not the case with undertreatment, when partial response can “freeze” therapeutic response at a suboptimal level. Diagnostic uncertainty or therapeutic timidity on the part of the clinician may lead to these outcomes. A good rule of thumb is to increase dosages until clinical response is clear; if response diminishes or plateaus before complete remission, dosages should be increased again, with the ceiling defined as the development of minor side effects that do not remit over several days. At this point, minor dosage reduction may be appropriate. In this way, the clinician can be reasonably confident that the most effective (i.e., the highest) dosage possible for that patient has been reached. Of course, with agents for which a true therapeutic window exists (possibly including nortriptyline), this approach requires particularly close monitoring of clinical response and determination of serum drug levels when available.

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•

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Beware of inducing withdrawal or overdose. When a patient is hospitalized and his or her “regular dosage” of medication is continued in the hospital, problems may occur. Unreported undermedication or overmedication before admission can render the prescribed dosage much too low or too high. Maintain an optimistic and supportive attitude. This stance is particularly important during the first few days and weeks of therapy, when the ratio of side effects to clinical gain is particularly high. Optimism does not entail or justify unrealistic expectations but helps to maximize the placebo effect, which has been shown to account for about one-half of the efficacy of psychopharmacological agents.

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Royall DR, Palmer R, Chiodo LK, et al: Executive control mediates memory’s association with change in instrumental activities of daily living: the Freedom House Study. J Am Geriatr Soc 53:11–17, 2005 Salthouse TA: The processing-speed theory of adult age differences in cognition. Psychol Rev 103:403–428, 1996 Scarmeas N, Stern Y: Cognitive reserve and lifestyle. J Clin Exp Neuropsychol 25:625– 633, 2003 Schaie KW: Developmental Influences on Adult Intelligence: the Seattle Longitudinal Study. New York, Oxford University Press, 2005 Schneider BA, Pichora-Fuller MK: Implications of perceptual deterioration for cognitive aging research, in Handbook of Aging and Cognition, 2nd Edition. Edited by Craik FIM, Salthouse TA. Mahwah, NJ, Lawrence Erlbaum, 2000, pp 155–219 Schulman SP: Cardiovascular consequences of the aging process. Cardiol Clin 17:35– 49, viii, 1999 Small GW: The Memory Prescription. New York, Hyperion, 2004 Staudinger UM, Pasupathi M: Life-span perspectives on self, personality, and social cognition, in Handbook of Aging and Cognition, 2nd Edition. Edited by Craik FIM, Salthouse TA. Mahwah, NJ, Lawrence Erlbaum, 2000, pp 633–688 Thompson WJL, Dumke HA: Age differences in everyday problem-solving and decision-making effectiveness: a meta-analytic review. Psychol Aging 20:85–99, 2005 U.S. Senate Special Committee on Aging: Aging America—Trends and Projections. Washington, DC, U.S. Department of Health and Human Services, 1987–1988 Uttl B, Van Alstine CL: Rising verbal intelligence scores: implications for research and clinical practice. Psychol Aging 18:616–621, 2003 Verhaeghen P, Marcoen A, Goossens L: Improving memory performance in the aged through mnemonic training: a meta-analytic study [published erratum appears in Psychol Aging 8:338, 1993]. Psychol Aging 7:242–251, 1992 Victoroff J: Central nervous system changes in normal aging, in Kaplan & Sadock’s Comprehensive Textbook of Psychiatry, 7th Edition. Edited by Sadock BJ, Sadock VA. Philadelphia, PA, Lippincott Williams & Wilkins, 2000, pp 3010–3021 Wechsler D: Wechsler Adult Intelligence Scale—III. San Antonio, TX, Psychological Corporation, 1997 Wilder D, Cross P, Chen J, et al: Operating characteristics of brief screens for dementia in a multicultural population. Am J Geriatr Psychiatry 3:96–107, 1995 Winblad R, Palmer K, Kivipelto M, et al: Mild cognitive impairment—beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256:240–246, 2004

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3 Mood Disorders—Diagnosis

Depression is the most common mood disorder in later life. It can have

serious consequences, including “disability, functional decline, diminished quality of life, mortality from comorbid medical conditions or suicide, demands on caregivers, and increased service utilization” (Charney et al. 2003, p. 664). Because of the seriousness of these consequences, geriatric depression has been identified as a major public health problem, yet it is undiagnosed in about 50% of cases (Mulsant and Ganguli 1999). Even when it is recognized, depression in the elderly tends to be undertreated: Steffens and colleagues (2000) found that only 35.7% of elderly patients with major depression were taking an antidepressant; of these, it is likely that a substantial minority were less than optimally compliant with treatment (Katon et al. 1999). Several factors contribute to this suboptimal response by the medical profession, including 1) the “normative fallacy”—that is, the belief that symptoms of depression are “normal” or “expectable” given the patient’s age, social circumstances (including recent losses), and medical condition; 2) the tendency of clinicians to attribute neurovegetative symptoms and signs (such as loss of energy, poor appetite, and disturbed sleep) to concomitant medical problems; 3) the reluctance of many older patients to acknowledge “mental” problems, 67

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which, especially when exacerbated by memory impairment, may force the clinician into an uncomfortable reliance on third parties for historical information; and 4) the complementary tendency of many older patients to express psychic distress in physical terms (Gallo and Rabins 1999), leading to unnecessary, expensive, and sometimes risky diagnostic searches for nonexistent physical conditions. Clinically significant depression takes many forms in the elderly, and the well-defined diagnostic categories recognized in DSM-IV-TR (American Psychiatric Association 2000) may not cover every clinical presentation. Depressive signs and symptoms are commonly seen in normal and complicated grief, are associated with several medical illnesses and medications, present as welldefined “primary” syndromes (including major depression and dysthymia), and occur as features of diagnostic entities that remain under study, such as minor depressive disorder and depressive personality disorder, both listed in Appendix B (“Criteria Sets and Axes Provided for Further Study”) of DSM-IV-TR. The first part of this chapter is organized accordingly. It assumes that the clinician has identified clinically significant symptoms and signs of depression and is attempting to make a definitive diagnosis. The chapter sections comprise a differential diagnosis of depressive features, beginning with “normal” grief and complicated grief, then addressing depression secondary to a general medical condition, next focusing on substance-induced depression, then discussing the primary syndromes of major depression (including some common variations in clinical presentation) and dysthymia, and finally attending to the proposed primary syndromes of minor depression and depressive personality disorder. Subsequent sections tackle laboratory and psychological tests and depression rating scales useful in the diagnostic process, discuss suicidality in the elderly, and provide a brief review of theories of the pathogenesis of depression.

“Normal” Grief (Bereavement) Studies generally concur that uncomplicated grief or bereavement may include any or all of the features of major depression except suicidality, psychosis, severe loss of self-esteem and/or functionality, and psychomotor retardation. Appetite and sleep disturbance, multiple somatic complaints, anhedonia, anxiety, mild feelings of self-deprecation, the passive wish to “join the loved one,” sadness,

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and other dysphoric moods are common but generally less severe than in major depression. Depressed patients are more prone to focus on themselves and their role in the loss and, consequently, are more likely to feel guilt and reduced selfesteem than are nondepressed mourners, who tend to think more of the lost object (Gallagher et al. 1982). One series of studies found that 35% of a group of 109 bereaved widows (average age=61 years) were depressed 1 month after the death of their spouse, but only 17% remained depressed after 13 months. Moreover, the best predictor was depression itself: 75% of those depressed at 13 months were depressed at 1 month (Bornstein et al. 1973; Clayton et al. 1972). In a sample of 133 widows and widowers (average age=70.6 years), only 10% had symptoms that met DSM-III-R (American Psychiatric Association 1987) criteria for major depression 13 months after the death of a spouse, but 14% had symptoms that met criteria at 25 months. In this study, the authors also observed “clinically significant” depressive symptoms in the 86% whose conditions did not meet formal diagnostic criteria (Zisook et al. 1994). In another series of studies, Glick et al. (1974) and Parkes (1965, 1972) discerned the following approximate stages of normal bereavement: 1. The first few weeks after the death of a loved one: During this initial period, numbness, shock, disbelief, and emptiness are often accompanied by intense anxiety, sleep disturbance, and somatic complaints. 2. The first year after the death of a loved one: This is a period of adjustment, during which cognitive and affective “working through” occurs via a process of recollection, fantasy, and rationalization. This phase is completed when acceptance occurs. 3. After the first year postloss: A recovery phase ensues, during which “redefinition” of self without the lost loved one occurs. Although the studies cited earlier did not address the specific circumstances surrounding the onset and course of bereavement, they do suggest that the time course of normal grief in the individual patient is fairly variable and that most patients should be at, or clearly moving toward, baseline status by the end of the first year. But specific circumstances also appear to be important. A study of 217 caregivers of family members with dementia (Schulz et al. 2003) found that 72% of the caregivers reported feeling relief after the death of their loved one. Their scores on the Center for Epidemiologic Stud-

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ies Depression Scale increased about 50% over prebereavement scores immediately after the death but returned to prebereavement levels within 15 weeks; within 1 year, scores were below the levels reported when these persons had been active caregivers.

Complicated Grief A syndrome of complicated grief, which occurs in 10%–20% of bereaved individuals, has been differentiated from both normal grief (bereavement) and clinical depression or anxiety. Proposed diagnostic criteria for this syndrome are shown in Table 3–1. Complicated grief symptoms are clearly distinct from normal bereavement–related depressive and anxiety symptoms and may endure for several years in some cases. These symptoms predict substantial morbidity and adverse health behaviors over and above depressive symptoms (e.g., cardiac events, high blood pressure, cancer, ulcerative colitis, suicidality, social dysfunction, anergia, changes in food, alcohol, and tobacco intake, and global dysfunction) and, unlike depressive symptoms, are not effectively reduced by interpersonal psychotherapy and/or tricyclic antidepressants. These findings revealed a need to identify and treat complicated grief as a psychiatric disorder distinct from major depressive disorder (MDD). (Prigerson and Jacobs 2001, p. 1370)

Depression Due to a General Medical Condition DSM-IV-TR specifies that mood disorder due to a general medical condition must be judged to be the “direct physiological consequence of a general medical condition,” whereas depression that co-occurs with a general medical condition, but is judged not to be a direct physiological consequence of it, is recorded separately on Axis I, and the general medical condition is recorded on Axis III. In the latter situation, the general medical condition may be regarded as a “risk factor,” but in the former, it is considered a “causal factor”; however, clear guidelines for making the distinction are lacking. Accordingly, in this section, we ignore the distinction and consider the conditions most closely associated with depression, regardless of the direction, if any, of causality.

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Table 3–1. Proposed criteria for complicated grief Criterion A Person has experienced the death of a significant other, and response involves 3 of the 4 following symptoms, experienced at least daily or to a marked degree: 1.

Intrusive thoughts about the deceased

2.

Yearning for the deceased

3.

Searching for the deceased

4.

Excessive loneliness since the death

Criterion B In response to the death, at least 4 of the following 8 symptoms are experienced at least daily or to a marked degree: 1.

Purposelessness or feelings of futility about the future

2.

Subjective sense of numbness, detachment, or absence of emotional responsiveness

3.

Difficulty acknowledging the death (e.g., disbelief )

4.

Feeling that life is empty or meaningless

5.

Feeling that part of oneself has died

6.

Shattered worldview (e.g., lost sense of security, trust, control)

7.

Assumes symptoms, or harmful behaviors of, or related to, the deceased person

8.

Excessive irritability, bitterness, or anger related to the death

Criterion C Disturbance must endure for at least 6 months. Criterion D The disturbance causes clinically significant impairment in social, occupational, or other important areas of functioning. Source. Prigerson HG, Jacobs SC: “Caring for Bereaved Patients: ‘All the doctors just suddenly go.’” Journal of the American Medical Association 286:1369–1376, 2001. Copyright © 2001, American Medical Association. All rights reserved.

Chronic Illness Major depression is a common accompaniment of many chronic medical illnesses. Dunlop and colleagues (2004) studied 7,825 subjects ages 54–65 in a national probability sample and found a strong association between chronic

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illness and depression: only 3.6% of the subjects without chronic illness had major depression, but 9.9%–18.5% of the subjects with chronic illness had major depression. Of the conditions studied, which included arthritis, cancer, diabetes, heart disease, hypertension, lung disease, stroke, and obesity, heart disease and arthritis were most often associated with major depression, and the combination of heart disease and arthritis had the strongest association of any combination of two conditions. In the Longitudinal Aging Study Amsterdam (N= 2,288), Bisschop et al. (2004) also found heart disease and arthritis to be most frequently associated with major depression, but the two studies disagreed on the role of functional disability. In the former study, the risk of major depression in both conditions (as well as in all the other conditions studied) was strongly mediated by functional disability, whereas the latter study found no mediating role for functional disability in the association between either cardiac disease or arthritis and depression.

Heart Disease The relation between depression and ischemic heart disease is particularly complex. Depression is a risk factor for myocardial infarction (Ariyo et al. 2000), and major depression occurring in the weeks after a myocardial infarction significantly increases 6- and 18-month mortality (Frasure-Smith et al. 1995). Moreover, patients with ischemic heart disease who are taking serotonin reuptake inhibitors (but not other classes of antidepressants) have a reduced risk of myocardial infarction (Sauer et al. 2001). The mechanism of this protective effect has been hypothesized to be related to the inhibiting effects of selective serotonin reuptake inhibitors on platelet aggregation, which tends to be abnormally increased in patients with ischemic heart disease or depression and even higher in patients with both diseases. This protective effect is robust enough that some authors have proposed that selective serotonin reuptake inhibitors be prescribed for all patients with ischemic heart disease (Jiang and Krishnan 2004). Congestive heart failure is also associated with a high prevalence of depression. Gottlieb et al. (2004) examined 155 patients of average age (64 [±12]) who had a mean left ventricular ejection fraction of 24. Of these patients, 46% had ischemic heart disease, and 38% were diabetic; 48% met study criteria for depression (Beck Depression Inventory [BDI; Beck et al. 1961] score of 10 or higher). Interestingly, the depressed patients were slightly

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younger than the nondepressed patients (average age= 62 vs. 65). The authors concluded that “pharmacologic or non-pharmacologic treatment of depression could conceivably reduce morbidity and, perhaps, mortality” (p. 1548) from congestive heart failure.

Stroke Between 20% and 50% of stroke patients have poststroke depression, with women about twice as likely to be affected as men (Paradiso and Robinson 1998). Of stroke patients have poststroke depression, about half have a major depression–like syndrome that is clinically indistinguishable from primary major depression, and the other half meet criteria for dysthymia (if the duration requirement is waived). Poststroke depression is mediated by functional impairment (Bisschop et al. 2004), and patients with major depression following dominant-hemisphere stroke have more severe cognitive impairment (Robinson et al. 1986) than is seen in stroke without depression. The effect of poststroke depression on long-term prognosis is also negative. House and colleagues (2001) found that major depression within 1 month poststroke was not statistically associated with mortality at 12 and 24 months poststroke, but the presence of depressive symptoms was associated, even after adjusting for other confounding variables such as age and cognitive impairment. L.S. Williams et al. (2004) analyzed a Veterans Affairs database of more than 50,000 stroke patients and found that those who received a diagnosis of depression within 3 years of the stroke were 13% more likely to die during the study period than were those who had no diagnosis of mental illness. Interestingly, this study found a comparable risk of death if mental conditions other than depression, including substance abuse, anxiety disorders, schizophrenia, and personality disorder, were diagnosed within 3 years of the stroke. Despite the well-documented clear association between stroke and depression, a systematic literature review (Hackett et al. 2004) found “no evidence to support the routine use of pharmacotherapeutic or psychotherapeutic treatment for depression after stroke” (p. 1).

Alzheimer’s Disease and Vascular Dementia Although depressive symptoms are commonly seen in patients at various stages of Alzheimer’s disease, major depression per se is relatively uncommon. Ballard et al. (2000) found a 1-month prevalence of 8% (on the basis of

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DSM-III-R criteria), compared with 19% in patients with vascular dementia. In the Alzheimer’s disease group, depression was equally common at all severities, whereas in vascular dementia, depression was more frequent in patients with Mini-Mental State Examination (MMSE) scores lower than 20. Vascular dementia patients with major depression in the month prior to assessment were significantly older, more likely to have a history of depression, and less likely to have experienced a major stroke event than were those without major depression. Lyketsos and colleagues (2000) reported a similar prevalence when the Neuropsychiatric Inventory was used. They found depression in 20% of the subjects with a diagnosis of Alzheimer’s disease, compared with 32% of the participants with vascular dementia. When data for the two groups were combined, the prevalence of depression was not related to stage of progression of dementia.

“Vascular Depression” Alexopoulos and colleagues (1997) have argued for the recognition of a distinct category of depression due to a general medical condition called vascular depression; they have cited the high rate of depression in patients with hypertension, diabetes, and coronary disease, the high rate of depression in patients who have had a stroke, the frequent occurrence of silent stroke and white matter hyperintensities in lateonset depression, and the infrequent family history of mood disorders in depression occurring in the context of silent stroke. (p. 562)

The validity of this syndrome remains controversial. Validity was supported by de Groot and colleagues (2000), who found that elderly subjects with severe white matter lesions (as detected by magnetic resonance imaging of the brain) were three to five times more likely to have depressive symptoms than were those with only mild or no white matter lesions. Mast et al. (2004) also published supportive data. They found that geriatric rehabilitation patients with two or three cardiovascular risk factors had greater depressive symptoms at 6and 18-month follow-up assessments than did patients with only one or no cardiovascular risk factors (Mast et al. 2004). Alexopoulos et al. (1997) compared 33 elderly patients with late-onset vascular depression with a control group of elderly depressed patients without features of vascular disease. The authors found that those patients with vascular depression were more cognitively

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impaired and more disabled, had more psychomotor retardation and less insight, and had less depressed mood than those with nonvascular depression. They hypothesized that disruption by vascular lesions of striato-pallidothalamo-cortical pathways may constitute the pathogenesis of depression in such patients, and they suggested that further research may define a distinctive pharmacological approach to the prevention and treatment of this syndrome. This pathogenetic hypothesis was only partially supported by Thomas et al. (2001), who studied postmortem tissue from 20 elderly patients with a history of depression and 20 with no such history. They found a significant increase in atheroma overall in the depressed group (this increase was mainly a result of the difference in the cerebral arteries and aorta) but found no evidence for increased microvascular disease in the four neocortical lobes or within the deep white matter of the frontal lobe. Other studies have cast doubt on the strength of association between vascular disease and late-onset depression. Stewart and colleagues (2001) examined the association between stroke, vascular risk factors, and depression in a community-based Caribbean-born population ages 55–75 years living in the United Kingdom. In the 287 subjects who were studied, depression (diagnosed with a cutoff score of 3/4 on the 10-item Geriatric Depression Scale [GDS]) was positively associated with a history of stroke but not with other indicators of vascular disease or risk factors for vascular disease. Kim and colleagues (2004) found a similar association between depression (diagnosed with a community version of the Geriatric Mental State Schedule) and previous stroke but not other vascular risk factors (except an atherogenic lipid profile) in 732 Korean subjects whose average age was 72.8. These findings did not change when the small number of subjects who reported onset of depressive episodes before age 60 were eliminated from the analysis. Cervilla and colleagues (2004) studied genetic material from 370 subjects to determine whether polymorphic variation at three genes (APOE, encoding for apolipoprotein E; VLDLR, encoding for the very low-density lipoprotein cholesterol receptor; and DCP1, encoding for angiotensin-converting enzyme) that are related to vascular disease, and other vascular disease risk factors, determined late-life depression. These authors found “no association between late-life depression and three polymorphisms related to vascular disease. Depression was found to be independently associated with smoking, female gender, poorer cognitive functioning, and higher diastolic blood pressure” (p. 202). The

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authors concluded that “this study does not seem to support the notion of a specific link between the studied vascular risk factors or these vascular-related loci and late-life depression” (p. 202), but they did not limit their sample to subjects with late-onset depression. Finally, Devanand and colleagues (2004) found no higher prevalence of cardiovascular disease in elderly patients with late-onset (after age 60) as compared with early-onset major depression (but the prevalence of vascular disease was increased in patients with late-onset dysthymic disorder). In light of these conflicting data, “vascular depression” remains a hypothetical entity at present.

Parkinson’s Disease A similar prevalence of depression (i.e., about 40%) has been observed in patients with Parkinson’s disease, in a similar 50:50 ratio of major depression to dysthymia (Nuti et al. 2004). As in stroke, depression in Parkinson’s disease patients increases the risk for and severity of dementia and exacerbates disability, and so is an important focus of diagnostic and therapeutic attention for geriatric psychiatrists (Tröster et al. 2000). Treatment generally follows guidelines for primary mood disorder as detailed in Chapter 4 (“Mood Disorders— Treatment”).

Substance-Induced Mood Disorder Substance-induced mood disorder is defined in DSM-IV-TR (American Psychiatric Association 2000, p. 409) as “a prominent and persistent disturbance in mood” that is characterized by “depressed mood or markedly diminished interest or pleasure in all, or almost all, activities” and/or “elevated, expansive, or irritable mood” along with “evidence from the history, physical examination, or laboratory findings” that the symptoms “developed during, or within a month of, Substance Intoxication or Withdrawal” or that “medication use is etiologically related to the disturbance [in mood].” Substance-induced mood disorder may not be diagnosed if depressive symptoms occur exclusively during the course of a delirium. Diagnostic criteria further require that the depression not be better accounted for by a non-substance-induced mood disorder and that “the symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.”

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Two broad categories of substances can be distinguished in this context. The first comprises substances with primarily psychoactive properties that are prone to abuse and can become addictive. This category includes alcohol; opiates and related compounds such as ketamine; barbiturates; benzodiazepines and other central nervous system depressants; stimulants, including amphetamines; cocaine and related compounds such as methylenedioxymethamphetamine (MDMA; “Ecstasy”); phencyclidine (PCP); marijuana and hashish; hallucinogens such as lysergic acid diethylamide (LSD) and mescaline; inhalants; and miscellaneous substances such as γ-hydroxybutyrate (GHB). The second category comprises substances whose psychoactive properties are incidental to their main therapeutic effects. This category includes numerous medications used for acute and chronic nonpsychiatric conditions. With regard to psychoactive substance–induced depression, Bakken and colleagues (2003) found that 48% of 241 substance abusers (age unspecified) studied at some time in their lives had experienced a substance-induced major depression, and 41% had experienced at least one episode of dysthymia; the great majority of subjects had also had non-substance-induced mental disorders. Comparable estimates for nonpsychoactive substances have not been published, but case histories have implicated all of the substances listed in Table 3–2. The critical diagnostic procedure is a careful drug ingestion history, along with detailed assessment of mood symptoms. A depressive syndrome that begins within a month of commencing regular ingestion of any of the medications listed in Table 3–2 is adequate presumptive evidence to justify dosage adjustment or discontinuation, when medically feasible, of the suspected agent. A 75-year-old woman with no history of mood disorder denied symptoms of depression but admitted to experiencing “waves of doom” coming over her and fearfully described “crazy” thoughts of suicide, both feelings she had never experienced before. She had lost almost 20 pounds in the preceding 4– 6 weeks and came to psychiatric attention when her dermatologist found her “weeping in his waiting room.” Careful questioning determined that the β-blocker nadolol had been prescribed for a minor cardiac dysrhythmia about 3 weeks before the onset of symptoms. All symptoms disappeared with no specific treatment within 1 week of discontinuing the medication.

Interestingly, Ko and colleagues (2002) conducted a meta-analysis of 42 selected articles and found no association between β-blocker therapy and

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Table 3–2. Medications that can cause symptoms of depression Analgesics Narcotics, including synthetics Codeine Meperidine Nonsteroidal anti-inflammatory agents (ibuprofen, indomethacin, naproxen) Antiepileptic agents Antihypertensive agents Acetazolamide Calcium channel blockers (e.g., diltiazem, flunarizine, nicardipine, nifedipine, nimodipine, verapamil) Clonidine Guanethidine Methyldopa Propranolol and related β-blockersa Reserpine Thiazide diuretics Antipsychotic agents, including Phenothiazines (e.g., chlorpromazine, fluphenazine, thioridazine, thiothixene) Haloperidol Molindone Anxiolytic agents, including Alcohol Benzodiazepines Cancer chemotherapeutic agents L-Asparaginase

Dactinomycin Cisplatin Cycloserine Mitotane Dacarbazine

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Table 3–2. Medications that can cause symptoms of depression (continued) Cancer chemotherapeutic agents (continued) Nitrogen mustard Procarbazine Tamoxifen Vinblastine Vincristine Sedative-hypnotics, including Barbiturates Ethchlorvynol Glutethimide Methyprylon Miscellaneous Asparaginase Baclofen Cimetidine Dexamethasone Digoxin Disulfiram Isotretinoin Levodopa Levonorgestrel implant Mefloquine Methysergide Metoclopramide Metronidazole Oral contraceptives Prednisone Ranitidine hydrochloride Steroids aRelatively

common offenders in the authors’ experience.

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depressive symptoms. However, the studies analyzed had few elderly subjects, and in almost every study the method of assessing depressive symptoms was not specified. As the preceding case illustrates, merely asking elderly patients about “depression” may elicit misleading responses.

Major Depression Epidemiology Major depression, as defined in DSM-IV-TR, is the most serious presentation of primary mood disorder in the elderly. The prevalence of major depression in the elderly has varied in large-scale studies from 1%–2% (Heithoff 1995) to 3.7% (Steffens et al. 2000), and the prevalence appears to increase with age; one study of subjects (average age=85) found a community prevalence of 4% (Forsell and Winblad 1999). Depression accounts for more than 60% of admissions to geriatric psychiatry units and is present in about 30% of elderly patients with acute and chronic medical illnesses (Okimoto et al. 1982) and in about 15% of nursing home residents (Falck et al. 1999).

Risk Factors As discussed in earlier sections, chronic illness in general, a few specific illnesses, and exposure to certain substances are clear risk factors for the onset of major depression in the elderly. The role of stressful life events as precipitants of major depression has been studied by several groups, although none has focused on elderly patients per se. Kendler et al. (2003) studied 98,592 person-months in 7,322 male and female twin pairs and found that the baseline risk per month for the onset of an episode of major depression was 0.6%. Of the stressful life events studied (which were categorized as loss, humiliation, entrapment, and danger), only loss and humiliation events were statistically significantly associated with onset of major depression in the month of occurrence. Loss included death, respondent-initiated separation, and other key losses, whereas humiliation included only other-initiated separation. Because old age is a time of loss, less so of other-initiated separation, loss events likely play an increasingly significant role in the provocation of major depression in the elderly.

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Diagnostic Criteria The diagnosis of major depression in an elderly person begins with a detailed history of the present illness, focusing on relatively abrupt changes in one or more neurovegetative functions. For example, the patient may report that his or her usual pattern of unsatisfactory sleep became noticeably worse around the time that feelings of hopelessness and apathy were first experienced. Similarly, the gradual decline in activity and appetite that had been occurring for quite a while also may have been abruptly accelerated around the same time. Informants such as a spouse or a child, a board and care home operator, or the family physician can be invaluable in establishing the timing of these changes (Wiener et al. 1997). DSM-IV-TR criteria for major depressive episode are summarized in Table 3–3. Major depression affects the elderly in many of the same ways that it affects young adults. Nelson et al. (2005) analyzed data from 728 elderly subjects with nonpsychotic major depression and found that depressed mood, loss of interest in work and activities, psychic anxiety, somatic anxiety, lack of energy, guilt, middle and late insomnia, and suicidal ideation best described the presentation of depression in their subjects and were the symptoms most sensitive to change during treatment with either sertraline or placebo. Brodaty et al. (1997) reported that diminished self-esteem and guilt were less common in older depressed patients (i.e., 60 or older), but these patients had more severe depression (higher Hamilton Rating Scale for Depression [HamD] scores), more appetite loss and weight loss, and higher rates of psychotic and melancholic depression. Caine et al. (1994) reviewed the literature and concluded that “medical illness emerges consistently as the most common clinical feature associated with depressive symptoms and diagnoses in community, outpatient, and inpatient samples” (p. 38). Still, accurate detection of major depression in old age can be challenging because several features of normal aging overlap with complaints of depression. Table 3–4 lists the most troublesome of these normal aging changes. Signs and symptoms associated with normal and complicated bereavement can also complicate diagnosis. Finally, recognition and diagnosis of major depression may be complicated by variable presentation of illness, as discussed in the following subsection.

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Table 3–3. Summary of DSM-IV-TR criteria for major depressive episode A.

Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one is either (1) depressed mood or (2) loss of interest or pleasure. (1) depressed mood most of the day, nearly every day (2) markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (3) significant weight loss when not dieting or weight gain, or decrease or increase in appetite nearly every day (4) insomnia or hypersomnia nearly every day (5) psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down) (6) fatigue or loss of energy nearly every day (7) feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick) (8) diminished ability to think or concentrate, or indecisiveness, nearly every day (9) recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

B.

The symptoms do not meet criteria for a mixed episode.

C.

The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

D. The symptoms are not due to the direct physiological effects of a substance or a general medical condition. E.

The symptoms are not better accounted for by bereavement, i.e., after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.

Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000, p. 356. Copyright © 2000, American Psychiatric Association. Used with permission.

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Table 3–4. Functional complaints common to elderly persons Complaint

Comment

Sleep disturbance

Reduced total sleep time Increased sleep latency More frequent awakenings More time spent in bed Reduced sleep efficiency

Reduced appetite

Reduced energy expenditure Reduced activity Exacerbated by diminished taste and olfactory sensation, poor dentition, or unappealing diet

Reduced energy, fatigue

Exacerbated by chronic illness, especially obstructive lung disease and heart failure Also exacerbated by β-blockers, clonidine, α-methyldopa, anticonvulsants, and benzodiazepines

Impaired concentration and memory

Normal forgetfulness may be experienced as a symptom Exacerbated by sensory losses, especially diminished vision and hearing Exacerbated by medications with central anticholinergic effects

Variations in Clinical Presentation Late Versus Early Onset Devanand et al. (2004) studied 211 patients (average age=70) who had received diagnoses of major depression. When they used a cutoff of first episode of major depressive disorder after age 60, they found that late-onset major depressive disorder was less severe (based on the 24-item Ham-D scores) and less frequently associated with melancholia (31% vs. 50%) than was early-onset major depressive disorder and that fewer than half as many late-onset patients as early-onset patients reported a family history of mood disorder. Age, burden of medical illness (according to the Cumulative Illness Rating Scale), and presence of cardiovascular illness did not differentiate the early- from the late-onset cases. Psychotic Depression Psychotic features (delusions or hallucinations or both) occur in about 25% of elderly patients with major depression, and in one large epidemiological survey

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(N=18,980), subjects who reported feelings of worthlessness or guilt were the most likely to have psychotic features (Ohayon and Schatzberg 2002). Most studies find that depressive symptoms are more severe in patients with psychotic features than in those without psychosis, but suicide attempts are probably not more frequent (Lykouras et al. 2002). Identification of psychotic depression as a mood disorder is relatively straightforward when symptoms occur in the classic sequence; that is, when mood and neurovegetative changes occur before the development of hallucinations, delusions, and bizarre behavior. The clinician’s task is rendered easier still when typical depressive delusions (i.e., moodcongruent delusions) are present or when the patient has a history of mood disorder. More challenging are patients in whom the presenting complaint, often registered by family members, is of a persecutory delusion accompanied by prominent behavior disturbance. The following cases are illustrative: A 76-year-old woman changed apartments because she believed that her neighbors were aware of her responsibility for the president’s “losing his veto power,” which was going to lead to a “communist takeover.” The delusion had emerged in the course of a series of unsatisfactory transactions with an air conditioner repairman who had told the patient that, lacking proper parts, he would attempt to jerry-rig something for her. By the time she was hospitalized, her thinking was extremely disorganized, and the term jerry-rigged had acquired magical significance; she attributed her failure to grasp its meaning as being directly responsible for the president’s downfall. Several days of treatment with high-potency neuroleptics were required before the patient was able to give the history of change in mood, loss of appetite and weight, and anhedonia that accompanied and, to some extent, preceded the onset of her delusion. She responded very well to treatment for depression. A 72-year-old woman was an ongoing problem for neighbors and police because she was convinced that men were following her and wanted to put her in a “car with a large dog that would attack and kill” her. Although neuroleptics partially controlled her fear and her bizarre behavior, her symptoms were not completely ameliorated until antidepressant treatment was initiated, at which time her mood also greatly improved.

Accurate diagnosis is also impeded when patients cannot or will not report hallucinations or express the content of delusions and when the presence of hallucinations or delusions must be inferred from bizarre behavior or severe thought disorder. Near-catatonic behavioral withdrawal is one such particu-

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larly common type of bizarre behavior and is often accompanied by refusal to eat, to maintain personal grooming, or to take medications. In the absence of a history of psychosis, late-life presentation of this syndrome should be regarded as psychotic depression until proven otherwise. Masked Depression The literature has long reflected awareness by clinicians that depression in the elderly can be masked by physical complaints (Kielholz 1973). In the classic version of this presentation, subjective complaints of mood changes per se are replaced or masked by multiple somatic complaints. In the course of medical diagnosis and treatment, these complaints are found to be either unaccompanied by anatomical or physiological abnormalities or out of proportion to the severity of these abnormalities. The prevalence of this syndrome in the elderly is not known. One study (Posse and Hallstrom 1998) found that major depression presented as somatic complaints in 13 (14%) of 93 mixed-age primary care patients, and it is likely that this proportion is higher in elderly patients. Identification of this syndrome is particularly difficult when it occurs in patients with somatic complaints that are associated with clear physical causes. DSM-IV-TR criteria are usually adequate to diagnose such presentations, but the clinician must be particularly sensitive to objective indicators of depressed mood and must investigate carefully to discern associated neurovegetative features of major depression. A relatively sharp increase in the number and severity of physical complaints at or around the time of onset of neurovegetative signs, or the occurrence of physical symptoms that are illogical or that are temporally linked to social stressors (e.g., losses) typically associated with mood changes, can alert the clinician to the possibility of “underlying” major depression. A perhaps more common version of this syndrome presents with a similar acute exacerbation of physical complaints accompanied by significant psychological distress (e.g., complaints of depression and anxiety). In this presentation, the depressive syndrome is only partially masked by the patient’s insistence that the psychological distress is “because of ” the physical complaints (Simon and VonKorff 1991). A 90-year-old woman complained of her “arms and legs twisting,” along with a feeling of “buzzing” from the top of her head radiating into her chest, abdomen, arms, and hands. She insisted that the symptoms reflected a “heart

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attack” and made frequent unproductive visits to her local emergency department. Careful interviewing found that the onset of these symptoms was associated with marital conflict, and exacerbation tended to occur when marital tensions escalated. Over the long run, she responded well to psychotherapy but refused antidepressants. She eventually gained a modest degree of insight into the functional nature of her complaints.

The variant of major depression depicted in this case differs from somatization disorder with depressed mood in 1) the number of physical symptoms, which is typically as high as 20 or more in somatization disorder; 2) the history, which is typically much more chronic and unremitting in somatization disorder; and 3) the presence of neurovegetative features of depression, which are typically not present in somatization disorder. Elderly patients with masked depression may vary considerably in their hypochondriacal preoccupation with physical symptoms. At one extreme, they may be simultaneously disabled by but relatively indifferent to their symptoms, whereas at the other extreme, they may have a near-delusional conviction that symptoms reflect life-threatening illness, along with appropriate levels of psychic distress, and may make a lifestyle of doctor and diagnostic procedure shopping. Unfortunately, available data do not support precise criteria for establishing the diagnosis of masked depression. Indeed, Bschor (2002) has argued that the concept of masked depression has been “abandoned” and replaced with “somatization disorder, somatoform disorder, psychosomatic disorder, conversion disorder, neurasthenia or hypochondriasis” (p. 207). He cites the expansion of that diagnosis onto a vast number of disorders, the continuing lack of clarity of the concept (disorder of recognition vs. disorder of communication; the positive proof of psychic symptoms as a prerequisite vs. the positive proof of psychic symptoms as an exclusion criterion for that diagnosis)…and the introduction of DSM-III and ICD-10 as operationalized, purely descriptive and rather theory-free systems of diagnostic classification (p. 207)

as reasons for its disappearance. Unfortunately, some patients still present with multiple somatic complaints that do not meet criteria for any of the disorders listed by Bschor and that dramatically melt away with appropriate antidepressant treatment. We believe that a reasonable diagnostic approach is to use DSM-IV-TR criteria (American Psychiatric Association 2000) for major depressive episode, modifying criterion A as follows:

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Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood; (2) loss of interest or pleasure (p. 356); or (3) persistent physical symptoms that do not meet DSM-IV-TR criteria for any somatoform or other disorder, cannot be explained by structural or functional pathology, or have a distinctly bizarre or unusual quality that is not consistent with any known medical diagnosis. (italicized text added by authors)

Depression With Cognitive Impairment A substantial proportion of elderly individuals with depression have concurrent cognitive impairment, particularly in visuospatial ability, psychomotor speed, and executive functioning. Moreover, executive deficits in particular may be strongly associated with late-onset depression and vegetative symptoms (Butters et al. 2000). Depression with functionally significant cognitive impairment, sometimes known as depressive pseudodementia or the dementia syndrome of depression (DSD), is distinguished from the milder, clinically silent cognitive impairment associated with depression that may be detected by neuropsychological testing. The prevalence of the former syndrome is not well established and depends on where one draws the line defining functional impairment. One study of hospitalized depressed elderly patients (La Rue et al. 1986) found that 12 of 55 scored below 23 on the MMSE, suggesting functionally significant cognitive impairment. Milder cognitive impairment is much more common and tends to be positively correlated with the severity of depressive symptoms. Differentiating DSD from early dementia of the Alzheimer’s or vascular type can be quite difficult. Patients with DSD often score in the moderately impaired range on cognitive mental status examinations (e.g., 15– 22 on the MMSE) and may perform poorly on more detailed intellectual and memory testing. Minor functional deficits, such as forgetting staff names or repetitive asking of questions, also may be observed. Patients with DSD may show poor grooming, slumped posture, and poor eye contact and may appear to exaggerate or dramatize their cognitive deficits on mental status examination. However, they typically do not have grossly disordered behavior, such as attempting to eat pencils, placing underwear over outerwear, climbing into other patients’ beds, or picking at their clothing. When severely disturbed behavior of this type is seen in a patient who otherwise meets criteria for a mood

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disorder, the presence of underlying organic brain disease or superimposed delirium must be ruled out. Table 3–5 lists features that can help differentiate DSD from organic dementia in troublesome cases. Because these guidelines have not been validated by prospective investigation, they should be applied cautiously. Often, it may be necessary to observe response to treatment before forming a firm opinion about the presence of DSD. In our own work in this area, we found that elderly depressed patients with functionally significant cognitive impairment responded as well to antidepressant therapy as did those without cognitive impairment. However, a lengthier and more aggressive course of treatment was required to achieve equivalent improvement (La Rue et al. 1986). Kalayam and Alexopoulos (1999) found that psychomotor retardation and deficits in initiation-perseveration predicted poorer response to treatment in elderly depressed patients, and Alexopoulos et al. (2000) found that executive dysfunction (including abnormal initiation and perseveration scores), but not memory impairment, was associated with relapse and recurrence of geriatric depression. However, Butters and colleagues (2004) failed to replicate the latter finding in a later study with a larger series of subjects. The relation between late-life depression, with or without DSD, and the subsequent development of dementia and Alzheimer’s disease remains unclear. One study found that a substantial proportion of patients with DSD progressed to a more profound dementia within a few years (Kral and Emery 1989), and several other studies have reported that depression per se is a risk factor for the development of dementia. Two studies conducted in the Netherlands found that depression in older patients that was not accompanied by significant cognitive impairment at baseline predicted cognitive decline (defined as a decline of 3 or more points on the MMSE) and the development of Alzheimer’s disease at follow-up an average of 3.2 years later, but only in subjects with more than 8 years of education. The authors interpreted the findings to support the notion that depression is “a subclinical expression or an early symptom of an underlying dementia process, which may become apparent in a subgroup of more highly educated older people in whom commonly used mental status tests do not yet detect a decline from a previous level of cognitive functioning” (Geerlings et al. 2000, p. 574). Support for this hypothesis was provided by Wilson et al. (2002), who studied Catholic clergymen over a 7-year period and found that scores on a modified, 10-item

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Table 3–5. Differences between depression with cognitive impairment and dementia Depression with cognitive impairment

Dementia

Clinical course and history Onset fairly well demarcated

Onset indistinct

History short

History quite long before consultation

Course rapidly progressive

Early deficits often go unnoticed

History of psychiatric difficulty or recent life crisis

History of psychiatric problem or emotional crisis uncommon

Clinical behavior Detailed complaints of cognitive loss

Few complaints of cognitive loss

Distress caused by cognitive problems

Varied reaction to cognitive loss

Behavior does not reflect cognitive loss

Behavior compatible with cognitive loss

Persistent mood disorder

Mood apathetic or environmentally responsive

Nocturnal exacerbation rare

Nocturnal exacerbation common

Mood-congruent delusions

Mood-incongruent delusions Examination findings

Patients expend little effort during examination

Patients commonly struggle to perform cognitive tasks

Patients frequently answer, “I don’t know” Patients usually make an effort to answer questions Memory loss is inconsistent for recent and Memory impairments are greater for remote events recent than for remote events Patients may have specific memory gaps

Patients do not have specific memory gaps

Inconsistent performance across similar types of tasks

Consistently impaired performance on tasks of a particular ability

Prompting and semantic organization are helpful in improving recall

Prompting and semantic organization have limited benefit

Recognition memory is relatively intact

Recognition memory is impaired; there may be false-positive errors

Source. Adapted from Strub and Black 1988; Kaszniak and Christenson 1994.

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Center for Epidemiologic Studies Depression Scale were associated with both the risk of developing Alzheimer’s disease and the rate of cognitive decline. For each depressive symptom, the risk of developing Alzheimer’s disease increased by an average of 19%, and annual decline on a global cognitive measure increased by an average of 24%. Anorexia A less common presentation of depression in the elderly is profound anorexia, which may occur in the absence of any other neurovegetative features of depression and in the presence of what otherwise appear to be normal mood and affect. This form of depression seems to occur mainly in the old-old and is often accompanied by multiple chronic, often “end-stage,” medical illnesses. It can be thought of as the “anorexia of aging” (Morley 2001), severely exacerbated by concomitant mood disorder, and is classified here as a form of major depression mainly because of its severity. The typical clinical picture is of a visibly aged, deteriorated, dysphoric patient who has “given up” and, by refusing to eat, appears to be committing passive suicide. Hospitalization of such patients may be complicated by passive refusal of treatment and family discord around the issue of the patient’s “right to quit”; similar ambivalence is not uncommon among treatment staff, who may be prone to engage in prolonged discussion of the appropriateness of hospitalization, the quality of life required to warrant aggressive treatment, and so forth. In some patients, particularly those from non-Western cultures, this clinical picture is interpreted by friends and family as an indication of the patient’s wish to die, and the rendering of treatment aimed at restoring appetite is regarded as an insult to the elderly patient. These and similar considerations notwithstanding, a reasonable proportion of patients in this category respond to antidepressant treatment with restoration of normal appetite, weight gain, and the emergence of a new will to live. Behavioral Regression Major depression in the elderly occasionally presents with a picture of behavioral regression. The patient gradually becomes less physically and socially active, neglects personal hygiene and necessary medical treatment, loses contact with friends and family, allows the home environment to become disordered and filthy, and discontinues shopping and begins living off canned or other-

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wise easily obtained food. On mental status examination, subjective change in mood and anhedonia may be denied, and objective signs of depression may be minimal. Dementia is commonly suspected in such individuals, and mental status examination may indicate some of the features described in patients with DSD. As with anorexia, response to antidepressant medications may be dramatic.

Dysthymic Disorder Dysthymic disorder in adults as described in DSM-IV-TR is a chronic depression of mood (for at least 2 years) that is variably accompanied by associated symptoms of appetite disturbance, sleep disturbance, low energy or fatigue, low self-esteem, poor concentration or difficulty making decisions, and feelings of hopelessness. It occurs in about 1.8% of elderly individuals during any given month. Dysthymic disorder is similar to but less severe and more chronic than major depression and has a somewhat earlier onset in elderly individuals. The average age of onset of dysthymic disorder in 68 subjects over age 55 was 31, while the average age of onset of major depression in 61 subjects over age 55 was 53 (Beekman et al. 2004). Dysthymic disorder may be preceded by an Axis I (nonmood) or Axis III disorder (“secondary dysthymia”), may occur as an isolated syndrome (“primary dysthymia”), or may present as “double depression” (i.e., with major depressive disorder superimposed on dysthymic disorder). Kirby and colleagues (1999) studied 40 dysthymic individuals (average age= 74.4) and found a relatively low rate (15%) of comorbid Axis I disorder (3 with generalized anxiety, 3 with agoraphobia without panic) and a high prevalence of hopelessness: 47.5% felt that life was not worth living, 17.5% expressed a death wish, and 7.5% had suicidal ideation. Overall, the prevalence of dysthymic disorder, like major depressive disorder, appears to decline with age (Beekman et al. 2004); it is more common in women, although the difference declines with age, and almost half of elderly patients with dysthymic disorder have a history of major depressive disorder. This figure increases to 80% if the presenting illness is “double depression.” The risk of developing dysthymic disorder appears to be related to environmental factors (e.g., relative lack of social and emotional support, history of traumatic events) and personal vulnerability factors (e.g., female sex,

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family history). Age at onset also may be important; Devanand et al. (2004) found that elderly patients with late-onset (i.e., after age 60) dysthymic disorder were more likely to have cardiovascular disease and less likely to have comorbid anxiety disorder than were those with early-onset dysthymia, but the two groups were similar otherwise. One potential cause of a dysthymia-like syndrome is partial treatment of major depression, either with anxiolytics alone or with inadequate doses of antidepressants, resulting in amelioration of enough signs and symptoms as to no longer qualify as major depression. This condition is properly termed major depressive disorder, in partial remission (American Psychiatric Association 2000), and is usually identifiable with an accurate treatment history.

Minor Depression The importance of minor or “subthreshold” depression (i.e., depression that causes clinically significant distress or impairment in social, occupational, or other functioning but does not meet criteria for major depression or dysthymia) has been recognized at least since 1980, when Blazer and Williams found that 14.7% of a community sample of subjects age 65 or older had “substantial depressive symptoms” but only 3.7% met DSM-III (American Psychiatric Association 1980) criteria for major depression (Blazer and Williams 1980). Interest in subthreshold depression was further stimulated by the Epidemiologic Catchment Area studies (Regier et al. 1988), which confirmed Blazer and Williams’s findings of low prevalence of major depression in this age group. These findings challenged geriatric psychiatrists to reconcile their clinical impressions of a relatively high prevalence of mood disturbance among the elderly with the scientific fact that major depression and dysthymia were actually less prevalent among the elderly than among young and middle-aged persons. The relatively high prevalence of what has come to be known by many investigators as minor depression, based on criteria presented in Appendix B to DSM-IV-TR (“Criteria Sets and Axes Provided for Further Study”), seems to resolve this apparent contradiction. These criteria are presented in Table 3–6. Beekman and colleagues (1997) found that minor depression, unlike major depression, was closely associated with physical illness in elderly subjects.

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However, it also was associated with as much disability (e.g., affecting general functioning as well as specific functions such as housekeeping, socializing, and exercising) as major depression was, even after controlling for the effects of chronic physical illness. Minor depression also was associated with a significant (but less than in major depression) reduction in the subjective sense of well-being, which was independent of general health status and, in a later study, was associated with an increased risk of dying (1.80 times the risk to nondepressed control subjects) (Penninx et al. 1999). A 10-year longitudinal study of 131 elderly individuals with minor depression (defined by Center for Epidemiologic Studies Depression Scale scores) found chronic illness to be a significant risk factor for minor depression: the co-occurrence of just two diseases doubled the risk for minor depression, when compared with persons with no diseases or just one chronic disease. Functional decline also appeared as a highly significant risk factor, especially deteriorating eyesight: people with poorer than average visual acuity had more than twice as high a risk for minor depression as did those with better than average eyesight. This study (Heikkinen and Kauppinen 2004) also found that people who had difficulties in the use of public transport had three times the risk of minor depression compared with those with no such difficulties. The authors concluded that “minor depression among the elderly is most typically a dynamic and episodic phenomenon. Adverse life-events such as the loss of a spouse or some other close person had predictive value for depressive symptoms in our study. We also found the same impact from deteriorating health, deteriorating financial situation and increased loneliness” (p. 248). Psychotic features also have been reported in subsyndromal depression. Ohayon and Schatzberg (2002) investigated the associations between depressive symptoms and psychotic features in a sample of 18,980 subjects in five European countries and found that as many as 10% of the subjects with just two depressive symptoms (with or without a diagnosis of major depressive episode) had psychotic features. Other studies have generally confirmed these findings, and in a review of this topic, Pincus and colleagues (1999) proposed that “subthreshold” categories for all of the major phenomenological groups of DSM-IV-TR might serve as more precise and more useful categories than the current “adjustment disorder.”

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Table 3–6. Summary of DSM-IV-TR research criteria for minor depressive disorder A.

A mood disturbance, defined as follows: (1) At least two (but less than five) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (a) or (b): (a) depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful) (b) markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others) (c) significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day (d) insomnia or hypersomnia nearly every day (e) psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down) (f ) fatigue or loss of energy nearly every day (g) feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick) (h) diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others) (i)

recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

(2) The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. (3) The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism). (4) The symptoms are not better accounted for by bereavement (i.e., a normal reaction to the death of a loved one). B.

There has never been a major depressive episode and criteria are not met for dysthymic disorder.

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Table 3–6. Summary of DSM-IV-TR research criteria for minor depressive disorder (continued) C.

There has never been a manic episode, a mixed episode, or a hypomanic episode and criteria are not met for cyclothymic disorder. Note: This exclusion does not apply if all of the manic-, mixed-, or hypomanic-like episodes are substance or treatment induced.

D. The mood disturbance does not occur exclusively during schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, or psychotic disorder not otherwise specified. Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

Depressive Personality Disorder As defined in DSM-IV-TR, the essential feature of depressive personality disorder is “a pervasive pattern of depressive cognitions and behaviors that begins by early adulthood and that occurs in a variety of contexts” (American Psychiatric Association 2000, p. 788). Elderly patients with depressive personality disorder also may have episodes meeting criteria for more specific mood disorders, such as dysthymic disorder or major or minor depression, but even between such episodes, these patients are dejected, discouraged, and hopeless. A perhaps less stable but persistent variant of this condition is commonly seen as a complication of other personality disorders, including narcissistic, borderline, avoidant, and dependent personality disorder. The difficulty that patients with these personality disorders typically have in establishing and maintaining interpersonal relationships seems to catch up with them late in life, when they are forced to confront the loneliness and isolation that their personality problems have caused.

Laboratory Evaluation of Depression Laboratory evaluation of the elderly patient with clinically significant depression is aimed at ruling out endogenous etiological or contributing factors, such as hypothyroidism and adrenal insufficiency, and establishing the pretreatment baseline status of physiological systems likely to be affected by psychoactive med-

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ications. A recommended battery of tests with their potential uses is listed in Table 3–7. Several laboratory procedures have been reported to be useful in establishing or ruling out a diagnosis of major depression. These include the dexamethasone suppression test (DST), the thyrotropin-releasing hormone (TRH) test, and the sleep electroencephalogram. Unfortunately, the rates of false-positive and false-negative results for both the DST and the TRH test are quite high in elderly patients. Moreover, the diagnostic confidence associated with these tests depends on the underlying base rate (i.e., prevalence) of major depression in the population being studied, which is typically quite variable, so neither test is recommended for routine clinical purposes. Similarly, although the sleep electroencephalogram is acceptably reliable—typically indicating an increased proportion of rapid eye movement (REM) sleep (Beck et al. 1974), a longer first REM sleep period, a shorter REM sleep latency (period of non-REM sleep before the first REM episode), and an increased density of phasic eye movements in elderly depressed patients compared with nondepressed age-matched control subjects (Reynolds et al. 1988)—it has not been shown to increase diagnostic accuracy beyond that of the clinical evaluation alone and is too expensive to be of widespread clinical use.

Psychological Tests Table 3–8 lists some of the psychological assessment procedures that may be useful in older patients whose depressive symptoms are complicated or unclear. Psychodiagnostic tests document current mood, thought patterns, and social tendencies and can suggest personality features that may affect the presentation of major depression or response to treatment. For example, a Minnesota Multiphasic Personality Inventory–2 profile in which elevated scores on the hysteria or hypochondriasis scales are combined with depressive symptoms is often observed in individuals with masked depression. More generally, personality disorders amplify the effect of depression and have been associated with long-term reductions in function and quality of life. In older patients with a combination of depressive and cognitive symptoms, a referral for neuropsychological testing may be appropriate. Such testing provides a detailed survey of cognitive functions, which is compared with normative values for healthy older people and patient populations with depression or dementia (see Chapter 5, “Dementia and Alzheimer’s Disease”). If an individual’s scores closely

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Table 3–7. Screening laboratory tests for evaluation of depression in the elderly Test

Potential diagnosis

Complete blood count with differential white blood cell count

Folate deficiency anemia, viral infection

Serum thyroid-stimulating hormone, thyroxine, serum cortisol (A.M. and P.M.)

Hypothyroidism and hyperthyroidism; hypoadrenocorticism and hyperadrenocorticism

Sequential multiple analysis of 18 chemical constituents of blood (SMA-18)

Hypercalcemia, hypokalemia, hyperglycemia

Urinalysis, serum urea nitrogen

Uremia

Computed tomography or magnetic resonance imaging of head (as indicated by results of above tests, physical examination)

Brain tumor, stroke

approximate those of other depressed patients, neuropsychological findings might serve to strengthen a clinical impression of DSD. Information on a depressed individual’s cognitive strengths and weaknesses also can be helpful for treatment planning and psychosocial management. Because full response to antidepressant therapies may take weeks or months, patients whose depression-related deficits in attention, executive skills, or memory that exceed mild levels may require the support of another person to participate fully in therapies (e.g., to take medications as prescribed or attend therapy sessions regularly), and their ability to complete complex work assignments or self-care tasks may be undermined.

Symptom Rating Scales and Depression Screening Although depression rating scales were originally designed for research purposes, use of such scales in clinical practice can enhance the uniformity and reliability of assessment. Symptom rating scales are not sufficient to establish a diagnosis of depression, but they can help to identify individuals whose depressive symptoms exceed the norm and they can provide a means of tracking treat-

Type of test

Name of test

Description

Indications

Outcomes

Objective personality

Minnesota Multiphasic Personality Inventory–2 (MMPI-2)a

Self-rated questionnaire

Anchored to DSM Helps establish differential Personality profile, categoriesb estimate of response diagnosis, severity of bias, diagnosis, depression presence of suicidality; may detect masked depression, uncooperative or confused patient

Millon Clinical Multiaxial Inventory–III (MCMI-III)c

Self-rated questionnaire

Same as for MMPI-2

Revised NEO Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI)d

Self-rated questionnaire

Five-dimension taxonomy Ratings on dimensions Traits (e.g., neuroticism) may of personality of personality relevant predict use of to everyday coping medical services, adjustment to stresses

Same as for MMPI-2

Comment

Anchored to DSM Axis II categoriesb; fewer data available for older adults than with MMPI-2

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Table 3–8. Psychological tests useful in assessing geriatric depression

Table 3–8. Psychological tests useful in assessing geriatric depression (continued) Type of test

Name of test

Description

Indications

Outcomes

Comment

Projective personality

Rorschach Inkblot Teste

Patient describes complex unfamiliar patterns

Many older adults Same as for MMPI-2; also Description of reluctant to prominent concerns, useful for assessment of respond, see test as thought patterns, and thought disorder and in too ambiguous; pathological patients unaware of or may give too few tendencies unwilling to admit answers to score b psychiatric problems

Thematic Apperception Test (TAT)f

Patient creates stories about pictures of people in different situations

Same as for MMPI-2 and Same as for Rorschach test Rorschach test, but also identifies interpersonal concerns and habits

Geriatric version also availableg

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a Butcher JN, Dahlstrom WB, Graham JR, et al: Manual for the Restandardized Minnesota Multiphasic Personality Inventory: MMPI-2. Minneapolis, University of Minnesota Press, 1989. bComputerized scoring and interpretation available. cMillon T: Millon Clinical Multiaxial Inventory Manual, 3rd Edition. Minneapolis, MN, National Computer Systems, 1983. d Costa PT, McCrae RR: Revised NEO Personality Inventory (NEO-PI-R) and NEO Five-Factor Inventory (NEO-FFI): Professional Manual. Odessa, FL, Psychological Assessment Resources, 1992. eRorschach H: Psychodiagnostics: A Diagnostic Test Based on Perception. Translated by Lemkau P, Kronenburg B. Berne, Switzerland, Huber, 1942. f Murray HA: The Thematic Apperception Test. Cambridge, MA, Harvard University Press, 1943. gWolk RL, Wolk RB: The Gerontological Apperception Test. New York, Behavioral Publications, 1971.

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ment-related change. Table 3–9 lists some of the self-rated and observer-rated scales that have proved useful in assessing severity of depression in older adults. The GDS (Yesavage et al. 1982) is a self-rated measure developed specifically for older adults (see the Appendix for GDS items and scoring instructions). Mood is extensively examined in this 30-item scale, and the questions assess cognitive complaints and social behavior; in contrast, most somatic items have been omitted from the GDS to prevent inflation of scores due to normal aging changes. A simple yes-no answer format is another attractive feature. The GDS has been shown to be reliable and valid in clinical research with elderly medical and psychiatric patients, and it is often the standard against which other rating scales are compared in clinical research with older patients. A cutoff score of 11 or higher is useful in identifying persons who may be experiencing clinically significant levels of depression and who may benefit from more thorough diagnostic assessment. A 15-item short form of this scale has been developed that includes most of the key items for assessing dysphoria and hopelessness; however, it includes only a single cognitive item that does not correlate strongly with the other cognitive items on the full GDS (Adams et al. 2004). For most mental health assessment settings, the full 30-item GDS is recommended. The full form typically takes 10 minutes or less to complete, and most older adults can complete it independently or with only brief task orientation. The BDI (Beck et al. 1961) is another self-rated scale that has been widely used with older adults. The BDI is particularly useful for assessing psychological features of depression, including dysphoric mood, pessimism, self-criticism, and guilt. This instrument is recommended for tracking symptom severity in older persons with relatively clear-cut depression that is not complicated by psychosis or prominent somatization. It also may help to distinguish normal or complicated bereavement from major depression because bereaved individuals would not be expected to obtain high scores on items evaluating guilt, self-criticism, or risk of suicide. The most recent version of the BDI, the BDI-II (Beck et al. 1996), is a 21-item questionnaire that has been modified from the original to coincide more closely with DSM-IV-TR diagnostic criteria for depression. Most items are still rated on a 4-point scale, but rating options on the sleep and appetite items have been expanded to allow for both increases and decreases in those areas. Items on the initial version that pertained to body image, weight loss,

Table 3–9. Depression rating scales and screening procedures for older adults

Number of items

Approximate time to complete (min)

Type

Geriatric Depression Scale (GDS)

Self-rated

30 or 15

5–10

Screening in mental health or medical settings; tracking symptom changes with treatment

Beck Depression Inventory (BDI and BDI-II)

Self-rated

21

5–10

Screening in mental health or medical settings; tracking symptom changes with treatment

Hamilton Rating Scale for Depression (Ham-D)

Observer-rated, by trained professional, based on interview of patient

17–28 17- and 21-item versions most commonly used

20–25

Screening in mental health or medical settings; tracking symptom changes with treatment

Cornell Scale for Depression in Dementia

Observer-rated, by trained professional; both patient and caregiver interviewed

19

30

Recommended uses

Screening cognitively impaired patients; tracking symptom changes with treatment

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Scale or procedure

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Number of items

Approximate time to complete (min)

Scale or procedure

Type

Recommended uses

Beck Depression Inventory for Primary Care (BDI-PC)

Self-rated

7

≤5

Screening in medical settings

Depression items from the Patient Health Questionnaire (PHQ-9)

Self-rated

9

≤5

Screening in medical settings

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Table 3–9. Depression rating scales and screening procedures for older adults (continued)

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and somatic preoccupation were replaced in the BDI-II with questions pertaining to agitation, concentration, and energy loss. The BDI-II and original BDI correlate highly, but the BDI-II averages nearly 3 points higher than the original version. Scores of 14 or higher suggest clinically significant elevations in depression. In a study of 130 psychiatric inpatients age 55 years and older (Steer et al. 2000), internal consistency of the BDI-II was found to be acceptably high, and factor analysis identified the same cognitive and noncognitive dimensions of depression that had been previously identified in younger adult psychiatric outpatients; scores on the BDI-II did not vary significantly with age, sex, or ethnicity. (The BDI-II is a copyrighted instrument and is available for purchase through the Psychological Corporation.) Because both the GDS and the BDI-II minimize items assessing somatic symptoms, they may underestimate the severity of depression in patients in whom depression is expressed primarily through physical complaints or in whom the subjective effect of the medical disorder is amplified by depression. In general, a high score on the BDI or the GDS is useful in suggesting the presence of depression, but somatic symptoms also must be considered before a low score is interpreted to mean the absence of depression. Most depression rating scales were initially studied with predominantly white populations, so it has been unclear whether these measures are as applicable to persons of different racial, ethnic, or language backgrounds. However, translations of commonly used scales are now available, and validity studies with diverse populations are becoming more frequent. A public access Web site (http://www.stanford.edu/~yesavage/GDS.html) created by the authors of the GDS provides links to translations of the scale in 24 languages, but published information on the various translated versions varies, and users are strongly encouraged to contact persons responsible for translations before using translated instruments. One small-scale study found comparable GDS scores for Englishand Spanish-speaking elderly people with and without dementia (Taussig et al. 1992). However, another study found that the GDS was ineffective in detecting depression in elderly black persons with psychiatric disorder, perhaps because of the paucity of somatic symptoms included in this scale (Baker et al. 1995). A Spanish version of the BDI-II is available from the Psychological Corporation, and translations into other languages also have been reported. In a study comparing white and Mexican American older adults, no differences were found in BDI scores or reliability indices (Gatewood-Colwell et al. 1989).

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Self-rated scales may not be appropriate for some elderly patients, especially those who have visual deficits, limited education, poor language proficiency, psychosis, or masked depression. An observer-rated instrument, such as the Ham-D (Hamilton 1980), is recommended for these situations. Observer ratings also may be used in conjunction with patient ratings to obtain a more complete view of symptom presentation or change. The Ham-D is weighted toward the types of symptoms that antidepressant medications would be expected to alter early in the course of treatment (e.g., sleep, weight change, psychomotor speed), although it also taps depressive mood, anxiety, and other psychological features. It has been widely used as an outcome measure in studies of efficacy of pharmacotherapies with both elderly and younger adults. Several different cutoff scores have been used in the literature, but we have found that scores of 16 or higher are best for detecting significant depression when the 21-item scale is used. A structured interview guide that may help to increase interrater reliability of the Ham-D has been published (J.B. Williams 1988). The following is a sample item from this scale: Depressed Mood (rate) 0=Absent 1=These feeling states indicated only on questioning 2=These feeling states spontaneously reported verbally 3=Communicates feeling states nonverbally, i.e., through facial expression, posture, voice and tendency to weep 4=Patient reports VIRTUALLY ONLY these feeling states in his spontaneous verbal and nonverbal communication. (p. 744)

Concerns have been raised about interrater reliability of the Ham-D, even for the structured form. However, a recent study reported significantly higher item- and total-score reliabilities for the structured interview version compared with the original Ham-D, with intraclass correlations ranging from 0.78 to 1.0 for individual items (Moberg et al. 2001). Nonetheless, considerable training and experience are needed for this scale to yield reliable results. Although self-rated depression scales can be used effectively by persons with mild levels of cognitive impairment, observer-rated measures are needed for assessing depression in older adults with moderate to severe cognitive impairment. The Ham-D can be useful in some cases, but scales developed specifically for cognitively impaired populations should be considered. The Cornell Scale for Depression in Dementia (Alexopoulos et al. 1988) includes content similar to

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that in the Ham-D, but ratings are assigned on the basis of semistructured interviews with both the person with dementia and his or her caregiver. Although intended as a severity rating instrument once a diagnosis of depression has been established, the Cornell scale has been shown to be effective in identifying depression in nursing home patients with dementia. Internal consistency and interrater reliability are acceptable when the scale is used by trained examiners. Procedures for identifying depression in medically ill populations have received increased attention in recent years, especially since the U.S. Preventive Services Task Force (2002) endorsed depression screening in primary care. Although the scales described earlier have been shown to be useful for case finding in medically ill populations, these measures have been criticized for including nondiscriminating items or, in the case of observer-rated scales such as the Ham-D, for being too lengthy and impractical for most medical situations. Existing scales have been revised for medical applications, and several new scales have been developed. The Beck Depression Inventory for Primary Care, a seven-item version of the BDI, has been used to screen for major depression in both primary and secondary care settings (Beck et al. 1996). New scales include a nine-item depression module (Kroenke et al. 2001) from the Patient Health Questionnaire (PHQ-9), and a self-report questionnaire for medically ill persons that establishes DSM-IV psychiatric diagnoses (Spitzer et al. 1999). A recent study with more than 900 elderly patients in the multisite Improving Mood: Promoting Access to Collaborative Treatment (IMPACT) intervention trial reported that the PHQ-9 was sensitive and reliable in detecting depression in primary care patients and responsive to treatment-related improvements in depressive symptoms (Löwe et al. 2004). Other studies have shown that systematically asking even one or two questions about mood (“Do you often feel sad or depressed?” [Mahoney et al. 1994] or “Over the past two weeks, have you felt down, depressed, or hopeless?” and “Over the past two weeks, have you had little interest or pleasure in doing things?” [Whooley et al. 1997]) substantially improves identification of depressed individuals in busy medical settings where time is at a premium.

Assessing Suicidality in the Elderly One of every five suicides in the United States involves an adult age 65 years or older (Edelstein et al. 1999). This high rate of suicide has prompted a re-

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port by the surgeon general specifically targeting older adults for prevention efforts (U.S. Public Health Service 1999). White, male, older adults are at the greatest risk for suicide, followed by black males; white, female, older adults have the third highest suicide rate. Other risk factors include physical illness, especially cancer, and loss of a significant other. Older adults often use more lethal methods than do younger adults and are less likely to directly express suicidal ideation or to have a history of suicide attempts. Despite the obvious importance of assessing suicidality in older persons, few interview or rating scales have been developed to help with detection of increased suicide risk in the elderly. The Beck Hopelessness Scale (Beck et al. 1974), a short true-false inventory, may be helpful in this regard, and norms are available that include some older adults; a new scale for suicidal ideation has been developed by Beck and colleagues but has not yet been studied adequately with older adults. Studies have found that most older people who commit suicide consult their primary health care providers within days or months of their deaths, so all health care personnel must be alert to the possibility of suicide in older adults. Screening for suicidal ideation is best accomplished as part of a general diagnostic interview conducted by a health professional with whom the individual has ongoing close rapport. Areas to cover include current sources of stress, such as recent losses; signs and symptoms of depression; vague somatic complaints or complaints of severe, unremitting pain; family and personal history of mental health problems, including depression, alcoholism, or substance abuse; and past suicide attempts. If answers to these questions raise concern about suicidality, direct questions should be asked to assess the severity of suicidal thoughts and any possible plan that may involve injury to self or others. Whenever possible, family members should be interviewed for suicide clues that they may have observed, such as the elder purchasing a gun, stockpiling medications, or abruptly changing a will. Table 3–10 lists some of the factors that have been associated with increased risk of suicide in older adults, as well as protective factors associated with lower risk of suicide. Holkup (2003) has provided a protocol for assessing suicidality in older adults; although designed primarily for nurses, the concrete suggestions provided could be useful to a wide range of health professionals. Other thorough discussions of geriatric suicide can be found in Gallagher-Thompson and Osgood (1997) and McIntosh and colleagues (1994).

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Table 3–10.

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Risk and protective factors for geriatric suicide

Increased risk Age ≥75 years Male White Widowed or divorced Living alone, isolated, or recently moved Retired or unemployed Poor physical health, terminal illness, multiple or debilitating illnesses, or pain Depression, substance abuse or dependence, hopelessness History of suicide, depression, or other mental illness in close family members Compensatory or protective Able to learn from experience and accept help; sense of meaning in life; sense of humor and capacity for loving; able to reminisce about positive life experiences History of successful transitions and coping with life challenges Caring and available family member or supportive community network; accessible and caring health care provider Membership in a religious community, especially Catholic or Jewish Source. Adapted from Holkup 2003.

Theories of Depression The causes of clinically significant depression in the elderly are not known. A genetic vulnerability is strongly suggested by the increased prevalence of depression in the families (particularly first-degree relatives) of affected individuals and is supported by evidence from twin studies (Jansson et al. 2004). Genetic influences tend to be stronger in bipolar disorder than in unipolar mood disorder and in early-onset cases than in late-onset cases. As discussed earlier in this chapter (in the section “Substance-Induced Mood Disorder” and in Table 3–2), some cases of depression in the elderly appear to be at least partially caused or provoked by medications or other chemical agents and by general medical conditions, such as hypothyroidism; and several other chronic medical conditions appear to be “risk factors” for the development of

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depression in old age. Three schools of thought have weighed in on the etiology and pathogenesis of depression, and they are summarized in the following subsections.

Psychodynamic Theories Psychodynamic theories of depression were among the earliest published, beginning with Freud’s elaborations on the theories of Karl Abraham regarding psychopathological developments in the process of mourning. In Freud’s conception, the image of the lost object (which may be an abstract object, such as professional status) is eventually introjected and becomes part of the self. Subsequent rage at the object—for leaving and for past hurts and disappointments—thereby becomes directed at the self. The resultant guilt, loss of selfesteem, and need for punishment form the core of the symptom complex of pathological grief (not to be confused with complicated grief, a clinically defined condition discussed earlier in this chapter). More recently, Blatt and Zuroff (1992) proposed that certain personality configurations are predisposed to depression. These configurations derive from distinct developmental lines: the anaclitic (or dependent) line, which concerns the establishment of satisfying interpersonal relationships, and the introjective (self-critical) line, which focuses on the achievement of a positive and cohesive sense of self. These configurations seem to fit well with analytical conceptualizations of geriatric depression, which focus on helplessness experienced by the ego in light of failed attempts to live up to one’s ideals, and the narcissistic injuries inevitably associated with the functional declines of aging. Loss or threatened loss during childhood also has been a focus of psychodynamic formulations of depression. Although psychoanalytical theories of depression have not emphasized late life, the relatively high frequency of losses confronting many older individuals lends a measure of pertinence to each of these dynamic approaches to geriatric depression. The interested reader is directed to useful reviews by Blau (1983) and Bemporad (1988).

Cognitive and Behavioral Theories Seligman’s concept of “learned helplessness” offers a theoretical connection between certain unavoidable losses of later life (such as declines in physical vigor, sexual function, and general health) and the sensation of passive helplessness

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often expressed by elderly depressed patients (Seligman and Maier 1967). Similarly, cognitive theorists point to the interaction between these losses and subsequent activation of deeply ingrained, stable thought schemas as resulting in negative self-perceptions, negative interpretations of life events, and pessimism about the future, which lead to depressed mood (Sadavoy 1994). Contemporary research on cognitive-behavioral therapy in late-life depression (e.g., Thompson et al. 2001) accepts (with little critical analysis) “negative cognitions” as the proper focus of therapeutic attention, and the reported effectiveness of cognitive-behavioral therapy indirectly supports the claim that these cognitions play a role in the psychogenesis of depressive mood.

Neurobiological Theories A consensus conference held by the National Institutes of Health concluded that “the hallmark of depression in the elderly is its association with medical comorbidity” (National Institutes of Health Consensus Conference 1992, p. 1023). This conclusion was based on data associating late-life depression, particularly the late-onset variant, with a broad spectrum of medical disorders, including cardiovascular, cerebrovascular, musculoskeletal, metabolic, and pulmonary illnesses and malignancies. Possible mediating mechanisms to account for these associations have focused on cerebrovascular pathology (the “vascular depression” hypothesis discussed earlier in the subsection “Vascular Depression”) and on decreases in brain volume, which have been reported in the prefrontal lobe, caudate nucleus, and hippocampus of elderly depressed subjects. Several authors (Duman 2004; Jacobs et al. 2000) have proposed that decreased neurogenesis contributes to hippocampal atrophy and thereby underlies the pathophysiology of depression, and they cite several lines of indirect evidence in support of this theory. Other authors have challenged this theory, however (Henn and Vollmayr 2004), and it remains provocative but essentially untested at this time. A path analysis conducted by Kumar and colleagues (2000) found two distinct pathways to late-life major depression: One path proceeded via vascular and nonvascular medical comorbidity—which contributed equally to high-intensity lesions, which led to major depressive disorder. The second path proceeded from frontal lobe atrophy (apparently not consequent to medical morbidity) to late-life major depressive disorder. Other neurobiological theories of late-life depression are similar in their focus on central neurotransmitter function to the theories of middle-age

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depression, with emphasis on the role of age-related reductions in brain concentrations of norepinephrine, serotonin, dopamine, and acetylcholine and agerelated increases in brain concentrations of monoamine oxidase (Lipton 1976). The often observed temporal association between ingestion of certain medications (see Table 3–2) known to affect particular neurotransmitters and their presynaptic and postsynaptic receptors and the onset of depressive symptoms has provided support for several of these theories. Other investigators have studied endogenous rhythms, noting the similarity between certain abnormalities found in depression (e.g., advances in the phase of circadian cortisol secretion, increased body temperature, decreased nocturnal secretion of melatonin and thyroid-stimulating hormone, changes in sleep architecture) and those seen in normal aging (Sack et al. 1987). In adult and elderly depressed patients, abnormalities in brain concentrations of monoamine neurotransmitters and their metabolites and in platelet α2-adrenoreceptor and 3H-imipramine binding also have been reported (Alexopoulos 1994), but to date no single neurobiological theory of depression in the elderly is widely accepted. Chaisson-Stewart (1985) attempted to synthesize behavioral, cognitive, cultural, and biological factors into a comprehensive model of geriatric depression based on the work of Adolf Meyer and Sir Aubrey Lewis. In summary, her view is that depression in the elderly represents the final result of an interaction between biological (e.g., cerebrovascular lesions and cortical atrophy) and/or psychosocial stressors (e.g., losses) and “defenses,” which include both learned psychological and genetically determined psychobiological mechanisms that have been variably weakened by age and age-related infirmity. Costa and McCrae (1994) supported this model by arguing that “there are individual differences in the tendency to experience dysphoric affect” (p. 155). They conceptualized this tendency as an enduring personality trait that can be measured by appropriate assessment instruments and that predisposes its owner to episodes of clinical depression. This trait is a definer of the personality factor known as neuroticism and, as such, fits neatly into Chaisson-Stewart’s model in the place of what she calls “defenses.”

Hypomania and Mania With or without hallucinations and delusions, signs and symptoms of elevated mood—including reduced need for sleep, irritability, distractibility, hyperactivity, pressured speech, flight of ideas, circumstantiality and tangentiality, grandiosity,

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impulsivity, and excessive involvement in pleasurable activities that have a high potential for painful consequence—may occur in the context of certain medical illnesses, as an adverse reaction to certain medications or electroconvulsive therapy, and as one phase (or “pole”) of bipolar disorder. Mania is diagnosed when signs and symptoms are severe enough to cause marked impairment in occupational functioning or in usual social activities or relationships with others, when signs and symptoms are severe enough to necessitate hospitalization to prevent harm to self or others, or when psychotic features are present. Hypomania is diagnosed if the disturbance does not cause marked impairment in occupational functioning or in usual social activities or relationships with others, if the disturbance does not necessitate hospitalization, and if psychotic features are not present.

Mania Due to a General Medical Condition Mania or hypomania due to a general medical condition may be clinically indistinguishable from the functional variety. Endogenous illnesses that have been associated with the manic syndrome are listed in Table 3–11. Several investigators have suggested that mania due to a general medical condition is more likely than primary mania to be of late onset and to occur in patients with a negative family history, but a review of the literature by Chen and colleagues (1998) fails to support this claim.

Substance-Induced Mania Substances known to induce mania include sympathomimetic agents (iproniazid, procarbazine), psychostimulants (e.g., amphetamines, methylphenidate, cocaine, phencyclidine), tricyclic antidepressants, monoamine oxidase inhibitors, levodopa, yohimbine, bromide, alprazolam, corticosteroids, and many other substances (Table 3–11). In this regard, hypomania or mania that begins during or within 1 month of treatment with one or more of the medications listed here should be considered substance induced.

Bipolar Disorder Epidemiology The Epidemiologic Catchment Area study found a 1-year prevalence of 0.1% of bipolar disorder among adults older than 65 living in the community. In light of the 1%–2% prevalence of major depression, this finding suggests that about

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Table 3–11. Medical and neurological conditions and drugs associated with secondary mania Category

Specific agent or condition

Drugs

Amphetamines, anabolic steroids, angiotensin-converting enzyme inhibitors, antidepressants, antiepileptics, baclofen, benzodiazepines, bromide, chloroquine, clarithromycin, cocaine, corticosteroids, cyclobenzaprine, dopamine agonists (bromocriptine, amantadine), histamine H2 blockers (cimetidine, ranitidine), hydralazine, iproniazid, isoniazid, levodopa, metoclopramide, metrizamide, phencyclidine, procyclidine, propafenone, selegiline, thyroxine, yohimbine

Metabolic disturbances

Hemodialysis Postoperative state Uremia, hyperthyroidism, pellagra, carcinoid syndrome, hyperbaric chamber use, cyanocobalamin deficiency

Infectious diseases

Influenza, Q fever Encephalitis Human immunodeficiency virus Cryptococcal meningitis

Neoplasms

Diencephalic glioma Parasagittal meningioma, suprasellar diencephalic tumor, spheno-occipital tumor Right inferior temporal lobe glioma, bilateral orbitofrontal meningioma Medial frontal tumor, hypothalamic tumor

Vascular lesions

Right head of caudate nucleus, thalamus, right dorsolateral frontal cortex, right basotemporal cortex, inferior temporal lobe

Closed head injury

Temporal basal polar lesions Right orbitofrontal white matter

Seizure disorder

Right temporal focus

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Table 3–11. Medical and neurological conditions and drugs associated with secondary mania (continued) Category

Specific agent or condition

Other neurological conditions

Multiple sclerosis, Pick’s disease, Klinefelter’s syndrome, general paresis, Kleine-Levin syndrome, thalamotomy, Huntington’s disease, Wilson’s disease

Source. Chen ST, Altshuler LL, Spar JE: “Bipolar Disorder in Late Life: A Review.” Journal of Geriatric Psychiatry and Neurology 11:29–35, 1998. Reprinted by permission of Sage Publications, Inc.

5%–10% of elderly patients with major mood disorder have bipolar disorder. Relatively little research has been published on bipolar disorder in the elderly. Depp and Jeste (2004), in a review, stated, “To date, there have been no published large-scale multi-center studies of prevalence, etiology, or clinical features of bipolar disorder in late life, nor have there been any double-blind randomized controlled trials of pharmacologic treatments in this population” (p. 343). Diagnostic Criteria DSM-IV-TR criteria for manic episode and hypomanic episode are listed in Table 3–12 (please refer to DSM-IV-TR for criteria for the various forms of bipolar disorder). Clinical Presentation Bipolar disorder typically is first diagnosed in young adulthood, but cases in which the first episode of mania occurs after age 50 are not rare. Depp and Jeste (2004) reviewed 13 studies of older bipolar disorder patients (sampleweighted mean age=68.2) in which age at onset of any psychiatric illness and of mania were reported and 8 studies in which age at onset of mania was reported. The average age at onset of any mood disorder was 48, and the average age at onset of mania was 56. These ages are significantly later than the reported age at onset of mixed-age patients with bipolar disorder, which tends to be in the 20s. Few other consistent findings distinguish bipolar disorder in the elderly from bipolar disorder in young and middle-aged adults, but Depp and Jeste did conclude that older bipolar patients are less likely to have comorbid substance abuse than are younger patients and that late-onset mania is associated with more neurological impairment.

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Table 3–12. Summary of DSM-IV-TR criteria for manic episode and hypomanic episode Manic episode A.

A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary).

B.

During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree: (1) inflated self-esteem or grandiosity (2) decreased need for sleep (3) more talkative than usual or pressure to keep talking (4) flight of ideas or subjective experience that thoughts are racing (5) distractibility (6) increase in goal-directed activity or psychomotor agitation (7) excessive involvement in pleasurable activities that have a high potential for painful consequences

C.

The symptoms do not meet criteria for a mixed episode.

D. The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features. E.

The symptoms are not due to the direct physiological effects of a substance or a general medical condition.

Note: Manic-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, electroconvulsive therapy, light therapy) should not count toward a diagnosis of bipolar I disorder. Hypomanic episode A.

The same as criterion A for manic episode above, but only 4 days’ duration is required, and the mood must be clearly different from the usual nondepressed mood.

B.

The same as criterion B for manic episode above.

C.

The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person when not symptomatic.

D. The disturbance in mood and the change in functioning are observable by others.

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Table 3–12. Summary of DSM-IV-TR criteria for manic episode and hypomanic episode (continued) Hypomanic episode (continued) E.

The episode is not severe enough to cause marked impairment in social or occupational functioning, or to necessitate hospitalization, and there are no psychotic features.

F.

The symptoms are not due to the direct physiological effects of a substance or a general medical condition.

Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

Pathogenesis—Psychodynamic Theories Relatively little has been written about the psychodynamics of hypomania and mania in elderly patients per se. Early psychodynamic considerations about mania compared the relative importance of predisposing personality characteristics with that of precipitating events. Investigators such as Emil Kraepelin were influenced by what seemed to be an inconsistent relationship between manic episodes and external life events. Although the question remains open, the psychodynamic literature from that point has generally agreed on the primary importance of constitutional factors in the development of the illness. Analytical theorists beginning with Abraham attempted to understand these constitutional factors in terms of predisposing personality characteristics and the interplay of classic psychodynamic mechanisms. In this regard, Abraham saw mania as a psychic regression to a state of intense ambivalence directed toward love objects, reflected in behavior by primitive impulsiveness. Later theorists conceptualized mania as a defense and tended to see the manic personality as immature, egocentric, chronically depressed, dependent on others for self-esteem, and dominated by feelings of interpersonal competitiveness and envy. Generally, psychodynamic theories of mania have come to be seen as more relevant to shifts in mood in nonmanic individuals and have largely been supplanted by neurobiological theories in attempts to understand frank hypomania and mania.

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Table 3–13. Laboratory tests for evaluation of hypomania and mania in the elderly Test

Potential diagnosis

Blood studies Thyroid-stimulating hormone, thyroxine

Hyperthyroidism

Cortisol (A.M. and P.M.)

Hyperadrenocorticism

Sedimentation rate

Collagen vascular disease, especially lupus

Lumbar puncture

Encephalitis

Computed tomography or magnetic resonance imaging of head

Brain tumor, stroke, multiple sclerosis

Pathogenesis—Neurobiological Theories A postmortem study of brain tissue (Young et al. 1994) found decreases in serotonin turnover in the frontal, parietal, and temporal cortices from subjects with bipolar disorder, as well as decreased dopamine turnover in the parietal and occipital cortices and increased norepinephrine turnover in the thalamus and frontal, temporal, and occipital cortices. Also, some evidence indicates that the configuration of γ-aminobutyric acid (GABA)A receptors in the frontal cortex of subjects with bipolar disorder is altered (Dean et al. 2001) compared with nonbipolar subjects, but the significance of this finding remains unclear. Similarly, changes in various neurotransmitter receptor–G-protein interactions (which modulate neurotransmission at the intracellular level) and certain “downstream” signal transduction components (e.g., inositol) also have been described in subjects with bipolar disorder (Dean 2004), but no coherent theory has yet emerged from these findings.

Laboratory Evaluation of Hypomania and Mania Laboratory evaluation of the elderly patient with mania or hypomania is aimed at ruling out general medical causes such as hyperthyroidism and at establishing the pretreatment baseline status of physiological systems likely to be affected by antimanic medications. A recommended battery of tests with their potential uses is listed in Table 3–13.

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Table 3–14. A.

B.

C.

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Summary of DSM-IV-TR criteria for mixed episode

The criteria are met both for a manic episode [Table 3–12] and for a major depressive episode [Table 3–3] (except for duration) nearly every day during at least a 1-week period. The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

Note. Mixed-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, electroconvulsive therapy, light therapy) should not count towards a diagnosis of bipolar I disorder. Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Used with permission. Copyright 2000 American Psychiatric Association.

Mixed Mood Disorder Elderly patients with major mood disorder commonly present with a syndrome of mixed manic and depressive features. A typical picture might include severe psychomotor agitation accompanied by intrusive and demanding behavior, irritability, flight of ideas and circumstantiality, anorexia, and insomnia. The question of whether agitated depression or mixed manic-depressive syndrome is the correct diagnosis usually can be resolved by applying DSM-IV-TR criteria for “mixed episode” (Table 3–14).

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122 Clinical Manual of Geriatric Psychiatry Ko DT, Hebert PR, Coffey CS, et al: β-Blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA 288:351–357, 2002 Kral VA, Emery OB: Long-term follow-up of depressive pseudodementia of the aged. Can J Psychiatry 34:445–446, 1989 Kroenke K, Spitzer RL, Williams JB: The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 16:606–613, 2001 Kumar A, Mintz J, Bilker W, et al: Autonomous pathways to late-life major depressive disorder identified using a path analytic approach (abstract). Abstr Soc Neurosci 26:495, 2000 La Rue A, Spar J, Hill CD: Cognitive impairment in late-life depression: clinical correlates and treatment implications. J Affect Disord 11:179–184, 1986 Lipton MA: Age differentiation in depression: biochemical aspects. J Gerontol 31:293– 299, 1976 Löwe B, Unützer J, Callahan CM, et al: Monitoring depression treatment outcomes with the Patient Health Questionnaire–9. Med Care 42:1194–1201, 2004 Lyketsos CG, Steinberg M, Tschanz JT, et al: Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am J Psychiatry 157:708–714, 2000 Lykouras L, Gournellis R, Fortos A, et al: Psychotic (delusional) major depression in the elderly and suicidal behaviour. J Affect Disord 69:225–229, 2002 Mahoney J, Drinka TJ, Abler R, et al: Screening for depression: single question versus GDS. J Am Geriatr Soc 42:1006–1008, 1994 Mast BT, Yochim B, MacNeill SE, et al: Risk factors for geriatric depression: the importance of executive functioning within the vascular depression hypothesis. J Gerontol A Biol Sci Med Sci. 59:1290–1294, 2004 McIntosh JL, Santos JF, Hubbard RW, et al: Elder Suicide: Research, Theory and Treatment. Washington, DC, American Psychological Association, 1994 Moberg PJ, Lazarus LW, Mesholam RI, et al: Comparison of the standard and structured interview guide for the Hamilton Depression Rating Scale in depressed geriatric inpatients. Am J Geriatr Psychiatry 9:35–40, 2001 Morley JE: Anorexia, body composition, and ageing. Curr Opin Clin Nutr Metab Care 4:9–13, 2001 Mulsant BH, Ganguli M: Epidemiology and diagnosis of depression in late life. J Clin Psychiatry 60 (suppl 20):9–15, 1999 National Institutes of Health Consensus Conference: Diagnosis and treatment of depression in late life. JAMA 268:1018–1024, 1992 Nelson JC, Clary CM, Leon AC, et al: Symptoms of late-life depression: frequency and change during treatment. Am J Geriatr Psychiatry 13:520–526, 2005

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Nuti A, Ceravolo R, Piccinni A, et al: Psychiatric comorbidity in a population of Parkinson’s disease patients. Eur J Neurol 11:315–320, 2004 Ohayon MM, Schatzberg AF: Prevalence of depressive episodes with psychotic features in the general population. Am J Psychiatry 159:1855–1861, 2002 Okimoto JT, Barnes RF, Veith RC, et al: Screening for depression in geriatric medical patients. Am J Psychiatry 139:799–802, 1982 Paradiso S, Robinson RG: Gender differences in poststroke depression. J Neuropsychiatry Clin Neurosci 10:41–47, 1998 Parkes CM: Bereavement and mental illness, part 2: classification of bereavement reactions. Br J Med Psychol 38:13–26, 1965 Parkes CM: Bereavement: Studies of Grief in Adult Life. New York, International Universities Press, 1972 Penninx BWJH, Geerlings SW, Deeg DJH, et al: Minor and major depression and the risk of death in older persons. Arch Gen Psychiatry 56:889–895, 1999 Pincus HA, Davis WW, McQueen LE: “Subthreshold” mental disorders: a review and synthesis of studies on minor depression and other “brand names.” Br J Psychiatry 174:288–296, 1999 Posse M, Hallstrom T: Depressive disorders among somatizing patients in primary health care. Acta Psychiatr Scand 98:187–192, 1998 Prigerson HG, Jacobs SC: Perspectives on care at the close of life. Caring for bereaved patients: “all the doctors just suddenly go.” JAMA 286:1369–1376, 2001 Regier DA, Boyd JH, Burke JJ, et al: One-month prevalence of mental disorders in the United States: based on five Epidemiologic Catchment Area sites. Arch Gen Psychiatry 45:977–986, 1988 Reynolds CF, Kupfer DJ, Houck PR, et al: Reliable discrimination of elderly depressed and demented patients by electroencephalographic sleep data. Arch Gen Psychiatry 45:258–264, 1988 Robinson RG, Bolla-Wilson K, Kaplan E, et al: Depression influences intellectual impairment in stroke patients. Br J Psychiatry 148:541–547, 1986 Sack DA, Rosenthal NE, Parry BL, et al: Biological rhythms in psychiatry, in Psychopharmacology: The Third Generation of Progress. Edited by Meltzer HY. New York, Raven, 1987, pp 669–686 Sadavoy J: Integrated psychotherapy for the elderly. Can J Psychiatry 39:S19–S26, 1994 Sauer WH, Berlin JA, Kimmel SE: Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 104:1894–1898, 2001 Schulz R, Mendelsohn AB, Haley WE, et al: End-of-life care and the effects of bereavement on family caregivers of persons with dementia. N Engl J Med 349:1936– 1942, 2003 Seligman ME, Maier SF: Failure to escape traumatic shock. J Exp Psychol 74:1–9, 1967

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Simon GE, VonKorff M: Somatization and psychiatric disorder in the NIMH Epidemiologic Catchment Area study. Am J Psychiatry 148:1494–1500, 1991 Spitzer RL, Kroenke K, Williams JB, et al: Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. JAMA 282:1737–1744, 1999 Steer RA, Rissmiller DJ, Beck AT: Use of the Beck Depression Inventory-II with depressed geriatric inpatients. Behav Res Ther 38:311–318, 2000 Steffens DC, Skoog I, Norton MC, et al: Prevalence of depression and its treatment in an elderly population: the Cache County study. Arch Gen Psychiatry 57:601– 607, 2000 Stewart R, Prince M, Richards M, et al: Stroke, vascular risk factors and depression: cross-sectional study in a UK Caribbean-born population. Br J Psychiatry 178:23– 28, 2001 Strub RL, Black FW: Neurobehavioral Disorders: A Clinical Approach. Philadelphia, PA, FA Davis, 1988, p. 171 Taussig IM, Henderson VW, Mack W: Spanish translation and validation of a neuropsychology battery: performance of Spanish- and English-speaking Alzheimer’s disease patients and normal comparison subjects. Clin Gerontol 11:95–108, 1992 Thomas AJ, Ferrier IN, Kalaria RN, et al: A neuropathological study of vascular factors in late-life depression. J Neurol Neurosurg Psychiatry 70:83–87, 2001 Thompson LW, Coon DW, Gallagher-Thompson D, et al: Comparison of desipramine and cognitive/behavioral therapy in the treatment of elderly outpatients with mildto-moderate depression. Am J Geriatr Psychiatry 9:225–240, 2001 Tröster AI, Fields JA, Koller WC: Parkinson’s disease and parkinsonism, in The American Psychiatric Press Textbook of Geriatric Neuropsychiatry, 2nd Edition. Edited by Coffey CE, Cummings JL. Washington, DC, American Psychiatric Press, 2000, pp 559–600 U.S. Preventive Services Task Force: Screening for depression: recommendations and rationale. Ann Intern Med 136:760–764, 2002 U.S. Public Health Service, Office of the Surgeon General: The Surgeon General’s Call to Action to Prevent Suicide. Washington, DC, U.S. Public Health Service, Department of Health and Human Services, 1999 Whooley MA, Avins AL, Miranda J, et al: Case-finding instruments for depression: two questions are as good as many. J Gen Intern Med 12:439–445, 1997 Wiener P, Alexopoulos GS, Kakuma T, et al: The limits of history-taking in geriatric depression. Am J Geriatr Psychiatry 5:116–125, 1997 Williams JB: A structured interview guide for the Hamilton Depression Rating Scale. Arch Gen Psychiatry 45:742–747, 1988

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Williams LS, Ghose SS, Swindle RW: Depression and other mental health diagnoses increase mortality risk after ischemic stroke. Am J Psychiatry 161:1090–1095, 2004 Wilson RS, Barnes LL, Mendes de Leon CF, et al: Depressive symptoms, cognitive decline, and risk of AD in older persons. Neurology 59:364–370, 2002 Yesavage JA, Brink TL, Rose TL, et al: Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 17:37–49, 1982 Young LT, Warsh JJ, Kish SJ, et al: Reduced brain 5-HT and elevated NE turnover and metabolites in bipolar affective disorder. Biol Psychiatry 35:121–127, 1994 Zisook S, Shuchter SR, Sledge P: Diagnostic and treatment considerations in depression associated with late-life bereavement, in Diagnosis and Treatment of Depression in Late Life: Results of the NIH Consensus Development Conference. Edited by Schneider LS, Reynolds CF III, Lebowitz BD, et al. Washington, DC, American Psychiatric Press, 1994, pp 419–435

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4 Mood Disorders—Treatment

T

reatment of mood disorders in the elderly generally follows the same principles that apply to young and middle-aged adults but is typically complicated by one or more of the confounding factors listed in Table 4–1. To avoid repetition and redundancy, treatment trials should be conducted in a systematic and logical sequence. For purposes of discussion, in the first part of this chapter, we focus mainly on nonpsychotic major depression, but the treatment principles apply, with modifications as indicated, to all of the depressive variants discussed in Chapter 3 (“Mood Disorders—Diagnosis”). Treatment of bipolar depression is discussed at the end of the chapter in the “Bipolar Disorder” section.

Psychotherapy for Geriatric Depression A variety of psychotherapeutic approaches can be effective with depressed older adults. Factors that are important to consider in selecting an approach include the nature of the problems involved; the clinical goals; the immediate situation; and the individual patient’s characteristics, preferences, and place on the continuum of care (American Psychological Association 2004). Older adults frequently face chronic illness and disability, grief for the loss of loved ones or cherished 127

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assets or roles, and demands of caregiving, and these problems often form the content of psychotherapy. For persons with high levels of disability or recurrent mental and physical problems, appropriate clinical goals may be to manage, rather than eliminate, symptoms and to sustain as high a level of independence as possible. Higher-functioning older adults often do well with the usual forms of individual, group, or family therapies that are provided in outpatient settings. Depressed elders with cognitive impairment may benefit more from systematic adjustments in the social or physical environment to maximize functional skills, behavior modification (e.g., to increase participation in pleasurable activities), or specialized cognitive training techniques (see Chapter 6, “Other Dementias and Delirium”). For individuals with chronic health problems or significant physical disabilities, techniques for addressing specific medical comorbidities (e.g., pain or insomnia) can be especially beneficial. Helping with a specific, tangible problem can strengthen the provider-patient relationship and increase the likelihood that other issues can be successfully addressed. Problem solving and learning new behaviors may progress more slowly with older adults than with young or middle-aged patients (Gallagher-Thompson and Thompson 1996). Home visits may be needed for older patients with limited mobility. For patients with memory impairment, a simple written summary of topics covered in a session can help to support continuity from one session to the next (see Chapter 6, “Other Dementias and Delirium”). Adjustments for sensory losses (e.g., amplification for hearing-impaired patients and large-print homework or educational materials) may be required, and as discussed in Chapter 1 (“Introduction”), current cohorts of older adults may lack familiarity with psychotherapy or may have negative attitudes toward mental illness that need to be addressed in initial sessions. The best-studied psychotherapeutic interventions with older adults are behavior therapy, cognitive-behavioral therapy, and problem-solving therapy (Areán and Cook 2002; Gatz et al. 1998). All share a common theoretical framework that emphasizes the importance of learning adaptive responses. These interventions have been examined in well-controlled studies in relatively diverse populations by several independent investigators, and clear benefits have been shown relative to no-intervention and wait-list control subjects. In major depression, benefits for those who respond to such therapies have been shown to persist for at least 1–2 years. Most studies have found little difference in efficacy between these procedures. Cognitive-behavioral therapy has been

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Table 4–1. Confounds in the diagnosis and treatment of depression in elderly patients Concurrent nonpsychotropic medications may Cause depression Change blood antidepressant levels Increase antidepressant side effects Biochemically block antidepressant effects Require modifying the oral dose Concurrent medical illnesses may Cause depression biologically Reduce the efficacy of antidepressant medication or psychotherapy Create disability, contributing to both chronicity and reduced treatment efficacy Increase the need for simplified medication dosing schedules (e.g., once daily) Concurrent nonmood psychiatric conditions may Cause depression (e.g., early Alzheimer’s disease) Necessitate different medications Impair participation in psychotherapy Reduce response to antidepressant medications (e.g., personality disorder) Worsen prognosis of the depression (e.g., alcoholism) Other issues are that Slower metabolism with age often requires lower doses Transportation difficulties may restrict access to care Increased interview time may be needed Fixed income may limit availability of therapy and nongeneric antidepressant medications because of cost Source. Adapted from Rush AJ: “Overview of Treatment Options in Depressed Elderly,” in Diagnosis and Treatment of Depression in Late Life. Edited by Schneider LS, Reynolds CF, Lebowitz BD, et al. Washington, DC, American Psychiatric Press, 1994, pp. 171–180. Copyright © 1994, American Psychiatric Press. Used with permission.

adapted for use over distance (e.g., with homebound elderly) through use of written materials and periodic telephone contacts (Landreville 1998). Interpersonal psychotherapy, which combines elements of psychodynamic therapy with cognitive-behavioral approaches, also has been shown to be effective in alleviating geriatric depression, but it has been studied less often than

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the learning-based therapies and typically has been assessed in combination with medication rather than as an independent therapy. Brief dynamic therapy has been found to be effective in a few studies, but in one investigation, it was less effective than cognitive-behavioral therapy for older adults with major depression. Reminiscence therapy (Haight and Webster 1995), based on Eriksonian developmental theory and developed specifically for use with older adults, also appears to have some promise for reducing depressive symptoms, but research on this approach has been less methodologically rigorous than for some other psychotherapy approaches. A recent study that compared reminiscence therapy with a social services support control condition found improvement in the level of depressive symptoms and increased life satisfaction in the reminiscence therapy group (Serrano et al. 2004). Although individual psychotherapy has been studied most extensively, group and family therapies are also appropriate for many older adults. Exercising care in selecting patients for group treatment is particularly important for older patients because cognitive impairment, sensory deficits, and physical illness may limit an individual’s capacity to tolerate and benefit from group therapy and may negatively influence group process. Patients with moderate to severe cognitive impairment, psychosis, significant involuntary movements, severe pain, or dyspnea are relatively poor candidates for group therapy. Major depression commonly presents a crisis for families, particularly if diagnosis and administration of treatment are significantly delayed and significant deterioration of function is allowed to develop. By the time adequate medical attention is obtained, the lives of two or three generations of the family often have been considerably disrupted. Because family members are often required to provide details of medical and psychiatric history and are frequently involved in patient management (e.g., assisting with transportation, encouraging compliance with treatment), the family therapy format is the preferred approach in many cases (Tisher and Dean 2000).

New Directions in Psychotherapy Research Although studies of older adults’ preferences for mental health treatments have shown an openness to talk therapy, depressed older persons are rarely referred for psychotherapy, and advancements in learning how best to tailor psychotherapy techniques to serve their needs are hampered by the paucity of new studies

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(e.g., in the 5 years preceding the 2002 review by Areán and Cook, only 9 psychotherapy trials had been published, compared with 700 medication trials). Additional studies of psychotherapy and combined medication and psychosocial approaches are clearly needed. One promising line of research is examining the effectiveness of brief, structured psychotherapeutic interventions for treating depression within primary care. The multisite IMPACT (Improving Mood: Promoting Access to Collaborative Treatment) project has been providing either medication, psychotherapy, or combined therapies to depressed older adults identified in primary care (Unützer et al. 2003). Choice of treatment is determined jointly by the patient, the primary care provider, a depression care manager (either a nurse or a psychologist), and a consulting psychiatrist. Problem-Solving Treatment in Primary Care (PST-PC) is the principal psychotherapeutic intervention being studied, and it is provided by a nurse, generally a nurse clinical specialist or psychiatric nurse practitioner. Specific problems are identified, and a seven-stage approach to problem solving is introduced and practiced for each problem. Typically, one problem is addressed per session for a total of four to eight sessions, followed by less frequent maintenance sessions as needed. Areán and colleagues (2001) provide a more detailed description of PST-PC procedures suitable for older adults, and Haverkamp et al. (2004) present a case example of its application with a chronically depressed older person. Individuals participating in the IMPACT intervention program have experienced significantly lower depression for at least 12 months compared with patients in usual care, for black and Latino elderly as well as white patients (Areán et al. 2005), and despite the presence of multiple medical comorbidities (Harpole et al. 2005). Such collaborative models for intervention offer the hope of access to effective treatments for depression to a broader range of older adults and offer opportunities for psychiatrists with geriatric expertise to educate about depression and other mental health conditions within a general medical context. Other studies have been examining methods for countering older adults’ negative attitudes toward depression and its treatment and for increasing adherence to recommended therapies. Dropout rates in therapeutic studies of antidepressant medications run as high as 33%, and in clinical practice, discontinuation rates of psychoactive medications are even higher (Pampallona et al. 2002). Studies of interventions aimed at helping older people adhere to medication regimens have tended to be small scale and of poor methodological quality (Higgins and Regan 2004), but most suggest that one-time, education-only

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approaches are ineffective. A recent meta-analysis that focused on adherence as an outcome in clinical trials found no difference in dropout rates between pharmacotherapy only and combined psychotherapy and pharmacotherapy in the short term (less than 12 weeks), but over longer periods, combination treatment was clearly superior in reducing dropout rates (Pampallona et al. 2004). The authors speculated that it may be possible to develop briefer and less expensive “compliance-enhancing” interventions than psychotherapy per se, but they also noted that “psychological treatment may have a stronger effect than pharmacotherapy on patient satisfaction and social functioning or other dimensions of well being” (p. 718).

Combined Psychotherapy and Pharmacotherapy Only a few studies have compared the efficacy of psychotherapy with that of antidepressant medication in treating depression in older adults, and outcomes have been mixed. However, the combination of antidepressant medication with psychotherapy has shown effectiveness for treatment of major depression. This effect has been most clearly documented for interpersonal psychotherapy, less often examined for cognitive-behavioral therapy, and not yet investigated for some other psychotherapeutic approaches (Areán and Cook 2002). Thase and colleagues (1997) conducted a “mega-analysis” (a meta-analysis of their own original data) of five studies. They administered interpersonal therapy, cognitive-behavioral therapy, and “clinical management” to elderly patients with major depression, in various combinations with standard pharmacotherapy, and found that psychotherapy alone was as effective as pharmacotherapy or the combination of psychotherapy with pharmacotherapy in patients with “mild” depression (defined as a pretreatment Hamilton Rating Scale for Depression [Ham-D] score of 19 or less). However, patients with “severe” depression (Ham-D score of 20 or higher) did significantly better with combination therapy (Thase et al. 1997).

Psychopharmacotherapy for Geriatric Depression Taylor and Doraiswamy (2004) reviewed the randomized, placebo-controlled trials of antidepressants in populations older than 55 and found only 18 trials

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that met their criteria: 12 trials studied tricyclics, 5 studied selective serotonin reuptake inhibitors (SSRIs), 2 studied bupropion, and 1 studied mirtazapine. They concluded that there is a paucity of published controlled antidepressant trials in the elderly. Most published studies examine small sample sizes and do not include common comorbid conditions. Efficacy studies examining relapse prevention are lacking. Large placebo response rates, lack of controlled head to head comparisons, and other methodological design differences make cross-trial comparisons difficult. (p. 2285)

With this limited “evidence base” in mind, in the following section, we review the advantages and disadvantages of currently available antidepressants in the treatment of nonpsychotic depression, including major depression, dysthymia, and minor depression. Because the presence of psychosis (hallucinations, delusions, severe thought disorder, or behavioral regression) appears to significantly reduce the rate of response to antidepressant therapy, even when concomitant antipsychotic medications are prescribed, psychotic depression is discussed under a separate heading later in this chapter (“Psychopharmacotherapy for Psychotic Depression”). The most well-studied and widely used psychopharmacotherapy for nonpsychotic depression in the elderly is the reuptake-inhibiting antidepressants— which include the tricyclic antidepressants (TCAs), the SSRIs, and several nonselective reuptake-inhibiting antidepressants (trazodone, bupropion, venlafaxine, and mirtazapine)—all of which act, at least indirectly, by blocking central presynaptic reuptake of norepinephrine, serotonin, or both. Some also agonize or antagonize various presynaptic and postsynaptic receptors. The controlledresearch literature indicates that these medications are about twice as effective as placebo in elderly depressed patients and that remission rates of 65%–75% may be expected in nonpsychotic patients, including those age 76 and older (Gildengers et al. 2002), given an adequate trial of medication. Because little evidence of superior efficacy of one agent over another exists, the choice of first treatment is usually based on side-effect profiles, which are related to each agent’s affinity for central muscarinic receptors (anticholinergic effects), histaminic (H1) receptors (drowsiness and appetite stimulation), and noradrenergic receptors (orthostatic hypotension) (Table 4–2). Because they have a relatively low side-effect profile, and the side effects they

Agent Amitriptyline Imipramine Doxepin Nortriptyline Desipramine Sertraline Fluoxetine Paroxetine Citalopram Bupropion Trazodone Venlafaxine Mirtazapine Duloxetine

Daily dosage (mg) 75–150 75–150 75–200 25–100 75–200 50–150 5–20 10–20 20–40 150–300 150–300 37.5–75 15–45 40–120

H1 affinitya +++ ++ ++++ ++ + 0 0 0 + 0 +d 0 +++ e 0

α1-Adrenergic affinityb ++++ +++ +++ +++ ++ + 0 0 0 0 ++++ 0 ++(?) 0

Muscarinic affinityc ++++ +++ +++ ++ ++ + 0 ++ 0 0 0 0 + 0

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Table 4–2. Cyclic antidepressant receptor affinities

Table 4–2. Cyclic antidepressant receptor affinities (continued) Note. 0= no effect; += weak effect; ++= moderate effect; +++= strong effect; ++++ =very strong effect. aApproximately correlates with potential for appetite stimulation and sedation. bApproximately correlates with potential for orthostatic hypotension. c Approximately correlates with potential for anticholinergic symptoms. dDespite relatively low H affinity, trazodone is very sedating. 1 eSedative effects predominant at low doses, tend to be overcome by noradrenergic effects at higher doses. Source. Based on data from Richelson E: “The Pharmacology of Antidepressants at the Synapse: Focus on Newer Compounds.” Journal of Clinical Psychiatry 55 (suppl A):34–39, 1994; Kent JM: “SnaRIs, NaSSAs, and NaRIs: New Agents for the Treatment of Depression.” Lancet 355:911–918, 2000; Fawcett J, Barkin RL: “Review of the Results From Clinical Studies on the Efficacy, Safety and Tolerability of Mirtazapine for the Treatment of Patients With Major Depression.” Journal of Affective Disorders 51:267–285, 1998; and Thase ME, Tran PV, Wiltse C, et al: “Cardiovascular Profile of Duloxetine, a Dual Reuptake Inhibitor of Serotonin and Norepinephrine.” Journal of Clinical Psychopharmacology 25:132–140, 2005.

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Category First-line agents SSRIs Bupropion

Venlafaxine Mirtazapine Duloxetine Second-line agents Tricyclics

Trazodone

Advantages

Disadvantages

Benign side effects Once-daily dosing Benign side effects Relatively unlikely to cause rapid cycling Benign side effects Stimulates appetite Benign side effects Benign side effects

Sexual side effects Interact with many medications prescribed for elderly patients Three-times-daily dosing required Contraindicated in patients with seizures, eating disorder Sexual side effects Weight gain may be a problem in the long run. Sexual side effects

Dangerous side effects: May be more effective than Orthostatic hypotension nontricyclics in severe depression Delayed cardiac conduction Inexpensive Once-daily dosing Inexpensive Dangerous side effects: Orthostatic hypotension Can cause priapism, although rare

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Table 4–3. Advantages and disadvantages of major categories of antidepressants

Table 4–3. Advantages and disadvantages of major categories of antidepressants (continued) Category Third-line agents MAOIs

Lithium Psychostimulants (methylphenidate, amphetamines) Note.

Advantages

Disadvantages

Inexpensive Effective in atypical depression

Dietary and medication restrictions required Potentially fatal interaction with meperidine, sympathomimetics, SSRIs Only two-thirds as effective as above agents No controlled studies Development of tolerance common

Inexpensive Immediately effective Benign side effects

MAOIs= monoamine oxidase inhibitors; SSRIs =selective serotonin reuptake inhibitors.

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do cause tend to be less dangerous than those caused by tricyclics, the SSRIs (including fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram) and the nonselective amine inhibitors bupropion, venlafaxine, and mirtazapine are generally preferable to the TCAs and are therefore regarded here as first-line agents. It must be noted that some authorities still prefer TCAs in patients with severe, melancholic depression; however, even these experts avoid the tertiary tricyclics (e.g., amitriptyline, imipramine, doxepin, trimipramine) because of their greater sedating, anticholinergic, and cardiac side effects and their relatively greater tendency to cause orthostatic hypotension than their demethylated counterparts, the secondary tricyclics (e.g., desipramine, nortriptyline, protriptyline). All TCAs have type 1 antiarrhythmic effects and are relatively contraindicated in patients with ischemic heart disease or preexisting cardiac conduction disturbance (increased P-R interval, bundle-branch block, increased QRS). Trazodone is an effective and safe antidepressant in the elderly, but it is sedating enough to be difficult for many elderly patients to tolerate in effective doses and thus is regarded along with the tricyclics as a second-line agent in the discussion below and in the summary presented in Table 4–3. Because the tetracyclic agent maprotiline has a relatively strong association with seizures and has no advantages that are not matched by other less risky agents, it is not recommended for elderly patients. Similarly, the dibenzoxazepine amoxapine has mixed neuroleptic-antidepressant properties and attendant risks of extrapyramidal symptoms and tardive dyskinesia and is not recommended.

First-Line Agents—Selective Serotonin Reuptake Inhibitors SSRIs have been studied in elderly depressed patients and have been shown to be effective and generally well tolerated and to have few side effects (Newhouse 1996). Some side effects, such as mild anorexia, nausea, gastrointestinal upset, jitteriness, and headache, typically diminish within the first few days to weeks of initiation of therapy; others, such as sexual dysfunction (including inhibited desire, delayed ejaculation, and anorgasmia) and later-onset weight gain, may not diminish at all. The SSRIs all competitively inhibit several cytochrome P450 (CYP) isoenzymes that are responsible for the hepatic metabolism of several pharma-

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ceutical agents (Table 4–4); the SSRIs can therefore cause clinically significant increases in serum levels of other medications if administered concurrently. In this regard, paroxetine is the most potent, followed by fluoxetine, sertraline, citalopram, escitalopram, and fluvoxamine. SSRIs all have an elimination half-life of about 1 day, except fluoxetine, which has a significantly longer half-life (discussed in the following subsection). Fluoxetine, paroxetine, and, to a lesser extent, fluvoxamine (but not citalopram, escitalopram, or sertraline) inhibit their own metabolism, producing nonlinear increases in plasma concentrations with dosage increases. SSRIs also attenuate platelet activation by depleting serotonin storage and have been shown in at least one study (Sauer et al. 2003) to reduce the risk of myocardial infarction, although the effect is modest. Citalopram is metabolized predominantly by the CYP isoenzymes 2C19 and 3A4, and at least six polymorphisms of 2C19 that result in slowed metabolism of citalopram have been identified. Patients with these phenotypes will have higher blood levels of citalopram at any given dose than will patients with the wild-type allele, and dosages must be adjusted accordingly. Although there is no practical way to determine any given patient’s 2C19 phenotype, the “slow metabolizer” variant is present in about 13%–23% of individuals of Asian descent and in only 2%–5% of non-Asian persons (Yu et al. 2003). All of the SSRIs can produce serious, potentially fatal interactions with monoamine oxidase inhibitors (MAOIs) and should not be administered within 2 weeks of discontinuation of an MAOI; similarly fatal interactions have been reported with the antihistamines terfenadine and astemizole, both of which have been withdrawn from the U.S. market but are still available in other countries. Fluoxetine Advantages. Fluoxetine has mild psychostimulant-like effects and is very weakly anticholinergic. As is true of the other SSRIs, the final dosage of 20 mg/day (for the vast majority of patients) is only twice the recommended starting dosage of 10 mg/day, which vastly simplifies the process of dosage adjustment in the induction phase of therapy. Disadvantages. Stimulant-like properties may interfere with sleep and appetite, particularly in the first few weeks of therapy. Fluoxetine has a long elimi-

Psychotropic agent

CYP isoenzyme affected

Effect

Inhibitors Antidepressants Fluoxetinea Paroxetinea Clomipramine Sertraline Citalopram Antipsychotics Haloperidol

2D6

May increase levels of Antidepressants: Amitriptyline, imipramine, nortriptyline, desipramine, clomipramine, venlafaxine, paroxetine Antipsychotics: Haloperidol, chlorpromazine, perphenazine, thioridazine, clozapine, risperidone, fluphenazine ACE inhibitors: Captopril Antihistamines: Chlorpheniramine β-Blockers: Propranolol, metoprolol, propafenone, timolol Opioids: Codeine, hydrocodone Others: Dextromethorphan, tramadol, ondansetron, tamoxifen

Inhibitors Antidepressants Fluoxetinea Fluvoxaminea Sertraline Inducers Anticonvulsants Carbamazepine Phenobarbital

3A4

Inhibitors will raise, inducers will lower levels of Antidepressants: Amitriptyline, imipramine, sertraline, citalopram, trazodone Benzodiazepines: Diazepam, alprazolam, triazolam, midazolam Hypnotics: Zolpidem Antihistamines: Loratadine, astemizoleb Calcium channel blockers: Diltiazem, felodipine, nifedipine, verapamil Others: Amiodarone, aripiprazole, astemizole,b carbamazepine, cisapride,b erythromycin, clarithromycin, pimozide,b propafenone, terfenadine,b quinidine, lovastatin, corticosteroids, quetiapine

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Table 4–4. Psychotropic medications that inhibit or induce cytochrome P450 (CYP) isoenzymes

Table 4–4. Psychotropic medications that inhibit or induce cytochrome P450 (CYP) isoenzymes (continued) Psychotropic agent Inducers (continued) Antidepressants Citalopram Fluvoxaminea

1A2

2C9

2C19

Effect May lower levels of Antidepressants: Amitriptyline, imipramine, fluvoxamine Antipsychotics: Phenothiazines, haloperidol, clozapine Others: Acetaminophen, caffeine, ciprofloxacin, estradiol, theophylline, warfarin May lower levels of Diclofenac, ibuprofen, naproxen, phenytoin, warfarin

May lower levels of Antidepressants: Amitriptyline, clomipramine Proton pump inhibitors: Omeprazole, lansoprazole, pantoprazole Others: Diazepam, phenytoin, progesterone

Note. ACE =angiotensin-converting enzyme. a Relatively more potent inhibitor. bAdministration of nefazodone (or other nonpsychotropic inhibitors of CYP isoenzyme 3A4) with these agents may lead to potentially fatal torsades de pointes ventricular arrhythmia.

Mood Disorders—Treatment

Antidepressants Fluoxetinea Fluvoxaminea Sertraline Antidepressants Fluoxetine Fluvoxaminea

CYP isoenzyme affected

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nation half-life (more than 24 hours) and has at least one active metabolite (norfluoxetine) with a half-life of up to 15 days. Therefore, at least 5 weeks must elapse after discontinuing fluoxetine therapy before an MAOI can be safely administered. Sertraline Advantages. Sertraline has a relatively low potential for competitive inhibition of any of the CYP isoenzymes and is therefore a good choice for patients taking complex multidrug regimens. It is also a relatively potent reuptake inhibitor of dopamine, at least in vitro, and may have theoretical advantages in patients with Parkinson’s disease, although several authorities recommend against the use of SSRIs in such patients because of the risk of confusion. Sertraline has the most linear dose–plasma level relation of the SSRIs. Disadvantages. Possibly because of its dopaminergic properties, sertraline is somewhat stimulating and may interfere with sleep if administered late in the day. Paroxetine Advantages. Paroxetine has no active metabolites and is less activating than either fluoxetine or sertraline and therefore may be given at bedtime. Disadvantages. Paroxetine causes relatively potent inhibition of CYP2D6 and therefore may pose a problem for patients taking multidrug regimens. It also has mild anticholinergic effects, but a study conducted by Nebes and colleagues (1999) showed that “the slight increase in serum anticholinergicity seen in some elderly patients treated with paroxetine did not significantly impair cognitive function, even in patients with a preexisting cognitive impairment” (p. 26). Fluvoxamine Advantages. Fluvoxamine is the most sedating of the SSRIs and may be administered at bedtime. Disadvantages. Fluvoxamine causes potentially clinically significant inhibition of CYP1A2 and CYP2C19 (and probably a third, CYP3A3/4) and therefore may elevate serum levels of propranolol and omeprazole, as well as citalopram and venlafaxine. It has been studied relatively little in geriatric depression.

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Citalopram Advantages. Citalopram is a very weak inhibitor of all the CYP isoenzymes and therefore is the SSRI of choice for patients with complex multidrug regimens. It has mild gastrointestinal side effects associated with all of the SSRIs (nausea, diarrhea), which appear to be less frequent in elderly than in middleaged patients; a weak tendency to cause bradycardia (in about 2%–3% of patients) appears to increase with age. Disadvantages. Citalopram is contraindicated in patients receiving pimozide. An incompletely understood interaction results in significant increases in the QTc interval, with consequent risk of serious arrhythmia. Escitalopram Advantages. Escitalopram, the S-enantiomer of citalopram, is similar to citalopram but more selective and may cause side effects less frequently than does citalopram. Disadvantages. derly patients.

Few studies on escitalopram have been done to date in el-

First-Line Agents—Non–Selective Serotonin Reuptake Inhibitors Bupropion Advantages. The dopaminergic properties of bupropion may be beneficial for patients with Parkinson’s disease. It does not cause sexual side effects or orthostatic hypotension, and it is very safe in overdose. It does not cause weight gain; a review (Settle et al. 1999) of three clinical trials found that the sustained-release form of bupropion produced dose-related weight loss in all three studies. Disadvantages. Bupropion must be given in divided doses at least 4 hours apart (usually three times a day), and no single dose may be greater than 150 mg; the extended-action form (Wellbutrin SR) may be given twice a day, and the Wellbutrin extended-release version is given once daily. Bupropion is contraindicated in patients with seizure disorder, even if only by history, or in patients with a history or current diagnosis of anorexia or bulimia. Significant

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inhibition of CYP2D6 may result in increased blood levels of certain antipsychotic medications, β-blockers, and type 1C antiarrhythmic agents. Venlafaxine Advantages. Although venlafaxine blocks reuptake of serotonin and norepinephrine, its side-effect profile is generally benign and very similar to that of the SSRIs, making it one of the preferred therapeutic agents in the elderly. One study (Trick et al. 2004) found that venlafaxine actually increased the “critical flicker fusion” threshold in 88 depressed patients (average age=71), whereas the comparator medication, dothiepin (a TCA not available in the United States), reduced the critical flicker fusion threshold. The authors concluded that venlafaxine does not cause cognitive impairment in elderly patients. Disadvantages. The advantages notwithstanding, sexual dysfunction, weight gain, and gastrointestinal upset are seen fairly commonly. Venlafaxine also causes supine blood pressure elevations in 3%–5% of patients, so monitoring is advisable in the early phases of treatment. Downward adjustment of dosage is recommended in patients with liver or kidney disease. Mirtazapine Advantages. Mirtazapine is an atypical antidepressant with α 2-adrenergic antagonist and serotonin type 2 and type 3 receptor–blocking activity. It is well tolerated and has few side effects other than sedation, which tends to diminish as the dosage is increased and noradrenergic effects overcome antihistaminic effects. One controlled study comparing mirtazapine with paroxetine in elderly patients found that mirtazapine produced an earlier therapeutic response, had fewer side effects in general, and resulted in significantly more weight gain than did paroxetine (Schatzberg et al. 2002). The latter effect is consistent with clinical experience suggesting that mirtazapine is particularly effective as an appetite stimulant in elderly depressed patients with poor appetite and weight loss. Disadvantages. Weight gain may be intolerable for many patients. Only one double-blind, placebo-controlled study in elderly patients has been published to date.

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Duloxetine Advantages. Duloxetine is an inhibitor of norepinephrine and serotonin reuptake and has been shown to be effective for depression, neuropathic pain, and stress urinary incontinence in women. Disadvantages. to date.

Data on duloxetine in elderly depressed subjects are lacking

Second-Line Agents—Tricyclic Antidepressants TCAs produce side effects that warrant a pretreatment evaluation whenever possible. The physical examination is specifically oriented toward detection of signs of narrow-angle glaucoma, prostatism, and xerostomia, all of which may be aggravated by anticholinergic effects of TCAs, and congestive heart failure, which may predispose to the development of significant orthostatic hypotension. A 12-lead electrocardiogram is obtained to determine the presence of cardiac conduction disturbance and ischemic heart disease. Although bundlebranch block presents the greatest risk for development of complete heart block, caution is also recommended in patients with first-degree block (i.e., prolonged P-R interval) and prolonged QRS interval. Other potentially important findings include sinus node dysfunction (sick sinus syndrome), which precludes augmentation with lithium salts (see “Pretreatment Evaluation— Lithium Therapy” subsection later in this chapter), and supraventricular arrhythmia, which could be aggravated by anticholinergic effects of TCAs. Roose and Glassman (1994) originally raised the possibility that because TCAs have type 1A antiarrhythmic properties, these drugs may increase the risk of sudden death in patients with arrhythmia of any type or who have had myocardial infarction. Finally, liver function tests (e.g., bilirubin, aspartate transaminase [AST], alanine transaminase [ALT], and alkaline phosphatase) also are obtained because significant hepatic disease is a relative contraindication to use of TCAs and may lead to very high serum levels and possible toxicity. Nortriptyline Advantages. Reynolds and colleagues (Reynolds et al. 1999; Thase et al. 1997) published results of a series of very-well-designed treatment studies with elderly subjects that clearly showed the safety and efficacy of nortrip-

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tyline, administered in dosages adjusted to achieve plasma levels between 80 and 120 ng/mL, for treatment of major depression. Disadvantages. Nortriptyline has the side effects and cardiac risks described earlier for TCAs as a group. Desipramine Advantages. Desipramine has a low side-effect profile, is relatively activating, and is generally well tolerated. In nonelderly adults, desipramine appears to have a roughly linear serum level response relation (i.e., no therapeutic window), with the likelihood of response increasing as serum level rises above 115 ng/mL (Nelson et al. 1982). Thompson et al. (2001), in the absence of desipramine levels for all subjects, found that desipramine in dosages at or greater than 100 mg/day (when combined with cognitive-behavioral therapy), was more effective than either desipramine alone or cognitive-behavioral therapy alone in subjects with an average age of approximately 67; lower desipramine dosages did not appear to be effective. Response to desipramine may be predicted by a methylphenidate challenge (see “Predictors of Response to Cyclic Antidepressants” later in this chapter). Disadvantages. Desipramine is not as well studied as nortriptyline, especially in patients with cardiac conduction disturbance and congestive heart failure, and it may not be as safe as nortriptyline. As a purely noradrenergic agent, desipramine may be less effective in patients whose depression responds better to a mixed noradrenergic-serotonergic agent such as nortriptyline.

Second-Line Agents—Nontricyclics Trazodone Advantages. Trazodone has no anticholinergic effects and is extremely sedating, so it may have a role in the treatment of patients with significant sleep disturbance. Disadvantages. Trazodone may cause mild gastrointestinal upset and orthostatic hypotension. Its sedative properties limit its usefulness in many patients.

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Predictors of Response to Cyclic Antidepressants Several clinical and demographic factors have been studied as possible predictors of response to treatment of acute depression in the elderly. Age at onset of illness has produced conflicting results. In one study, patients with earlyonset depressive disorder who received treatment with nortriptyline and interpersonal therapy achieved remission of the index episode more slowly (Reynolds et al. 1998); in another study, later age at onset was the strongest predictor of slow recovery (Alexopoulos et al. 1996). In the latter study, age and chronicity of episode were also significantly associated with time to recovery. In a study conducted by Flint and Rifat (1997), high baseline anxiety level was associated with delayed response (median of 5 weeks vs. 4 weeks for patients with low anxiety scores), whereas hospitalization for the index episode of depression and attempted suicide predicted shorter time to response. Cognitive dysfunction also may affect treatment response. Kalayam and Alexopoulos (1999) found that depressed patients who remained symptomatic after treatment had more abnormal initiation and perseveration scores and longer P300 latency (elapsed time between a stimulus and the occurrence of one voltage peak in a cortical evoked potential) compared with control subjects and depressed patients who achieved remission. The researchers concluded that prefrontal dysfunction was associated with poor or delayed antidepressant response in depressed elderly patients. Specific laboratory measures and the interaction between specific life events and personality–cognitive characteristics (Mazure et al. 2000) have been reported to have predictive power with respect to subsequent antidepressant response. These laboratory measures include serum cortisol response to administration of oral dexamethasone (Spar and La Rue 1983); pretreatment measures of orthostatic hypotension (Diehl et al. 1993; Jarvik et al. 1983); response to a test dose of methylphenidate (Spar and La Rue 1985); pretreatment red blood cell counts (Mentre et al. 1998); pretreatment folate blood levels (Alpert et al. 2003); specific polymorphisms of the norepinephrine transporter gene (Yoshida et al. 2004); subacute reduction in prefrontal cortical activity per quantitative electroencephalography (Cook and Leuchter 2001); and dopaminergic supersensitivity as measured by the apomorphine challenge test (Healy and McKeon 2000). However, none of these laboratory measures has yet gained widespread clinical utility.

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Initiation and Dosage Adjustment of Cyclic Antidepressant Therapy In general, starting dosages for SSRIs and other non-TCA agents are half the usual adult dosage and are increased, as side effects allow, to the full adult dosage within the first week or two of therapy. This dosage is maintained for 6 weeks before dosage increase is considered. The likelihood of obtaining improved response by increasing the dosage beyond the recommended level is generally low, but an increase is worth trying because the side effects of these agents are so benign. Initiation of TCA therapy follows the same guidelines but typically calls for a gradual increase of dosage, as limited by side effects, to produce a plasma level of 80–120 ng/mL for nortriptyline, or the highest dosage that is safely tolerated for the other TCAs. Compliance is usually enhanced by minimizing the number of doses administered during any 24-hour period. In this regard, most of the antidepressants discussed in this chapter have an elimination half-life of about 24 hours and can be administered in a single dose, preferably in the morning for the activating agents such as fluoxetine or at bedtime for the sedating agents such as trazodone, paroxetine, fluvoxamine, mirtazapine, and the TCAs. Sertraline, citalopram, and escitalopram activate some patients and sedate others, so the timing of dosage is by trial and error. Venlafaxine and bupropion must be administered in divided doses; bedtime doses of venlafaxine are generally well tolerated, but bupropion is quite activating, and the last daily dose should not be given after 4:00 or 5:00 P.M.

Management of Cyclic Antidepressant Side Effects Most side effects caused by non-TCA agents are managed symptomatically; for example, antacids for nausea and analgesics for headache are often effective. Sexual side effects of SSRIs, which have been reported in up to 50% of adults, may respond to treatment with cyproheptadine, amantadine, yohimbine, bupropion, or central nervous system stimulants such as methylphenidate, but controlled studies are lacking (Ashton and Rosen 1998; Woodrum and Brown 1998). No effective treatment, other than dosage reduction or switching to another class of antidepressant, has been reported for SSRIinduced weight gain.

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Side effects of TCAs include anticholinergic effects (dry mouth, constipation, blurry vision, urinary hesitancy, and delirium) and orthostatic hypotension. Most of the anticholinergic effects can be managed with dosage adjustment and adjunctive agents. Dry mouth is relieved by sucking on hard, preferably sugarless candies or by chewing gum. A 1% solution of pilocarpine used as a mouthwash every 3 or 4 hours also has been reported to be helpful (Bernstein 1983). Constipation can be managed with stool softeners, bulk laxatives, and adequate fluid intake. Blurry vision may respond to 1% pilocarpine eyedrops, one drop every 4–6 hours as needed. In milder cases, artificial tears usually suffice. Urinary hesitancy is often responsive to oral bethanechol, 10– 30 mg three times a day. Patients, particularly men, are instructed to be aware of the possibility of complete urinary obstruction and to have appropriate plans should complete obstruction occur (e.g., to report to the nearest emergency department). Delirium can be life threatening and is usually responsive to discontinuation of the offending agent and supportive treatment. In the extreme case, 1–2 mg of physostigmine administered by slow intravenous push is effective. Orthostatic hypotension is a more difficult problem. This symptom tends to occur early in treatment and appears to be a “threshold” phenomenon that occurs at a certain dosage but does not necessarily worsen if the dosage is increased. Because it is worsened by dehydration and by pooling of blood in the lower extremities, orthostatic hypotension may be ameliorated by increasing salt in the patient’s diet or by administering small doses of salt-retaining steroids (e.g., 0.025–0.05 mg of fluorohydrocortisone). Support hose can be helpful, as can careful, repeated patient instruction in arising slowly and holding on to something stable for support.

Third-Line Agents—Monoamine Oxidase Inhibitors Third-line agents are usually reserved for patients who have not responded to first- and second-line treatments or who have a history of good response to agents in this class. MAOIs irreversibly inhibit monoamine oxidase (MAO), the enzyme responsible for synaptic degradation of the monoamine neurotransmitters norepinephrine, dopamine, and serotonin. MAO occurs in two forms, called MAO A and MAO B. MAO A is found in brain only and primarily oxidizes dopamine, and MAO B is found in both brain and gut and oxidizes norepinephrine, serotonin, and dopamine. MAOIs have not been as well studied

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as cyclic antidepressants in elderly patients, but they appear to be as effective (Georgotas et al. 1986). In the United States, phenelzine and tranylcypromine are available for treatment of depression, and selegiline, which selectively inhibits MAO B, is marketed primarily for adjunctive treatment of Parkinson’s disease but also has been studied in depression. Moclobemide, one of the first reversible inhibitors of MAO A, is available in Canada but not in the United States at the time of this writing. Phenelzine is administered at an initial dosage of 15 mg twice a day, gradually increasing to a maximum of 60–75 mg/day; tranylcypromine is administered at an initial dosage of 10 mg twice a day, increasing to a maximum of 50 mg/day. Selegiline is administered at dosages of 5–15 mg/day (with levodopa) for Parkinson’s disease; at this dosage, it is selective for MAO B and enhances dopaminergic transmission. But at antidepressant dosages (i.e., 40 mg/day), it loses this selectivity. Each of these agents is relatively free of sedative and anticholinergic effects and does not appear to affect cardiac conduction. These agents do cause orthostatic hypotension, however, and in the presence of sympathomimetic drugs, dietary monoamine precursors such as tryptophan or naturally occurring pressor substances such as tyramine, phenelzine, and tranylcypromine can cause severe hypertensive reactions that can be life threatening. Because of these properties, patients taking these MAOIs need to be on restricted diets and need to be strongly cautioned against ingesting certain drugs. Selegiline does not interact with dietary amines at low dosages, but it probably does interact at antidepressant dosages. Orthostatic hypotension from MAOIs is somewhat different from that produced by TCAs in that it tends to be dose related, occurs later in therapy, and may gradually subside at a fixed dosage. Phenelzine Advantages.

Phenelzine is nonstimulating and may be mildly sedating.

Disadvantages. Phenelzine causes irreversible degradation of MAO and therefore may continue to exert effects for 2 weeks or longer after discontinuation of administration, as total body MAO is gradually replaced. Tranylcypromine Advantages. Tranylcypromine is mildly stimulating and may be preferable for patients with psychomotor retardation. It is more reversibly bound to

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MAO and therefore requires only a 1-week washout period before sympathomimetic agents or diet ad libitum can be administered safely. Disadvantages. Because of its psychostimulant effects, tranylcypromine may have greater abuse potential than phenelzine. Selegiline Advantages. As mentioned, selegiline is selective for MAO B and will not interact with dietary tyramine in low dosages. However, it is probably not, by itself, an antidepressant at these dosages. Disadvantages. Selegiline is poorly studied at antidepressant dosages and, like all MAOIs, is prone to potentially dangerous interactions with other drugs. Moclobemide Advantages. Moclobemide is selective for MAO A and does not require dietary restriction. It has been well studied as an antidepressant, including in elderly subjects, and has been shown to be comparable to TCAs and SSRIs in efficacy (Amrein et al. 1997). Reversibility of MAO inhibition makes it less likely to pose a problem interacting with other agents. Disadvantages. Like all MAOIs, moclobemide is prone to potentially dangerous interactions with other drugs. General Principles of Treatment With MAOIs Pretreatment physical and laboratory examinations should be conducted as described earlier for cyclic antidepressants, including determination of pretreatment orthostatic changes in blood pressure and, based on the medical history and physical examination, assessment of the patient’s likelihood of requiring sympathomimetic agents. Elderly patients with chronic asthma or bronchitis who must take indirect-acting bronchodilators and patients with Parkinson’s disease who may require treatment with levodopa are not candidates for MAOI therapy. The patient’s reliability vis-à-vis dietary and medication restrictions must be assessed carefully. Specifically, patients who have dementia and who are monitoring their own diet and medications are poor candidates for MAOI therapy.

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Initiation of MAOI Therapy and Determination of Final Dosage Typical starting dosages are 15 mg twice a day for phenelzine, 10 mg twice a day for tranylcypromine, and 400 mg/day for moclobemide. Antidepressant effects of selegiline tend to appear at 60 mg/day. Although it has been shown in nongeriatric subjects that platelet MAO inhibition must reach 80% or more to maximize response, in clinical practice this laboratory test is rarely available, and maximum tolerable dosage or clear clinical response remains the end point of dosage titration. Practically speaking, most elderly patients experience dosage-limiting orthostatic hypotension at or before 60 mg/day of phenelzine or 40 mg/day of tranylcypromine. Management of MAOI Side Effects Orthostatic hypotension may be managed via the approaches described earlier in this chapter for cyclic antidepressants. Hypertensive crisis is usually signaled by headache, flushing, diaphoresis, and palpitations and may progress to frank hypertensive encephalopathy and neurological dysfunction. α-Adrenergic blocking agents such as phentolamine (2–5 mg intravenously) or chlorpromazine (50–100 mg intramuscularly) followed by smaller doses titrated against blood pressure may be lifesaving. The common practice of giving patients a 50- or 100-mg tablet of chlorpromazine to carry with them for ingestion in an emergency has been criticized on the grounds that after ingestion, many older patients may be so incapacitated as to be unable to reach the nearest emergency department or may experience life-threatening loss of alertness while driving for help. Special Considerations Regarding MAOIs A particular hazard is the use of sympathomimetic drug–containing cold tablets and nasal sprays (e.g., ephedrine, pseudoephedrine, phenylephrine [NeoSynephrine], phenylpropanolamine), which may not be regarded as “real medicine” by older patients. Patients must be most strenuously cautioned against taking these medications. Meperidine, for reasons that are not yet clear, interacts with MAOIs to produce an extremely serious syndrome of hyperpyrexia, muscular rigidity, and coma that has been fatal in several reported instances. Other synthetic narcotics such as dextromethorphan also have been implicated in causing this syndrome, which apparently does not occur with natural narcotics such as morphine or codeine. For added safety, patients may

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wear MedicAlert bracelets indicating that they are taking MAOIs and specifying that they should not receive meperidine. Similarly, dental procedures should be performed with local anesthetics that do not contain epinephrine.

Third-Line Agents—Psychostimulants Although controlled studies in elderly patients are lacking, a relatively large body of clinical literature supports the use of psychostimulants in elderly depressed patients, particularly those in whom medical illness precludes the use of cyclic antidepressants or MAOIs (Emptage and Semla 1996). Both amphetamines and methylphenidate have been administered, although methylphenidate is generally preferred because of its relatively lower cardiovascular side-effect profile. Dosages range from 5 to 20 mg administered orally twice a day, generally immediately before breakfast and lunch so as not to interfere with appetite or sleep. Cardiovascular side effects are typically limited to very minor increases in blood pressure and heart rate. The most common side effect is mild jitteriness, which may be managed with small doses of benzodiazepine anxiolytics, but severe dysphoria and agitation, appetite disturbance, and insomnia requiring discontinuation of treatment may occur rarely. One retrospective comparison of methylphenidate and nortriptyline found that both medications produced comparable rates of remission in patients with poststroke depression but that the time to peak response for methylphenidate was 2.4 days compared with 27 days for nortriptyline (Lazarus et al. 1994). A double-blind, placebo-controlled study of poststroke depression found that 3 weeks of treatment with methylphenidate (in dosages up to 15 mg twice daily) produced statistically significant but mild improvement in mood and was well tolerated (Grade et al. 1998). Modafinil, a more recently developed wake-promoting agent with psychostimulant properties, has been proposed as an adjunct to antidepressant therapy, and results from several open-label studies in nongeriatric subjects are encouraging (DeBattista et al. 2004; Ninan et al. 2004).

Strategies for Antidepressant Treatment Resistance Depressed patients whose symptoms have not responded to an adequate trial of a single antidepressant are candidates for one or more alternative treatment strategies: switching, augmenting, or combining antidepressants. For pur-

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poses of this section, nonresponse means that significant residual symptoms persist despite 6 weeks of treatment at adequate dosages of medication. Of course, the meaning of “adequate dosage” depends on the medication used. For nortriptyline, the dosage is adequate if it produces a plasma level between 80 and 120 ng/mL; for other TCAs and MAOIs, adequate means the highest dosage tolerated; and for trazodone, bupropion, venlafaxine, mirtazapine, and duloxetine, it means the full recommended adult dosage. For the SSRIs, a small percentage of patients may become responders if the adult dosage is doubled. Switching to Another Antidepressant The literature suggests that the preferred strategy is to switch from a single neurotransmitter–reuptake blocker (e.g., an SSRI) to a combined serotonin and norepinephrine–reuptake blocker (venlafaxine, duloxetine, or a TCA)— or if the first agent is a combined reuptake blocker, to switch to a different class of medication (i.e., TCA, MAOI, SSRI, or other reuptake inhibitor) that is likely to be safely tolerated given the patient’s overall medical status (Hirschfeld et al. 2002). The switch 1) from a TCA to an MAOI or venlafaxine or 2) from an MAOI to a TCA or venlafaxine also has been reported to be effective in some cases. This literature generally focuses on nonelderly adults, but in one study by Flint and Rifat (1996), the cumulative response rate was 85% in 101 elderly patients receiving nortriptyline, which achieved a 61% response rate; patients who did not respond to nortriptyline were then switched to phenelzine, which achieved a 64% response rate. Augmenting Ongoing Antidepressant Treatment Augmentation involves adding to an ongoing antidepressant regimen a medication that in amount or kind would not be expected to have antidepressant effects. Medications used as augmenters include lithium, thyroid hormone (levothyroxine or triiodothyronine), pindolol, methylphenidate, buspirone, bupropion, risperidone, and olanzapine. Although no double-blind, placebocontrolled, random-assignment studies of any of these approaches have been done in elderly patients, the published database for lithium augmentation of a cyclic antidepressant or an MAOI and thyroid hormone augmentation of a TCA is most substantial and warrants review (Nelson 2000). The following procedure for lithium augmentation is recommended: after an adequate trial

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of cyclic antidepressant or MAOI, lithium is added in low doses (e.g., 300 mg twice daily) and titrated to at least 0.4 mEq/mL. Rapid response (i.e., within 3–5 days) is common, but some patients require up to 2 weeks of augmentation before peak response occurs. Generally, side effects are additive. Thyroid augmentation involves the addition of 25–50 µg/day of triiodothyronine to an ongoing regimen of a TCA. Combining Antidepressants Combination therapy involves the simultaneous administration of two or more agents in dosages that would be expected to have antidepressant effects if administered alone. Combinations that appear, on the basis of largely uncontrolled, small studies, to be safe and to provide some enhanced effectiveness over either agent administered alone include a TCA plus an MAOI, a TCA plus an SSRI, an SSRI plus trazodone, an SSRI plus another SSRI, moclobemide (a reversible MAOI) plus an SSRI, bupropion plus an SSRI, bupropion plus venlafaxine, mirtazapine plus an SSRI, venlafaxine plus an SSRI, and reboxetine plus an SSRI (Lam et al. 2002). Combinations chosen to produce reuptake inhibition of both serotonin and norepinephrine may be most effective. One double-blind, random-assignment study of middle-aged adults with nonpsychotic major depression found that desipramine (norepinephrine reuptake blocker) and fluoxetine (SSRI) together were significantly more effective than either drug alone in inducing remission after 6 weeks of treatment. Side effects (orthostatic hypotension, tachycardia) were those typical for desipramine (Nelson et al. 2004). Which Strategy Is Best? Because switching antidepressants requires tapering the first agent, then a washout period, followed by administration of the second agent (with its own latency of onset of action), and combination therapy exposes patients to at least additive side effects and risks of adverse reactions, augmentation would appear to be the optimal strategy for older patients with treatment-resistant depression. Given the increased sensitivity of older patients to side effects and adverse reactions, combination therapy must be regarded as the least advisable of the three approaches to treatment resistance discussed in this section.

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Maintenance Treatment It is now well established that relapse and recurrence are best prevented by maintaining patients on the same dose of antidepressant required to induce remission. Reynolds (1994) used this approach with nortriptyline (titrating blood levels between 80 and 120 ng/mL) and reported that 80% of remissions were sustained for a year or more.

Psychopharmacotherapy for Psychotic Depression The proportion of depressed patients who present with delusions and/or hallucinations appears to increase with age but does not seem to be related to age at onset of depression (Brodaty et al. 1997). Treatment entails the simultaneous administration of high-potency, low-dose antipsychotic medications such as haloperidol, risperidone, or olanzapine in combination with a TCA, SSRI, or other antidepressant. The Texas Medication Algorithm Project used this combination successfully to treat psychotic depression in nonelderly adults. Their algorithm specified that partial responders were switched from a TCA plus an antipsychotic to a non-TCA plus an antipsychotic or from a non-TCA plus an antipsychotic to a TCA plus an antipsychotic; patients who still did not respond were switched to electroconvulsive therapy (ECT), and partial responders to ECT were treated with a previously untried antidepressant with lithium augmentation (Trivedi et al. 2004). The typical pattern of response is marked by rapid (i.e., within days) reduction of anxiety, fear, social withdrawal, insomnia, hypervigilance, and disordered behavior related to the delusional beliefs, followed by gradual improvement (i.e., within a few weeks) in mood, neurovegetative symptoms, and hallucinations (if present), followed finally (i.e., within weeks to months) by fading of the delusional beliefs per se. Remission rates are usually much lower than is typical for nonpsychotic depression. Flint and Rifat (1998a) reported a 50% response rate in elderly persons with psychotic depression who received treatment for 7 weeks with nortriptyline, perphenazine, and lithium augmentation. Maintenance treatment requires full dosages of both categories of medication because evidence indicates that the prognosis for successful long-term remission is relatively poor when antidepressant monotherapy is administered (Flint and Rifat 1998b).

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Psychopharmacotherapy for Bipolar Depression For patients with bipolar depression, treatment may be initiated with mood stabilizers alone, and both lithium and lamotrigine have been shown to be effective antidepressants (Young et al. 2004). Dosing of lithium is as per guidelines in the section “Psychopharmacotherapy for Bipolar Disorder” later in this chapter, and dosing of lamotrigine follows the same guidelines as for young and middle-aged adults. If monotherapy is ineffective, antidepressants may be added, following the principles spelled out earlier, with an important modification. TCAs are the third-line treatment option in bipolar depression because TCAs may be more prone to induce a switch into mania or hypomania than either 1) the SSRIs or other first-line agents (including venlafaxine, duloxetine, and mirtazapine) or 2) MAOIs, the second-line treatment. Although switch rates for elderly patients per se have not been published, Gijsman et al. (2004) reviewed six clinical trials in middle-aged adults and found a 10% switch rate for TCAs and only 3.2% for all other antidepressants combined (although the difference was not statistically significant). Antidepressant treatment alone may be prescribed, but the most cautious approach calls for simultaneous treatment with a mood stabilizer; in this context, lithium, lamotrigine, valproate, and carbamazepine are all appropriate.

Electroconvulsive Therapy ECT remains the single most effective treatment for major depression with or without psychosis in elderly patients. Remission rates in the range of 75%– 90% or greater can be obtained in “naïve” patients (i.e., those who have not tried and failed other treatments), but in the more typical elderly patient who has had an inadequate response to other treatments, response rates (defined as a decline of 50% or more in pretreatment depression ratings) are in the 80%–90% range, even in the “old-old” (i.e., older than 75), and side effects are usually limited to transient memory impairment (Tew et al. 1999). ECT is about equally effective in psychotic and nonpsychotic depression; however, because psychopharmacological therapy has relatively limited effectiveness in psychotic depression, this condition is the strongest indication for ECT as a first-line therapy. Other indications for ECT as the treatment of first choice include

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• • • •

Active suicidality Severe anorexia High likelihood of inability to tolerate antidepressant side effects High likelihood of medication noncompliance

ECT is more commonly used, however, after psychopharmacological treatment failure. Unilateral, nondominant electrode placement minimizes memory impairment, but suprathreshold dosages of current (2.5 times seizure threshold or more) are required to match the therapeutic efficacy of bilateral treatment in elderly patients (Tew et al. 1999). One effective approach is to use brief-pulse, bilateral electrode placement at levels just above seizure threshold (typically between 60 and 140 millicoulombs), administering three treatments per week. The switch to high-dose unilateral electrode placement is made only if memory impairment threatens to endanger the patient or causes sufficient subjective distress to threaten continued compliance with treatment. Psychopharmacological treatments— other than low-dose benzodiazepines, haloperidol, or an atypical antipsychotic medication (e.g., risperidone, olanzapine, ziprasidone, quetiapine) as needed for control of anxiety, sleep, agitation, or psychosis—are discontinued during the course of ECT. Theophylline has been linked to status epilepticus during ECT and also should be discontinued if possible (Fink and Sackeim 1998). Seizure generalization and duration are monitored via the cuff-isolation technique, and stimuli producing a seizure that lasts for less than 25 seconds are repeated. Treatments are administered until symptom reduction has reached a plateau, defined retrospectively as “no further improvement over the past three treatments.” This approach is more aggressive than that used by either the typical community-based program or most clinical trials. A naturalistic study of ECT as administered in the community found that outcomes were significantly worse (i.e., remission achieved in only 30%–47%) than those reported in clinical trials, and the investigators concluded that the most likely explanation for the unexpectedly low remission rate was that community practitioners often discontinued treatment before full remission was reached (Prudic et al. 2004). Our approach produces outcomes similar to (or better than) those achieved in clinical trials and typically requires about 9 treatments to produce full remission (although the range can be from 6 to 20). Our approach also

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seems to produce a more enduring response, at least in the first several weeks after treatment, than that reported by most investigators. Prophylactic antidepressant treatment is initiated immediately after the last ECT treatment. The associated anterograde memory impairment, which is cumulative over the course of treatment, typically reaches the level of mild disorientation to time and mild to moderate anterograde and retrograde memory loss. All of these symptoms usually clear rapidly and are clinically undetectable a week or so after the last treatment, but in some cases, they may persist for as long as 3 or 4 weeks. Retrograde memory loss, especially for events occurring during the course of treatment, may persist much longer, and memory for some intrahospitalization events may be permanently lost. Given this information, along with the recovery statistics mentioned earlier, and the extremely low mortality rate of ECT (less than 1 death per 10,000 patients), the great majority of patients are willing to accept this degree of memory loss as part of the cost of treatment.

Experimental Therapies Repetitive Transcranial Magnetic Stimulation Repetitive transcranial magnetic stimulation (rTMS) uses a rapidly changing magnetic field (produced by electrical coils placed near the scalp) to induce electrical current in brain tissue. It has been studied as an adjunct to antidepressants and as a solo treatment for depressive disorders and is regarded by some investigators as a potential alternative to ECT. Results from open studies have been mixed, and a meta-analysis by Martin et al. (2003) concluded that “current trials are of low quality and provide insufficient evidence to support the use of rTMS in the treatment of depression” (p. 480). Studies published since that review offer little to challenge that assessment. A doubleblind, controlled study found “a modest, clinically nonrelevant decrease in HAM-D scores in both rTMS and sham patients over 2 weeks of treatment” (p. 1323), but over the subsequent 12-week follow-up, the rTMS group continued to improve significantly compared with the placebo group. The authors concluded that “decrease of depressive symptoms may continue after the cessation of rTMS stimulation” (Koerselman et al. 2004, p. 1323). An

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open study supported this conclusion, finding persistent antidepressant effects of rTMS over a 4-month follow-up period (Benadhira et al. 2005).

Vagus Nerve Stimulation Brain stimulation via application of pulsed electrical current to the left cervical vagus nerve has established efficacy as adjunctive therapy in treatmentresistant epilepsy and also has been studied in treatment-resistant depression. The procedure requires surgical implantation of a device that applies small doses (typically less than 1.5 mA) of electrical current to the vagus nerve multiple times per second (a typical frequency is 20 Hz) for varying periods, with a typical schedule being 30 seconds every 5 minutes. The dose is externally controllable and is typically set to cycle continuously, 24 hours per day. Side effects are usually minimal and include voice alteration, neck pain, and dyspnea. Psychotropic medications are commonly administered concomitantly, and even ECT has been administered to patients with an implanted stimulator, although the device was turned off during ECT (Marangell et al. 2002). Results of several small, open studies have been promising: Rush et al. (2000) reported 40% improvement in 30 patients receiving treatment for 10 weeks, and a 1-year follow-up study of the same subjects (Marangell et al. 2002) found that the response rate was sustained and that the remission rate actually increased (from 17% [5 of 30] to 29% [8 of 28]). On the basis of these and other results, a large-scale, multicenter, double-blind, randomized, parallel-group, sham-controlled study is under way at 21 academic sites in North America. Preliminary results from a subset of 21 subjects (11 who received active treatment for 22 weeks and 10 who received active treatment for 10 weeks and sham treatment for 12 weeks) in this study indicated no statistically significant difference in outcome, as measured by Ham-D and Clinical Global Impression Scale scores, but there was a trend toward greater reduction in Ham-D scores in the subjects who received 22 weeks of active treatment (Carpenter et al. 2004). None of the studies of vagus nerve stimulation has focused on elderly patients, and a more definitive conclusion regarding the role of vagus nerve stimulation in geriatric depression must await the results of the larger study.

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Complementary and Alternative Approaches According to a recent national survey, 50% or more of patients who report severe depression have used complementary and alternative therapies in an attempt to alleviate symptoms (Kessler et al. 2001). These approaches include cognitive techniques such as relaxation and biofeedback, oral medications such as herbal medicine and homeopathy, physical treatments such as massage and chiropractic, and other approaches such as spiritual healing and dietary modification. Most persons using these approaches also seek treatment professionally (e.g., by a psychiatrist, psychologist, or general physician), which provides an opportunity to assess for possible adverse effects of combining alternative therapies with pharmacotherapies (e.g., mild serotonin syndrome from mixing St. John’s wort and SSRIs). Clinicians need to inquire about the use of complementary and alternative approaches, become familiar with current data on efficacy, and inform patients of any potential known risks. A recent meta-analysis on adverse effects of St. John’s wort concluded that it is safe and well tolerated if taken under control of a physician (Knuppel and Linde 2004), but use of this supplement appears to have declined among adults in the United States from a peak in the 1990s (Kelly et al. 2005). Encouraging lifestyle modifications such as regular exercise may be useful in reducing depressive symptoms, especially in combination with other therapies. Group therapy that used an eclectic approach that combined exercise and preventive health behaviors with psychotherapies (including cognitive and reminiscence therapies) and social skills training was effective in reducing depressive symptoms among a large group of older women living in subsidized housing; however, it was more effective among relatively young (55- to 75-year-old) white women than among minority women and individuals older than 75 (Husaini et al. 2004). Educational materials that explain geriatric depression and its effect on family systems (e.g., Miller and Reynolds 2003) are a potentially beneficial adjunct to family, group, or individual therapy. However, few controlled studies of the effectiveness of such self-help materials in treating depression have been done. A recent meta-analytic review (Anderson et al. 2005) not limited to studies of geriatric patients found beneficial effects compared with a delayed-treatment control condition for bibliotherapies that use the popular

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book Feeling Good (Burns 1999); however, many other self-help depression books on the market have not been systematically studied.

Hypomania and Mania The treatment of signs and symptoms of elevated mood (including reduced need for sleep, irritability, distractibility, hyperactivity, pressured speech, flight of ideas, circumstantiality and tangentiality, grandiosity, impulsivity, and excessive involvement in pleasurable activities that have a high potential for painful consequences), with or without hallucinations and delusions, in elderly patients generally follows the same principles as for young and middleaged adults. In hypomania or mania due to a general medical condition, the underlying medical condition is typically treated in parallel with psychosocial and psychopharmacological management of signs and symptoms of hypomania. Similarly, substance-induced hypomania or mania is treated by discontinuing or adjusting the dosage of offending substances, when possible. Although this discontinuation or adjustment may be adequate to bring signs and symptoms under control, safety considerations may warrant initiating psychosocial and psychopharmacological management of signs and symptoms while waiting for the substance effects to wear off and euthymia to return.

Bipolar Disorder The site of treatment of bipolar disorder depends on the urgency of the clinical situation. In the acute manic phase, inpatient treatment is indicated, whereas outpatient management is often sufficient for hypomania or bipolar depression without suicidality.

Psychosocial Therapy for Bipolar Disorder Psychosocial treatment of mania and hypomania is typically aimed at optimizing compliance with somatic therapies and assisting patients and families with the often daunting task of establishing and maintaining appropriate behavioral boundaries. Counseling and support are also useful in the aftermath of a hypomanic or manic episode, when patients may find themselves alien-

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ated from friends, family, treating physicians, and other caregivers. Generally, insight-oriented therapies are avoided during the acute phase of illness but may be quite effective when the most severe symptoms are under control. Both individual and family therapy approaches can be used, whereas group settings may not provide enough structure to allow the elderly bipolar patient to benefit. Psychosocial treatment of bipolar depression is similar to the treatment of unipolar depression but calls for more psychoeducation of the patient and family regarding the early signs of a switch into mania, which can occur spontaneously or be provoked by antidepressant therapy.

Psychopharmacotherapy for Bipolar Disorder Depending on the acuity of illness, psychopharmacological management of hypomania or mania in elderly patients may occur in an inpatient or an outpatient setting. Inpatients are typically more impaired and may require a twophase approach to treatment. In phase one, the most dangerous or crippling symptoms are rapidly brought under control, and in phase two, remission is sought. Phase One—Acute Stabilization and Phase Two—Acute Treatment A widely used approach to phase one entails administration of high-potency, low-dose neuroleptic medications such as oral or intramuscular haloperidol, olanzapine, or ziprasidone, or comparable oral doses of risperidone. Initial doses are in the range of 0.5–2.0 mg for each and are gradually raised until side effects supervene or symptoms are controlled. Typical effective dosages are 1–2 mg/day of haloperidol, 1–4 mg/day of risperidone, 5–10 mg/day of olanzapine, and 10–20 mg/day of ziprasidone (which is contraindicated in patients who have a prolonged QTc interval, recent myocardial infarction, or uncompensated congestive heart failure or who are taking other medications that can prolong the QTc interval). Once symptoms are controlled, phase two entails oral administration of lithium carbonate, divalproex, or another mood-stabilizing agent. If lithium is selected, the appropriate pretreatment evaluation is conducted (see subsection “Pretreatment Evaluation—Lithium Therapy” later in this chapter), and then dosages are adjusted to achieve serum levels in the 0.4–0.8 mEq/mL range. It is important to remember that elderly patients typically have reduced

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glomerular filtration rates (by 30%–50%) compared with young adults, and the elimination half-life of lithium may be increased up to 36 hours. Therefore, elderly patients generally require smaller dosages of lithium to reach therapeutic serum levels; a typical starting dosage may be as low as 150 mg/ day. The increased half-life allows once-a-day dosing, which is also believed to reduce side effects compared with divided doses (Hardy et al. 1987). After 6–7 days at a steady daily dosage, serum for determination of lithium level is drawn, and an approximately linear dose–serum level relation is assumed within therapeutic dosage ranges. Divalproex is an acceptable alternative to lithium in manic elderly patients, particularly in those who develop deterioration of cognitive performance during lithium treatment (Young et al. 2004). Dosages of divalproex range from 400 to 1,000 mg/day (in divided doses) and are adjusted to produce serum levels between 50 and 120 µg/mL. Divalproex may be of particular value in rapid-cycling patients and those with mixed mania (i.e., with depressive symptoms and manic symptoms). Side effects are usually minimal and include sedation, nausea, and ataxia. Other agents that have been proposed for acute and maintenance treatment of geriatric bipolar disorder include the anticonvulsants carbamazepine, oxcarbazepine, lamotrigine, topiramate, and gabapentin, but none has been studied in elderly bipolar patients per se. Studies in middle-aged subjects suggest that carbamazepine and lamotrigine both have acute (i.e., phase two) antimanic effects and also may be effective for prophylaxis of mania and hypomania (Ichim et al. 2000; Sachs et al. 2000). Carbamazepine may be most effective in manic patients who cycle rapidly and who have predominantly irritable rather than euphoric mood, features that have been reported to occur relatively commonly in elderly manic patients. Dosages of carbamazepine (typically beginning at 200 mg orally twice a day) are adjusted to produce blood levels in the range of 4–12 ng/mL, and antimanic effects appear after 4–7 days. Because carbamazepine induces its own metabolism, dosage increase is commonly required after 4–6 weeks of therapy to maintain therapeutic blood levels. Side effects of and adverse reactions to carbamazepine include sedation, dizziness, ataxia, nausea and vomiting, mild anticholinergic effects, skin rash (rarely including Stevens-Johnson syndrome and toxic epidermal necrolysis), and worsening of congestive heart failure, hypertension, and hypotension. Rare cases of aplastic anemia and agranulocytosis also

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have been reported; thus, baseline blood studies and periodic reevaluations are necessary for patients taking this drug. Carbamazepine undergoes hepatic microsomal metabolism, so the general pharmacokinetic and pharmacodynamic considerations discussed in Chapter 2 (“Normal Aging”) apply. Lamotrigine in nonelderly manic patients is as effective as lithium for phase two management, and one study in elderly patients found that lamotrigine added to lithium or divalproex led to remission (Robillard and Conn 2002). To reduce the risk of rash, a rigid schedule of dosage increases is required: for nonelderly adults, it is 25 mg once daily for 1 week, 50 mg once daily for the second week, and 100 mg once daily for the last 2 weeks. Elderly patients may require even smaller dosages at each step. Phase Three—Long-Term Management of Bipolar Disorder Once remission of mania, hypomania, or bipolar depression is achieved, the next goal of treatment is long-term prevention of recurrence. As is the case for young adults, divalproex, carbamazepine, other anticonvulsants, and lithium are the primary agents in widespread use. Plasma levels of lithium in the elderly are generally lower than those required for reduction of acute symptoms, typically in the range of 0.3–0.8 mEq/mL. Dosages required to sustain these levels are typically lower than those needed for middle-aged adults, and elderly patients are somewhat more prone to develop toxicity at any given plasma level of lithium; otherwise, principles of management are essentially the same as for younger patients. Divalproex and carbamazepine are also effective for longterm management, and dosages are adjusted to minimize side effects while maintaining blood levels in the therapeutic range described earlier. Pretreatment Evaluation—Lithium Therapy Physical and neurological examination, laboratory studies, and a 12-lead electrocardiogram are recommended. The physical and neurological examination should be specifically oriented toward detecting thyroid enlargement, evidence of renal dysfunction, and tremor, all of which may be exacerbated by lithium therapy. Evidence of congestive heart failure, which may require initiation of diuretic therapy, is particularly important because diuretics can significantly increase lithium blood levels. In patients with musculoskeletal disease who may require treatment with nonsteroidal anti-inflammatory agents or patients with hypertension who may require angiotensin-converting

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enzyme inhibitors, caution is necessary because both categories of medication can cause clinically significant increases in serum lithium levels. The electrocardiogram is aimed at ruling out sick sinus syndrome, which is a strong relative contraindication to lithium therapy because significant bradycardia or dysrhythmia may be precipitated. Benign nonspecific T-wave abnormalities and U waves that reverse with cessation of treatment are common in patients taking lithium and do not require discontinuation of treatment. The laboratory evaluation is oriented toward detection of renal dysfunction (i.e., serum creatinine, serum urea nitrogen, electrolytes) and establishment of pretreatment thyroid function (thyrotropin, total triiodothyronine). Because lithium therapy can affect thyroid function, periodic (e.g., every 6 months) physical examination of the thyroid and reevaluation of serum thyrotropin and triiodothyronine levels are recommended. Management of Lithium Side Effects Acute side effects include nausea, diarrhea, mild polydipsia and polyuria, and generalized fine tremor. Nausea can be minimized by administering doses after meals and by preceding doses with prophylactic antacids. Diarrhea is usually mild and intermittent and rarely requires concomitant antidiarrheal therapy. Tremor is not usually of clinical significance and rarely requires dosage manipulation. Delirium, sedation, and “cognitive dulling” can occur but are typically seen at higher serum levels (i.e., >1.0 mEq/mL). Side effects of long-term lithium therapy may include hypothyroidism and goiter, and the question of renal tubular damage remains controversial. Pretreatment Evaluation—Other Mood Stabilizers Divalproex can cause thrombocytopenia, and carbamazepine can cause neutropenia, hepatic toxicity, and, rarely, agranulocytosis. A complete blood count is recommended prior to initiating treatment with either agent, and liver function studies should be done prior to initiating carbamazepine therapy.

References Alexopoulos GS, Meyers BS, Young RC, et al: Recovery in geriatric depression. Arch Gen Psychiatry 53:305–312, 1996

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Alpert M, Silva RR, Pouget ER: Prediction of treatment response in geriatric depression from baseline folate level: interaction with an SSRI or tricyclic antidepressant. J Clin Psychopharmacol 23:309–313, 2003 American Psychological Association: Guidelines for psychological practice with older adults. Am Psychol 59:236–260, 2004 Amrein R, Stabl M, Henauer S, et al: Efficacy and tolerability of moclobemide in comparison with placebo, tricyclic antidepressants, and selective serotonin reuptake inhibitors in elderly depressed patients: a clinical overview. Can J Psychiatry 42:1043–1050, 1997 Anderson L, Lewis G, Araya R, et al: Self-help books for depression: how can practitioners and patients make the right choice? Br J Gen Pract 55:387–392, 2005 Areán PA, Cook BL: Psychotherapy and combined psychotherapy/pharmacotherapy for late life depression. Biol Psychiatry 52:293–303, 2002 Areán PA, Hegel MT, Reynolds CF: Treating depression in older medical patients with psychotherapy. Journal of Clinical Geropsychology 7:93–104, 2001 Areán PA, Ayalon L, Hunkeler E, et al: Improving depression care for older, minority patients in primary care. Med Care 43:381–390, 2005 Ashton AK, Rosen RC: Bupropion as an antidote for serotonin reuptake inhibitor– induced sexual dysfunction. J Clin Psychiatry 59:112–115, 1998 Benadhira R, Saba G, Samaan A, et al: Transcranial magnetic stimulation for refractory depression (letter). Am J Psychiatry 162:193, 2005 Bernstein JG: Drug Therapy in Psychiatry. Boston, MA, Wright, 1983 Brodaty H, Luscombe G, Parker G, et al: Increased rate of psychosis and psychomotor change in depression with age. Psychol Med 27:1205–1213, 1997 Burns DD: Feeling Good: The New Mood Therapy. New York, Avon Books, 1999 Carpenter LL, Moreno FA, Kling MA, et al: Effect of vagus nerve stimulation on cerebrospinal fluid monoamine metabolites, norepinephrine, and gammaaminobutyric acid concentrations in depressed patients. Biol Psychiatry 56:418– 426, 2004 Cook IA, Leuchter AF: Prefrontal changes and treatment response prediction in depression. Semin Clin Neuropsychiatry 6:113–120, 2001 DeBattista C, Lembke A, Solvason HB, et al: A prospective trial of modafinil as an adjunctive treatment of major depression. J Clin Psychopharmacol 24:87–90, 2004 Diehl DJ, Houck PR, Paradis C, et al: Pretreatment systolic orthostatic blood pressure and treatment response in geriatric depression: a revisit. J Clin Psychopharmacol 13:189–193, 1993 Emptage RE, Semla TP: Depression in the medically ill elderly: a focus on methylphenidate. Ann Pharmacother 30:151–157, 1996

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Fink M, Sackeim HA: Theophylline increases the risk of status epilepticus in ECT. J ECT 14:286–290, 1998 Flint AJ, Rifat SL: The effect of sequential antidepressant treatment on geriatric depression. J Affect Disord 36:95–105, 1996 Flint AJ, Rifat SL: Effect of demographic and clinical variables on time to antidepressant response in geriatric depression. Depress Anxiety 5:103–107, 1997 Flint AJ, Rifat SL: The treatment of psychotic depression in later life: a comparison of pharmacotherapy and ECT. Int J Geriatr Psychiatry 13:23–28, 1998a Flint AJ, Rifat SL: Two-year outcome of psychotic depression in late life. Am J Psychiatry 155:178–183, 1998b Gallagher-Thompson D, Thompson LW: Applying cognitive-behavioral therapy to the psychological problems of later life, in A Guide to Psychotherapy and Aging: Effective Clinical Interventions in a Life-Stage Context. Edited by Zarit SH, Knight BG. Washington, DC, American Psychological Association, 1996, pp 61–92 Gatz M, Fiske A, Fox LS, et al: Empirically validated psychological treatments for older adults. Journal of Mental Health and Aging 4:9–46, 1998 Georgotas A, McCue RE, Hapworth W, et al: Comparative efficacy and safety of MAOIs versus TCAs in treating depression in the elderly. Biol Psychiatry 21:1155–1166, 1986 Gijsman HJ, Geddes JR, Rendell JM, et al: Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry 161:1537– 1547, 2004 Gildengers AG, Houck PR, Mulsant BH, et al: Course and rate of antidepressant response in the very old. J Affect Disord 69:177–184, 2002 Grade C, Redford B, Chrostowski J, et al: Methylphenidate in early poststroke recovery: a double-blind, placebo-controlled study. Arch Phys Med Rehabil 79:1047– 1050, 1998 Haight BK, Webster JD (eds): The Art and Science of Reminiscing: Theory, Research, Methods, and Applications. Bristol, PA, Taylor & Francis, 1995 Hardy BG, Shulman KI, Mackenzie SE, et al: Pharmacokinetics of lithium in the elderly. J Clin Psychopharmacol 7:153–158, 1987 Harpole LH, Williams JW Jr, Olsen MK, et al: Improving depression outcomes in older adults with comorbid medical illness. Gen Hosp Psychiatry 27:4–12, 2005 Haverkamp R, Areán P, Hegel MT, et al: Problem-solving treatment for complicated depression in late life: a case study in primary care. Perspect Psychiatr Care 40:45– 52, 2004 Healy E, McKeon P: Dopaminergic sensitivity and prediction of antidepressant response. J Psychopharmacol 14:152–156, 2000

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Higgins N, Regan C: A systematic review of the effectiveness of interventions to help older people adhere to medication regimes. Age Ageing 33:224–229, 2004 Hirschfeld RM, Montgomery SA, Aguglia E, et al: Partial response and nonresponse to antidepressant therapy: current approaches and treatment options. J Clin Psychiatry 63:826–837, 2002 Husaini BA, Cummings S, Kilbourne B, et al: Group therapy for depressed elderly women. Int J Group Psychother 54:295–319, 2004 Ichim L, Berk M, Brook S: Lamotrigine compared with lithium in mania: a doubleblind randomized controlled trial. Ann Clin Psychiatry 12:5–10, 2000 Jarvik LF, Read SL, Mintz J, et al: Pretreatment orthostatic hypotension in geriatric depression: predictor of response to imipramine and doxepin. J Clin Psychopharmacol 3:368–372, 1983 Kalayam B, Alexopoulos GS: Prefrontal dysfunction and treatment response in geriatric depression. Arch Gen Psychiatry 56:713–718, 1999 Kelly JP, Kaufman DW, Kelley K, et al: Recent trends in use of herbal and other products. Arch Intern Med 165:281–286, 2005 Kessler RC, Soukup J, Davis RB, et al: The use of complementary and alternative therapies to treat anxiety and depression in the United States. Am J Psychiatry 158:289–294, 2001 Knuppel L, Linde K: Adverse effects of St. John’s wort: a systematic review. J Clin Psychiatry 65:1470–1479, 2004 Koerselman F, Laman DM, van Duijn H, et al: A 3-month, follow-up, randomized, placebo-controlled study of repetitive transcranial magnetic stimulation in depression. J Clin Psychiatry 65:1323–1328, 2004 Lam RW, Wan DD, Cohen NL, et al: Combining antidepressants for treatment-resistant depression: a review. J Clin Psychiatry 63:685–693, 2002 Landreville P: Cognitive bibliotherapy for depression in older adults with a disability. Clin Gerontol 19:69–75, 1998 Lazarus LW, Moberg PJ, Langsley PR, et al: Methylphenidate and nortriptyline in the treatment of poststroke depression: a retrospective comparison. Arch Phys Med Rehabil 75:403–406, 1994 Marangell LB, Rush AJ, George MS, et al: Vagus nerve stimulation (VNS) for major depressive episodes: one year outcomes. Biol Psychiatry 51:280–287, 2002 Martin JL, Barbanoj MJ, Schlaepfer TE, et al: Repetitive transcranial magnetic stimulation for the treatment of depression. Systematic review and meta-analysis. Br J Psychiatry 182:480–491, 2003 Mazure CM, Bruce ML, Maciejewski PK, et al: Adverse life events and cognitivepersonality characteristics in the prediction of major depression and antidepressant response. Am J Psychiatry 157:896–903, 2000

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Mentre F, Golmard JL, Launay JM, et al: Relationships between low red blood cell count and clinical response to fluoxetine in depressed elderly patients. Psychiatry Res 81:403–405, 1998 Miller MD, Reynolds CF: Living Longer Depression Free: A Family Guide to Recognizing, Treating, and Preventing Depression in Later Life. Baltimore, MD, Johns Hopkins University Press, 2003 Nebes RD, Pollock BG, Mulsant BH, et al: Cognitive effects of paroxetine in older depressed patients. J Clin Psychiatry 60:26–29, 1999 Nelson JC: Augmentation strategies in depression 2000. J Clin Psychiatry 61 (suppl 2):13–19, 2000 Nelson JC, Jatlow P, Quinlan DM, et al: Desipramine plasma concentration and antidepressant response. Arch Gen Psychiatry 39:1419–1422, 1982 Nelson JC, Mazure CM, Jatlow PI, et al: Combining norepinephrine and serotonin reuptake inhibition mechanisms for treatment of depression: a double-blind, randomized study. Biol Psychiatry 55:296–300, 2004 Newhouse PA: Use of serotonin selective reuptake inhibitors in geriatric depression. J Clin Psychiatry 57:12–22, 1996 Ninan PT, Hassman HA, Glass SJ, et al: Adjunctive modafinil at initiation of treatment with a selective serotonin reuptake inhibitor enhances the degree and onset of therapeutic effects in patients with major depressive disorder and fatigue. J Clin Psychiatry 65:414–420, 2004 Pampallona S, Bollini P, Kupelnick B, et al: Patient adherence in the treatment of depression. Br J Psychiatry 180:104–110, 2002 Pampallona S, Bollini P, Tibaldi G, et al: Combined pharmacotherapy and psychological treatment for depression: a systematic review. Arch Gen Psychiatry 61:714– 719, 2004 Prudic J, Olfson M, Marcus SC, et al: Effectiveness of electroconvulsive therapy in community settings. Biol Psychiatry 55:301–312, 2004 Reynolds CF III: Treatment of depression in late life. Am J Med 97:39S–46S, 1994 Reynolds CF III, Dew MA, Frank E, et al: Effects of age at onset of first lifetime episode of recurrent major depression on treatment response and illness course in elderly patients. Am J Psychiatry 155:795–799, 1998 Reynolds CF III, Frank E, Dew MA, et al: Treatment of 70(+)-year-olds with recurrent major depression: excellent short-term but brittle long-term response. Am J Geriatr Psychiatry 7:64–69, 1999 Robillard M, Conn DK: Lamotrigine use in geriatric patients with bipolar depression. Can J Psychiatry 47:767–770, 2002

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Roose SP, Glassman AH: Antidepressant choice in the patient with cardiac disease: lessons from the Cardiac Arrhythmia Suppression Trial (CAST) studies. J Clin Psychiatry 55 (suppl A):83–87, 1994 Rush AJ, George MS, Sackeim HA, et al: Vagus nerve stimulation (VNS) for treatmentresistant depressions: a multicenter study. Biol Psychiatry 47:276–286, 2000 Sachs GS, Printz DJ, Kahn DA, et al: The Expert Consensus Guideline Series: medication treatment of bipolar disorder 2000. Postgrad Med (Spec No):1–104, 2000 Sauer WH, Berlin JA, Kimmel SE: Effect of antidepressants and their relative affinity for the serotonin transporter on the risk of myocardial infarction. Circulation 1:32–36, 2003 Schatzberg AF, Kremer C, Rodrigues HE, et al: Mirtazapine vs. Paroxetine Study Group: double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients. Am J Geriatr Psychiatry 10:541–550, 2002 Serrano JP, Latorre JM, Gatz M, et al: Life review therapy using autobiographical retrieval practice for older adults with depressive symptomatology. Psychol Aging 19:270–277, 2004 Settle EC, Stahl SM, Batey SR, et al: Safety profile of sustained-release bupropion in depression: results of three clinical trials. Clin Ther 21:454–463, 1999 Spar JE, La Rue A: Major depression in the elderly: DSM-III criteria and the dexamethasone suppression test as predictors of treatment response. Am J Psychiatry 140:844–847, 1983 Spar JE, La Rue A: Acute response to methylphenidate as a predictor of outcome of treatment with TCAs in the elderly. J Clin Psychiatry 46:466–469, 1985 Taylor WD, Doraiswamy PM: A systematic review of antidepressant placebo-controlled trials for geriatric depression: limitations of current data and directions for the future. Neuropsychopharmacology 29:2285–2299, 2004 Tew JD, Mulsant BH, Haskett RF, et al: Acute efficacy of ECT in the treatment of major depression in the old-old. Am J Psychiatry 156:1865–1870, 1999 Thase ME, Greenhouse JB, Frank E, et al: Treatment of major depression with psychotherapy or psychotherapy-pharmacotherapy combinations. Arch Gen Psychiatry 54:1009–1015, 1997 Thompson LW, Coon DW, Gallagher-Thompson D, et al: Comparison of desipramine and cognitive/behavioral therapy in the treatment of elderly outpatients with mildto-moderate depression. Am J Geriatr Psychiatry 9:225–240, 2001 Tisher M, Dean S: Family therapy with the elderly. Australian and New Zealand Journal of Family Therapy 21:94–101, 2000

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Trick L, Stanley N, Rigney U, et al: A double-blind, randomized, 26-week study comparing the cognitive and psychomotor effects and efficacy of 75 mg (37.5 mg b.i.d.) venlafaxine and 75 mg (25 mg mane, 50 mg nocte) dothiepin in elderly patients with moderate major depression being treated in general practice. J Psychopharmacol 18:205–214, 2004 Trivedi MH, Rush AJ, Crismon ML, et al: Clinical results for patients with major depressive disorder in the Texas Medication Algorithm Project. Arch Gen Psychiatry 61:669–680, 2004 Unützer J, Katon W, Callahan CM, et al: Depression treatment in a sample of 1,801 depressed older adults in primary care. J Am Geriatr Soc 51:505–514, 2003 Woodrum ST, Brown CS: Management of SSRI-induced sexual dysfunction. Ann Pharmacother 32:1209–1215, 1998 Yoshida K, Takahashi H, Higuchi H, et al: Prediction of antidepressant response to milnacipran by norepinephrine transporter gene polymorphisms. Am J Psychiatry 161:1575–1580, 2004 Young RC, Gyulai L, Mulsant BH, et al: Pharmacotherapy of bipolar disorder in old age: review and recommendations. Am J Geriatr Psychiatry 12:342–357, 2004 Yu BN, Chen GL, He N, et al: Pharmacokinetics of citalopram in relation to genetic polymorphism of CYP2C19. Drug Metab Dispos 31:1255–1259, 2003

5 Dementia and Alzheimer’s Disease Identifying the Dementia Syndrome History An accurate history of the current illness is particularly important in the diagnostic evaluation of dementia, in order to 1) establish the temporal relationship between possible etiological factors and the onset of cognitive decline, which can help to identify the underlying pathophysiological process causing dementia; and 2) permit the potentially important distinction between early- and late-onset Alzheimer’s disease. Accordingly, multiple sources of information, including the patient’s medical records, should be used to supplement information provided by the patient and the patient’s primary caregiver, and an attempt should be made to establish detailed timelines. It is particularly important to focus on trauma; signs or symptoms of neurological or psychiatric illness; substance use, including alcohol and medications; past and present exposure to potential toxins; past surgeries; and past and present psychosocial stressors. The family history should include inquiry about Down syndrome, dementia, and neurological or mental illness.

Mental Status Examination A comprehensive clinical mental status examination remains the cornerstone of the diagnosis of dementia. General categories of appearance; level of alertness; degree of cooperation; mood; affect (direction and degree); form, flow, 173

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and content of thought; psychomotor activity; presence or absence of hallucinations, delusions, and other morbid thought content; and judgment and insight are assessed along with cognitive function. Clinical assessment of mental status may be supplemented by administration of a structured examination of the type described in the next section. Results of these procedures can provide a valuable baseline for assessing treatment-related cognitive changes and also can be used to determine whether a referral for neuropsychological assessment is desirable or feasible.

Standardized Measures for Rating Cognition The choice of a cognitive screening tool should be based on several considerations. The selected screen should tap the core cognitive processes of the disorders most commonly represented in the practice setting, should have acceptably high diagnostic accuracy, and should meet the practical needs of the situation (e.g., available time and personnel). All cognitive screens perform better in practice settings where dementia is commonly observed and less well in community-based settings or primary care, where the base rate of serious cognitive problems is lower. As a result, it is generally not appropriate to extrapolate from initial studies of new instruments that rely on well-characterized, clinically distinct samples of dementia patients and control subjects in estimating how the instrument will perform in a more heterogeneous practice setting. As additional validation studies accumulate for a particular instrument, it becomes easier to determine whether a particular screening scale is right for a given situation. Table 5–1 lists several cognitive mental status examinations appropriate for geriatric patients, and the Appendix provides test forms or additional information on several of these scales. Some tests, such as Animal Naming, the Mini-Cog, and the short form of the Orientation-Memory-Concentration Test, are very brief and are intended only for gross screening. The Mini-Mental State Examination (MMSE; Folstein et al. 1975), the Cognitive Abilities Screening Instrument (CASI; Teng et al. 1994), and the Neurobehavioral Cognitive Status Examination (Kiernan et al. 1987) are of intermediate length and may be useful in a wide range of psychiatric and medical settings. The Dementia Rating Scale (DRS; Mattis 1976), now available in an updated form (DRS-2; Jurica et al. 2001), is the most comprehensive of the mental status instruments developed for older adults. Items are hierarchically ar-

Table 5–1. Cognitive mental status examinations and brief screening tools Administration time (min)

Advantages and applications

Description

Mini-Mental State Examination (MMSE; Folstein et al. 1975)

11-item, 30-point scale assesses orientation, registration and delayed recall, language, attention, visuoconstruction

5–10

Insensitive to mild or focal Brief; examines several deficit; high falsefunctions; wide application; good norms positive rate with poorly educated patients

20 items from modified Cognitive Abilities form of the MMSE and Screening Instrument (CASI; Teng et al. 1994) Hasegawa Dementia Screening Scale, plus judgment question

10–15

May not be more sensitive 100-point scoring range to dementia than the may make it sensitive to standard MMSE for mild impairment; most populations different versions developed in different locales and languages

20–30

Profile format assists in giving feedback; screen and metric allow quick testing of intact persons

Cognistat (Neurobehavioral Cognitive Status Examination [NCSE]; Kiernan et al. 1987)

Separate scales assess attention, orientation, language, memory, visuoconstruction, calculation, reasoning

Limitations

Limited data on validity of separate scales or applicability to diverse samples

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Measure

Description

Scales assess attention, Dementia Rating Scale conceptualization, (DRS; Mattis 1976) DRS-2 (Jurica et al. 2001) memory, initiation and perseveration, visuoconstruction Naming animals as quickly Animal Naming task (e.g., Duff Canning et al. as possible for 60 seconds 2004)

Clock Drawing Test (e.g., Shulman 2000)

Drawing the face of a clock and setting hands to a specified time

Administration time (min) 30–45

Advantages and applications

Limitations

May detect subcortical or Take too much time to administer in some frontal brain deficit; sensitive to wider range of situations; limited data on use with diverse dementia than are briefer samples scales

1

Extremely brief; will detect Insensitive to mild deficit or conditions affecting moderate to severe nonlanguage skills; dementia; may be useful cutoff scores likely to as an initial screen when vary by education level time is very limited and ethnicity

2–5

Very brief; well accepted by Insensitive to mild deficit; no generally accepted patients; sensitive to method of parietal function and administration and some aspects of frontal or scoring; does not assess executive function; will detect moderate to severe memory processes most directly affected by dementia Alzheimer’s disease

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Table 5–1. Cognitive mental status examinations and brief screening tools (continued)

Table 5–1. Cognitive mental status examinations and brief screening tools (continued) Administration time (min)

Advantages and applications

Description

Mini-Cog (Borson et al. 2000)

Three-word learning and recall task plus clock drawing

2–4

Insensitive to mild deficit; Very brief; will detect relatively new test, and moderate to severe independent validation dementia; developed for studies are needed use with ethnically and linguistically diverse populations

Orientation-MemoryConcentration Test (OMCT; Katzman et al. 1983)

Six items assess temporal orientation, recall of an address, mental control

3–5

Very brief; will detect moderate to severe dementia

3–5

Very brief; designed to tap Limited data available on applicability to diverse memory processes most samples; assesses only impaired in early one cognitive domain dementia

Free and cued recall of four Memory Impairment words Screen (MIS; Buschke et al. 1999)

Limitations

Insensitive to mild deficit and visuospatial impairment

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Measure

177

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ranged within sections, so that the first item serves as a screen for intact ability in each domain. This scale provides more extensive assessment of language, memory, and praxis than do most mental status examinations and includes items that may be sensitive to frontal-lobe impairment (initiation and perseveration sections). The DRS is recommended for use in patients who have mild impairment when a detailed assessment of abilities is desired and when time permits complete administration. A Closer Look at the MMSE Table 5–2 presents sample items from the popular MMSE. The widespread use of this test with diverse populations is likely to ensure its continued popularity, despite some recognized limitations. The MMSE, initially validated with elderly psychiatric groups and nonpsychiatric community control subjects, has been translated into several languages, and a modified form suitable for hearingimpaired patients is also available. The MMSE has high interrater reliability and adequate retest reliability in stable conditions. Folstein and colleagues (1975) have emphasized that the MMSE does not establish a diagnosis of dementia; instead, as with all screening instruments, it identifies individuals with possible cognitive impairment that may warrant further assessment. Initially, a score of 23 or fewer correct items was recommended as a cutoff to screen for cognitive impairment. However, subsequent studies have shown that this cutoff score is likely to overidentify poorly educated persons as impaired and fail to detect true decline in well-educated individuals. Table 5–3 presents median values and scores at the twenty-fifth percentile for several age and educational groups, based on an epidemiological survey of more than 18,000 persons from several areas within the United States. Scores at the twenty-fifth percentile are above typical cutoffs for impairment, but if the history or other observations raise a question of decline, a score at this level may warrant further assessment or monitoring. It is obvious from the values shown in the table that both age and education influence MMSE scores and that a specific score for a particular individual must be interpreted in light of these characteristics and other historical and medical information. Although the MMSE was not specifically designed to screen for Alzheimer’s disease, certain items—most notably, delayed recall and copying of pentagons—are likely to be failed by patients with Alzheimer’s disease. Recalling of only two of three words, or even one word, may fall within normal limits for

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Table 5–2. Sample items from the Mini-Mental State Examination (MMSE) Cognitive skill

Task(s)

Score

Orientation for timea “What is the date?”

0–1

Registration

0–3

“Listen carefully, I am going to say three words. You say them back after I stop. Ready? Here they are… HOUSE (pause), CAR (pause), LAKE (pause). Now repeat those words back to me.” (Repeat up to five times, but score only the first trial.)

Naming

“What is this?” (Point to a pencil or pen.)

0–1

Written command

“Please read this and do what it says.” (Show examinee the words on the stimulus form: CLOSE YOUR EYES.)

0–1

aComponent

of the MMSE that is particularly sensitive to mild Alzheimer’s disease (Galasko et al. 1990; Teng et al. 1987). Source. Reproduced by special permission of the Publisher, Psychological Assessment Resources, Inc., 16204 North Florida Avenue, Lutz, FL 33549, from the Mini Mental State Examination, by Marshal Folstein and Susan Folstein, Copyright 1975, 1998 by Mini Mental LLC, Inc. Published 2001 by Psychological Assessment Resources, Inc. Further reproduction is prohibited without permission of PAR, Inc. The MMSE can be purchased from PAR, Inc., by calling (813) 968–3003.

some older persons, but inability to recall any words, particularly when prompts are provided, strongly suggests a problem with retention characteristic of Alzheimer’s disease or other disorders producing amnesia. Many patients with Alzheimer’s disease will have forgotten that they were asked to remember some words when delayed recall is requested. Other items on the MMSE that are sensitive to early or mild Alzheimer’s disease are design copying and temporal orientation. This scale is not sensitive to executive or psychomotor changes, and as a result, it is less useful in screening for frontotemporal dementia or subcortical dementia (see Chapter 6, “Other Dementias and Delirium”). Despite careful attempts at translation, research suggests that some MMSE items may be biased for use with populations whose primary language is not English or whose cultural identification differs from that of normative samples, which are largely white and middle class. Several items showed significant ethnicity or language differences in a comparison of white

Age (years) Education

50–54

55–59

60–64

65–69

70–74

75–79

80–84

≥85

0–4 years Median

22

22

22

22

21

21

19

20

25th percentile

20

20

19

19

19

18

16

15

Median

27

27

27

27

26

26

25

24

25th percentile

25

25

24

24

24

22

22

21

Median

29

29

28

28

28

27

26

26

25th percentile

27

27

27

27

26

25

23

23

Median

30

29

29

29

29

28

28

28

25th percentile

28

28

28

28

27

27

26

25

5–8 years

9–12 years

Some college or higher

Source. Adapted from Crum RM, Anthony JC, Bassett SS, et al.: “Population-Based Norms for the Mini-Mental State Examination by Age and Educational Level.” Journal of the American Medical Association 269:2386–2391, 1993. Copyright © 1993, American Medical Association. All rights reserved.

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Table 5–3. Mini-Mental State Examination scores by age and educational level

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and Hispanic adults, and another study found that the MMSE misclassified more nonimpaired Hispanic elderly persons as cognitively impaired than did a memory test based on learning and recall of 10 common objects (Loewenstein et al. 1995). However, some of the items most sensitive to Alzheimer’s disease (delayed recall and design copying) are minimally affected by ethnicity and educational differences. The CASI (Teng et al. 1994) (see Table 5–1) includes items from the MMSE and the Hasegawa Dementia Scale (Tsai and Gao 1989) that have been modified to accommodate translation problems and differential difficulty across various countries as suggested by pilot testing. Developed initially for patients in Japan and the United States, this test has now been used in several large-scale studies that provide normative reference points (e.g., McCurry et al. 1999). Performance on the CASI, like the MMSE, is influenced by age and education in older adults without dementia. Abbreviated Cognitive Screens There has been an emphasis in recent research on the development and validation of very brief cognitive assessment tools that might be suitable for dementia screening in primary care settings or other situations when time is very limited (Lorentz et al. 2002). Category fluency measures, especially Animal Naming, have long been included in neuropsychological testing batteries to evaluate retrieval from semantic memory, and recent studies examining the diagnostic accuracy of such tasks suggest that they could play a role as brief, initial screens for dementia of several types. In two independent cohorts of older adults being followed up for dementia, a 60-second Animal Naming task performed as well in detecting Alzheimer’s disease as did the MMSE, and when the Animal Naming task was combined with recall of a five-item name and address (“John Brown 42 Market Street Chicago”), sensitivity and specificity surpassed those of the MMSE (Kilada et al. 2005). Another study (Duff Canning et al. 2004) that examined well-diagnosed cases of Alzheimer’s disease and vascular dementia found the Animal Naming task to be the best of several verbal fluency tasks in differentiating patient groups from control subjects; sensitivity to dementia was high, even among persons with MMSE scores greater than 24. In that study, which mainly included well-educated older adults, a cutoff score of less than 14 animals in 60 seconds was highly effective in detecting dementia. However, optimal verbal fluency cutoff scores are likely to vary by education

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level and, possibly, ethnic and linguistic background, and care must be taken to use appropriate normative reference points. Animal Naming is not recommended as a stand-alone cognitive screen, but it may be useful as part of a multistep screening procedure in which persons with low fluency scores are then given additional screens or tests. Clock drawing tests also have been widely used for very brief cognitive screening. Attempting to re-create such a familiar item is generally acceptable to patients, and the visual outcomes can be useful in showing undetected cognitive problems to patients or their family members. Administration time varies depending on the version used and the patient’s psychomotor skills, but many patients can complete the task in 1 or 2 minutes. A recent review of clock drawing procedures for dementia screening (Shulman 2000) found fairly high sensitivities and specificities (about 85%), and outcomes usually were not affected by linguistic background. However, very old persons, or those with little or no education, are likely to perform less well. A practical drawback to clock drawing is the lack of standard procedures for administration and scoring. Some methods require the patient to draw the circle for the clock face, whereas others present a predrawn circle. Scoring ranges from a simple pass-or-fail method to relatively elaborate systems of 20 or more points (see Appendix for references to scoring systems). Another limitation is that clock drawing does not directly test for impaired memory, which is the core early deficit in Alzheimer’s disease and certain other dementias. Because of these drawbacks, the Clock Drawing Test is generally not used as a stand-alone screening measure. The Mini-Cog (Borson et al. 2000) is composed of a three-item word learning and recall task and a simple clock drawing task. By combining the most sensitive item used in the MMSE and CASI (i.e., word-list recall) with a visual task that can detect parietal dysfunction and some aspects of frontal and executive deficits, the Mini-Cog has been shown to perform as well as or slightly better than the full MMSE in identifying probable Alzheimer’s disease and some other dementias. Administration time runs from 2 to 4 minutes, and scoring is relatively simple and straightforward. An additional advantage is that this test was designed for and has been validated with multiethnic elderly populations (black, Asian American, and Hispanic) and appears less likely to be biased by low education and literacy than is the full MMSE (Borson et al. 2005). A recent review of the performance of cognitive screening tests in diverse groups (Parker and Philp 2004) concluded that, in general,

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short tests yield more consistent data across varying cultures and education levels and may be better accepted by patients compared with lengthier and more demanding measures. The Orientation-Memory-Concentration Test (OMCT), a six-item version of the Blessed Information Memory Concentration Test (Katzman et al. 1983), takes approximately 5 minutes to administer. It taps several skills often affected in dementias of various types, including temporal orientation, mental control (counting backward and reciting months backward), and memory for verbal narrative (a spoken phrase). The OMCT correlates highly with the MMSE, but in at least one study, it was found to be more sensitive to mild or subclinical dementia (Brooke and Bullock 1999). Advanced age and very low education adversely affect scores. The Memory Impairment Screen (Buschke et al. 1999) looks in a brief but well-designed way at a single skill: the ability to learn and retrieve new information. The patient is shown four large-print words on a page and is asked to read each word and then point to and name each word again in response to a category cue (e.g., the cue word for “apple” would be “fruit”). After a delay of about 2 minutes filled with an unrelated task (counting forward and backward from 1 to 20), both free and cued recall are assessed. Administration time is about 4 minutes, and the total score combines both free and cued recall. For populations with different base rates of disease, the authors provide recommended cutoff scores for use in screening for dementia and for Alzheimer’s disease. Preliminary data from a small number of patients suggested that the Memory Impairment Screen may be more sensitive to mild dementia than are most other screens. The Memory Impairment Screen is more effective in identifying Alzheimer’s disease than is the three-word recall task from the MMSE (Kuslansky et al. 2002), has been adapted for telephone screening, and has been translated into Spanish. Although the Memory Impairment Screen is a promising screening tool, it has not been used widely yet, and the relative lack of independent validation data is a limitation.

Rating Functional Skills Although testing of cognitive function is useful in the detection and diagnosis of dementia, most treatment and management decisions revolve around the patient’s functional abilities. Ability to perform everyday activities in an independent fashion is only modestly correlated with outcomes of mental status

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examinations or neuropsychological tests, and thus it is important to assess these skills in addition to testing mental status when dementia or other cognitive impairments are suspected. Also, because persons with little or no education often perform poorly on mental status examinations, a very brief mental status examination, combined with functional assessment, may be preferable to more extensive cognitive assessment for screening or diagnosing dementia (Wilder et al. 1995). Several brief rating scales have been developed for use with family members or other caregivers to identify problems in everyday functioning. A widely used functional scale is the Instrumental Activities of Daily Living measure developed by Lawton and Brody (1969) (see Appendix), which consists of eight items assessing areas of function considered crucial for maintaining independent living in the community (e.g., using the telephone, shopping, being responsible for medications). The Direct Assessment of Functioning Scale (Loewenstein et al. 1989) presents tasks to the patient—such as making change, addressing an envelope, or telling time—instead of relying on informants’ reports of everyday function. Developed for use with elderly persons with mild to moderate dementia, this scale yields generally comparable outcomes for both English- and Spanish-speaking patients.

Other Rating Measures Other observer-rated scales have been developed to aid in screening for dementia or to identify specific psychiatric symptoms that can accompany dementia. Examples of such scales include the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE; Jorm et al. 1991) and the Neuropsychiatric Inventory (NPI; Cummings 1997). The IQCODE relies on observations of caregivers or others familiar with everyday behaviors and abilities of the patient. The scale measures a single general factor of cognition, has high reliability, and performs as well as brief cognitive screening tests in detection of dementia (Jorm 2004). Unlike scores on many cognitive screening tests, scores on the IQCODE are relatively unaffected by education, premorbid ability levels, or language proficiency. The NPI (Cummings et al. 1994) is rated by physicians or trained professionals on the basis of observation of the patient and input from caregivers. The NPI provides frequency and severity ratings for 12 psychiatric and behavior problems commonly observed in dementia, including agitation, delusions and hallucinations, and apathy and indifference (see Appendix for NPI items). It has

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been translated into several languages for use in cross-cultural investigations and has acceptable validity and reliability (Cummings 1997). A modified version for use in nursing homes is also available.

Laboratory Evaluation Laboratory evaluation is aimed at identifying illnesses known to cause dementia and generally begins with a selected standardized battery of tests with relatively high sensitivity and low specificity. The screening battery presented in Table 5–4 was recommended by Reichman (1994). Table 5–4. Laboratory evaluation of dementia Routine workup Complete blood count Electrolyte panel Screening metabolic panel Thyroid function tests Vitamin B12 and folate levels Tests for syphilis Tests for human immunodeficiency virus antibodies, as indicated by history Urinalysis Electrocardiogram Chest X ray Additional studies to rule out specific conditions Computed tomography (CT) of head—to rule out mass lesion, normal-pressure hydrocephalus, recent bleed Magnetic resonance imaging of head—same indications as for CT; is more sensitive for ischemia or infarction, subcortical or brain-stem pathology Electroencephalogram—to evaluate ictal or episodic features of history or mental status examination Lumbar puncture—to rule out central nervous system infection suggested by physical examination Positron emission tomography and single photon emission computed tomography—to differentiate Alzheimer’s disease from other dementing illnesses

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Neuropsychological Tests Neuropsychological tests are often performed to corroborate an impression of dementia and to identify specific cognitive strengths and weaknesses that may affect treatment or placement. Table 5–5 summarizes some of the tests that we have found useful in diagnostic assessment for possible dementia. Each of these tests has been developed for measures applicable to geriatric populations or has been studied extensively with older patients. Other measures may be useful as well, but any battery for dementia evaluation should tap a full range of cognitive abilities, including general intelligence, attention, language, learning and memory, visuospatial performance, and reasoning or problem solving. If coexisting psychiatric disturbance is suspected, psychodiagnostic measures also should be included (see Chapter 3, “Mood Disorders—Diagnosis”). Neuropsychological testing alone is generally not sufficient to establish a particular etiology of dementia. However, the pattern of performance on these tests can either strengthen or weaken the case for certain types of dementia. For example, on tests of learning and memory, a very shallow learning curve, sharply reduced delayed recall, and impaired recognition are commonly observed in dementia of the Alzheimer’s type but are less often noted in subcortical dementia (e.g., Huntington’s chorea or Parkinson’s disease), in frontotemporal dementia, or in major depression.

Common Etiologies of Dementia Dementia may result from a diverse set of disorders and conditions; some disorders invariably produce a dementia (e.g., Alzheimer’s disease), whereas others result in dementia only in some cases. For some etiologies, dementia is chronic, progressive, and irreversible by currently available approaches, whereas for other causes of dementia, symptoms may be arrested or reversed to varying degrees with specific treatments. Table 5–6 lists general medical conditions and medications that can produce symptoms of dementia. In general, the list of factors capable of causing dementia increases with the age of the patient, as declining functional brain reserve reduces the individual’s ability to tolerate physiological derangement. The remainder of this chapter and the next chapter are devoted to the differential diagnosis of dementia, beginning with the most common cause of dementia—Alzheimer’s disease.

Table 5–5. Examples of neuropsychological assessment instruments Description

Functions assessed

Interpretation

Comment

Wechsler Adult Intelligence Scale— Third Edition (WAIS-III)

General adult intelligence battery with 14 subtests; normed to age 89

Verbal and nonverbal skills, including vocabulary, attention, reasoning, perceptual organization, and processing speed

IQ scores lower than estimated baseline or low age-scaled subtest scores may indicate impairment

Influenced by education

Wechsler Memory Scale—Third Edition (WMS-III)

Low scores on immediate Sensitive to mild Orientation; mental Battery of verbal and amnesia, dementia or delayed memory control; memory span; nonverbal memory indices may indicate tests; normed to age 89 immediate and delayed impairment recall of stories, word pairs, faces, scenes, and abstract designs

California Verbal Learning Test (CVLT)

Memorization of a 16item shopping list; normed to age 80

Short-term and secondary (recent) memory; strategy use, benefits of cues, recognition; effect of interference

Slow rate of learning or Sensitive to mild cortical and subcortical impaired delayed recall dementia suggests amnestic deficit; forgetfulness suggested by better cued than free recall, good recognition memory

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Test

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Test

Description

Functions assessed

Consortium to Establish Memorization of a list of Verbal learning and delayed recall 10 words; developed a Registry for and normed for older Alzheimer’s Disease adults (CERAD) Word List Learning

Interpretation

Comment

Slow rate of learning or Sensitive to mild dementia of the impaired delayed recall Alzheimer’s type; easier suggests amnestic than CVLT deficit

Object Memory Evaluation

Delayed recall <50% or Good test of secondary Storage and retrieval Memorization of 10 memory for patients very low rate of learning from secondary common objects; with low education level suggests amnestic normed for ages 70–90 memory, delayed recall deficit and recognition

Boston Naming Test (BNT)

Naming of drawings of Confrontation naming, access to semantic objects; normed to age memory 90+

Controlled Oral Word Association Test (COWAT)

Naming of words beginning with specified letters; normed to age 90+

Cutoff scores vary with age and education

More sensitive to mild anomic aphasia than is mental status examination

Verbal fluency, access to Cutoff scores vary with age and education semantic memory, ability to organize rapid retrieval

Intrusions may be noted in early Alzheimer’s disease, perseverations or loss of set in subcortical dementias

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Table 5–5. Examples of neuropsychological assessment instruments (continued)

Table 5–5. Examples of neuropsychological assessment instruments (continued) Test

Description

Interpretation

Comment

Trail Making Test (TMT) Lines drawn to connect number and letter sequences; normed to age 80+

Composite index of visual scanning speed, sequencing, mental flexibility, visuomotor integration

Cutoff scores vary with age and education

Failure on alternating sequence noted in mild brain impairment of various types; slowing in subcortical dementia

Wisconsin Card Sorting Test (WCST)

Inferring concepts, cognitive flexibility

Cutoff scores vary with age and education

May be more sensitive than memory tests to frontotemporal and subcortical dementias

Sorting of multidimensional patterns into categories; normed to age 80

Note. For references to tests and further discussion, see La Rue A: “Geriatric Neuropsychology: Principles of Assessment,” in Handbook of Assessment in Clinical Gerontology. Edited by Lichtenberg PA. New York, Wiley, 1999, pp. 381–416; Spreen O, Strauss E (eds): A Compendium of Neuropsychological Tests, 2nd Edition. New York, Oxford University Press, 1998; and Lezak M, Howieson D, Loring D: Neuropsychological Assessment, 4th Edition. New York, Oxford University Press, 2004.

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Functions assessed

189

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Table 5–6. General medical conditions and substances that can produce symptoms of dementia General medical conditions Dementia syndrome of depression Endocrine disorders Thyroid diseasea Parathyroid disease Adrenal disease Pituitary disease Infections Acquired immunodeficiency syndromea Creutzfeldt-Jakob disease and other viral and prion encephalitides Cryptococcosis Encephalitis Leptomeningitis Neurosyphilis Progressive multifocal leukoencephalopathy Neurological disorders Alzheimer’s diseasea Amyotrophic lateral sclerosisb Cerebellar and spinocerebellar degeneration Huntington’s chorea Dementia with Lewy bodiesa Multiple system atrophy Normal-pressure hydrocephalus Olivopontocerebellar degeneration Parkinsonism-dementia complex of Guam Parkinson’s diseasea Pick’s diseaseb Progressive subcortical gliosisb Progressive supranuclear palsy Nutritional disorders Folate deficiency Pellagra

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Table 5–6. General medical conditions and substances that can produce symptoms of dementia (continued) Nutritional disorders (continued) Pernicious anemia Thiamine deficiencya Space-occupying lesions Brain tumor, primary and metastatica Chronic subdural hematoma Obstructive hydrocephalus Systemic disorders Anemia Paraneoplastic dementia Pulmonary disease with hypoxia or hypercarbia Vascular disorders Atherosclerosis, arteriosclerosisa Hypertensiona Repeated episodes of cerebral ischemia or hypoxiaa Vasculitis Substances Medications Antihypertensives Corticosteroids Digitalis Opiates and synthetic narcoticsa Psychoactive agents with anticholinergic propertiesa Other chemicals Carbon disulfide Carbon monoxide Lead Manganese Mercury Most drugs of abuse a

Common offender. may present as having “frontotemporal dementia.”

bPatient

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Alzheimer’s Disease Alzheimer’s disease, including both early-onset (age 65 or younger, accounting for about 1% of all Alzheimer’s disease cases) and late-onset (older than 65) subtypes, accounts for about 50% of all cases of primary dementia and may combine with other conditions, primarily vascular dementia, in another 10%–20% (Langa et al. 2004). Because the definitive diagnosis of Alzheimer’s disease requires direct visualization of characteristic neuropathology (i.e., amyloid β-peptide–containing senile plaques, neurofibrillary tangles [NFTs] consisting of hyperphosphorylated tau protein, neuritic degeneration and loss) in brain tissue of affected patients and brain biopsy is prohibitively risky, Alzheimer’s disease is at best a probable diagnosis in the living patient.

Epidemiology—Risk Factors and Protective Factors Age is the major risk factor for Alzheimer’s disease, which is rare before age 50 and uncommon in early old age, but prevalence climbs steeply after age 65. Estimates of prevalence vary depending on the extent of diagnostic workup performed and whether mild (i.e., possible) cases are included in the survey (see Figure 5–1). Conservative estimates suggest that 1 in 20 persons age 65 and older, 1 in 4 persons age 80 and older, and half of persons age 95 and older have Alzheimer’s disease. The risk of “sporadic” (as opposed to “familial”; see subsection “Genetics of Alzheimer’s Disease” later in this chapter) disease is increased in persons with a history of head injury and is very high in individuals with Down syndrome who survive to middle age. Diabetes, hypertension, hypercholesterolemia, atherosclerotic cerebrovascular disease, obesity, and other factors also have been associated with increased risk of Alzheimer’s disease. Rates of diagnosis of Alzheimer’s disease in women are higher than in men, and persons with minimal education are at increased risk (Katzman 1993). The other well-established risk factor for Alzheimer’s disease is the apolipoprotein ε4 allele (APOE4). There are three alleles— ε2, ε3, and ε4—of the gene on chromosome 19, which codes for the production of apolipoprotein, a substance involved in cholesterol metabolism and probably in neuronal protection and repair. Presence of one ε4 allele is associated with about 2.5 times the risk of developing Alzheimer’s disease (compared with those homozygous for the ε3 allele), and presence of two ε4 alleles is associated with a 12- to 15fold risk of developing Alzheimer’s disease. This effect of APOE4 is mediated

193

Prevalence of Alzheimer’s disease (%)

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Age (years)

Figure 5–1. Prevalence of Alzheimer’s disease in the Framingham Study and the East Boston Study. Source. Data from Bachman et al. 1992 and Evans et al. 1989. in part by earlier onset of Alzheimer’s disease in those who are APOE4 positive, and it is attenuated in black and Hispanic individuals (Harwood et al. 2004). APOE4 is also associated with the presence of concomitant Lewy bodies in autopsy studies of patients with Alzheimer’s disease (Tsuang et al. 2005), decreased longevity, increased plasma cholesterol levels, and prevalence of cardiovascular disease and tends to worsen response to head trauma, age-related cognitive decline, and several other disorders (Smith 2000). In a meta-analysis of 11 retrospective and prospective studies, Szekely et al. (2004) concluded that long-term exposure to nonsteroidal anti-inflammatory drugs (NSAIDS) is associated with a reduced risk for developing Alzheimer’s disease. The literature reviewed did not allow any conclusions regarding which

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NSAIDs are best, and the most effective duration of treatment or dosage of medication is unknown. Hormone replacement therapy (estrogen with or without progestins) in postmenopausal women was reported to reduce the risk of developing Alzheimer’s disease (LeBlanc et al. 2001). This observational report was contradicted by the Women’s Health Initiative Memory Study, a randomized, double-blind, placebo-controlled primary prevention trial in women age 65 years or older, which found that estrogen with or without progestin increased the risk of developing both Alzheimer’s disease and mild cognitive impairment (Shumaker et al. 2004). A possible explanation for these discrepant findings was reported by Henderson et al. (2005), who found that hormone replacement therapy was protective against the development of Alzheimer’s disease, but only in women ages 50–63; older subjects did not sustain the same benefit. The risk of developing Alzheimer’s disease also appears to be reduced in people who ingest adequate amounts of the antioxidants vitamin E and vitamin C, in food or supplement form, according to several investigators. Engelhart et al. (2002) reported findings from the Rotterdam study and concluded that “high intake of vitamin C and vitamin E from food may be associated with a lower incidence of Alzheimer disease after a mean follow-up period of 6 years” (p. 3228, emphasis added). In this study, vitamin E and C supplements did not reduce the risk of Alzheimer’s disease. However, Zandi et al. (2004) did find a significantly lower incidence and prevalence of Alzheimer’s disease in individuals who ingested the combination of supplemental vitamin E (400 IU/day or more) and vitamin C (at least 500 mg/day of ascorbic acid), but not either vitamin alone, over a 3-year follow-up period. Morris and colleagues (2005) reported data that may partially resolve the disagreement between the two studies discussed in the prior paragraph. They followed up 1,041 subjects age 65 or older for a median of 3.9 years and found that dietary α-, γ-, and δ-tocopherols were significantly and inversely associated with incident Alzheimer’s disease, with reductions in risk of 34% per 5-mg/day increase in α-tocopherol, 40% per 5-mg/day increase in γ-tocopherol, and 25% per 1-mg/day increase in δ-tocopherol. There was no evidence of an association between intake of β-tocopherol and Alzheimer’s disease risk. The authors concluded that “various tocopherol forms rather than α-tocopherol alone may be important in the vitamin E protective association with Alzheimer disease” (p. 508). Several cross-sectional observational studies raised the possibility that statins, which reduce cholesterol, might reduce the risk of Alzheimer’s disease.

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To examine this relation, Zandi et al. (2005) followed up with 4,895 participants in the Cache County Study, an investigation of the genetic and environmental antecedents of dementia among the elderly population of Cache County, Utah, which began in 1995 with the enrollment of 5,092 individuals age 65 or older. Statin use was less frequent in subjects with prevalent dementia, but the authors found no association between statin use and subsequent onset of dementia or Alzheimer’s disease. This finding is surprising given the known relation between atherosclerosis and cerebrovascular disease. The authors acknowledged several methodological and statistical factors that may have obscured a real association, among them the short duration (about 3 years) of exposure to statins, the small number of subjects who reported taking statins, and the small number who developed Alzheimer’s disease. The role of statins in the prevention of dementia and Alzheimer’s disease remains to be determined.

Diagnostic Criteria In DSM-IV-TR (American Psychiatric Association 2000), the term dementia of the Alzheimer’s type is applied to patients whose condition meets clinical and laboratory criteria for probable Alzheimer’s disease; dementias associated with other neurological diseases (e.g., Pick’s disease or Creutzfeldt-Jakob disease) are coded separately. General criteria for dementia must be met, and a history of insidious onset and gradual progression must be present; if all other causes of dementia are ruled out by the history, physical examination, and laboratory tests, dementia of the Alzheimer’s type is diagnosed (Table 5–7). NINCDS Criteria The National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) published a set of diagnostic criteria for research purposes that are somewhat more narrow than the DSM-IV-TR criteria (McKhann et al. 1984). Separate standards are listed for the clinical diagnosis of probable and possible Alzheimer’s disease (Table 5–8). Neuropathological Criteria At present, at least three pathological criteria for Alzheimer’s disease are internationally acceptable: 1) Braak’s criteria (Braak and Braak 1991); 2) Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) criteria (Mirra et al. 1991) and their combination; and 3) National Institute on Aging and

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Table 5–7. Summary of DSM-IV-TR diagnostic criteria for dementia of the Alzheimer’s type A.

The development of multiple cognitive deficits manifested by both (1) memory impairment (2) one (or more) of the following cognitive disturbances: (a) aphasia (b) apraxia (c) agnosia (d) disturbance in executive functioning

B.

These deficits cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning.

C.

The course is characterized by gradual onset and continuing cognitive decline.

D. The cognitive deficits are not due to any of the following: (1) other central nervous system conditions that cause progressive deficits in memory and cognition (2) systemic conditions known to cause dementia (3) substance-induced conditions E.

The deficits do not occur exclusively during the course of a delirium.

F.

The disturbance is not better accounted for by another Axis I disorder.

Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

Ronald and Nancy Reagan Institute of the Alzheimer’s Association criteria (National Institute on Aging and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease 1997). Braak’s criteria are based on the distribution of NFTs (described in the subsection “Neuropathology of Alzheimer’s Disease” later in this chapter) as Alzheimer’s disease progresses: NFTs first appear in the transentorhinal area (stage I), spread to the entorhinal region (stage II), extend to the hippocampus proper (stage III), increase in number there (stage IV), and then involve the association neocortex (stage V) and finally the primary cortex (stage VI). The CERAD pathological criteria are based on the density of neuritic plaques (also discussed in the subsection “Neuropathology of Alzheimer’s Disease” later in this chapter) in three areas: 1) the second frontal gyrus at the

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level of the caudate-putamen complex, 2) the first temporal gyrus at the level of the amygdala, and 3) the supramarginal gyrus with parieto-occipital sulcus. Density is rated as follows: stage A =less than 2, stage B =approximately 6, and stage C = more than 30 neuritic plaques per 100× light microscopic field. Alzheimer’s disease is diagnosed when stage A is identified in patients younger than 50 years, when stage B is seen in patients between 50 and 75 years, and when stage C occurs in patients older than 75 years, along with a definite clinical history of dementia (Murayama and Saito 2004).

Clinical Presentation As is true for all dementing illnesses, the clinical presentation of Alzheimer’s disease depends on the stage of illness and may be obscured or complicated by symptoms related to concomitant physical and psychiatric illness, including depressive or anxiety disorders, psychosis, and delirium. Table 5–9 summarizes the clinical and laboratory findings typically observed in uncomplicated cases as the disease progresses (Group for the Advancement of Psychiatry 1988). Functional symptoms nearly indistinguishable from those of concomitant psychiatric illness are part of the presentation of Alzheimer’s disease, even in the early stages, and patients may present to general psychiatric clinical settings. Gormley and Rizwan (1998) reported that one-third of Alzheimer’s disease patients had delusions, and 11% had hallucinations within the month before evaluation, and this prevalence was not affected by severity of dementia or of depressive symptoms. Farber and colleagues (2000) found that 63% of patients with Alzheimer’s disease had psychosis at some point in the course of illness and that those with psychosis had 2.3 times the density of neocortical NFTs than did those without psychosis. In some patients with Alzheimer’s disease, the psychosis is clinically prominent enough to obscure the underlying cognitive impairment and delay accurate diagnosis. Delusions are usually persecutory in nature and are typically fragmented and inconsistent, unlike those seen in the common functional disorders (e.g., schizophrenia, delusional disorder, or mood disorder with psychosis). Common delusional content includes the belief that one is being threatened, deprived, or abused by caregivers or that possessions are being stolen; hypochondriacal delusions and Capgras’ syndrome are also common (Migliorelli et al. 1995). Delusions in Alzheimer’s disease typically do not have the elaborate “connectedness” seen in functional delusions (i.e., the myriad ways in

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Table 5–8. Criteria for clinical diagnosis of Alzheimer’s disease from the NINCDS-ADRDA Work Group Probable Alzheimer’s disease Dementia: established by clinical examination; documented by Mini-Mental State Examination, Blessed Dementia Scale, or similar examination; confirmed by neuropsychological tests Deficits in two or more areas of cognition Progressive loss of memory and cognitive functions No disturbance of consciousness Onset between ages 40 and 90 Absence of systemic disorders or other brain diseases that in and of themselves could account for deficits Diagnosis of probable Alzheimer’s disease supported by Progressive loss of specific cognitive functions (e.g., language, motor skills, perception) Impaired activities of daily living and altered behavior patterns Family history of similar disorders, especially if neuropathologically confirmed Laboratory results of normal lumbar puncture; normal or nonspecific changes on electroencephalogram Computed tomography—cerebral atrophy with progression documented by serial observation Other features consistent with probable Alzheimer’s disease Plateaus in course of progression of illness Associated symptoms (e.g., depression, incontinence, weight loss) Seizures in advanced disease Computed tomography normal for age Probable Alzheimer’s disease uncertain if Sudden onset; focal neurological findings; seizures or gait disturbance early in course of illness

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Table 5–8. Criteria for clinical diagnosis of Alzheimer’s disease from the NINCDS-ADRDA Work Group (continued) Possible Alzheimer’s disease Dementia syndrome in absence of other causes and in presence of variations in onset, presentation, or clinical course A second systemic or brain disorder sufficient to produce dementia but not considered the cause Single, gradually progressive, severe cognitive deficit Definite Alzheimer’s disease Clinical criteria for probable Alzheimer’s disease with neuropathological confirmation Subtypes Familial Onset before age 65 Presence of trisomy 21 Other relevant disorders (e.g., parkinsonism) Note. ADRDA =Alzheimer’s Disease and Related Disorders Association; NINCDS= National Institute of Neurological and Communicative Disorders and Stroke. Source. Adapted from McKhann et al. 1984.

which the patient is able to tie the delusional belief to all aspects of his or her experience), and hallucinations—usually auditory but sometimes visual, olfactory, or tactile—are intermittent and of varying and usually trivial content, lacking the ordered, meaningful quality typical of functional hallucinations. Depressive symptoms and apathy occur in about 20%–25% of Alzheimer’s disease patients at any given time (Lyketsos et al. 2000b), but full depressive syndromes (e.g., major depression) are relatively rare.

History The history of Alzheimer’s disease is typically one of insidious onset and gradual progression of cognitive and functional impairment, with few of the

Function/test

Early cognitive decline

Moderate cognitive decline

Severe cognitive decline

Orientation

Fully oriented

Frequent mistakes, but usually knows date, familiar persons

Severe disorientation

Concentration

Mild deficits; some errors in serial calculation

Moderate deficits; usually has difficulty counting backward

Can barely count to 10

Recent memory

Misplaces items; forgets names, Poor knowledge of current and recent events recent events

Remote memory

Some deficits in recall of remote Many deficits in recall of remote Almost no recall of any past events events events

Language and speech

Word-finding problems, poor word-list generation, mild anomia

Limited vocabulary and sentence Fluent aphasia with unintelligible structure, repetitive speech

Praxis

Normal to minimal deficit

Ideomotor apraxia; difficulty with finances, hobbies, marketing

Cannot feed or toilet self

Visuospatial skills

May get lost in unfamiliar settings; poor construction on tests

Poor constructions and spatial disorientation; can travel to familiar places

Agraphia; may have neurological signs

Self-care

Normal

May require assistance choosing Requires assistance in multiple spheres; occasional or persistent clothing; may need coaxing to problems with bladder or bowel bathe incontinence

Unaware of almost all recent experiences

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Table 5–9. Natural history of Alzheimer’s disease: clinical and laboratory findings

Table 5–9. Natural history of Alzheimer’s disease: clinical and laboratory findings (continued) Early cognitive decline

Moderate cognitive decline

Severe cognitive decline

Complex or new tasks

Decreased performance

Decreased performance; may withdraw from challenging situations

Cannot perform

Personality

Possible apathy, depression, or irritability

Denial common; apathy and indifference

Agitation or anxiety, psychosis, abulia, obsessiveness

CT scan

Normal

Normal to atrophic cortices and Cortical atrophy and ventricular dilated ventricles enlargement

EEG

Normal

Background slowing

Diffuse slowing

PET and SPECT

Bilateral temporoparietal hypoperfusion

Bilateral temporoparietal hypoperfusion

Bilateral temporoparietal and frontal hypoperfusion

Note. CT=computed tomography; EEG= electroencephalogram; PET=positron emission tomography; SPECT= single photon emission computed tomography. Source. Copyright 1988 from The Psychiatric Treatment of Alzheimer’s Disease by Group for the Advancement of Psychiatry. Reproduced by permission of Routledge/Taylor & Francis Group, L.L.C.

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Function/test

201

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sharp downward steps in function typical of vascular dementia or the more abrupt onset and rapid progression of the dementia syndrome of depression. Unlike frontotemporal dementia, memory impairment (especially the ability to recall new information after a short delay [Welsh et al. 1991]) is invariably present and is often the presenting symptom. Later, marked impairments in expressive and receptive language, ability to plan and organize activities, and virtually all other aspects of cognition are affected. The rate of progression of cognitive impairment varies among individuals, but a decline of 2–3 points per year on the Folstein MMSE is typical. Some studies find nonlinear progression, with less rapid decline in the early and late stages and relatively more rapid decline in midcourse. Functional decline generally parallels cognitive decline, but basic activities of daily living tend to be preserved until cognitive function has reached the “moderately impaired” stage, whereas instrumental activities of daily living are affected earlier. Perhaps because of this slow progression, in the early stages, cognitive deficits often can be concealed or compensated for, and friends and family who have only superficial interactions with patients may be unaware of relatively major deficits. Sometimes close family members who have observed declining cognition attempt to rationalize away the significance of their observations. Because of these possibilities, multiple sources of historical data may be necessary to establish a reliable history.

Mental Status Examination Some of the major mental status findings typical of each stage of Alzheimer’s disease are included in Table 5–9. Although relatively synchronous decline in cognitive capacities is the general rule, in some patients, language disturbance may be severe enough to prevent accurate evaluation of memory and higher cognitive functions; similarly, suspiciousness or social withdrawal may lead to an exaggerated estimate of the degree of cognitive decline in a relatively intact individual.

Neuropsychological Tests In probable Alzheimer’s disease, multiple neuropsychological impairments are seen, including anomic or mixed aphasia, apraxia, deficits in reasoning, and prominent learning and memory impairment. Patients with Alzheimer’s disease rapidly forget new information and often do not benefit from cueing

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or memory reminders, implying deficits in encoding or learning as well as problems with retrieval. Early in the course of illness, neuropsychological deficits may be restricted to one or two areas—most often, learning and memory. Brief versions of tests like those described in Table 5–5 have been combined by CERAD to form a screening battery that may be useful in detecting and staging Alzheimer’s disease (Welsh et al. 1994). List-learning tasks are among the most sensitive for detecting the memory deficits of early Alzheimer’s disease and for differentiating such deficits from the milder memory changes of age-associated memory impairment. Table 5–5 describes three such tasks, including Word List Learning from the CERAD battery. No single cutoff score can be used to classify impairment on learning tasks; rather, results for individuals must be interpreted relative to normative tables for age and education level.

Laboratory Evaluation Laboratory evaluation of Alzheimer’s disease is the same as that described earlier in this chapter for dementia (Table 5–4). Despite the promise of the experimental diagnostic procedures discussed in the following subsection, the laboratory evaluation of patients with possible Alzheimer’s disease is primarily aimed at ruling out other causes of dementia. If this evaluation does not identify another cause of dementia, and either DSM-IV-TR or NINCDS–Alzheimer’s Disease and Related Disorders Association clinical criteria are applied, the diagnosis of “probable Alzheimer’s disease” has reasonable sensitivity (approximately 80%) and specificity (approximately 70%), as confirmed by subsequent neuropathological diagnosis (Knopman et al. 2001).

Advanced and Experimental Diagnostics Research studies that used single photon emission computed tomography (SPECT), positron emission tomography (PET) measuring glucose metabolism or amyloid burden, magnetic resonance spectroscopy, magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI) with activation, measurement of cerebrospinal fluid antigens, and analysis of apolipoprotein alleles all have produced promising results. Dougall et al. (2004) reviewed the diagnostic accuracy of SPECT in Alzheimer’s disease and concluded that “diagnostic accuracy can be improved with SPECT in dementia patients who present with possible comorbid

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symptoms of vascular disease or who do not entirely conform to clinical criteria …especially in ruling in AD [Alzheimer’s disease] as a cause when the SPECT result is positive and vice versa” (p. 562). Patwardhan and colleagues (2004) used rigorous inclusion criteria to conduct a meta-analysis of nine studies in which the operating characteristics of PET were assessed in the diagnosis of Alzheimer’s disease. Although specificity and sensitivity were both estimated at 86%, the authors found several methodological problems in the studies that they believed limited the validity and therefore the utility of their results. Kulasingam et al. (2003) analyzed the available PET data in light of the risk-benefit ratio of available treatments for Alzheimer’s disease and concluded that cholinesterase inhibitors (discussed in the subsection “Cholinesterase Inhibitors” later in this chapter) should be prescribed on the basis of the history, physical examination, neuropsychiatric evaluation, and structural neuroimaging to rule out other causes of dementia, without recourse to PET or SPECT imaging and examination. If treatments entailing more serious risk are developed, the addition of PET to the diagnostic battery would be warranted. Despite their limitations, both SPECT and PET appear to have a role in the evaluation of some cases of suspected Alzheimer’s disease, although specific indications have yet to be published. Klunk and associates (2004) used PET to study the distribution of labeled Pittsburgh Compound-B (PIB), a benzothiazole, thioflavin-T derivative that crosses the blood-brain barrier and binds to amyloid β-peptide. They found PIB to be a reliable marker of amyloid in vivo and proposed a possible future role for the PET-PIB procedure in the diagnosis and staging of Alzheimer’s disease, as well as for assessment of anti-amyloid treatment response. de Leon and colleagues (2004) conducted a series of studies in which MRI and cerebrospinal fluid biomarkers were used to diagnose Alzheimer’s disease, and results were promising but not yet applicable to the clinical setting. Dickerson and associates (2004) studied memory-associated activation of the medial temporal lobe regions with fMRI in subjects with mild cognitive impairment and found that greater activation was associated with better memory performance. However, the subjects who recruited the largest area of the parahippocampal gyrus were the most impaired at baseline; more important, the 44% who deteriorated over the ensuing 2.5 years (more than 25% of whom developed probable Alzheimer’s disease) activated significantly larger areas of the parahippocampal gyrus despite similar memory performance. These in-

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vestigators concluded that greater activation of the parahippocampal gyrus may be compensating for greater Alzheimer’s disease pathology and could be a diagnostic sign of impending Alzheimer’s disease. Finally, Mayeux and colleagues (1998) studied the diagnostic value of the presence of APOE4 in a sample of 2,188 patients with dementia who underwent autopsy. The clinical diagnosis of Alzheimer’s disease had 93% sensitivity and 55% specificity, compared with 65% and 68%, respectively, for APOE4 alone. However, adding APOE4 data to the clinical diagnosis increased the specificity to 84% but lowered the sensitivity. To date, these and other experimental approaches have not reached the stage of widespread acceptability in the diagnosis of Alzheimer’s disease.

Differential Diagnosis of Alzheimer’s Disease Functional Disorders Certain functional conditions can mimic Alzheimer’s disease. They include depressive pseudodementia (see Chapter 3, “Mood Disorders—Diagnosis”), mania, hypomania, personality disorder, Ganser syndrome, hysteria, and malingering. In most patients, the signs and symptoms of functional illness are clear, cognitive impairment is readily identified as secondary, and diagnostic error is easily avoided. Nevertheless, some cases of depression can be particularly misleading, and several authorities have recommended antidepressant treatment trials in selected patients (see related discussion in Chapter 4, “Mood Disorders—Treatment”). Other Dementias Alzheimer’s disease must be distinguished from the other degenerative dementias such as frontotemporal dementia and dementia with Lewy bodies, vascular dementia, and the dementias due to general medical conditions and substances. These are all discussed in detail in Chapter 6 (“Other Dementias and Delirium”). Amnestic Disorders Amnestic disorders can be misdiagnosed as dementia, even though in amnestic disorder, intellectual functions other than memory are spared. The most common amnestic disorder in elderly patients is Korsakoff ’s psychosis, which is caused by prolonged thiamine deficiency usually associated with long-term, high-dose ingestion of alcohol. In addition to sparing of intellect, confabulation is often a prominent feature of this syndrome.

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Delirium Alzheimer’s disease is usually easily differentiated from delirium, which has a much more acute onset and progression and entails more severe impairment of attention and concentration and more disorganization of thought. However, delirium superimposed on Alzheimer’s disease may be more difficult to diagnose, often requiring reevaluation after potential causes of delirium have been eliminated and the underlying dementia has been allowed to emerge.

Neuropathology of Alzheimer’s Disease The gross neuropathology of Alzheimer’s disease consists of cortical atrophy, particularly involving anterior frontal and temporoparietal areas. Microscopic findings include NFTs, senile plaques, and granulovacuolar degeneration. Neurofibrillary tangles are densely packed microfibrils found in the cytoplasm of dead neurons. Under an electron microscope, these microfibrils have been shown to consist of paired helical filaments, composed primarily of an abnormally phosphorylated tau protein, that are 100 Å wide and twist every 800 Å. Senile plaques are extracellular deposits of the 42–amino acid amyloid βpeptide that is derived from the amyloid precursor protein (APP). They are 5–150 µm in diameter and appear in three major forms: 1) diffuse plaques, which consist of formed filamentous and nonstructured amyloid β-peptide without attached abnormal neurites; 2) neuritic plaques, which are composed of dense bundles of amyloid fibrils and dystrophic neurites (usually containing paired helical filaments); and 3) “burned out” plaques, in which a dense amyloid core is surrounded by reactive astrocytes but no abnormal neurites. A “primitive” form of neuritic plaque lacking the amyloid component of the core also has been described (Terry et al. 1994). APP is a transmembrane protein that is present in almost all tissues. It undergoes proteolytic cleavage by α-, β-, and γ-secretase enzymes to generate either nonamyloidogenic or amyloidogenic peptides. When full-length APP is cut by α-secretase and then by γ-secretase, it generates a harmless peptide, but when APP is cut by β-secretase and then by γ-secretase, it generates peptides of 39–43 amino acids, of which amyloid β-peptide 1–40 is the most common and considered harmless, whereas amyloid β-peptide 1–42, which accounts for about 10% of amyloid β-peptide, is neurotoxic and involved in the formation of senile plaques in Alzheimer’s disease brains (Kamboh 2004).

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Granulovacuolar degeneration primarily affects hippocampal pyramidal neurons and consists of groups of intracytoplasmic vacuoles about 5 µm in diameter, each containing a small granule. Other histopathological findings in Alzheimer’s disease include congophilic angiopathy, consisting of amyloid deposits in the walls of small arteries of the frontal and parietal cortex, and generalized loss of neuronal dendrites in affected cortical areas. Loss of cholinergic neurons of the nucleus basalis of Meynert, loss of noradrenergic neurons of the locus coeruleus, and loss of serotonergic neurons of the dorsal raphe nucleus also have been described. The first two changes have been correlated with reduced cortical tissue levels of choline acetyltransferase and norepinephrine and its metabolites, respectively (discussed in the next section below, “Neurobiochemistry of Alzheimer’s Disease”); reduced cortical concentrations of serotonin have been less consistently reported. Other investigators have identified synaptic loss, neuronal loss, and volume reduction in the hippocampus that is detectable with MRI (de Leon et al. 2004).

Neurobiochemistry of Alzheimer’s Disease The first and most thoroughly confirmed neurobiochemical abnormality found in brain tissue affected by Alzheimer’s disease neuropathology was reduced temporoparietal and hippocampal cortical activity of choline acetyltransferase, an enzyme found only in cholinergic cells, which catalyzes the synthesis of acetylcholine. Biopsy studies have detected significant losses of this enzyme as early as the first symptomatic year, and autopsy studies have reported a strong correlation (r=0.8) between the degree of choline acetyltransferase loss and premortem measurements of cognitive and functional decline. Concentrations of acetylcholinesterase and acetylcholine, both of which are less specific indicators of cholinergic cell activity than is choline acetyltransferase, also have been found to be reduced in affected brain tissue. Altogether, these findings support a working analogy between Alzheimer’s disease and Parkinson’s disease, in which a single neurotransmitter (dopamine) is also deficient. This analogy ultimately led to the development of tacrine, donepezil, and other acetylcholinesterase inhibitors (see subsection “Cholinesterase Inhibitors” later in this chapter), which are modestly effective treatments for Alzheimer’s disease. However, less profound abnormalities in

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other neurotransmitter systems have been documented (American Psychiatric Association 2000), and at least one noncholinesterase inhibitor—memantine—has been shown to be at least modestly effective in Alzheimer’s disease.

Genetics of Alzheimer’s Disease Alzheimer’s disease is transmitted as an autosomal dominant trait in about 2% of all cases. In these familial cases, which typically have early onset, several genes are responsible: one (presenilin 1), found in about half of Alzheimer’s disease families, is on chromosome 14; two others—presenilin 2, on chromosome 1, and the gene that encodes for APP, on chromosome 21—are present in far fewer Alzheimer’s disease families. Each of these genes in its pathological variant results in abnormal β-APP processing with resultant overproduction of the amyloid β-peptide 42 (St George-Hyslop 2000). The other 98% of individuals with Alzheimer’s disease have sporadic disease, which appears to result from an interaction between a genetic vulnerability and environmental factors. Gatz et al. (1997) found a concordance rate for prevalence of Alzheimer’s disease among monozygotic twin pairs of 67%, whereas the corresponding figure for dizygotic pairs was 22%. Pedersen et al. (2004) examined incident Alzheimer’s disease in a cohort of 662 twin pairs followed up for 5 years and found a concordance rate of about 32% for monozygotic twins and about 9% for dizygotic twins, regardless of whether onset was before or after age 80. Studies of incidence are likely to find a lower concordance rate than are studies of prevalence, because affected twins are not included in the baseline sample.

Psychosocial Therapy for Persons With Alzheimer’s Disease Psychosocial therapies developed for persons with Alzheimer’s disease and other dementias have attempted to minimize disruptive behaviors or increase positive behaviors, support mood and a sense of well-being, or improve or support memory. In early studies with a single dementia patient or a small number of patients, behavior modification approaches using techniques such as time-outs, activity diversion, and selective reinforcement were shown to be effective in reducing urinary incontinence or reinstating important self-care

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activities such as bathing or walking (Gatz et al. 1998). More recent work addressing behavior problems has used cued recall procedures adapted from the cognitive rehabilitation literature; Bird and colleagues (1995) provide good examples of successes and failures of this approach. Reminiscence therapy, which involves the discussion of past activities, events, and experiences, usually with the aid of tangible prompts such as photographs or music, has become an increasingly popular intervention. It can be used by staff at activity centers and long-term-care facilities and lends itself to involvement of family members. A recent review of the literature on reminiscence therapy in dementia found four controlled trials, all of which reported beneficial effects on cognition or mood in comparison with no-treatment or social-contact control subjects. However, studies were small in size, and all used different types of reminiscence procedures (Woods et al. 2005). Early studies of memory training for patients with dementia used techniques developed for normal older adults (e.g., group or individual practice of mnemonics such as visual imagery), and results showed either no benefit or very circumscribed benefit. Recently, more promising results have been demonstrated with the use of specialized training techniques (e.g., spaced retrieval) that have proven effective in work with memory-impaired braininjured populations. These interventions typically involve a relatively intense initial encoding phase in which the person with dementia is asked to say or do a to-be-remembered action repeatedly, with the interval between the cue and the desired response gradually lengthened from immediately to over an hour or more. In an interesting case study, Clare and colleagues (2001) described how a 74-year-old man with mild but progressive dementia (MMSE score decreased from 26 to 22 across the study period) was able to learn name–face associations for 11 members of his social club, sustain recall of nearly all these names with daily self-practice over 9 months, and still retain 7 or 8 names over the next 2 years with only weekly club visits to rehearse the associations. Individualization of the training and selecting objectives that meet a real-life need are thought to be important by many contemporary researchers studying the limits and benefits of a cognitive rehabilitation approach for dementia patients. However, there are also ongoing new investigations of the effects of predetermined training regimens for persons with early Alzheimer’s disease, especially as an adjunct to cholinesterase inhibitor therapies (e.g., Loewenstein et al. 2004).

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The potential benefits of psychotherapy for persons with Alzheimer’s disease and other dementias are also undergoing a reexamination, with clinicians beginning to more systematically combine techniques drawn from the rehabilitation literature with general psychotherapy procedures. The role of individual psychotherapy in the overall medical management of Alzheimer’s disease depends on the stage of illness, the patient’s premorbid pattern of ego strengths and vulnerabilities, and the presence or absence of concomitant functional complications. In general, supportive therapy is most useful in the early stages of illness and is aimed at ameliorating the anxiety and loss of selfesteem accompanying awareness and anticipation of lost cognitive capabilities. Many patients at this stage of illness use primitive defenses, resulting in characteristic symptom complexes such as accusations that family members are stealing from them (denial and projection), hypercritical and hostile behavior directed toward family members (denial and displacement), and, sometimes, multiple bizarre somatic complaints (somatization). For some of these patients, the capacity for insight is preserved, and gentle interpretation may lead to adaptive behavior change, particularly if accompanied by practical advice and encouragement. Later in the course of illness, individual psychotherapy has more limited goals, often limited to provision of a constant, caring, healing authority figure whose attention can have significant, if nonspecific, anxiety-relieving and mood-elevating effects (Group for the Advancement of Psychiatry 1988). Throughout the course of therapy, it may be beneficial to view the coping with illness as a partnership between the patient and family members and other key social support persons, with the degree of responsibility for independent behavior gradually shifting from the individual to these supportive others (Judd 1999). Adapting the process of therapy to take diminished memory into account (e.g., spending the first minutes of each session reviewing what was last discussed, sending home for review a short outline of what was covered in each session, and writing out specific suggestions for activities or coping approaches to practice at home) may also increase the effectiveness of psychotherapy.

Psychosocial Therapy for Dementia Caregivers Caring for a family member with Alzheimer’s disease or other dementia is challenging at best and overwhelmingly stressful at worst. Increased levels of

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depression and anxiety, higher use of psychotropic medications, poorer physical health, and increased mortality have all been documented for family caregivers. Recognition of caregiver burden has led to numerous psychosocial interventions aimed at alleviating stress and adverse health consequences. Early forms of interventions such as peer support groups and education were found to have only very small benefits when subjected to careful study. A second generation of caregiver interventions has included individual and family counseling, case management, skills training, and combinations of these approaches. In general, multicomponent approaches that offer options to fit individual caregivers’ needs and relatively intensive as opposed to brief interventions have been found to be most beneficial (Schulz et al. 2002). In the most ambitious study of caregiver interventions to date in the United States, the multisite Resources for Enhancing Alzheimer’s Caregiver Health (REACH) investigation included a sample of over 1,200 caregivers. The meta-analysis of 6-month outcomes found a significant decrease in caregiver burden for a diverse group of active treatments (e.g., skills training, family-based in-home intervention, telephone-linked computer consultation, coping-with-caregiving classes, and professional-enhanced support groups) compared to usual care control (e.g., information packets and referrals), and caregivers consistently rated the interventions as helpful (Gitlin et al. 2003). Another encouraging result was that African American and Hispanic caregivers benefited as much as white caregivers in terms of reduced burden. However, the effect size associated with interventions was modest (0.15 standard deviation), and some subgroups of caregivers (e.g., men and well-educated persons) did not experience a significant reduction in burden. Researchers studying caregiver interventions have underscored the diversity of caregiver backgrounds and needs and the persistent, yet changing, stresses associated with the role, and they caution against one-size-fits-all approaches. Other recent research has shown that the distress experienced by many caregivers may not be automatically alleviated when help is hired in the home (Pot et al. 2005) or when the family member with dementia enters a nursing home (Schulz et al. 2004). Spouses may have an especially difficult time adjusting to the nursing home placement of a husband or wife (Schulz et al. 2004). Psychiatrists and other mental health professionals can offer the option of family therapy for caregivers who are experiencing depression, anxiety, or

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other clinically significant mental health symptoms. Family intervention can be useful at all stages of Alzheimer’s disease (Jarvik and Winograd 1988). Initially, key elements of family therapy include dissemination of practical advice, provision of information and education, referral to appropriate community resources, and opportunities to express emotions and fears related to the diagnosis. Later, family therapy may be more focused on amelioration of caregiver anxiety, demoralization, and depression. In the final stages of illness, consultation and support vis-à-vis the often painful decision to institutionalize and providing assistance with the process of grieving a lost loved one may become the foci of family therapy. Being able to continue a supportive psychotherapeutic relationship with the family over the long haul of caregiving is ideal but often difficult to achieve. Being available by telephone for brief follow-up contacts as the patient’s illness proceeds to advanced stages can help to sustain a sense of support. Systematically assessing the behavioral deficits in the patient and determining which deficits cause the most distress to the caregiver can be helpful in the initial evaluation and in monitoring response to treatment. Brief structured questionnaires such as the Memory and Behavior Problems Checklist and the NPI (see subsection “Other Rating Measures” earlier in this chapter, and Appendix) can be completed by the caregiver or by a professional on the basis of caregiver input. Memory loss per se is generally less distressing to caregivers than are emotional and behavior problems such as depression, delusions, belligerence, and agitation. Treatment of these associated symptoms often can be the difference between continuation of home care and institutionalization for a patient with dementia. In therapeutic work with family caregivers, it is important to keep in mind that the caregiving role, despite its demands, can be a source of gratification and increased self-efficacy. Caregivers may derive satisfaction from repaying older relatives for their own past care or may feel relief from knowing that their loved one is receiving the best possible care (Scharlach 1994). In caring for older relatives who are frail or who have dementia, African American and Hispanic families rely more heavily on relatives and friends than do white families and are less likely to place their older family members in nursing homes. In the REACH study, Hispanic women who were dementia caregivers reported lower levels of caregiving stress, greater perceived benefits of caregiving, and a greater use of religious coping than did their white counter-

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parts (Coon et al. 2004). It is unclear whether such findings reflect cultural differences in filial roles and obligations or limited knowledge of or access to alternative means of care (Aranda and Knight 1997). In any family that has a relative with dementia, the therapist must assess the possibility of caregiver distress and provide information about in-home, community, and institutional resources. Organizations such as the Alzheimer’s Association offer information and help-line support for dementia caregivers, and many self-help books and Web sites are available. Examples of resources that can be helpful to caregivers, especially when used in conjunction with family therapy or other interventions, are included at the end of this chapter, following the references.

Psychopharmacotherapy for Cognitive Decline in Alzheimer’s Disease Cholinesterase Inhibitors Several cholinesterase inhibitors (tacrine, donepezil, rivastigmine, and galantamine) are available for treatment of the cognitive deficits of mild to moderate Alzheimer’s disease. All of these agents increase central cholinergic neurotransmission by inhibiting breakdown of acetylcholine by acetylcholinesterase. Of these, tacrine is not recommended because of its hepatotoxicity, and the other three are about equally effective and equally tolerable; 10 mg/day of donepezil, 6–12 mg/day of rivastigmine, and 16–18 mg/day of galantamine can be expected to produce, on average, about a three-point improvement on the cognitive subscale of the Alzheimer’s Disease Assessment Scale (Ritchie et al. 2004). Continuation treatment with cholinesterase inhibitors slows the progression of Alzheimer’s disease and reduces the likelihood of nursing home placement. One 36-month follow-up study found that almost 80% fewer cholinesterase inhibitor–treated subjects were admitted to nursing homes compared with untreated subjects (Lopez et al. 2005). Memantine Memantine is the first noncholinesterase inhibitor that has been shown, in randomized controlled clinical trials, to be effective in reversing or slowing cognitive and functional decline in Alzheimer’s disease (Areosa et al. 2005). The drug is an antagonist of the N-methyl-D-aspartate (NMDA)–type glutamate recep-

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tor and appears to exert its effects at the cellular level by reducing glutamatemediated excitotoxicity, which leads to neuronal injury or death. Unlike the cholinesterase inhibitors, memantine is effective in patients with moderate to severe Alzheimer’s disease and seems to exert at least additive effects when combined with cholinesterase inhibitors (Tariot et al. 2004). Improvement in agitation and mood has been observed in several clinical trials, but cognitive and functional decline in Alzheimer’s disease remains the main indication. The initial dose is 5 mg/day, which is increased in 5-mg/day increments over 4 weeks to the final dose of 10 mg twice per day. Side effects are minimal, with dizziness, confusion, headache, and constipation being most often reported. Memantine undergoes little metabolism, and adverse drug-drug interactions have not been reported and are unlikely. Table 5–10 shows the clinical pharmacology of the cholinesterase inhibitors and memantine. Other Agents NSAIDS, hormones, statins, and ginkgo biloba have been studied in patients with Alzheimer’s disease, and some positive results have been reported, but to date definitive evidence of the efficacy of any of these agents remains unpublished. Sano et al. (1997) reported that patients with Alzheimer’s disease who were taking 2,000 IU of vitamin E showed no improvement in cognitive function but did take significantly longer to require institutionalization than did those receiving either placebo or 10 mg/day of selegiline. Although this finding has not been replicated, it has stimulated some clinicians to add highdose vitamin E to the treatment regimen of patients with Alzheimer’s disease.

Psychopharmacotherapy for Noncognitive Symptoms of Alzheimer’s Disease Agitation Perhaps the most common and most debilitating symptom complex seen in patients with Alzheimer’s disease is agitation, a syndrome that occurs in almost all patients with Alzheimer’s disease as they progress into the middle and late stages of illness. Agitation typically presents as restlessness, pacing, irritability, anger, anxiety and fearfulness, and refusal to accept care, often accompanied by persecutory beliefs that may reach delusional severity and verbal or physical aggressiveness. Agitation is often accompanied by impaired attention and concentration, elevated heart rate and blood pressure, and tachypnea.

Table 5–10.

Clinical pharmacology of agents useful for reducing the signs of dementia

Characteristic Time to maximal serum concentration (hr) Absorption affected by food? Serum half-life (hr) Protein binding (%)

Donepezil

Rivastigmine

Galantamine 0.5–1

Memantine

3–5

0.5–2

3–7

No

Yes

Yes

No

70–80

2a

5–7

60–80

40

0–20

45

Nonhepatic

2D6, 3A4

Nonhepatic

Dose (initial/maximal)

5–10 mg/day

1.5–6 mg twice daily

4–12 mg twice daily

5–10 mg twice daily

Mechanism of action

Cholinesterase inhibitor

Cholinesterase inhibitor

Cholinesterase inhibitor

NMDA receptor antagonist

Note. CYP= cytochrome P450; NMDA=N-methyl-D-aspartate. a Rivastigmine is a pseudoirreversible acetylcholinesterase inhibitor that has an 8-hour half-life for the inhibition of acetylcholinesterase in the brain. Source. Adapted from Cummings JL: “Alzheimer’s Disease.” New England Journal of Medicine 351:56–67, 2004. Copyright © 2004 Massachusetts Medical Society. All rights reserved.

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Metabolism (CYP enzyme)

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Verbalizations range from perseverative expressions of apprehension and fear to pressured incoherence, screaming, and cursing. Episodes of agitation often occur during the late afternoon or early evening (“sundowning”). Before medications are prescribed for agitation, it is important to examine the patient and his or her physical and social environment to determine what, if any, unmet needs are contributing to the agitation. Interventions may include providing optimal levels of sensory stimulation, engaging activities, and social contact; timely toileting; better communication; and adequate treatment of pain. Behavioral interventions based on an operant conditioning model and interventions to reduce overstimulation and stress also have been reported to be effective, but specific guidelines for which intervention is best for which patient remain to be determined (Cohen-Mansfield 2001). When nonpharmacological measures have been applied and symptoms remain, conventional and atypical neuroleptics, benzodiazepines, trazodone, anticonvulsants (including carbamazepine, valproic acid, and gabapentin), or lithium may be prescribed. All of these medications have been reported to be effective, but conventional (Devanand et al. 1998) and atypical (Fujikawa et al. 2004; Rabinowitz et al. 2004) neuroleptic medications have been the beststudied and most commonly used agents for agitation, at least until April 2005. At that time, the U.S. Food and Drug Administration (FDA) issued a public health advisory, citing 17 placebo-controlled trials of olanzapine, aripiprazole, risperidone, and quetiapine in elderly patients with dementia who also had behavior disorders. In 15 of those trials, which included more than 5,106 patients, a 1.6- to 1.7-fold increase in mortality was seen, mainly from “heart-related events,” including heart failure and sudden death, or infections, mostly pneumonia. The atypical antipsychotics fall into three drug classes based on their chemical structure, but because the increase in mortality was seen with medications in all three chemical classes, the FDA concluded that the increased mortality was probably related to the common pharmacological effects of all atypical antipsychotic medications, including those that had not been systematically studied in the dementia population. Accordingly, the FDA requested manufacturers of all atypical antipsychotic medications to add a boxed warning to their drug labeling that describes this risk and that notes that these drugs are not approved for the treatment of behavior disorders in elderly patients with dementia. The FDA is also considering adding a warning to the labeling of older antipsychotic medications because limited

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data also suggested a similar increase in mortality for these agents. Accordingly, clinicians should consider this risk before recommending antipsychotic medications for agitation in elderly individuals with dementia. (The FDA advisory is available at http://www.fda.gov/cder/drug/infopage/antipsychotics/ default.htm.) Typical dosage ranges of neuroleptic medications are 0.5–3 mg/day of haloperidol, 1–3 mg/day of risperidone, 5–10 mg/day of olanzapine, and 25– 200 mg/day of quetiapine, administered in two or three doses orally or, with conventional agents, by intramuscular injection. Low-potency, high-dose conventional agents such as thioridazine are generally avoided because of their greater anticholinergic potency, which can increase confusion in patients with Alzheimer’s disease, and their propensity to cause other side effects such as orthostatic hypotension. High-potency agents are also effective when agitation is accompanied by hallucinations, delusions, belligerent and hostile behavior, or physical aggressiveness. In one unreplicated double-blind, randomassignment study, Sultzer and associates (1997) found that trazodone (50– 250 mg/day) was as effective as haloperidol (1–5 mg/day) for agitation and somewhat more effective in the subgroup of patients with repetitive, verbally aggressive, and oppositional behaviors. Street and associates (2000) found that olanzapine (in dosages of 5 and 10 mg/day) was superior to placebo for control of agitation or aggression and psychosis in nursing home residents with Alzheimer’s disease; side effects were limited to somnolence and gait disturbance, and no extrapyramidal or anticholinergic symptoms were seen. If symptoms of agitation do not respond to neuroleptic therapy at dosages low enough to avoid significant side effects, switching to trazodone or augmenting with lorazepam, 0.5–1 mg administered orally or by intramuscular injection, may be effective. A typical daily regimen would include a standing order for 2 mg of haloperidol or risperidone orally at bedtime and either 1) 0.5 mg of lorazepam orally every 4–6 hours as a standing order or as needed or 2) 25–50 mg of trazodone orally every 4–6 hours as a standing order or as needed. Refractory symptoms may require treatment with neuroleptics and trazodone. Several rating scales, including the Behavior Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD; Reisberg et al. 1987), the Cohen-Mansfield Agitation Inventory (Cohen-Mansfield et al. 1989), and the Agitated Behavior in Dementia scale (Logsdon et al. 1999), are available to track treatment effect.

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Anticonvulsants such as valproic acid also have a role in the pharmacological management of behavioral disturbance in patients with Alzheimer’s disease (Sival et al. 2004) and may be particularly effective in patients with a history of mood instability or those with prominent mood instability as a feature of their agitation. Finally, evidence indicates that cholinesterase inhibitors such as donepezil and rivastigmine, in addition to improving cognitive function in Alzheimer’s disease, have salutary effects on noncognitive symptoms, including agitation, hallucinations, delusions, disinhibition, and apathy (Aupperle et al. 2004; Holmes et al. 2004). Table 5–11 shows the clinical pharmacology of agents useful for the control of symptoms and signs of agitation. Anxiety Patients with Alzheimer’s disease are also susceptible to anxiety in various forms and degrees of severity. Although treatment with anxiolytics is generally guided by the same principles that apply to elderly patients without dementia (see Chapter 7, “Anxiety Disorders and Late-Onset Psychosis”), patients with Alzheimer’s disease may be unable to articulate subjective feelings of apprehension, psychomotor tension, or fear, and the clinician may be forced to rely on more objective signs. In this regard, mild agitation as described earlier can reflect an anxiety state and may respond to anxiolytics alone. Depression Although authorities disagree on the prevalence of clinical depressive disorders in patients with Alzheimer’s disease, such disorders do occur and can be quite disabling, often leading to increased cognitive impairment (a syndrome that has been termed pseudodementia). Tricyclics and selective serotonin reuptake inhibitors have been studied in this regard, with mixed results (Katona et al. 1998; Lyketsos et al. 2000a; Taragano et al. 1997). In general, the principles that guide treatment of depression in elderly patients without dementia apply (see Chapter 4, “Mood Disorders—Treatment”), with the following modifications: •

Patients with Alzheimer’s disease, by virtue of cholinergic system disruption, are particularly susceptible to adverse reactions ranging from subtle

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•

219

worsening of cognitive function to frank delirium while taking centrally acting anticholinergic agents. Accordingly, tricyclic antidepressants and other anticholinergic agents should be avoided when possible, in favor of selective serotonin reuptake inhibitors and the other nontricyclic antidepressants. Because patients with Alzheimer’s disease may have impaired ability to articulate subjective feelings of sadness, hopelessness, helplessness, or worthlessness, the clinician often must rely more on neurovegetative signs and nonverbal expression of mood as target symptoms for treatment. The latter may include refusal to eat, crying spells, facial expressions of sadness or pain, unexplained episodes of agitation or hostility, and increased confusion. Patients with Alzheimer’s disease also may not be able to describe subjective side effects of medications, such as postural light-headedness or dizziness, so routine measurements of orthostatic blood pressure and careful assessment of gait and balance may be more necessary than in the elderly patient without dementia.

Mood Instability, Insomnia, Apathy Lithium, valproic acid, and other mood-stabilizing agents may be prescribed for patients with Alzheimer’s disease who have concomitant bipolar disorder or its variants, following the considerations listed above. Similarly, benzodiazepine and nonbenzodiazepine hypnotic agents are prescribed for patients with Alzheimer’s disease, as for elderly persons without dementia. The common practice of prescribing diphenhydramine or other antihistamines as hypnotics is particularly inadvisable for patients with Alzheimer’s disease because these agents have significant anticholinergic potency and can cause increased cognitive impairment. Psychostimulants such as methylphenidate and modafinil have a minor role in treatment of Alzheimer’s disease. Although it has been repeatedly documented that these agents do not improve cognitive function, they can be effective for apathy and social withdrawal and are occasionally useful to reverse sedative side effects of other agents.

Clinical pharmacology of medications for agitation with and without psychosis

Medication

Indications

Dosage (mg/day)

Side effects and adverse reactions

Haloperidol

Agitation, psychosis

0.5–2.0

EPS, tardive dyskinesia, akathisia, drowsiness

Risperidone

Agitation, psychosis

0.5–2.0

EPS, tardive dyskinesia, akathisia, drowsiness, metabolic syndrome

May increase risk of stroke in patients with cerebrovascular disease

Olanzapine

Agitation, psychosis

2.5–10

Drowsiness, weight gain, metabolic syndrome

May increase risk of stroke in patients with cerebrovascular disease

Quetiapine

Agitation, psychosis

25–200

Drowsiness, weight gain, metabolic syndrome

Aripiprazole

Agitation, psychosis

5–30

Drowsiness, weight gain, metabolic syndrome

Trazodone

Agitation

25–200

Drowsiness, orthostatic hypotension

Valproate

Agitation, mood lability

250–1,500 Drowsiness, ataxia

Note. EPS=extrapyramidal side effects. a All (except trazodone and valproate) may increase risk of death from multiple causes.

Special considerationsa

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Table 5–11.

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Lyketsos CG, Sheppard J-M, Steele CD, et al: Randomized, placebo-controlled, double-blind clinical trial of sertraline in the treatment of depression complicating Alzheimer’s disease: initial results from the Depression in Alzheimer’s Disease study. Am J Psychiatry 157:1686–1689, 2000a Lyketsos CG, Steinberg M, Tschanz JT, et al: Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am J Psychiatry 157:708–714, 2000b Mattis S: Mental status examination for organic mental syndrome in the elderly patient, in Geriatric Psychiatry. Edited by Bellak L, Karasu TB. New York, Grune & Stratton, 1976, pp 77–121 Mayeux R, Saunders AM, Shea S, et al: Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer’s disease. Alzheimer’s Disease Centers Consortium on Apolipoprotein E and Alzheimer’s Disease [published erratum appears in N Engl J Med 338:1325, 1998]. N Engl J Med 338:506–511, 1998 McCurry SM, Edland SD, Teri L, et al: The Cognitive Abilities Screening Instrument (CASI): data from a cohort of 2524 cognitively intact elderly. Int J Geriatr Psychiatry 14:882–888, 1999 McKhann G, Drachman D, Folstein M, et al: Clinical diagnosis and Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944, 1984 Migliorelli R, Petracca G, Teson A, et al: Neuropsychiatric and neuropsychological correlates of delusions in Alzheimer’s disease. Psychol Med 25:505–513, 1995 Mirra SS, Heyman A, McKeel D, et al: The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), part II: standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41:479–486, 1991 Morris MC, Evans DA, Tangney CC, et al: Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutr 81:508– 514, 2005 Murayama S, Saito Y: Neuropathological diagnostic criteria for Alzheimer’s disease. Neuropathology 24:254–260, 2004 National Institute on Aging and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s Disease: Consensus recommendations for the postmortem diagnosis of Alzheimer’s disease. Neurobiol Aging 18:S1–S2, 1997 Parker C, Philp I: Screening for cognitive impairment among older people in black and minority ethnic groups. Age Ageing 33:447–452, 2004 Patwardhan MB, McCrory DC, Matchar DB, et al: Alzheimer disease: operating characteristics of PET—a meta-analysis. Radiology 231:73–80, 2004

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Pedersen NL, Gatz M, Berg S, et al: How heritable is Alzheimer’s disease late in life? findings from Swedish twins. Ann Neurol 55:180–185, 2004 Pot AM, Zarit SH, Twisk JWR, et al: Transitions in caregivers’ use of paid home help: associations with stress appraisals and well-being. Psychol Aging 20:211–219, 2005 Rabinowitz J, Katz IR, De Deyn PP, et al: Behavioral and psychological symptoms in patients with dementia as a target for pharmacotherapy with risperidone. J Clin Psychiatry 65:1329–1334, 2004 Reichman WE: Nondegenerative dementing disorders, in The American Psychiatric Press Textbook of Geriatric Neuropsychiatry. Edited by Coffey CE, Cummings JL. Washington, DC, American Psychiatric Press, 1994, pp 369–388 Reisberg B, Borenstein J, Salob SP, et al: Behavioral symptoms in Alzheimer’s disease: phenomenology and treatment. J Clin Psychiatry 48(suppl):9–15, 1987 Ritchie CW, Ames D, Clayton T, et al: Metaanalysis of randomized trials of the efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer disease. Am J Geriatr Psychiatry 12:358–369, 2004 Sano M, Ernesto C, Thomas RG, et al: A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med 336:1216–1222, 1997 Scharlach AE: Caregiving and employment: competing or complementary roles? Gerontologist 34:378–385, 1994 Schulz R, O’Brien A, Czaja S, et al: Dementia caregiver intervention research: in search of clinical significance. Gerontologist 42:589–602, 2002 Schulz R, Belle SH, Czaja SJ, et al: Long-term care placement of dementia patients and caregiver health and well-being. JAMA 292:961–967, 2004 Shulman KI: Clock-drawing: is it the ideal cognitive screening test? Int J Geriatr Psychiatry 15:548–561, 2000 Shumaker SA, Legault C, Kuller L, et al: Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA 291:2947–2958, 2004 Sival RC, Duivenvoorden HJ, Jansen PA, et al: Sodium valproate in aggressive behaviour in dementia: a twelve-week open label follow-up study. Int J Geriatr Psychiatry 19:305–312, 2004 Smith JD: Apolipoprotein E4: an allele associated with many diseases. Ann Med 32:118–127, 2000 St George-Hyslop PH: Molecular genetics of Alzheimer’s disease. Biol Psychiatry 47:183–199, 2000

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Street JS, Clark WS, Gannon KS, et al: Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities: a double-blind, randomized, placebo-controlled trial. The HGEU Study Group. Arch Gen Psychiatry 57:968–976, 2000 Sultzer DL, Gray KF, Gunay I, et al: A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia. Am J Geriatr Psychiatry 5:60–69, 1997 Szekely CA, Thorne JE, Zandi PP, et al: Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer’s disease: a systematic review. Neuroepidemiology 23:159–169, 2004 Taragano F, Lyketsos C, Mangone CA, et al: A double-blind, randomized, fixed-dose trial of fluoxetine vs. amitriptyline in the treatment of major depression complicating Alzheimer’s disease. Psychosomatics 38:246–252, 1997 Tariot PN, Farlow MR, Grossberg GT, et al: Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 291:317–324, 2004 Teng EL, Chiu HC, Schneider LS, et al: Alzheimer’s dementia: performance on the Mini Mental State Examination. J Consult Clin Psychol 55:96–100, 1987 Teng EL, Hasegawa K, Homma A, et al: The Cognitive Abilities Screening Instrument (CASI): a practical guide for cross-cultural epidemiological studies of dementia. Int Psychogeriatr 6:45–58, 1994 Terry RD, Masliah E, Hansen LA: Structural basis of the cognitive alterations in Alzheimer disease, in Alzheimer Disease. Edited by Terry RD, Katzman R, Bick K. New York, Raven, 1994, pp 179–196 Tsai N, Gao ZX: Validity of Hasegawa’s Dementia Scale for screening dementia among aged Chinese. Int Psychogeriatr 1:145–152, 1989 Tsuang DW, Wilson RK, Lopez OL, et al: Genetic association between the APOE 4 allele and Lewy bodies in Alzheimer disease. Neurology 64:509–513, 2005 Welsh KA, Butters N, Hughes J, et al: Detection of abnormal memory decline in mild cases of Alzheimer’s disease using CERAD neuropsychological measures. Arch Neurol 48:278–281, 1991 Welsh KA, Butters N, Mohs RC, et al: The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), V: a normative study of the neuropsychological battery. Neurology 44:609–614, 1994 Wilder D, Cross P, Chen J, et al: Operating characteristics of brief screens for dementia in a multicultural population. Am J Geriatr Psychiatry 3:96–107, 1995 Woods B, Spector A, Jones C, et al: Reminiscence therapy for dementia. Cochrane Database Syst Rev (2):CD001120, 2005

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Zandi PP, Anthony JC, Khachaturian AS, et al: Cache County Study Group. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol 61:82–88, 2004 Zandi PP, Sparks DL, Khachaturian AS, et al: Do statins reduce risk of incident dementia and Alzheimer disease? the Cache County Study. Arch Gen Psychiatry 62:217–224, 2005

Resources for Dementia Caregivers Alzheimer’s Association: (800) 272-3900, http://www.alz.org American Association of Retired Persons (AARP): http://www.aarp.org (information about the Family and Medical Leave Act) Kaplan M, Hoffman S (eds): Behaviors in Dementia: Best Practices for Successful Management. Baltimore, MD, Health Professions Press, 1998 Mace NL, Rabins PV (eds): The 36-Hour Day, 3rd Edition. Baltimore, MD, Johns Hopkins University Press, 1999 National Institutes of Health Clinical Trials: http://www.clinicaltrials.gov (clinical trials that are recruiting patients with Alzheimer’s disease) U.S. Department of Health and Human Services, Administration on Aging: (800) 677-1116, http://www.aoa.gov (click on “Elders and Families” for help with locating services and resources for older adults)

6 Other Dementias and Delirium Frontotemporal Dementia Frontotemporal dementia is a term used to describe a group of disorders that share a common pattern of relatively focal degeneration of the frontal and temporal lobes of the brain. Classic Pick’s disease, primary progressive aphasia, and several other histopathologically distinct conditions are the main contributors to this category.

Epidemiology Because of the histopathological heterogeneity of this syndrome (see “Pathology” below), and the overlap of its clinical features with those of Alzheimer’s disease and vascular dementia, it is difficult to estimate its prevalence. One Swedish study (Andreasen et al. 1999) found a prevalence of 3.2% in a clinically diagnosed sample of 619 patients referred for diagnostic evaluation (compared with 36.9% with Alzheimer’s disease), whereas Gustafson and colleagues (1992) estimated the prevalence as close to 10%. Ratnavalli and colleagues (2002) analyzed records from a university hospital in Cambridge, England, and found that frontotemporal dementia and Alzheimer’s disease had the same prevalence (15 per 100,000) in patients ages 45–64; the average age at onset of the frontotemporal dementia was 52.2 years.

Diagnostic Criteria Consensus criteria for diagnosing frontotemporal dementia were published in 1998 (Neary et al. 1998) and are presented in Table 6–1. 229

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Table 6–1. Clinical diagnostic features of frontotemporal dementia Core diagnostic features Insidious onset and gradual progression Early decline in social interpersonal conduct Early impairment in regulation of personal conduct Early emotional blunting Early loss of insight Supportive diagnostic features Behavior disorder Decline in personal hygiene and grooming Mental rigidity and inflexibility Distractibility and impersistence Hyperorality and dietary changes Perseverative and stereotyped behavior Utilization behavior Speech and language Altered speech output Aspontaneity and economy of speech Press of speech Stereotypy of speech Echolalia Perseveration Mutism Physical signs Primitive reflexes (e.g., grasp, snout, glabellar) Incontinence Akinesia, rigidity, and tremor Low and labile blood pressure Investigations Neuropsychology: significant impairment on frontal lobe tests in the absence of severe amnesia, aphasia, or perceptuospatial disorder Electroencephalography: conventional electroencephalogram findings are normal despite clinically evident dementia

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Table 6–1. Clinical diagnostic features of frontotemporal dementia (continued) Supportive diagnostic features (continued) Investigations (continued) Brain imaging (structural and/or functional): predominant frontal and/or anterior temporal abnormality Source. Adapted from Neary et al. 1998.

History, Clinical Presentation, and Mental Status Examination The typical age at onset of frontotemporal dementia is in the 50s and 60s, and a family history of dementia is present in about half of cases, with a dominant pattern of inheritance found in the majority (Chow et al. 1999). Some authorities subdivide frontotemporal dementia into three clinical subsyndromes based on its initial presentation: 1) frontal variant frontotemporal dementia (often called dementia of frontal type), 2) semantic dementia, and 3) progressive nonfluent aphasia. In the frontal variant, the main presenting feature is progressive personality change, with disinhibition, loss of empathy, change in eating patterns, ritualized or stereotypical behavior, and apathy (Bozeat et al. 2000). Semantic dementia is characterized by progressive loss of knowledge of people, objects, facts, and word meanings and is associated with primarily temporal lobe pathology. Progressive nonfluent aphasia is associated with primarily frontal (perisylvian) pathology, presents with deficits in the phonological and syntactic components of language (Grossman 2002), and may progress to corticobasilar degeneration (Gorno-Tempini et al. 2004). A recent longitudinal study (Seeley et al. 2005) found that after an average of 3 years, patients who initially presented with the semantic (left temporal) variant of frontotemporal dementia also developed the symptoms of right frontotemporal deficit (especially emotional flatness, irritability, and disruption of physiological drives such as sleep and appetite), and those with initially prominent behavioral symptoms developed semantic language deficits. Disinhibition, compulsions, altered food preferences, and weight gain emerged in both groups later in the disease, about 5–7 years after onset.

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Screening Instruments and Rating Scales Most brief mental status examinations do not assess frontal executive functions, and as a result, individuals with frontotemporal dementia may score in the normal range on brief examinations in the early to middle stages of disease. Several short batteries have been developed to help clinicians test for frontal lobe changes, including the Executive Interview (Royall et al. 1992) and the Frontal Assessment Battery (FAB; Dubois et al. 2000). Both measures take about 10 minutes to administer and cover several different aspects of behavior, cognition, or motor function affected by frontal lobe syndromes. The FAB differentiates better between frontotemporal dementia and Alzheimer’s disease than does the Mini-Mental State Examination (MMSE) (Slachevsky et al. 2004), and it is now used frequently in clinical research (e.g., Mendez et al. 2005). The Executive Interview correlates well with neuropsychological measures of executive function and is sensitive to differences in everyday functional level for older adults in residential care (Royall et al. 1992) and retirement facilities (Royall et al. 2005). If the referral question concerns differentiation between frontotemporal dementia and Alzheimer’s disease, these brief screens are a good starting point; however, brief screening is less likely to differentiate frontotemporal dementia from other syndromes that preferentially affect frontal executive function (e.g., dementia with Lewy bodies, schizophrenia, or major depression). In such cases, referral for neuropsychological assessment should be considered to document impairments and to differentiate changes due to dementia from affective illness or personality disorder. Informant rating scales also may help to ensure that a thorough picture of frontal deficits in everyday settings is obtained. The Frontal Systems Behavior Scale (Grace and Malloy 2001) provides standardized ratings of apathy, executive skills, and disinhibition and has parallel forms for the patient and informant that can be useful for assessing patients’ self-awareness of behavior changes. The Frontal Systems Behavior Scale has been shown to discriminate dementias with prominent frontal system neuropathology from other dementias and also has been used with psychiatric patients. The standardization sample for this measure included participants up to age 95 years, and norms are stratified by age, education, and gender. The Frontal Behavioral Inventory (Kertesz et al. 2000) is completed by a trained professional on the basis of a

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structured caregiver interview. Items for this scale were based on behaviors described in diagnostic consensus reports (e.g., Neary et al. 1998) for frontotemporal dementia. The Frontal Behavioral Inventory has good reliability and appears effective in discriminating clearly diagnosed frontotemporal dementia from Alzheimer’s disease or vascular dementia. However, norms for clinical use are lacking. The Neuropsychiatric Inventory (NPI; see Chapter 5, “Dementia and Alzheimer’s Disease,” and Appendix) is another behavior rating scale completed by professionals on the basis of a caregiver interview. It taps several behaviors that are often affected in frontotemporal dementia and has been used in clinical trials. A caregiver-completed form of the NPI has been developed (Kaufer et al. 2000), but data are limited on the clinical usefulness of this version. The symptoms of frontotemporal dementia, especially the frontal variant, are often very distressing to family members, and education is needed to help with understanding the avolitional nature of specific behavior changes and with developing management strategies. A systematic survey of affected behaviors, whether based on direct informant ratings or interviews, can provide a good starting point for tailoring interventions for caregivers.

Physical and Neurological Examination As shown in Table 6–1, grasp, snout, and glabellar reflexes may be present, and some patients will develop parkinsonian signs and symptoms or motor neuron abnormalities in the later stages.

Neuropsychological Tests On neuropsychological examination, frontotemporal dementias can be distinguished in early stages from dementia due to Alzheimer’s disease by the relative salience of executive function deficits as opposed to memory disorder or by the emergence of progressive alterations in speech (e.g., dysfluency, stereotypy) before notable memory deficits emerge. Neuropsychological tests sensitive to frontal executive dysfunction include motor programming tasks, cognitive speed and flexibility measures (e.g., the Trail Making Test), and reasoning tasks (e.g., the Similarities subtest of the Wechsler Adult Intelligence Scale—Third Edition), as well as naming and verbal fluency tests (see Table 5–5 in Chapter 5, “Dementia and Alzheimer’s Disease,” for test descriptions). The heterogeneity that has been noted in frontotemporal dementia is also

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apparent on testing, with some affected persons having striking changes in personality and social behavior early on, but preserved communication skills, and others showing prominent language deficits with relative preservation of personality. The Delis-Kaplan Executive Function System (Delis et al. 2001) provides representative norms for interpreting several commonly used executive function tests, as well as detailed information on qualitative features of performance that may be important diagnostically.

Laboratory Evaluation Depending on the underlying pathology, frontal and temporal hypoperfusion (on single photon emission computed tomography), reduced glucose metabolism (on positron emission tomography with fluorodeoxyglucose), and atrophy (on computed tomography or magnetic resonance imaging) may be seen in frontotemporal dementia.

Differential Diagnosis The other degenerative dementias (Alzheimer’s disease and dementia with Lewy bodies); vascular dementia; the dementias associated with Huntington’s disease, Parkinson’s disease, Creutzfeldt-Jakob disease, human immunodeficiency virus (HIV) infection, and head trauma; and those associated with other general medical conditions all must be ruled out before a diagnosis of frontotemporal dementia is made. Because of the lack of differentiating physical signs, and the tendency for Alzheimer’s disease to include signs and symptoms of frontal lobe involvement, the most challenging distinction is between frontotemporal dementia and Alzheimer’s disease. Table 6–2 summarizes the main differentiating features of these two conditions. Knopman et al. (2005) reviewed 433 cases that went to autopsy and found that frontotemporal dementia was correctly identified on the basis of clinical and laboratory findings in 29 of 34 autopsy-verified cases. This finding represents 85% sensitivity; the authors also reported 99% specificity.

Pathology The typical gross pathological finding is of frontal and anterotemporal atrophy. Microscopic findings have been subdivided according to the profile of immunohistochemical staining and the pattern of intracellular inclusions, as follows:

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1. Tau-positive pathology, including classic argyrophilic, tau-positive, intraneuronal Pick bodies (Pick’s disease); 2. Tau gene mutations (FTDP17) and diffuse tau-positive neuronal and astrocytic immunoreactivity; 3. Tau-positive astrocytic plaques and ballooned achromatic neurons (corticobasal degeneration); and 4. Tau-positive argyrophilic grain disease. The second and third subdivisions above include cases with tau-negative, ubiquitin-positive inclusions in the dentate gyrus and in the brain-stem motor nuclei (frontotemporal dementia with motor neuron inclusions) and dementia lacking distinctive histology (Hodges et al. 2004).

Treatment There is no specific treatment for the personality or cognitive changes seen in the frontotemporal dementias, but several aspects of disturbed behavior have been reported to respond to psychopharmacological treatment. Trazodone improved symptoms of irritability, agitation, depression, and eating disorders in one randomized, double-blind, placebo-controlled crossover study (Lebert et al. 2004), and similar results have been observed in open-label studies with moclobemide (Adler et al. 2003), rivastigmine (Moretti et al. 2004), and paroxetine (Moretti et al. 2003). However, a double-blind, placebo-controlled crossover study with paroxetine resulted in worsening cognition and no improvement in behavior (Deakin et al. 2004), suggesting that open-label treatment studies in frontotemporal dementia may be misleading.

Dementia With Lewy Bodies Dementia with Lewy bodies (McKeith et al. 1996) is a progressive, degenerative dementing condition with clinical and pathological features that overlap with those of Alzheimer’s disease and Parkinson’s disease. Its precise nosological status remains controversial because some authorities regard it as a variant of Alzheimer’s disease and others consider it a clearly distinct condition. This debate has led to the use of various terms for this condition, including senile dementia of the Lewy body type and diffuse Lewy body disease.

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Table 6–2. Differentiation of Alzheimer’s disease from frontotemporal dementia Alzheimer’s disease

Frontotemporal dementia

Symptom Behavior Affect Apathy Delusions Compulsions Eating

Socially correct

Early disinhibition

Normal Mild Simple Mild Weight loss

Remote, bizarre Severe Bizarre Severe Weight gain

Neuropsychological test performance Drawing Impaired Memory Impaired Executive function Impaired Generation Impaired Anomia Lexical Neuropathology Plaques Tangles Gliosis Abnormal genes

Neurochemistry Cholinergic deficit

Positron emission tomography

Yes Yes Proportional to neuronal loss Amyloid precursor protein, presenilin 1 and 2; apolipoprotein ε4; tau mutations Presynaptic cholinergic and serotonergic Temporoparietal hypometabolism

Spared Variable Severely impaired Severely impaired Semantic (often) No No (except for familial tauopathy) Out of proportion to neuronal loss

Postsynaptic cholinergic; presynaptic and postsynaptic serotonergic Frontotemporal hypometabolism

Source. Adapted from Miller BL, Gustavson A: “Alzheimer’s Disease and Frontotemporal Dementia,” in American Psychiatric Press Textbook of Geriatric Neuropsychiatry, 2nd Edition. Edited by Coffey CE, Cummings JL. Washington, DC, American Psychiatric Press, 2000, p. 521. Copyright © 2000, American Psychiatric Press. Used with permission.

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Epidemiology The prevalence and incidence of dementia with Lewy bodies are not well established, but autopsy series have found it to account for 15%–36% of cases of dementia (Hansen et al. 1990; Holmes et al. 1999), which would make it the second most common cause of dementia, after Alzheimer’s disease.

Diagnostic Criteria Consensus criteria published originally by McKeith et al. (1996) and recently revised (McKeith et al. 2005) require dementia and two of the following three core features to make a diagnosis of probable dementia with Lewy bodies: “fluctuating cognition with pronounced variations in attention and alertness; recurrent visual hallucinations that are typically well formed and detailed; and spontaneous motor features of parkinsonism” (McKeith et al. 2005, p. 1864). If one or more of the following suggestive features are present, a diagnosis of probable dementia with Lewy bodies can be made in the presence of only one core feature: “REM [rapid eye movement] sleep behavior disorder [“vivid and often frightening dreams during REM sleep, but without muscle atonia,” McKeith et al. 2005, p. 1866]; severe neuroleptic sensitivity; and low dopamine transporter uptake in basal ganglia as demonstrated by [single photon emission computed tomography] SPECT or [positron emission tomography] PET imaging” (McKeith et al. 2005, p. 1864). Supportive features include “repeated falls and syncope; transient unexplained loss of consciousness; depression; systematized delusions; hallucinations in other modalities; relative preservation of medial temporal lobe structures on computed tomography/magnetic resonance imaging scan; generalized low uptake on SPECT/PET perfusion scan with reduced occipital activity; abnormal (low uptake) MIBG (metaiodobenzyl guanidine—a measure of postganglionic sympathetic cardiac innervation) myocardial scintigraphy; and prominent slow wave activity on electroencephalogram with temporal lobe transient sharp waves” (McKeith et al. 2005, p. 1864). The diagnosis of dementia with Lewy bodies is less likely if “cerebrovascular disease evident as focal neurological signs or on brain imaging is present; in the presence of any other physical illness or brain disorder sufficient to account in part or in total for the clinical picture; and if parkinsonism only appears for the first time at a stage of severe dementia” (McKeith et al. 2005, p. 1864).

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Although the consensus criteria have enjoyed widespread acceptance, Serby and Samuels (2001) reexamined their usefulness via a critical analysis of 242 published cases of dementia with Lewy bodies and found visual hallucinations and fluctuating cognition to be of very limited value. The authors suggested that these features often may be a result of treatment rather than “core” features of the disease and concluded that “greater caution should be used in the establishment of a set of diagnostic criteria for DLB [dementia with Lewy bodies]. The presence of parkinsonism and, perhaps, its co-occurrence with dementia appear to be the most reliable indicators of the presence of DLB” (p. 215).

History The history of dementia with Lewy bodies is typically of a gradual, progressive decline in intellectual function that is almost always eventually accompanied by parkinsonism. Although marked day-to-day fluctuations in cognitive function and well-formed, silent visual hallucinations that typically appear as animals, objects, or people that the patient insists are real may turn out to be accidental features of the illness, their occurrence should be considered at least supportive, if not diagnostic. The history is likely to include repeated falls, syncope, transient loss of consciousness, neuroleptic sensitivity, systematized delusions, and hallucinations in other modalities, as well as extrapyramidal reactions to conventional neuroleptics (severe) and atypical neuroleptics (severe in comparison to patients with other conditions), all of which are also regarded as supportive of the diagnosis of dementia with Lewy bodies. REM sleep behavior disorder also may be present early in the disease (Ferman et al. 2002).

Clinical Presentation and Mental Status Examination The clinical presentation is of a dementia with intellectual changes that generally parallel those of Alzheimer’s disease, except the early memory impairment is more likely to represent a retrieval deficit than the impairment in new learning typically seen in Alzheimer’s disease. Deficits in attentional processes are also common in dementia with Lewy bodies, as are deficits in executive functions.

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Physical and Neurological Examination Physical and neurological examination in dementia with Lewy bodies is likely to detect bradykinesia and rigidity, particularly in the later stages of illness, but parkinsonian tremor may be absent. Evidence of stroke or other physical conditions that could account for the clinical features should be considered as evidence against a diagnosis of dementia with Lewy bodies.

Neuropsychological Tests Cognitive profiles of patients with dementia with Lewy bodies overlap with those of Alzheimer’s disease patients in that both show deficits in multiple areas, including memory dysfunction. Compared with patients with uncomplicated Alzheimer’s disease, however, individuals with dementia with Lewy bodies may have disproportionate problems with attention and working memory, visuoperceptual processing, and executive function. In dementia with Lewy bodies, low scores are likely to be seen on nearly all types of attention tasks, whereas simple attention (e.g., forward digit span) is usually preserved in Alzheimer’s disease. Similarly, persons with dementia with Lewy bodies often have more difficulty than do patients with Alzheimer’s disease on relatively simple visuoperceptual tasks such as recognizing fragmented letters or extracting meaning from pictures (Calderon et al. 2001). By contrast, delayed recall tends to be better preserved in dementia with Lewy bodies than in Alzheimer’s disease, especially if the newly learned information is organized in a natural way (e.g., stories) (Calderon et al. 2001); there may also be greater benefit from cues and recognition testing formats. Typically, more psychomotor slowing occurs early in the course of dementia with Lewy bodies, and patients have greater difficulty with motor programming and executive functions such as shifting from one thought or action to another. A recent study comparing autopsy-verified cases of Alzheimer’s disease, dementia with Lewy bodies, and combined Alzheimer’s disease and dementia with Lewy bodies (Kraybill et al. 2005) provided further support that neuropsychological testing may help in diagnostic differentiation. Participants in this study were tested early in the course of illness (about 1 year after the onset of memory problems), and at that point, no significant differences were seen between diagnostic groups on mental status examinations (either the MMSE or the Dementia Rating Scale; see Table 5–1). However, individuals later

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found to have pure Alzheimer’s disease or combined Alzheimer’s disease and dementia with Lewy bodies performed worse on verbal memory measures and confrontation naming than did those with pure dementia with Lewy bodies; by contrast, patients with dementia with Lewy bodies had more impairment at baseline on a measure of psychomotor speed and executive function (Trail Making Test) and on an attention test (digit span) (see Table 5–5 for descriptions of these measures). Interestingly, no differences were observed on brief screening measures of attention and executive function (Dementia Rating Scale subscales), suggesting that referral for detailed neuropsychological testing may be needed to improve antemortem diagnostic accuracy for dementia with Lewy bodies.

Differential Diagnosis The differential diagnosis of dementia with Lewy bodies includes essentially all of the dementing diseases, including Alzheimer’s disease, frontotemporal dementia, vascular dementia, Parkinson’s disease and Alzheimer’s disease, and Parkinson’s disease with dementia.

Pathology and Pathogenesis The micropathology of dementia with Lewy bodies involves extensive cortical neuritic plaques, as are seen in Alzheimer’s disease, with relatively few neurofibrillary tangles. Lewy bodies (intracytoplasmic spherical, eosinophilic neuronal inclusion bodies that can also be visualized via antiubiquitin immunocytochemical detection techniques [McKeith et al. 1996]) are widespread in the brain stem, subcortical nuclei, limbic cortex, and neocortex. Neurochemical analysis of neocortical brain tissue indicates loss of cholinergic markers (i.e., choline acetyltransferase and acetylcholinesterase) of a magnitude even greater than that reported in Alzheimer’s disease.

Treatment Because of the relatively severe loss of cholinergic innervation found in dementia with Lewy bodies, cholinesterase inhibitors such as donepezil and rivastigmine have been studied in this condition. A double-blind, placebo-controlled, double-crossover study of just seven subjects found donepezil to be statistically significantly superior to placebo, as measured by the MMSE and the Alzhei-

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mer’s Disease Assessment Scale–cognitive subscale, after 4 weeks of treatment (Beversdorf et al. 2004). In another double-blind, placebo-controlled, randomassignment study (Wesnes et al. 2002), subjects taking rivastigmine (6–12 mg/ day) had significantly improved attention, working memory, and episodic secondary memory, as assessed by a computerized test battery, compared with those taking placebo. Most treatment effects disappeared 3 weeks after rivastigmine was discontinued. Treatment of agitation or psychosis in dementia with Lewy bodies is complicated by severe extrapyramidal reactions to conventional neuroleptics, and even the atypical agents risperidone, olanzapine, and clozapine have been reported to cause significant extrapyramidal symptoms in dementia with Lewy bodies. Until a “class effect” is established, other atypical agents such as quetiapine, ziprasidone, and aripiprazole may therefore be preferable for symptoms of agitation and psychosis that remain after administration of cholinesterase inhibitors.

Vascular Dementia Epidemiology The prevalence of vascular dementia is difficult to estimate because no generally accepted and validated neuropathological criteria have been established to date, and this has impeded definitive validation of clinical diagnostic criteria for vascular dementia (Jellinger 2005). Still, community-based studies suggest that 1) the prevalence of clinical vascular dementia is age dependent, with prevalence rates doubling every 5 years; 2) the frequency of vascular dementia is higher in men; and 3) the prevalence differs substantially from nation to nation. Overall, the prevalence of vascular dementia ranges from 2.2% in 70- to 79-year-old women to 16.3% in men older than 80 (Leys et al. 1998).

Diagnostic Criteria The nosological status of vascular dementia has been called into question by autopsy studies indicating that the underlying neuropathology in clinical vascular dementia is commonly a “mixture” of vascular lesions and other degenerative conditions, usually Alzheimer’s disease. A report by Hulette and colleagues

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(1997) indicated that only 6 of nearly 2,000 brains of individuals with dementia that were surveyed by pathologists had “pure” vascular pathology. If this figure is at all representative, clinical vascular dementia should be thought of as a “vascular complication” superimposed on another dementing illness in many, if not most, cases. This view was supported by Chui (2005), who reviewed the status of cerebrovascular brain injury (CVBI) in relation to dementia and stated, “An emerging database suggests that CVBI contributes significantly to mild cognitive impairment and can precipitate the appearance of dementia in early stages of AD [Alzheimer’s disease] pathology. However, the effects of CVBI may become submerged once AD-pathology arrives at the isocortical stages” (p. 51). Korczyn (2005) came to a similar conclusion, stating that most patients diagnosed as VaD [vascular dementia] actually have evidence of hippocampal atrophy and cortical cholinergic deficiency, both previously regarded as markers of AD [Alzheimer’s disease]. Demented patients with vascular brain disease frequently have some degree of amyloid deposits and neurofibrillary changes, which, although possibly insufficient to fulfill the arbitrary criteria set for the diagnosis of AD, may nevertheless contribute to the cognitive changes. Like the AD changes, the vascular damage may accumulate slowly and impair neuronal metabolism and function, eventually causing neuronal death. (p. 5)

The DSM-IV-TR (American Psychiatric Association 2000) criteria for vascular dementia are summarized in Table 6–3, but other criteria sets have been proposed that offer different profiles of specificity and sensitivity (Wetterling et al. 1996). A rating scale (Rosen et al. 1980) (Table 6–4) designed to quantify the probability of underlying infarctions in the patient with dementia has been published on the basis of the clinical signs and symptoms described in the following subsections.

History The history of the current illness in vascular dementia is classically one of a more abrupt, stepwise course of cognitive impairment than the more gradual onset and decline typical of “pure” Alzheimer’s disease and other degenerative dementias. Risk factors identified by the history in vascular dementia are those associated with stroke—that is, arterial hypertension, atherosclerotic disease, low education level, alcohol abuse, and heart disease.

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Table 6–3. Summary of DSM-IV-TR diagnostic criteria for vascular dementia A.

The development of multiple cognitive deficits manifested by both (1) memory impairment (2) one (or more) of the following cognitive disturbances: (a) aphasia (b) apraxia (c) agnosia (d) disturbance in executive functioning B. The cognitive deficits in Criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning. C. Focal neurological signs and symptoms or laboratory evidence indicative of cerebrovascular disease that are judged to be etiologically related to the disturbance. D. The deficits do not occur exclusively during the course of a delirium. Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

Clinical Presentation and Mental Status Examination Vascular dementia is clinically very similar to other dementias, although certain features such as relative preservation of personality and insight, depressed mood, emotional lability, somatic complaints, and “patchiness” of cognitive deficits on mental status examination are reported to be more common in vascular dementia than in other types of dementia. “Patchiness” refers to the phenomenon of relatively well-preserved islands of function concurrent with relatively deteriorated areas of function (e.g., relatively well-preserved memory with severe disturbance of language and praxis, or relatively severe memory impairment with relative preservation of calculating ability and capacity for abstract thought).

Physical and Neurological Examination Patients with vascular dementia may have focal neurological signs associated with ischemic damage to motor cortex and descending tracts, such as exaggerated deep tendon reflexes or focal weakness or rigidity, or signs associated with more global cortical and subcortical damage, such as gait abnormalities,

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Table 6–4. Clinical features of the Modified Ischemic Score Feature Abrupt onset Stepwise deterioration Somatic complaints Emotional incontinence History or presence of hypertension History of strokes Focal neurological symptoms Focal neurological signs

Point value 2 1 1 1 1 2 2 2

Note. A score of 4 or more is consistent with vascular dementia. Source. Adapted from Rosen et al. 1980.

dysarthria, impaired gag reflex, extensor plantar reflex, and signs of “frontal release” such as grasp or snout reflex. Evidence of systemic atherosclerosis (e.g., bruits) and signs of poor peripheral circulation (e.g., diminished pulses, atrophic skin changes) also may increase the probability that dementia is at least partly of vascular origin. Physical and neurological examination may show abnormal findings associated with Parkinson’s disease (tremor, cogwheel rigidity, and akinesia), Huntington’s disease (choreoathetoid movements), head trauma (motor or sensory deficits), HIV infection (tremor, ataxia, atonia and hyperreflexia, frontal release signs), or Creutzfeldt-Jakob disease (ataxia, myoclonus).

Neuropsychological Tests Neuropsychological test findings in vascular dementia vary with the nature and severity of cerebrovascular illness. For patients who have had single or multiple large infarcts, deficits commensurate with the location and extent of infarction should be expected. For those whose cerebrovascular impairment is limited to lacunar infarcts or who have extensive deep white matter disease, deficits are more consistent with subcortical dementia, with impairments expected on tests of psychomotor speed and dexterity, frontal executive functions (e.g., difficulties with divided attention, attentional shifting, working memory, or behavioral planning and sequencing), and motor aspects of speech (e.g., dysarthria or reduced verbal output may be present) (Roman et al. 1993). Subtle frontal-subcortical deficits may precede clinically significant dementia in patients with

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deep white matter disease (leukoaraiosis) or lacunar infarcts, and abrupt change in mood and personality, with or without clear cognitive impairment, also may be observed in vascular dementia. A high rate of intertest scatter is not specific to vascular dementia and cannot be used to identify this condition or to differentiate it from Alzheimer’s disease or other dementias.

Laboratory Evaluation Laboratory evaluation generally begins with a selected standardized battery of tests with relatively high sensitivity and low specificity, as presented in Chapter 5 (“Dementia and Alzheimer’s Disease”; Table 5–4). As indicated in Table 6–3, to establish a diagnosis of vascular dementia in the absence of neurological signs and symptoms, laboratory evidence of cerebrovascular disease is required. Computed tomographic or magnetic resonance brain imaging that shows brain infarction is sufficient, if the number and location of infarcts are judged to account for the observed cognitive deficits.

Differential Diagnosis As is true of all of the dementing illnesses, the differential diagnosis of vascular dementia includes Alzheimer’s disease; frontotemporal dementia; dementia with Lewy bodies; the dementias associated with HIV disease, head trauma, Parkinson’s disease, Huntington’s disease, and Creutzfeldt-Jakob disease; dementia due to other medical conditions, such as brain tumor, normal-pressure hydrocephalus, and hypothyroidism; delirium; and functional disorders (see Table 5–6 in Chapter 5, “Dementia and Alzheimer’s Disease”). As discussed earlier, the history, clinical presentation, mental status examination, physical and neurological examination, and laboratory evaluation, including neuropsychological tests, have been considered to be adequate to differentiate vascular dementia from other dementing illnesses (which are discussed in detail below), but some studies have cast doubt on this claim. Reed et al. (2004) studied 18 individuals with autopsy-defined cerebrovascular disease and found that clinical features were quite variable; only 40% of cases with high CVD [cerebrovascular disease] levels had elevated Hachinski Ischemia Scale scores and neither abrupt onset nor stepwise progression was found in most high CVD cases, even when AD [Alzheimer’s disease] changes were essentially absent. The presence of dementia was predictably related to the level of neurofibrillary pathology, but was not related to the severity of CVD. (p. 63)

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Nonetheless, delirium is generally distinguishable from vascular dementia in that delirium is characterized by a much more acute onset and more rapid progression than vascular dementia, and patients with delirium have a disturbance in consciousness that is not seen in patients with uncomplicated vascular dementia. However, the diagnostic picture can be clouded in two situations: 1) when vascular dementia and true delirium occur simultaneously and 2) during an episode of acute agitation (e.g., “sundowning”) of the type to which patients with vascular dementia are prone, particularly in the early evening. Agitation, which is usually a self-limiting, transient state, may have many of the features of delirium without the implications of deranged physiology and poor prognosis characteristic of true delirium. Accurate diagnosis of vascular dementia in both cases depends on reevaluation when signs or symptoms of delirium or acute agitation have cleared, allowing the underlying dementia to be characterized. As described earlier, several functional illnesses can also mimic dementia of any type, including vascular dementia. Generally, these illnesses are identifiable by the rapid onset and progression of symptoms and the atypical overall clinical picture (i.e., absence of the neurological signs and symptoms and risk factors for vascular dementia) seen in the functional disorders.

Pathogenesis Vascular dementia is caused by varying combinations of vascular insults to the brain, including arterial territory infarcts, distal field (watershed/borderzone) infarcts, small and medium-sized lesions mainly in functionally important brain areas, lacunar infarcts and scars, white matter lesions, incomplete ischemic injury, hippocampal lesions, and sclerosis (Jellinger 2005). Several subtypes of vascular dementia have been described, based on either the number and distribution of lesions or the size of vessels involved (large vs. small vessels). An emerging consensus suggests that the “subcortical” pattern of damage is sufficiently homogeneous in terms of clinical, radiographic, and pathophysiological features to constitute a meaningful subtype, particularly with respect to treatment trials. Generalized arteriosclerosis secondary to hypertension, cerebral atherosclerosis, and diabetes usually are cited as the most common causes of thrombotic infarction, and cardiac disease and carotid atherosclerosis as the most common causes of embolic infarction. Increasing evidence suggests that the vascular lesions of vascular dementia may affect

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cholinergic pathways in vascular dementia, leading to a hypocholinergic state similar to that observed in Alzheimer’s disease (Mesulam et al. 2003). Some investigators (e.g., Roy and Rauk 2005) have hypothesized that both Alzheimer’s disease and vascular dementia are the result of a common pathophysiological process initiated by soluble β-amyloid, which is toxic to both neuronal and vascular tissue. Others support the view that ischemia due to vascular pathology triggers the cascade of events leading to the development of plaques and tangles (Casserly and Topol 2004; Honig et al. 2003).

Prevention of Vascular Dementia Treatment aimed at controlling hypertension has been shown to reduce the risk of dementia and cognitive impairment (Forette et al. 2002; Tzourio et al. 2003), and prevention of cardiac arrhythmia and prescription of aspirin or other antiplatelet-aggregating agents also may be of benefit (Nelson et al. 2003). Interestingly, statin therapy has not been of benefit in trials published to date (Shepherd et al. 2002).

Treatment of Cognitive Impairment in Vascular Dementia Three studies have reported the efficacy of cholinesterase inhibitors in vascular dementia: two studies with donepezil (Black et al. 2003; Wilkinson et al. 2003) and one study with galantamine (Erkinjuntti et al. 2002; in this study, only subjects with “mixed” Alzheimer’s disease and vascular dementia benefited from active treatment), and it is likely that rivastigmine and yet-to-bedeveloped cholinesterase inhibitors are equally effective. These results are presumably based on the cholinergic deficit that has been identified in vascular dementia, even though such a deficit is not required for cholinesterase inhibitors to be effective (Yesavage et al. 2002). Dosage and treatment outcomes in vascular dementia are comparable in magnitude to those seen in Alzheimer’s disease but appear to be a result of improvement in cognitive function compared with placebo-treated subjects rather than a reduced rate of cognitive decline, which is the typical pattern seen with cholinesterase inhibitors in Alzheimer’s disease. Memantine also has been shown to be effective in vascular dementia, although benefits are minimal (Orgogozo et al. 2002; Wilcock et al. 2002). Propentofylline, a glial cell modulator that has been shown to interfere with neuroinflammatory processes linked to the pathological activa-

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tion of microglial cells and reactive astrocytes (Kittner et al. 2000), has been effective in early Phase II trials and warrants watching.

Treatment of Behavioral Complications, Mood Disorder, and Psychosis in Vascular Dementia Psychosocial and psychopharmacological therapy for behavioral complications of vascular dementia follow the general principles outlined in Chapter 5 (“Dementia and Alzheimer’s Disease”) for Alzheimer’s disease, with the following caveat. In 2004, the U.S. Food and Drug Administration (FDA) concluded on the basis of its review of four randomized trials of risperidone in almost 1,800 elderly patients with dementia that risperidone was associated with an increased risk of ischemic stroke; a subsequent analysis of a comparably large data set led to the same conclusion about olanzapine. These findings led the FDA to issue advisories to physicians and led several investigators to conduct confirmatory studies. Moretti et al. (2005) studied 346 subjects with vascular dementia and “behavioral problems” who were randomly assigned to 12 months of treatment with conventional neuroleptics (about half received haloperidol, and half received promazine) or olanzapine. They found that olanzapine was equal to conventional neuroleptics for control of behavior problems but produced fewer negative effects on gait, balance, and equilibrium and was not associated with an increased incidence of stroke, myocardial infarction, or death. Herrmann et al. (2004) studied a Canadian database of more than 1.4 million patients age 65 or older and found no increase in the crude rate of stroke when patients taking risperidone or olanzapine were compared with those who received a typical neuroleptic. These studies and others like them are reassuring, but patients with vascular dementia who are taking atypical agents should be monitored closely for evidence of vascular complications.

Mixed Dementia In a review, Langa et al. (2004) defined mixed dementia as “cognitive decline sufficient to impair independent functioning in daily life resulting from the coexistence of AD [Alzheimer’s disease] and cerebrovascular pathology, documented either by clinical criteria or by neuroimaging findings” (p. 2902). As discussed earlier, the amyloid plaques and neurofibrillary tangles of Alzheimer’s disease and the large infarctions, multiple lacunar infarctions, and is-

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chemic periventricular leukoencephalopathy of vascular dementia are often found together in the brains of individuals with dementia. Depending on the source of pathological material, from 25% to 45% of Alzheimer’s disease brains have significant vascular pathology (Langa et al. 2004), and plaques and tangles are nearly always present in the brains of individuals with vascular dementia, all of which leads to the conclusion that vascular dementia is actually mixed dementia in a large percentage of cases. Treatment follows guidelines for Alzheimer’s disease, with preventive efforts aimed at control of blood pressure and other risk factors for vascular dementia.

Dementia Due to General Medical Conditions Although many other conditions can cause impairment in cognition severe enough to meet criteria for dementia (see Chapter 5, “Dementia and Alzheimer’s Disease,” Table 5–6), DSM-IV-TR specifically recognizes HIV disease, head trauma, Parkinson’s disease, Huntington’s disease, Creutzfeldt-Jakob disease, and Pick’s disease (a form of frontotemporal dementia, described earlier in the “Pathology” subsection of “Frontotemporal Dementia”) as capable of causing dementia via direct damage to brain structures (by infection, trauma, or degeneration). Differentiation of each of these conditions from Alzheimer’s disease, frontotemporal dementia, dementia with Lewy bodies, vascular dementia, and other dementing conditions depends on identification of the characteristic physical and laboratory abnormalities associated with each disease entity, supported by appropriate historical information. These characteristics are summarized in Table 6–5. Patients with the cognitive impairment associated with acquired immunodeficiency syndrome (AIDS)—the AIDS dementia complex—typically present with forgetfulness, inability to sustain attention to complex tasks, and generalized mental slowing; these patients progress to a frank frontotemporaltype dementia with apathy, loss of initiative, and significant psychomotor retardation. Highly active antiretroviral therapy (HAART) has been reported to improve memory, attention, and other cognitive functions in AIDS dementia (Robertson et al. 2004), even though HAART agents poorly penetrate the blood-brain barrier. Despite the benefits of HAART, most AIDS dementia patients continue to have significant cognitive impairment even when viral counts in brain tissue have declined to relatively low levels.

Type

History

Physical findings

Alzheimer’s disease

Gradual onset and progression; ± family history

Typically none until middle to late stages

Vascular dementia

Abrupt onset, stepwise decline; history of hypertension, atherosclerosis

HIV dementia

HIV-positive blood test; gradual onset of cognitive changes

Cognitive and behavioral function

Imaging and laboratory findings

Cortical atrophy, Language deficits early ventricular (word finding, anomia, enlargement on CT, fluent aphasia); clues MRI; temporal/parietal not helpful with hypometabolism on retrieval; visuospatial PET; hypoperfusion on deficits early SPECT Stroke; lacunae in basal Patchy impairment; Neurological signs and ganglia, white matter; depression, relative symptoms (e.g., gait periventricular lesions preservation of abnormalities, falls, very common, required personality common incontinence) for diagnosis if focal neurological signs absent Elevated CSF protein; Forgetfulness, apathy, Neurological signs and mild lymphocytosis slowness, poor symptoms may be concentration common may be present; present (e.g., ataxia, neuroimaging tremor, “frontal release” nonspecific; HIV signs) usually present in CSF

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Table 6–5. Differentiating the common dementias

Table 6–5. Differentiating the common dementias (continued) Physical findings

Head trauma

Head injury

Depends on location of injury; dysarthria, hemiparesis common

Parkinson’s disease

Dementia in later stages of neurological syndrome

Extrapyramidal signs (e.g., tremor, gait disturbance, rigidity, bradykinesia)

Huntington’s disease

“Fidgeting” progressing Autosomal dominant to choreoathetosis pattern of inheritance; onset generally in 30s– 40s; offspring of affected parent 50% likely to be affected

Depends on location, Memory impairment usually present; impulse extent of injury dyscontrol, irritability, personality change may be seen; nonprogressive unless head trauma repeated (e.g., in dementia pugilistica) Cognitive slowing, poor Subcortical atrophy on CT (e.g., increased recall, frontal signs intercaudate distance, (e.g., perseveration, ventricular decreased word-list enlargement) common; generation, impaired global cerebral behavioral metabolism also may be sequencing); clues diminished on PET helpful with memory retrieval Personality change, loss CT or MRI may show of judgment, irritability striatal atrophy; PET may show striatal early; memory hypometabolism impairment later; psychosis common

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History

Imaging and laboratory findings

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Type

Cognitive and behavioral function

Type

History

Pick’s disease

Frontal release signs (e.g., Personality change, emotional blunting, snout, grasp reflex) deterioration of social common skills, language deficits early; memory impairment, dyspraxia later Onset in 40s–60s; 5%– Myoclonus early, seizures Nonspecific symptoms (e.g., fatigue, later; ataxia, visual 15% have family diminished sleep and symptoms, gait history; rapid appetite early; global disturbance variably progression (i.e., 1-year cognitive deficits late) present course) typical; can be transmitted by corneal transplant or contact with infected brain tissue or CSF

Creutzfeldt-Jakob disease

Onset in 50s–60s

Physical findings

Cognitive and behavioral function

Imaging and laboratory findings CT or MRI may show frontal and temporal atrophy; PET may show frontal hypometabolism

CT and MRI may be normal; EEG may show sharp, triphasic synchronous discharges at 0.5–2 Hz

Note. CSF= cerebrospinal fluid; CT= computed tomography; EEG =electroencephalogram; HIV=human immunodeficiency virus; MRI=magnetic resonance imaging; PET= positron emission tomography; SPECT= single photon emission computed tomography.

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Table 6–5. Differentiating the common dementias (continued)

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Dementia associated with head trauma has been reported to respond to cholinesterase inhibitors, with improvement in short-term memory and sustained attention reported in one random-assignment, double-blind, placebocontrolled crossover study (Zhang et al. 2004) and similar positive results found in several open-label studies (Masanic et al. 2001; Morey et al. 2003). The dementias of Parkinson’s disease and Huntington’s disease, like some forms of vascular dementia, are sometimes described as “subcortical” because they are characterized by a cluster of clinical features (relative preservation of language function, visuoperceptual skills, and ability to do mathematical calculations, with comparatively severe deficits in frontal executive functions, including attention, verbal fluency, response inhibition, and ability to plan and execute multistep actions) that are relatively less common in dementing illnesses with primarily cortical pathology, such as Alzheimer’s disease. In the early stages of these illnesses, patients may have subtle changes in executive functions (especially problems in maintaining or shifting set) but do not yet meet criteria for dementia. As the disease progresses, impaired learning and retrieval efficiency appears, but problems with retention of learned material may be absent or mild, except in those who have concomitant Alzheimer’s disease, dementia with Lewy bodies, or other neurological disorders. Neuropsychological profiles of patients with Parkinson’s disease and dementia with Lewy bodies are similar, but executive dysfunction is generally less severe in Parkinson’s disease, and attentional fluctuations may be less pronounced. Functionally significant cognitive deficits in Parkinson’s disease are quite variable. Some patients with Parkinson’s disease develop noticeable cognitive deficits within a year or two of the onset of motor symptoms, others remain free of all but minor executive deficits for 5–10 years, and many never show the level of cognitive deficit that would be detected on mental status examinations. A substantial proportion of patients with Parkinson’s disease (20%– 45%, according to Rickards [2005]) have significant depressive symptoms that can compound mild cognitive impairments. Despite the differences in pathophysiology between Alzheimer’s disease and Parkinson’s disease, treatment trials with cholinesterase inhibitors have reported efficacy in Parkinson’s dementia comparable to that seen in Alzheimer’s disease (Aarsland et al. 2002; Emre et al. 2004; Giladi et al. 2003). However, no effective treatment for the dementia of Huntington’s disease has yet been developed. Family members caring for older adults with Parkinson’s disease, Huntington’s disease, or other

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progressive neurological disorders may benefit from some of the same interventions as caregivers of patients with Alzheimer’s disease (see Chapter 5, “Dementia and Alzheimer’s Disease”), including psychotherapy for marked caregiver strain (e.g., Secker and Brown 2005).

Dementia Due to Other General Medical Conditions Dementia also may be caused by other diseases with primarily central nervous system pathology, such as multiple sclerosis, amyotrophic lateral sclerosis, and various conditions (e.g., progressive subcortical gliosis, focal lobar atrophy) with mainly frontal lobe–type behavioral manifestations. Extracerebral pathology, both intracranial (brain tumor, subdural hematoma, hydrocephalus) and extracranial (hypothyroidism, hypercalcemia, hypoglycemia) processes, also can cause dementia via mechanical and biochemical effects on brain function. Accurate diagnosis usually depends on recognition of the characteristic clinical and laboratory features of the underlying illness. The battery suggested in Table 5–4 in Chapter 5 (“Dementia and Alzheimer’s Disease”) is designed to have relatively high sensitivity for this purpose.

Substance-Induced Persisting Dementia Certain substances with central nervous system activity can produce both intoxication, during which cognitive impairment severe enough to otherwise qualify as dementia may be present, and dementia per se, which persists for months or years after the substance use is terminated (see Table 5–6). Alcohol is perhaps the classic example of such a substance. Some patients with a diagnosis of alcoholic dementia have Korsakoff ’s syndrome, which is a pure amnesia due to damage to the mammillary bodies, dorsomedial nucleus of the thalamus, and periaqueductal gray matter, with varying amounts of cortical atrophy and ventricular enlargement. The syndrome is caused by thiamine deficiency, usually in the context of severe and prolonged alcohol intake, and has been reported to be responsive to cholinesterase inhibitors (Cochrane et al. 2005) in case reports but not in a placebo-controlled, single-blind study of malnutrition-related disease (Sahin et al. 2002). Other cases of “alcoholic dementia” are probably cases of concomitant Alzheimer’s disease or vascular dementia or reflect the effects of continued intoxication (Lishman 1987).

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However, evidence indicates that substantial cognitive deficits beyond “pure” amnesia are common in people who drink heavily and that even though these deficits tend to remit after drinking is discontinued, some deficits may persist for years and may in fact be permanent. On neuropsychological testing, older adults with alcohol-related dementia have relatively prominent subcortical dementia features, including reduced mental control and executive function impairments, and some may show learning and memory problems similar to those of patients with Alzheimer’s disease at comparable levels of dementia severity. For patients with Korsakoff ’s syndrome, memory deficits dominate the profile and may include tendencies to confabulate or intrude irrelevant but related information into recall attempts. Oslin and colleagues (1998) reviewed the literature and proposed the following diagnostic criteria for probable alcohol-related dementia: 1. A clinical diagnosis of dementia at least 60 days after the last exposure to alcohol. 2. Significant alcohol use, as defined by a minimum average of 35 standard drinks per week for men (28 for women) for more than 5 years. The period of significant alcohol use must occur within 3 years of the initial onset of dementia. Oslin and colleagues (1998) also proposed that supportive features include alcohol-related organ system damage (e.g., hepatic, renal, pancreatic), ataxia or peripheral sensory polyneuropathy, stabilization or improvement of the cognitive impairment, improvement of neuroimaging evidence of sulcal or ventricular dilatation after 60 days of abstinence, and neuroimaging evidence of cerebellar atrophy, especially of the vermis. The observation that cognition and functional status may improve, or at least stabilize, for older patients with alcohol-related dementia if they remain abstinent (Oslin and Cary 2003) underscores the importance of screening for alcohol problems in primary care and psychiatric settings.

Reversible Dementia Some dementias (mainly those due to a general medical condition), at least in principle, can be arrested or reversed if the underlying condition is successfully treated before significant brain damage occurs. Clarfield (1988) re-

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viewed several studies and found that 13% of dementias were potentially reversible, but only 11% partially and 3% fully reversed. With more conservative criteria (excluding the dementia syndrome of depression), only 8% reversed at all. Clarfield found that other than the dementia syndrome of depression, substance-induced persisting dementia; metabolic dementia (including thyroid and vitamin B12 [cobalamin] deficiency); and dementia secondary to normal-pressure hydrocephalus, subdural hematoma, or brain tumor were reversible. Osimani and colleagues (2005) confirmed the reversibility of the dementia due to vitamin B12 deficiency and suggested that neuropsychological evaluation could distinguish this syndrome from Alzheimer’s disease. They found more frequent psychosis, minimal language disturbance, and absence of ideomotor apraxia in dementia due to vitamin B12 deficiency as compared with Alzheimer’s disease. In 2003, Clarfield updated his meta-analysis and found that of more than 5,000 cases reviewed, potentially reversible causes were seen in 9%, and only 0.6% of the dementia cases actually reversed (0.29% partially, 0.31% fully). Clarfield attributed the decline to improved selection criteria and more rigorous methodology, resulting in the proportion of truly reversible dementias declining toward its “true” very low value. Since Clarfield’s last review, cases of reversible dementia also have been reported involving cerebral Whipple’s disease (Rossi et al. 2005); cryptococcal meningitis (Ala et al. 2004); bromide intoxication (Yu et al. 2004); systemic lupus erythematosus (Lee et al. 2004); cerebral amyloid inflammatory vasculopathy (Harkness et al. 2004); and dural arteriovenous fistula of the right transverse sinus and torcula, with occlusion of the right sigmoid sinus (Bernstein et al. 2003). In general, the list of organic etiologies that can cause dementia increases with the age of the patient, as declining functional brain reserve reduces the individual’s ability to tolerate physiological derangement.

Delirium Epidemiology The prevalence of delirium depends on the population at risk and the diagnostic criteria used. Bucht and associates (1999) reviewed the literature and found that about 15% of elderly inpatients on acute medical-surgical services have delirium at any time, and the rate is even higher among nursing home patients. The high-

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est prevalence of delirium is in intensive care units, where rates of 70%–87% have been reported (Ely et al. 2001; McNicoll et al. 2003). Well-established risk factors include age and cognitive impairment, but studies also have identified visual impairment, severe illness, and dehydration as risk factors, and use of physical restraints, malnutrition, addition of more than three medications while in the hospital, use of bladder catheter, and iatrogenic events as precipitating factors that sequentially increase the risk of delirium (Inouye 2000).

Diagnostic Criteria DSM-IV-TR diagnostic criteria for delirium due to a general medical condition are summarized in Table 6–6.

History and Clinical Presentation Four specific subtypes of delirium are recognized in DSM-IV-TR: 1) delirium due to a general medical condition, 2) delirium due to substance intoxication, 3) delirium due to substance withdrawal, and 4) delirium due to multiple etiologies. Obviously, the patient’s recent history is critical in distinguishing among these possibilities. Delirium due to a general medical condition usually develops over hours to days, and the medical history is typically that of the primary illness, with a superimposed history of the development of disturbance in consciousness and cognition. For obvious reasons, the patient with delirium usually cannot give a reliable history of the current illness, which is obtained from friends, family, hospital personnel, or the medical record. Because delirium occurs as an emergent complication of several life-threatening illnesses, it is important to complete the evaluation rapidly. A recent history of drug or alcohol ingestion will be present in cases of substance intoxication delirium, and a history of abrupt discontinuation of prolonged, high-dose ingestion will be present in cases of substance withdrawal delirium. Delirium frequently coexists with dementia and sometimes can be mistaken for dementia. Table 6–7 reviews the key differences between the two syndromes.

Mental Status Examination As indicated in Table 6–6, DSM-IV-TR recognizes the most prominent features of delirium as “reduced clarity of awareness of the environment” with “reduced ability to focus, sustain, or shift attention” (American Psychiatric

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Table 6–6. Summary of DSM-IV-TR diagnostic criteria for delirium due to a general medical condition A.

Disturbance of consciousness (i.e., reduced clarity of awareness of the environment) with reduced ability to focus, sustain, or shift attention. B. A change in cognition or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia. C. The disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. D. There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by the direct physiological consequences of a general medical condition. Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

Association 2000, p. 143). Several authorities on delirium have further subdivided the disorder into the following categories: 1) “somnolent or hypoactive” and 2) “activated or hyperactive.” In both types, the patient has either cognitive impairment, such as a deficit in orientation, memory, or language function, or “perceptual disturbance that is not better accounted for by…dementia” (American Psychiatric Association 2000, p. 143). Ross and colleagues (1991) found hallucinations and delusions to be far more common in patients with “activated” than with “somnolent” delirium, and our clinical experience is the same. Unlike uncomplicated dementia, the cognitive deficits in delirium are rarely disguised by the patient’s attempts to cover or minimize deficits but may nonetheless be overlooked by clinicians, particularly when the delirium is mild or accompanied by significant somnolence. More commonly, the patient with delirium cannot participate in a thorough mental status examination, and the syndrome is identified indirectly. Trzepacz and colleagues (Trzepacz and Dew 1995; Trzepacz et al. 1988) developed a 10-item Delirium Rating Scale, which can be used to quantify delirium severity and treatment response and may help to differentiate delirium from psychotic episodes or dementia; in 2000, this scale was updated to a 16-item version that has increased flexibility and breadth of symptom coverage, with comparable reliability and validity (Trzepacz et al. 2001). Another instrument, the Confusion Assessment Method (CAM; Inouye et al. 1990)

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Table 6–7. Differentiating delirium from dementia Feature

Delirium

Dementia

Onset Course Duration Alertness Sleep-wake Attention Orientation Working memory Episodic memory Thought Speech Perception

Abrupt/subacute Fluctuating Hours to weeks Abnormally high or low Disrupted Impaired Impaired Impaired Impaired Disorganized, delusions Slow/rapid, incoherent Illusions and hallucinations common Withdrawn or agitated

Insidious Slow progression Months to years Typically normal Typically normal Relatively normal Intact in early dementia Intact in early dementia Impaired Impoverished Word finding difficulty Usually intact in early dementia Varies, often intact early

Behavior

Source. Adapted from Butler C, Zeman AZ: “Neurological Syndromes Which Can Be Mistaken for Psychiatric Conditions.” Journal of Neurology, Neurosurgery, and Psychiatry 76:i31–i38, 2005. Reproduced with permission from the BMJ Publishing Group.

(Table 6–8), is based on diagnostic criteria from DSM-III-R (American Psychiatric Association 1987) and has very high (i.e., >90%) positive predictive accuracy for the recognition of delirium. The relatively shorter and easier to administer CAM and the Delirium Rating Scale (original 10-item version) showed good to very good agreement in the classification of delirium among older acutely ill hospital inpatients in a study of 94 subjects (Adamis et al. 2005); agreement was strongest with the more sensitive Delirium Rating Scale cutoff point of 10. An even shorter version of the CAM, which can be administered to intubated patients and does not require verbal responses, has been developed and appears to have specificity and sensitivity comparable to the “standard” version (McNicoll et al. 2005).

Laboratory Evaluation Proper evaluation of delirium requires comprehensive medical evaluation, including a complete physical and neurological examination and laboratory

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Table 6–8. Confusion Assessment Method (CAM) algorithm 1.

Acute onset and fluctuating course Indicated by positive responses to the following questions: Is there evidence of an acute change in mental status from the patient’s baseline? AND Did this behavior fluctuate during the past day—that is, tend to come and go or increase and decrease in severity?

2.

Inattention Indicated by a positive response to the following question: Does the patient have difficulty focusing attention—for example, being easily distractible or having difficulty keeping track of what is being said?

3.

Disorganized thinking Indicated by a positive response to the following question: Is the patient’s speech disorganized or incoherent, with rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject?

4.

Altered level of consciousness Indicated by any response other than alert (normal) to the following question: Overall, how would you rate this patient’s level of consciousness? Alert (normal) Vigilant (hyperalert) Lethargic (drowsy, easily aroused) Stupor (difficult to arouse) Coma (unarousable)

Note. The diagnosis of delirium requires a present or abnormal rating for criteria 1, 2, and 3 or 4. Source. Adapted from Inouye et al. 1990.

tests as needed. Delirium is usually discovered by psychiatrists in a consultation role, after nonpsychiatric personnel have done the physical examination. Similarly, laboratory evaluation may have been substantially completed before consultation was requested; the battery of tests listed in Table 6–9 is rather broad and usually can be narrowed in the actual clinical situation, depending on the differential diagnosis of the primary illness.

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Table 6–9. Laboratory evaluation of delirium Screening studies Blood studies Complete blood count (hematocrit, white blood cell count and differential, mean corpuscular volume, sedimentation rate) Electrolytes, serum urea nitrogen, glucose, calcium, albumin, ammonia (NH4), liver function tests Drug levels (toxic screen, medication levels) Arterial blood gases Urinalysis, including acetone and glucose Chest X ray Electrocardiogram Additional studies based on clinical judgment, in light of above studies Blood studies Heavy metals Thiamine and folate levels Thyroid function tests Lupus erythematosus preparation Antinuclear antibodies Urinary porphobilinogen Lumbar puncture Computed tomography or magnetic resonance imaging of the head Electroencephalogram Source. Adapted from Wise MG, Trzepacz PT: “Delirium (Confusional States),” in The American Psychiatric Press Textbook of Consultation-Liaison Psychiatry. Edited by Rundell JR, Wise MG. Washington, DC, American Psychiatric Press, 1996, p. 267. Copyright © 1996, American Psychiatric Press. Used with permission.

Differential Diagnosis In addition to identifying the primary illness underlying delirium, the clinician must rule out other psychiatric illnesses that have signs and symptoms similar to those of true delirium. As mentioned earlier, dementia can mimic delirium, particularly when agitation, psychosis, or anxiety is superimposed. In these circumstances, the clinical picture of a disorganized, aroused, confused patient with poor attention and concentration is virtually indistinguishable

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from that of delirium, and even when the clinician knows that the patient has dementia, he or she is often obliged to conduct a rapid “mini-evaluation” in which potential causes of delirium, particularly medications with central anticholinergic effects and infection, are ruled out. This “pseudodelirium” is usually self-limited and of very brief duration (minutes to hours), is not accompanied by alterations in the level of consciousness, and may be rapidly responsive to simple reassurance or other behavioral interventions. Functional disorders, including mania, hypomania, depression, hysteria, and schizophrenia, particularly in the severe manifestations known as manic delirium and catatonic excitement, also can present with a clinical state that can be difficult to distinguish from delirium caused by a general medical condition or a psychoactive substance.

Pathogenesis The precise mechanism underlying the clinical picture of delirium is not known, although a final common pathway involving a disturbed balance between central cholinergic and dopaminergic neurons that mediate attention and arousal has been postulated (Trzepacz 2000). Indirect evidence for this hypothesis includes the fact that cholinergic neurons appear to be the most sensitive to cerebral ischemia and hypoxia, which are fairly potent clinical causes of delirium, and the observation that centrally acting anticholinergic drugs can produce a delirium in otherwise intact individuals that can be reversed by cholinergic-enhancing agents (Kobayashi et al. 2004; Noyan et al. 2003). Because aging is accompanied by reduced central cholinergic tone and many elderly patients have compromised cardiovascular and pulmonary functions, rendering them susceptible to ischemia and hypoxia, it is not surprising that age is a major risk factor for the development of delirium. Cognitive impairment is also a major risk factor for the development of delirium, probably because of the reduced central cholinergic tone common to Alzheimer’s disease, vascular dementia, and other common dementing illnesses (Korevaar et al. 2005). However, other mechanisms also have been proposed; in the delirium of hepatic encephalopathy, the role of an endogenous benzodiazepinelike substance is evident, the pathogenic activity of which may be partially blocked by benzodiazepine antagonists such as flumazenil.

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Treatment The first priority is to identify emergent, life-threatening causes of delirium and correct them if possible. The most hazardous of these causes are acute cerebral ischemia or hypoxia; infection of the central nervous system (meningitis, encephalitis, abscess); intracranial hemorrhage or infarction; acute intoxication with central nervous system depressants, stimulants, or anticholinergic agents, or combinations thereof; acute withdrawal of alcohol or other central nervous system depressants; hypoglycemia and hyperglycemia with or without ketoacidosis; acid–base or electrolyte imbalance; acute hyperthyroidism (i.e., “thyroid storm”); and hypertensive encephalopathy. However, treatment of delirium is important even if the underlying causes are not immediately life threatening because evidence shows that the presence of delirium per se (i.e., even when corrected for severity of underlying illness) at the time of admission adversely affects rates of posthospitalization mortality, functional decline, and nursing home placement (Inouye et al. 1998). Specific Psychopharmacotherapy Two subtypes of delirium call for specific pharmacological therapy. First, withdrawal of alcohol, benzodiazepines, or barbiturates can produce a characteristic delirium (delirium tremens, in its most severe form) that is rapidly responsive to replacement therapy with any of the three agents. Practically, benzodiazepines are the treatment of choice and are usually administered parenterally until symptoms are under control, at which time oral administration can be initiated. Lorazepam, a benzodiazepine with the most reliable absorption after intramuscular injection, has the additional advantages in elderly patients of having no active metabolites and undergoing one-step hepatic metabolism (i.e., conjugation) that is relatively insensitive to the presence of liver disease. Lorazepam may be administered in doses of 0.5 mg every hour until symptoms are under control; in more acute situations, intravenous administration provides more rapid onset of action. The second type of delirium responsive to specific psychopharmacotherapy is that caused by centrally acting anticholinergic agents. When withdrawal of the offending agent and supportive therapy are ineffective, further amelioration of symptoms can be attained with oral administration of cholinesterase inhibitors such as donepezil or parenteral administration of physostigmine, a more rapidly acting cholines-

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terase inhibitor. The typical dose of donepezil is 5–10 mg/day administered orally; the dosage of physostigmine is 2 mg administered intramuscularly or by slow intravenous push. Because physostigmine has a duration of action of only about 60 minutes, whereas most anticholinergic agents are somewhat longer acting, a switch to oral agents may be warranted after acute reversal of symptoms with physostigmine; alternatively, additional doses of physostigmine may be administered until the situation has stabilized. Nonspecific Psychopharmacotherapy In most other situations in which rapid control of symptoms of delirium is desired, a growing body of case reports suggests that empirical administration of oral cholinesterase inhibitors (donepezil, rivastigmine, galantamine) should be followed by administration of a high-potency neuroleptic agent such as haloperidol, risperidone, or olanzapine as necessary. Although neuroleptics may not correct the pathophysiology underlying delirium, they can control agitation and thereby reduce the danger of self-inflicted injury, exhaustion, or disconnection from vital extracorporeal supports and render the patient more cooperative with appropriate diagnostic and therapeutic interventions. Dosages and routes of administration vary depending on the severity of the clinical situation. Intravenous or intramuscular administration of 0.5–2.0 mg of haloperidol or intramuscular administration of 2.5–5.0 mg of olanzapine is appropriate when rapid control of symptoms is required. In a less acute situation, 0.5–1.0 mg of haloperidol or risperidone administered orally is effective (Han and Kim 2004). When symptoms are refractory, augmentation with 0.5 mg of lorazepam is usually very effective.

Prognosis One-quarter or more of elderly patients who develop delirium during acute hospitalization continue to have symptoms such as inattention, reduced awareness of the environment, and temporal disorientation for up to 6 months after discharge (Levkoff et al. 1994). The long-term prognosis of delirium is primarily determined by the underlying illnesses, and most of the literature in this area is disease specific; however, most studies agree that delirium per se increases the risk of functional decline and death.

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Slachevsky A, Villalpando JM, Sarazin M, et al: Frontal Assessment Battery and differential diagnosis of frontotemporal dementia and Alzheimer disease. Arch Neurol 61:104–107, 2004 Trzepacz PT: Is there a final common neural pathway in delirium? focus on acetylcholine and dopamine. Semin Clin Neuropsychiatry 5:132–148, 2000 Trzepacz PT, Dew MA: Further analyses of the Delirium Rating Scale. Gen Hosp Psychiatry 17:75–79, 1995 Trzepacz PT, Baker RW, Greenhouse J: A symptom rating scale for delirium. Psychiatry Res 23:89–97, 1988 Trzepacz PT, Mittal D, Torres R, et al: Validation of the Delirium Rating Scale— Revised–98: comparison with the Delirium Rating Scale and the Cognitive Test for Delirium. J Neuropsychiatry Clin Neurosci 13:229–242, 2001 Tzourio C, Anderson C, Chapman N, et al, for the PROGRESS Collaborative Group: Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med 163:1069–1107, 2003 Wesnes KA, McKeith IG, Ferrara R, et al: Effects of rivastigmine on cognitive function in dementia with Lewy bodies: a randomised placebo-controlled international study using the Cognitive Drug Research computerised assessment system. Dement Geriatr Cogn Disord 13:183–192, 2002 Wetterling T, Kanitz RD, Borgis KJ: Comparison of different diagnostic criteria for vascular dementia (ADDTC, DSM-IV, ICD-10, NINDS-AIREN). Stroke 27:30–36, 1996 Wilcock G, Mobius HJ, Stoffler A, for the MMM 500 Group: A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol 17:297–305, 2002 Wilkinson D, Doody R, Helme R, et al: Donepezil in vascular dementia: a randomized, placebo-controlled study. Neurology 61:479–486, 2003 Yesavage JA, Mumenthaler MS, Taylor JL, et al: Donepezil and flight simulator performance: effects on retention of complex skills. Neurology 59:123–125, 2002 Yu CY, Yip PK, Chang YC, et al: Reversible dysphagia and dementia in a patient with bromide intoxication. J Neurol 251:1282–1284, 2004 Zhang L, Plotkin RC, Wang G, et al: Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury. Arch Phys Med Rehabil 85:1050–1055, 2004

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7 Anxiety Disorders and Late-Onset Psychosis Anxiety Disorders Epidemiology The Epidemiologic Catchment Area survey found anxiety disorders to be the most common mental illnesses, with a 1-month prevalence of 7.3% in adults of all ages (Regier et al. 1988). However, a lower prevalence of 5.5% was found in adults older than 65; within this group, phobic disorders (4.8%), obsessive-compulsive disorder (OCD; 0.8%), and panic disorder (0.1%) were the most prevalent specific disorders. Generalized anxiety disorder (GAD) was not surveyed in the first wave of this study, but the second wave found a 6-month prevalence of GAD of 1.9% in adults age 65 or older, in whom only 3% of the cases began after age 65 (Blazer et al. 1991). Subsequent studies converge on higher prevalence rates than those reported by Regier and colleagues. Krasucki et al. (1998) and Ritchie et al. (2004) reported an overall prevalence of anxiety disorders of between 12% and 20%, depending mainly on how agoraphobia was defined. Accurate diagnosis of anxiety disorders in elderly patients can be particularly difficult because of the great overlap between symptoms of anxiety disorders and anxiety symptoms seen in other Axis I conditions, particularly depression, dementia, and late-onset psychosis. A Dutch study of 3,056 individuals ages 55–85 found that 47.5% of those with major depressive disorder also met criteria for anxiety disorders, whereas 26.1% of those with anxiety 273

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disorders also met criteria for major depressive disorder (Beekman et al. 2000). In some cases, it can also be difficult to distinguish anxiety symptoms from symptoms of physical illnesses such as cardiac and pulmonary conditions (e.g., palpitations, shortness of breath, chest pain) that are common in elderly persons.

Clinical Presentation Whether anxiety occurs in reaction to a transient situation, in reaction to a permanent or semipermanent life change, or as part of an anxiety disorder or other Axis I disorder, patients with anxiety present with a subjective state of dysphoric apprehension or expectation, accompanied by various combinations of the signs and symptoms listed in Table 7–1 (which includes features listed in DSM-IV-TR [American Psychiatric Association 2000] criteria for panic attack and for GAD). Because the current generations of elderly individuals are especially disinclined to complain of mental distress, anxious elderly patients often focus on these physical features rather than on the subjective state of apprehension or dysphoria per se. Unfortunately, their complaints often mislead the general practitioner or internist into an extensive medical evaluation before the correct diagnosis is established. Recognition and treatment of anxiety disorders is important because of the effect these disorders have on quality of life and because they are associated with a significantly increased risk of suicide attempts and completed suicide, even in the absence of other mental disorders (Khan et al. 2002). Geriatric depression is often slower to remit when the clinical picture is complicated by comorbid general anxiety symptoms, panic disorder, or posttraumatic stress disorder (Hegel et al. 2005; Steffens and McQuoid 2005). Anxiety also may be a predictor of cognitive decline, especially when accompanied by complaints of loss of memory (Sinoff and Werner 2003).

Anxiety Rating Scales Both observer-rated measures, such as the Hamilton Anxiety Rating Scale (Hamilton 1959), and self-rated instruments, such the Spielberger State-Trait Anxiety Inventory (Spielberger et al. 1970) and the Worry Scale (Wisocki et al. 1986), assess severity and type of anxiety symptoms. The Hamilton scale, which consists of 14 items to assess 89 symptoms, has been the most widely used test in psychiatric research, and a few studies support its utility with el-

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Table 7–1. Autonomic and psychomotor features of anxiety Generalized anxiety disorder Restlessness or feeling keyed up or on edge Being easily fatigued Difficulty concentrating or mind going blank Irritability Muscle tension Sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep) Panic attacka Palpitations, pounding heart, or accelerated heart rate Sweating Trembling or shaking Sensations of shortness of breath or smothering Feeling of choking Chest pain or discomfort Nausea or abdominal distress Feeling dizzy, unsteady, light-headed, or faint Derealization (feelings of unreality) or depersonalization (being detached from oneself ) Fear of losing control or going crazy Fear of dying Paresthesias (numbness or tingling sensations) Chills or hot flushes aPanic

attack is diagnosed if four or more of these symptoms develop abruptly and reach a peak within 10 minutes.

derly patients (J.G. Beck et al. 1996). The Spielberger scale includes items that assess both current (“state”) and habitual (“trait”) anxiety symptoms. It has proved useful as an outcome measure in studies of psychological interventions to reduce anxiety in both young adult and elderly subjects but has been less widely applied in pharmacological research. The Worry Scale was specifically developed for use with older adults; the 35 items reflect severity of worry about financial, health, and social concerns. It is useful in assessing severity of anxiety symptoms in both the general population of older adults and those with GAD (J.G. Beck et al. 1996). Other self-rated anxiety scales that have been used in clinical geriatric research include the Beck Anxiety Inven-

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tory (A.T. Beck et al. 1988) and the Penn State Worry Questionnaire (Hopko et al. 2003). Additional information on anxiety assessment procedures appropriate for older adults can be found in Carmin et al. (1999).

Laboratory Evaluation Laboratory evaluation of the elderly patient with anxiety is aimed at ruling out physical, chemical, and iatrogenic factors that can cause or exacerbate anxiety and related symptoms. When laboratory evaluation results in a diagnosis of a physical illness (e.g., hyperthyroidism) that can explain the anxiety symptoms, anxiety disorder due to a general medical condition is the correct diagnosis. If a medication or other chemical (e.g., aminophylline) is identified as the cause, substance-induced anxiety disorder is diagnosed. A functional anxiety disorder may be exacerbated, but not caused, by medical illness or substance use; thus, clinical judgment regarding the relative contribution of the medical illness or medication is required to determine the correct diagnosis. Table 7–2 lists common medical conditions, chemicals, and medications that can cause anxiety.

Differential Diagnosis Situational Anxiety Common situations in which elderly patients experience anxiety are very similar to those that affect adults of all ages. These situations include those conventionally acknowledged to provoke anxiety, such as a visit to the dentist or doctor or an airplane flight, as well as those that may seem more idiosyncratic, such as being asked simple mental status examination questions, conducting a transaction with an accountant or a bank teller, or being asked to drive an unfamiliar car. Unlike specific phobia, situational anxiety may not significantly interfere with the person’s normal routine and, in that sense, may be considered nonpathological; in fact, it does not appear in DSM-IV-TR. It is mentioned here as a “subsyndromal” complaint for which medications may be requested and may be effective. Adjustment Anxiety In elderly persons, adjustment reactions with anxiety may occur during or after periods of obvious personal crisis and in relation to crises that may not seem particularly stressful to evaluating professionals. For example, a simple

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Table 7–2. General medical conditions and medications that can produce symptoms of anxiety General medical conditions Hyperadrenocorticism Hyperthyroidisma Hypoadrenocorticism Hypoglycemia (any cause) Insulinoma with hypoglycemia Pheochromocytoma Medications Anticholinergics—atropine, scopolamine Antidepressants—fluoxetine,a tranylcypromine Caffeinea Psychostimulants—amphetamine, cocaine, methylphenidate Sympathomimetics Decongestants—phenylephrine, phenylpropanolamine, pseudoephedrine, ephedrine Bronchodilators—albuterol, epinephrine, isoproterenol, metaproterenol Xanthine derivatives—theophylline,a aminophyllinea Medication withdrawal—alcohol,a benzodiazepines (especially short-acting agents),a other central nervous system depressantsa aRelatively

common offenders in the authors’ experience.

move from one apartment to another, even within the same neighborhood, or from one room in a retirement hotel or nursing home to another may precipitate significant anxiety. Similarly, development of a new physical illness, even one that is not life threatening or particularly disabling, may precipitate significant anxiety. Other events that commonly elicit adjustment anxiety include divorce or illness in the family, business or financial reversals, marital strife, or even a long-awaited retirement. Generalized Anxiety Disorder GAD is the second most common anxiety disorder in the elderly (after phobic disorders) and the one most commonly comorbid with depressive illness. DSM-IV-TR diagnostic criteria for GAD are summarized in Table 7–3. As it is for phobic disorders, the female-to-male ratio for GAD is about 2:1. Lenze

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and colleagues (2000) found that 27% of 182 elderly patients with depressive disorder also met criteria for GAD and that symptoms of GAD were associated with a higher level of suicidality. In a follow-up study, Lenze and colleagues (2005a) found that the average age at onset of GAD in 103 elderly subjects was 48.8. Although 47% had onset “later in life,” few differences were found between early- and late-onset cases. GAD tended to be a single, chronic episode, whereas subjects with comorbid major depressive disorder tended to have recurrent depressive episodes. The most common lifetime pattern of comorbidity was GAD preceding major depressive disorder, and Lenze et al. (2005a) found that GAD tends to persist, with spontaneous remission (without treatment) unlikely even if comorbid major depressive disorder remits. The authors interpreted this finding as enhancing the rationale for longterm treatment of GAD. In another recent study (Le Roux et al. 2005), older adults with onset of GAD before age 50 years were found to have a higher rate of psychiatric comorbidity, greater psychotropic use, and more severe worry compared with GAD patients with later ages at onset, whereas late-onset patients reported more functional limitations resulting from physical problems. An earlier report based on the same sample compared frequency of DSM-IV (American Psychiatric Association 1994) anxiety symptoms for older adults with GAD, subsyndromal anxiety, or no mental disorder (Wetherell et al. 2003b). Frequency and uncontrollability of worry, degree of distress or impairment associated with worry, muscle tension, and sleep disturbance were the symptoms most likely to distinguish GAD from the other conditions. Worrying about family members was common in all groups (endorsed by 69% of control subjects with no mental disorder, 91% with subsyndromal anxiety, and 90% with GAD), whereas worries about oneself were elevated in the GAD group, with health concerns, worries about minor matters, and financial concerns predominating. About one-third of older individuals in each group reported worries about community or world affairs. Phobias Phobias include the DSM-IV-TR categories of specific phobia, social phobia, and agoraphobia without history of panic disorder. Taken together, phobias constitute the most common anxiety disorder among elderly individuals, with a reported prevalence between 0.7% and 12%, with results of most studies falling in the 3%–12% range, depending on inclusion criteria and the period of

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Table 7–3. Summary of DSM-IV-TR diagnostic criteria for generalized anxiety disorder A.

Excessive anxiety and worry (apprehensive expectation) occurring more days than not for at least 6 months, about a number of events or activities (such as work or school performance). B. The person finds it difficult to control the worry. C. The anxiety and worry are associated with three (or more) of the six symptoms listed under generalized anxiety disorder in Table 7–1, with at least some symptoms present for more days than not for the past 6 months. D. The focus of the anxiety and worry is not confined to features of an Axis I disorder (e.g., the anxiety and worry are not about having a panic attack, being embarrassed in public, or being contaminated), and the anxiety and worry do not occur exclusively during posttraumatic stress disorder. E. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. F. The disturbance is not due to the direct physiological effects of a substance or a general medical condition and does not occur exclusively during a mood disorder or a psychotic disorder. Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

prevalence (i.e., 1–6 months) studied. Most of the variability in prevalence seems to stem from different ways to define agoraphobia, because rates of specific phobia and social phobia are more consistently reported at about 2%–6% and 0.6%–1.2%, respectively, with the prevalence in elderly females about twice that in elderly males (Krasucki et al. 1998; Ritchie et al. 2004). DSMIV-TR criteria for specific phobia are summarized in Table 7–4. New onset of phobic symptoms in elderly patients requires thorough clinical investigation because in some cases, the fear actually may not be so unreasonable. For example, older patients may become reluctant to join friends for a game of bridge because they fear being unable to follow the action or having an episode of incontinence, and subsequent investigation by the clinician may detect for the first time that such mishaps have actually occurred. Obsessive-Compulsive Disorder Late onset of OCD appears to be quite rare, with most epidemiological studies reporting rates in the 1% range, with a predominance of females that is

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Table 7–4. phobia

Summary of DSM-IV-TR diagnostic criteria for specific

A.

Marked and persistent fear that is excessive or unreasonable, cued by the presence or anticipation of a specific object or situation. B. Exposure to the phobic stimulus almost invariably provokes an immediate anxiety response, which may take the form of a situationally bound or situationally predisposed panic attack. C. The person recognizes that the fear is excessive or unreasonable. D. The phobic situation is avoided or else is endured with intense anxiety or distress. E. The avoidance, anxious anticipation, or distress in the feared situation interferes significantly with the person’s normal routine, occupational functioning, or social activities or relationships, or there is marked distress about having the phobia. F. In individuals under age 18 years, the duration is at least 6 months. G. The anxiety, panic attacks, or phobic avoidance associated with the specific object or situation is not better accounted for by another mental disorder, such as obsessive-compulsive disorder or posttraumatic stress disorder. Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

significantly less pronounced than in other anxiety disorders. The pattern of symptoms is similar to that seen in younger patients, with a few minor differences: elderly patients have fewer concerns about symmetry, need to know, and counting rituals, whereas hand washing and fear of having sinned are more common in elderly patients (Kohn et al. 1997). Several reports suggested that late-onset OCD is frequently associated with organic brain disease, including stroke, transient ischemic attack, and organophosphate poisoning (Carmin et al. 2002; Philpot and Banerjee 1998; Weiss and Jenike 2000). Some older patients with chronic OCD seek medical attention only when supervening age-related changes or superimposed mood disorder or dementia forces them into treatment. In this situation, the likelihood that compulsive rituals have become ego-syntonic and are no longer seen as irrational is increased, and the clinician may need to explore the early history of the disorder to obtain a less misleading picture. Transient outbreaks of obsessive thoughts and compulsive rituals are not uncommon among elderly patients with major depression with or without psychosis. DSM-IV-TR allows a diag-

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nosis of OCD in this circumstance if the content of the obsessions or compulsions is not mood congruent (Table 7–5). Panic Disorder Elderly patients with panic disorder (with or without agoraphobia) report less severe and fewer panic symptoms, less anxiety and arousal, lower levels of depression, and higher levels of functioning than do middle-aged patients with panic disorder, and older patients with late-onset panic disorder report less distress related to panic symptoms than do elderly patients with early-onset panic disorder (Sheikh et al. 2004b). Many older patients with panic disorder, particularly of late onset, present first to their family physician or internist, who is likely to initiate an evaluation for possible myocardial infarction, transient ischemic attack, or other episodic, life-threatening physical illness. It may require several panic attacks accompanied by negative laboratory test results before the primary care physician identifies the correct diagnosis and seeks psychiatric consultation. Patients and family members are often reluctant to accept that something as terrifying as a panic attack can be “mental,” and patients may avoid evaluation by the mental health professional because they fear that they are “losing their minds” or “going crazy.” As defined by DSM-IV-TR (Table 7–6), the diagnosis of panic disorder requires the occurrence of panic attacks and significant anticipatory anxiety, and successful pharmacological amelioration of panic attacks is only part of the therapeutic challenge. Anticipatory anxiety itself, without panic attacks, can be quite disabling, and evidence is accumulating that combining pharmacotherapy with cognitive-behavioral, behavioral, or supportive psychotherapy results in more complete relief of symptoms. Posttraumatic Stress Disorder The literature on posttraumatic stress disorder (PTSD) in elderly individuals presents conflicting views. Some researchers believe that elderly people are more vulnerable to traumatic events than are younger people (Lyons and McClendon 1990). The “differential vulnerability hypothesis” suggests that adaptive capacities, coping resources, and external resources diminish with age, whereas exposure to traumatic events or illnesses increases. On the other hand, the “inoculation hypothesis” proposed by Eysenck (1983) maintains that exposure to stress or a previous crisis could increase resistance to subse-

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Table 7–5. Summary of DSM-IV-TR diagnostic criteria for obsessive-compulsive disorder A.

Either obsessions or compulsions: Obsessions as defined by (1), (2), (3), and (4): (1) recurrent and persistent thoughts, impulses, or images that are experienced, at some time during the disturbance, as intrusive and inappropriate and that cause marked anxiety or distress (2) the thoughts, impulses, or images are not simply excessive worries about real-life problems (3) the person attempts to ignore or suppress such thoughts, impulses, or images or to neutralize them with some other thought or action (4) the person recognizes that the obsessional thoughts, impulses, or images are a product of his or her own mind (not imposed from without as in thought insertion) Compulsions as defined by (1) and (2): (1) repetitive behaviors or mental acts (e.g., praying, counting, repeating words silently) that the person feels driven to perform in response to an obsession, or according to rules that must be applied rigidly (2) the behaviors or mental acts are aimed at preventing or reducing distress or preventing some dreaded event or situation; however, these behaviors or mental acts either are not connected in a realistic way with what they are designed to neutralize or prevent or are clearly excessive B. At some point during the course of the disorder, the person has recognized that the obsessions or compulsions are excessive or unreasonable. C. The obsessions or compulsions cause marked distress, are time-consuming (take more than 1 hour a day), or significantly interfere with the person’s normal routine, occupational functioning, or usual social activities or relationships. D. If another Axis I disorder is present, the content of the obsessions or compulsions is not restricted to it. E. The disturbance is not due to the direct physiological effects of a substance or a general medical condition. Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

quent stress and enable elderly people to develop the coping strategies to adapt successfully to traumatic events. However, data from a more recent study of 148 survivors of two traumatic events, an airplane crash and a train crash (Chung et al. 2004), suggest that neither the vulnerability hypothesis

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Table 7–6. Summary of DSM-IV-TR diagnostic criteria for panic disorder with or without agoraphobia A.

Both (1) and (2): (1) recurrent unexpected panic attacks (2) at least one of the attacks has been followed by 1 month (or more) of one (or more) of the following: (a) persistent concern about having additional attacks (b) worry about the implications of the attack or its consequences (c) a significant change in behavior related to the attacks B. Presence or absence of agoraphobia. C. The panic attacks are not due to the direct physiological effects of a substance or a general medical condition. D. The panic attacks are not better accounted for by another mental disorder, such as social phobia or specific phobia. Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

nor the inoculation hypothesis applied to this cohort of community residents. Instead, the investigators found that levels of intrusive thoughts, avoidance behavior, coping strategies used, and subsequent general health problems were similar across age groups. Diagnostic criteria for PTSD are summarized in Table 7–7. Mood Disorder With Anxiety Anxiety symptoms are often a prominent part of major depression, dysthymia, bipolar disorder, and cyclothymia, and as described earlier, co-occurrence of full mood and anxiety syndromes is common. One large-scale study of elderly primary care patients with major depression or dysthymia found that patients with comorbid panic disorder or PTSD had substantially greater psychiatric and medical illness than did those without comorbid anxiety. Patients with comorbid panic disorder or PTSD were more likely to report suicidal thoughts at baseline and had a higher prevalence of chronic medical illnesses, greater functional impairment, and a lower quality of life (Hegel et al. 2005). Differentiation of dysphoric states into depressed mood or anxiety may be particularly difficult with the current generations of elderly individu-

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Table 7–7. Summary of DSM-IV-TR diagnostic criteria for posttraumatic stress disorder A.

B.

C.

The person has been exposed to a traumatic event in which both of the following were present: (1) The person experienced, witnessed, or was confronted with an event or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others. (2) The person’s response involved intense fear, helplessness, or horror. The traumatic event is persistently reexperienced in one (or more) of the following ways: (1) recurrent and intrusive distressing recollections of the event, including images, thoughts, or perceptions (2) recurrent distressing dreams of the event (3) acting or feeling as if the traumatic event were recurring (includes a sense of reliving the experience, illusions, hallucinations, and dissociative flashback episodes, including those that occur on awakening or when intoxicated) (4) intense psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event (5) physiological reactivity on exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma), as indicated by three (or more) of the following: (1) efforts to avoid thoughts, feelings, or conversations associated with the trauma (2) efforts to avoid activities, places, or people that arouse recollections of the trauma (3) inability to recall an important aspect of the trauma (4) markedly diminished interest or participation in significant activities (5) feeling of detachment or estrangement from others (6) restricted range of affect (e.g., unable to have loving feelings) (7) sense of a foreshortened future (e.g., does not expect to have a normal life span)

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Table 7–7. Summary of DSM-IV-TR diagnostic criteria for posttraumatic stress disorder (continued) D. Persistent symptoms of increased arousal (not present before the trauma), as indicated by two (or more) of the following: (1) difficulty falling or staying asleep (2) irritability or outbursts of anger (3) difficulty concentrating (4) hypervigilance (5) exaggerated startle response E. Duration of the disturbance (symptoms in criteria B, C, and D) is more than 1 month. F. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. Specify if: Acute: if duration of symptoms is less than 3 months Chronic: if duration of symptoms is 3 months or more With delayed onset: if onset of symptoms is at least 6 months after the stressor Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

als, many of whom are uncomfortable with introspection and unfamiliar with conventional terms for subjective states. In most cases, neurovegetative signs and symptoms of mood disorder and the autonomic and psychomotor features of anxiety disorder facilitate accurate diagnostic classification. Schizophrenia With Anxiety Although the characteristic hallucinations, delusions, thought disorder, and bizarre behavior typical of schizophrenia and delusional disorder are clearly not a part of uncomplicated anxiety disorder, elderly patients with these conditions may be quite secretive about their psychotic experiences and can appear to have anxiety alone. Extra effort to establish rapport and develop the patient’s trust can be very important in this situation; hospitalized elderly patients often connect with a particular staff member (usually on the night shift) whom they trust and with whom they share their inner psychic content. If doubt persists, projective psychological tests (e.g., the Thematic Apperception Test, the Rorschach Inkblot Test; see Chapter 3, “Mood Disorders—

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Diagnosis”) can help to identify suppressed psychotic thought content. Another diagnostic challenge is confronted in the differentiation between obsessive thoughts (Simpson et al. 1999) and schizophrenic delusions. DSM-IVTR indicates that even when obsessions become ego-syntonic, “overvalued ideas” (in which case the specifier “with poor insight” is applied), they remain relatively vulnerable to challenge by evidence or logic (i.e., reality testing is intact), allowing the clinician to distinguish them from manifestations of psychosis (American Psychiatric Association 2000, p. 461).

Pathogenesis Psychodynamic Theories The general psychodynamic literature on the pathogenesis of anxiety is too voluminous to attempt to summarize here, although relatively little consideration has been given to anxiety in late life. In addition to intrapsychic conflict between libidinal impulses and emotions, the demands of conscience, and the limitations imposed by circumstances, which are postulated to account for anxiety throughout the life span, elderly individuals face anxiogenic circumstances unique to senescence. These include the growing discrepancy between past and present capabilities, the increasing likelihood of mental and physical incompetence, and the encroaching reality of death. Anxiety related to these concerns may emerge directly into consciousness, wherein it can be relatively easily identified, or may remain unconscious and be expressed indirectly as somatic dysfunction, memory impairment, or nonspecific illness. In support of this hypothesis, improved emotional well-being is often associated with increased conscious awareness of, and ability to come to terms with, these aspects of aging (Gurian and Miner 1991). Neurobiological Theories Contemporary hypotheses about neurobiological substrates of anxiety and fear focus on several interconnected subsystems of the central nervous system. One subsystem is composed of noradrenergic innervation arising from cell bodies in the locus coeruleus, a bilateral nucleus of cell bodies located in the central gray matter of the isthmus on the floor of the fourth ventricle. Axons from these cells provide the main noradrenergic input to the ipsilateral cortex, cingulate gyrus, hippocampus, and cerebellum. They also impinge on cells in the hypothalamus, thalamus, septal nuclei, and other subcortical structures,

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where their influence is augmented by input from noradrenergic cells in the lateral tegmental nuclei. Anatomical and pharmacological manipulation of this system in animal models provides convincing evidence of its role in regulating aspects of cerebral arousal. This arousal is postulated to be experienced as vigilance, anxiety, fear, or panic, in order of increasing intensity. Hypothesized pathogenic influences on this system include genetic mechanisms, early experiences, and the interaction of the two. Investigators theorize that early experiences lead to structural and functional alterations in the responsiveness of this system, which ultimately lead to pathological states of anxiety (Redmond 1987); moreover, studies of the noradrenergic system in elderly subjects suggest that an age-related decrease in central noradrenergic function may increase these subjects’ susceptibility to anxiety (Sunderland et al. 1991). More recent animal studies have examined the role of the medial prefrontal cortex–amygdala circuit in the pathogenesis of anxiety disorders, focusing on dopaminergic input to the amygdala from the ventral tegmental area (Gelowitz and Kokkinidis 1999) and lateralized serotonergic neurotransmission within the nondominant amygdala (Andersen and Teicher 1999). Findings of these studies have been partially supported by clinical evidence of the efficacy of serotonin reuptake inhibitors and dopamine receptor blockers in anxiety disorders. Another major area of investigation focuses on benzodiazepine receptors localized to central neurons. These receptors appear to be linked to a “supramolecular receptor complex” that includes a receptor for γ-aminobutyric acid (GABA) (Hommer et al. 1987) and a chloride ion channel. Binding of a benzodiazepine molecule to this receptor facilitates the ability of the GABAreceptor complex to open chloride channels, allowing negatively charged chloride ions to enter the cell and produce hyperpolarization, thereby reducing the cell’s reactivity to stimulation and its likelihood of conducting an impulse. Autoradiographic studies have shown benzodiazepine receptors in brain-stem structures, including the superior colliculus, the ventral nucleus of the lateral lemniscus, and the substantia nigra, all of which, together with the amygdala, constitute a component of the system that mediates the startle response. This response has been extensively studied in animal models, and pathological influences on its function have been postulated to underlie anxiety disorders in humans (Hommer et al. 1987). Evidence indicates that brain

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levels of GABA are reduced in older subjects, which could result in an increased propensity to anxiety with age (Sunderland et al. 1991). Finally, a key role for serotonin receptors in the development of “normal” anxiety behavior in humans has been delineated by Gross et al. (2002). They noted that agonists of the serotonin type 1A (5-HT1A) receptor have anxiolytic properties in both humans and animal models and that mice lacking this receptor (5-HT1A receptor knockout) show increased anxiety-like behavior in a variety of conflict tests. The 5-HT1A receptor is expressed in two distinct neuronal populations in the brain: as an autoreceptor on serotonin-containing neurons of the raphe nuclei and as a heteroreceptor on nonserotonin-containing neurons of the forebrain (mainly the hippocampus, septum, and cortex). Gross and colleagues used a tissue-specific and conditional 5-HT1A receptor rescue mouse and found that restoration of the forebrain 5-HT1A receptor alone was sufficient to reverse the anxiety-like phenotype of the knockout mice and argued that this particular receptor population critically modulates anxiety-like behavior. They also showed that receptor expression during the early postnatal period is needed to establish normal anxiety-like behavior in the adult. Despite these findings, no “unified” neurobiological theory of anxiety or anxiety disorders in the elderly is widely accepted at this time.

Treatment Psychosocial-Behavior Therapy Although definitive studies in geriatric patients are lacking, there is little clinical basis to doubt the efficacy of traditional psychotherapeutic approaches to anxiety in the elderly. However, cost considerations often favor use of more focused, time-limited techniques such as cognitive-behavioral therapy (CBT), which has been shown to be effective in nonelderly patients with anxiety disorders, including OCD (Simpson et al. 1999), social phobia (Cottraux et al. 2000), and panic disorder (Barlow et al. 2000). The more purely behavioral therapies are also preferred for reasons of cost and include relaxation techniques aimed at generalized reduction of muscle tension and anxiety; desensitization techniques that typically pair a state of induced relaxation with a real or imagined feared situation or object; and graded exposure approaches that attempt to extinguish anxiety, fear responses, or compulsive rituals gradually by increasingly prolonged and intense exposure to feared situations.

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A review by Mohlman (2004) of psychosocial treatment of GAD in the elderly concluded that “the existing body of work does not clearly indicate the superiority of CBT over alternative interventions [e.g., supportive therapy]” (p. 149). The author noted that the modest results in a trial of CBT may be related to learning difficulties in older patients and suggested that “age-appropriate principles of learning may need to be integrated to increase potency” (p. 161). A recent well-controlled intervention randomly assigned older adults with GAD to short-term (12-week) CBT, an active alternative psychosocial treatment (a discussion group addressing anxiety-evoking themes), or a wait-list condition. Patients who received active treatment showed clear improvements relative to those on the waiting list, with slightly greater benefit observed with CBT compared with the discussion group. Reduction in anxiety was clinically significant for one-third of the treated patients, and by 6month follow-up, one-half had achieved a high state of function, albeit with some persisting anxiety. Effect sizes associated with treatment were somewhat smaller than those that have been reported for CBT with younger GAD patients; however, the elderly participants in this study may well have been treatment resistant because they had experienced anxiety for an average of more than 30 years and almost 90% had tried other psychological or pharmacological therapies. The authors noted that outcomes in some CBT groups were better than in others, perhaps reflecting different levels of commitment and skill among therapists (Wetherell et al. 2003a). An Australian public health investigation of randomized controlled trials for the general adult population compared efficacy and cost of different interventions for GAD and panic disorder, including CBT and several antidepressants (Heuzenroeder et al. 2004). The conclusion was that CBT had greater total health benefits than drug interventions alone for both anxiety disorders, but limited access and variability in treatment delivery were noted as drawbacks to systemwide provision of this therapy. Successful treatment of a case of late-onset OCD with exposure and response prevention was described by Carmin et al. (2002), but large-scale studies in the elderly remain to be published. In general, results with exposure and response prevention are best when patients can clearly describe the situations that provoke anxiety or ritualistic behavior. For patients whose anxiety is generalized or pervasive, techniques such as hypnosis, meditation, and guided imagery may have a role. Although few outcome studies have been done, sig-

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nificant reductions in subjective anxiety have been reported for elderly patients in response to both progressive and imaginal relaxation procedures (Scogin et al. 1992). Following specific procedures for relaxation training (Bernstein and Borkovec 1973) is important to ensure an effective intervention and to compare results for a given patient with results of clinical investigations. Several rating scales have been designed to assess the effectiveness of relaxation interventions (Crist et al. 1989). Most therapists who use behavior techniques in the treatment of anxiety advocate the adjunctive use of antianxiety agents with behavior therapy; similarly, when phobic or obsessivecompulsive behaviors emerge as part of a depressive syndrome, pharmacological treatment of depression should be initiated before or during the application of behavior therapy. Psychopharmacotherapy Benzodiazepines remain the treatment of choice for anxiety of acute or subacute duration (Table 7–8). For very short-term anxiety associated with specific situations such as airplane travel, the longer-acting agents such as diazepam can be used safely; when treatment is required on a daily or neardaily basis for up to 4–6 weeks, such as in adjustment disorder with anxiety or in acute GAD, daily use of the longer-acting agents in elderly patients will lead to accumulation of clinically significant blood levels of long-acting active metabolites, most of which have half-lives of several days or longer. Therefore, in these situations, the shorter-acting benzodiazepines such as lorazepam or oxazepam, which undergo single-step conjugation in the liver and have no active metabolites, are generally preferable. These agents have the additional advantage of being relatively well tolerated by patients with even fairly advanced liver disease. However, some elderly patients experience acute withdrawal symptoms between doses of short-acting benzodiazepines; these symptoms are severe enough to render these agents intolerable. In this situation, one author of this book (J.E.S.) has had excellent results with clonazepam, which is long-acting but does not give rise to clinically significant amounts of active metabolite, making it the only long-acting benzodiazepine free of this disadvantage. Typical dosages are 0.5–1.0 mg by mouth twice daily (Calkin et al. 1997). Chronic GAD and the other anxiety disorders generally require continuous therapy beyond 4–6 weeks, at which point the effectiveness of benzo-

Table 7–8. Pharmacological properties of benzodiazepines

Trade name

Chlordiazepoxide Diazepam Clorazepate Alprazolam Lorazepam Oxazepam Temazepam Clonazepam

Librium Valium Tranxene Xanax Ativan Serax Restoril Klonopin

Intermediate Fast Fast Intermediate Intermediate Slow Slow Fast

aApproximate

Duration of action Long Long Long Intermediate Short Short Short Long

Active metabolites Yes Yes Yes Yes No No No Nod

Elimination half-life (hours) 5–30b 20–50b 36–200b 12–15c 10–14 5–10 10–20 20–50

Therapeutic dosage range (mg/day)a 10–40 2–20 7.5–30 0.25–4 0.5–6 15–60 15–90 0.5–3

range; some patients may require higher or lower dosages. Approximately 100% longer in elderly (i.e., use high end of range), longer in men than in women. cApproximately 50% longer in elderly. dDominant metabolic pathway is nitroreduction, producing inactive metabolites; a minor oxidative pathway producing potentially active metabolites also has been identified. Source. Adapted from American Psychiatric Association: “Treatment With Antianxiety Agents,” in Treatments of Psychiatric Disorders: A Task Force Report of the American Psychiatric Association, Vol. 3. Washington, DC, American Psychiatric Association, 1989, pp. 2036–2052. Copyright © 1989, American Psychiatric Association. Used with permission. b

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Drug

Rate of absorption

291

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diazepines may diminish and more reliable results may be obtained with heterocyclic antidepressants such as nortriptyline, sertraline, paroxetine, citalopram, escitalopram, mirtazapine, or venlafaxine. Dosages are similar to those required for treatment of depression, and peak effects on anxiety tend to occur sooner than peak antidepressant effects; otherwise, prescription follows the guidelines for treatment of mood disorder outlined in Chapter 4 (“Mood Disorders—Treatment”). Controlled trials in the elderly are scant; Lenze et al. (2005b) administered citalopram, 20–30 mg/day, in a doubleblind, placebo-controlled, random-assignment design to 34 subjects (average age=69.4). In each group, 15 subjects had GAD; the remaining 4 had panic disorder (3) and PTSD (1). In the citalopram group, 11 of 17 responded, whereas only 4 of 17 in the placebo group did. Buspirone is another nonbenzodiazepine that has been shown to be an effective anxiolytic agent in elderly patients (Goldberg 1994). It has several advantages over benzodiazepines: no sedative effects, no interaction with alcohol, and no tendency to produce dependence or withdrawal symptoms; therefore, buspirone has little or no abuse potential. A disadvantage is that it has little or no acute efficacy, and usually several weeks of daily dosage are required before effects are observed. Buspirone is contraindicated in patients taking monoamine oxidase inhibitors (presumably because of its serotonergic properties) and is less effective in patients who have been treated with benzodiazepines. In general, neuroleptics have a very minimal role in the treatment of uncomplicated GAD, but Morinigo et al. (2005) reported excellent results with lowdose risperidone (i.e., average dosage of about 1.3 mg/day) in a small study of 15 subjects (average age=74) with mixed anxiety disorders (including 10 with GAD) who had failed treatment with other agents. Treatment of panic disorder and OCD is somewhat more specific. Although efficacy of alprazolam in nonelderly adults with panic disorder has been reported, in general, benzodiazepines and buspirone are both relatively ineffective in inhibiting panic attacks. Heterocyclic antidepressants (including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake blockers, and monoamine oxidase inhibitors) have been shown to be effective in nonelderly patients, and one small, open-label study of 10 subjects (average age =72.5) who had panic disorder, with or without agoraphobia, found that 25–200 mg/day of sertraline (average dosage= 92.5 mg) eliminated panic attacks in 9 of 10 subjects by the end of the 12-week study

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(Sheikh et al. 2004a). Similarly, the adult literature has convincingly documented the efficacy of selective serotonin reuptake inhibitors for the treatment of OCD, and although they are generally well tolerated and should be effective in the elderly, definitive studies are lacking. Generally, dosages of antidepressants are similar to those used for depressive disorders, and cautions listed in Chapter 4 (“Mood Disorders—Treatment”) for treatment of depression apply.

Late-Onset Psychosis Epidemiology The prevalence of late-onset psychosis is difficult to estimate because of a lack of diagnostic consistency across investigations. DSM-IV recognized the possibility of late onset in all psychotic illnesses, including schizophrenia, delusional disorder, mood disorder with psychotic features, substance-induced psychotic disorder, and psychotic disorder due to a general medical condition. Besides these “functional” disorders, DSM-IV also allowed dementia, including Alzheimer’s type and vascular dementia, to be coded as “with delusions.” (DSM-IV-TR, following ICD-9-CM [World Health Organization 1978] convention, has a codable subtype of “with delusions” for vascular dementia only.) In the National Institute of Mental Health Epidemiologic Catchment Area Program (Regier et al. 1988), 0.1% of individuals age 65 or older were given a diagnosis of schizophrenia with DSM-III (American Psychiatric Association 1980) criteria, which did not allow onset of schizophrenia after age 45. Leuchter and Spar (1985) reported that first onset of psychosis after age 65 was recognized in 8% of 880 patients admitted to a university hospital–based geropsychiatric unit. The diagnostic breakdown was as follows: 3.4% had organic mental disorder (mainly primary degenerative or vascular dementia) with psychosis, 2.8% had mood disorder with psychosis, and 1.7% had disorders that would be diagnosed by DSM-III-R (American Psychiatric Association 1987) criteria as schizophrenia (10 of 15 patients) or delusional disorder (4 of 15 patients). A similar diagnostic distribution was found by Webster and Grossberg (1998), who reported on 1,700 consecutive admissions to a psychogeriatric unit. In their group, 10% had onset of psychotic symptoms after age 65, and the most common diagnoses were dementia of the Alzheimer’s type,

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followed by major depression, medical or toxic causes, delirium, bipolar disorder, delusional disorder, schizophrenia, and schizoaffective disorder. The International Late-Onset Schizophrenia Group (Howard et al. 2000), based on extensive review of the literature, concluded that onset after age 40 of psychotic symptoms typical for schizophrenia should be called late-onset schizophrenia-like psychosis, and onset after age 60 should be called very-late-onset schizophrenia-like psychosis (VLOSLP).

Risk Factors Risk factors for development of VLOSLP include age (the incidence increases by 11% with each 5-year increase in age [van Os et al. 1995]), female gender, and ethnic minority immigrant status. British investigators found that the incidence of VLOSLP was significantly higher in African- and Caribbean-born elders than in indigenous elders (Reeves et al. 2001). Compared with earlyonset schizophrenia patients, patients with VLOSLP are less likely to have a family history of schizophrenia, more commonly have sensory deficits (particularly conductive hearing loss), and less commonly have negative symptoms. Rodriguez-Ferrera et al. (2004) and Barak et al. (2002) found that patients with VLOSLP had higher levels of education and were more likely to be married than were members of a comparison group of early-onset schizophrenia patients. Despite the age association, VLOSLP appears to be a stable entity and not merely the harbinger of a progressive dementing condition, as indicated by follow-up studies conducted by Mazeh and colleagues (2005), Palmer et al. (2003), and Rabins and Lavrisha (2003).

Diagnostic Criteria DSM-IV-TR diagnostic criteria for schizophrenia and delusional disorder are summarized in Tables 7–9 and 7–10, respectively.

Clinical Presentation The clinical presentation of late-onset psychosis depends in large part on the underlying diagnosis. Mood disorder with psychosis is described in Chapter 3 (“Mood Disorders—Diagnosis”), and dementia with psychosis is discussed in Chapter 5 (“Dementia and Alzheimer’s Disease”); the typical picture of VLOSLP follows DSM-IV-TR diagnostic criteria for schizophrenia: there are

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Table 7–9. Summary of DSM-IV-TR diagnostic criteria for schizophrenia A.

Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated): (1) delusions (2) hallucinations (3) disorganized speech (4) grossly disorganized or catatonic behavior (5) negative symptoms, i.e., affective flattening, alogia, or avolition Note: Only one Criterion A symptom is required if delusions are bizarre or hallucinations consist of a voice keeping up a running commentary on the person’s behavior or thoughts, or two or more voices conversing with each other. B. For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning such as work, interpersonal relations, or selfcare are markedly below the level achieved prior to the onset. C. Continuous signs of the disturbance persist for at least 6 months, including at least 1 month of symptoms (or less if successfully treated) that meet Criterion A (i.e., active-phase symptoms) and may include periods of prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or two or more symptoms listed in Criterion A present in an attenuated form. D. Schizoaffective disorder and mood disorder with psychotic features have been ruled out because either (1) no major depressive, manic, or mixed episodes have occurred concurrently with the active-phase symptoms; or (2) if mood episodes have occurred during active-phase symptoms, their total duration has been brief relative to the duration of the active and residual periods. E. The disturbance is not due to the direct physiological effects of a substance or a general medical condition. F. If there is a history of autistic disorder or another pervasive developmental disorder, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations are also present for at least a month (or less if successfully treated). Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

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Table 7–10. Summary of DSM-IV-TR diagnostic criteria for delusional disorder A. B. C.

Nonbizarre delusions of at least 1 month’s duration. Criterion A for schizophrenia has never been met. Apart from the impact of the delusion(s) or its ramifications, functioning is not markedly impaired and behavior is not obviously odd or bizarre. D. If mood episodes have occurred concurrently with delusions, their total duration has been brief relative to the duration of the delusional periods. E. The disturbance is not due to the direct physiological effects of a substance or a general medical condition. Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

delusions that may be bizarre, hallucinations (which are more likely to be visual than in early- or late-onset cases), and a relative absence of formal thought disorder and affective blunting. The presentation of delusional disorder similarly follows DSM-IV-TR, although hallucinations are nonbizarre and functioning is relatively intact. However, the distinction between VLOSLP and delusional disorder has been called into question by several investigators, most notably Riecher-Rossler et al. (2003), who studied hospital case registers of more than 1,100 patients with schizophrenia or paranoid psychosis, 352 of whom had onset after age 40. They concluded that “the validity of the distinction between late-onset schizophrenia and other paranoid psychoses of old age would thus seem to be lacking at the descriptive as well as the predictive and construct levels. Rather, there would appear to be a broad overlap between the two diagnostic categories” (p. 602). Researchers in geriatric psychiatry seem to have agreed with this assessment, because published articles on late-onset psychosis in recent years are essentially all focused on VLOSLP, and the remainder of this chapter follows suit.

Neuropsychological Tests Most patients with schizophrenia spectrum disorders have neuropsychological deficits, with severity ranging from mild frontal executive deficits to clinical dementia. In a study of community-residing outpatients with schizophrenia (Heaton et al. 2001), the average global neuropsychological score was 1.62 stan-

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dard deviations (SDs) lower for patients compared with control subjects, and about 30% of the patients had “very impaired” cognitive scores (>3 SDs below the level of nonschizophrenic control subjects). Deficits of this magnitude contribute in significant ways to the functional and social limitations associated with schizophrenia-like conditions. However, in contrast to neurodegenerative disorders such as Alzheimer’s disease and dementia with Lewy bodies, most studies have found schizophrenia-related cognitive deficits to be stable over time. In the Heaton et al. study, for example, mean changes over time and test-retest reliabilities were the same for schizophrenic patients and control subjects across a wide range of cognitive measures. Both older and younger patients had this stable pattern. A related study compared performance on cognitive mental status examinations (the Mini-Mental State Examination and Dementia Rating Scale; see Chapter 5, “Dementia and Alzheimer’s Disease”) for older early-onset schizophrenia spectrum patients, late-onset schizophrenia-like psychosis patients (onset after age 45 years), patients with Alzheimer’s disease, and control subjects without mental disorders across retest intervals of 1–2 years. In this study, retest scores also remained stable or even slightly improved for both early- and lateronset schizophrenic-like disorder groups, whereas significant decline was noted for patients with Alzheimer’s disease, with and without psychotic symptoms. Longitudinal neuropsychological data for VLOSLP patients (e.g., age 75 and older) are scant, however, and more research is needed. Also, although most cross-sectional studies have not shown excess rates of dementia among patients with schizophrenia spectrum disorders when appropriate control comparisons have been made, a few studies, mainly with older institutionalized samples, have found higher dementia rates. For example, in a retrospective chart review study (Dwork et al. 1998) that examined brain autopsy findings for patients who had been institutionalized for severe mental disorder or dementia, a higher proportion of schizophrenic patients than those with severe depression were rated as having significant cognitive impairment prior to death (68% vs. 19%). The cognitively impaired schizophrenic patients had higher rates of Alzheimer-type brain changes (especially neocortical neuritic plaques) than did those without cognitive deficit, but the extent of these changes generally fell short of pathological criteria for Alzheimer’s disease. The investigators speculated that individuals with schizophrenia may have lowered cognitive reserve, which predisposes them to clinically significant cognitive changes at lesser levels of Alzheimer’s disease pathology.

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Differential Diagnosis The major diagnostic entities to be ruled out before diagnosing VLOSLP include mood disorder with psychosis and dementia with psychosis. Delirium, particularly if induced by medications, also should be considered. In psychotic mood disorder, sadness, dysphoria, anhedonia, and irritability are usually apparent enough to lead diagnostic efforts in the right direction; when these features are obscured by psychotic manifestations, the diagnosis may rest on identification of the characteristic neurovegetative signs and symptoms of depression and careful determination of a sequence of onset of symptoms in which mood and neurovegetative changes occur before delusions and hallucinations. Late-onset hypomania and mania can present a clinical picture very similar to that of VLOSLP (Spar et al. 1979). Again, correct diagnosis may require a detailed history obtained from multiple sources, including medical records, along with inpatient observation. Dementia with psychosis may be identified by mental status examination supplemented with neuropsychological tests (see Chapter 5, “Dementia and Alzheimer’s Disease”). It is important to remember that performance on neuropsychological tests may be impaired in the absence of organic brain disease if attention, concentration, and motivation are negatively affected by functional illness (i.e., pseudodementia). Accordingly, retesting after these symptoms are at least partly controlled may avoid false-positive findings suggestive of degenerative or vascular disease. Finally, delirium is rarely mistaken for VLOSLP, but medications or combinations of medications that produce psychomotor slowing and toxic hallucinations (e.g., low-potency neuroleptic medications with potent central anticholinergic effects) can lead to this potentially hazardous misdiagnosis.

Pathogenesis Psychodynamic Theories Several plausible psychodynamic theories have been proposed to explain the development of delusions in mental illness, although none has focused on late-onset disorders. These hypotheses assume that delusions are “secondary,” functioning to help maintain psychic equilibrium threatened by peculiar or frightening experiences. For instance, the common delusion expressed by pa-

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tients with dementia that people are stealing things from them becomes an “explanation” for the disappearance and reappearance of items that are actually moved around by the patient, who has no recall of the events. The delusion enables the individual to avoid the awareness of severely impaired memory function. Similarly, mood-congruent delusions of bodily malfunction (“I can’t eat because the food doesn’t go into my stomach anymore”) and delusional guilt (“The president has lost his veto power, and the Communists are going to take over because of me”), commonly seen in psychotic major depression, help the individual to explain and understand his or her pervasive sense of dysphoria, degradation, and helplessness. In late-onset schizophrenia and delusional disorder, in which intellectual deficits and mood disturbance are absent, both internal and external stimuli for the development of persecutory delusions have been described. Schwartz (1963) proposed that an inner sense of meaninglessness or insignificance results in a self-aggrandizing delusion of “centrality” (e.g., “The ill-intended actions of many other people are oriented around me, so I must be a powerful and important person”). Arnold (1999) proposed that in schizophrenia, a dysfunction in a “phylogenetically old apparatus of a memory of situations” results in familiar perceptions being experienced as novel, uncertain, vague, and alien. Psychic equilibrium is sustained by explaining these changes as the results of the covert hostile actions of others. Similarly, delusional beliefs often seem designed to explain hallucinatory experiences; for example, “The neighbors are pumping poison gas into my apartment” is a belief that might accompany olfactory hallucinations. Psychodynamic explanations of hallucinations, catatonic behavior, and flat affect, each of which is a feature of DSM-IV-TR schizophrenia, are generally inadequately articulated in the literature. Neurobiological Theories Neurobiological explanations of delusions and hallucinations are partly based on analogy with well-known drug-induced mental changes. The psychoses associated with long-term ingestion of dopaminergic agents such as amphetamine or cocaine have led to the hypothesis that “endogenous” dopaminergic hyperactivity causes functional psychosis, whereas psychotic symptoms associated with ingestion of serotonergic hallucinogens such as lysergic acid diethylamide (LSD) have implicated serotonergic dysfunction. More recent attention has been paid to the role of glutamate.

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Hirsch and colleagues (1997) proposed that “schizophrenia and phencyclidine psychosis are similar, and phencyclidine is known to block the N-methyl-D-aspartate (NMDA) subtypes of glutamate (receptor). Moreover, studies of messenger RNA [mRNA] suggest that glutamate receptor deficiencies occur in schizophrenia and are regionally and specifically distributed” (p. 797). Hirsch and colleagues reported findings of 1) a marked decrease in pyramidal cell dendritic spines in layer III of the frontal and temporal cortex and 2) a correlation greater than 0.90 between decrease in mRNA for the NMDA glutamate receptor and cognitive deterioration in elderly patients with schizophrenia. These findings support the hypothesis proposed by Glenthøj and Hemmingsen (1997), who observed that most abnormalities postulated to underlie schizophrenia “involve the cortico-striato-thalamo-cortical circuits, which are central for attention and information processing” (p. 24). The authors noted that clinical and experimental studies point to a primary/early cortical defect involving the glutamatergic system, and to a later developed intermittent hyperactivity of the dopaminergic system superimposed on a basal hypodopaminergic state.. .. A changed neuroplastic response to environmental stimulation due to dopaminergic sensitization can explain how an episodic, subcortical hyperactivity can act on a basic glutamatergic and dopaminergic hypofunction to produce psychotic symptoms. (p. 24)

Glenthøj and Hemmingsen present a hypothesis for spontaneous mesolimbic dopaminergic sensitization and progressive evolution of psychosis on the basis of their own clinical and experimental findings and those of others—the “filter” hypothesis for schizophrenia and the state dependence of schizophrenic symptoms. Other theorists have focused on structural abnormalities observed in the brains of schizophrenic patients (Harrison 1999), but to date no widely accepted neurobiological theory of “functional” psychosis has yet been articulated.

Treatment Psychosocial-Behavior Therapy Tarrier (2005) reviewed 20 controlled studies of CBT in schizophrenic patients and found an overall effect size of 0.37 (SD=0.39), which is modest at best. He

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concluded, “There is consistent evidence that CBT reduces persistent positive symptoms in chronic patients and may have modest effects in speeding recovery in acutely ill patients” (p. 131). Other reviewers (e.g., Turkington et al. 2004) have emphasized the value of CBT as an adjunct to antipsychotic medications and socially based remedial approaches such as social skills training. Although none of the controlled trials in these reviews focused on elderly patients per se, there is little reason to expect that CBT would be significantly less effective in older patients, as long as cognitive impairment were not present. A randomized controlled trial of cognitive-behavioral social skills training for middle-aged and older outpatients (average age=approximately 54) with chronic schizophrenia conducted by Granholm et al. (2005) found that patients receiving combined treatment performed social functioning activities significantly more frequently than the patients in treatment as usual, although general skill at social functioning activities did not differ significantly. Patients receiving cognitive behavioral social skills training achieved significantly greater cognitive insight…and demonstrated greater skill mastery. The overall group effect was not significant for symptoms, but the greater increase in cognitive insight with combined treatment was significantly correlated with greater reduction in positive symptoms. (p. 520)

Rector and Beck (2002) described in detail how cognitive therapists conceptualize and treat positive and negative symptoms of schizophrenia. The Beck Cognitive Insight Scale (Beck et al. 2004), which measures the ability to observe and question one’s own cognitive processes, provides a method for tracking the cognitive effect of CBT or other therapies that has been validated with older patients with psychotic disorders (Pedrelli et al. 2004). Besides CBT, individual supportive psychotherapy aimed at building trust, facilitating the flow of clinical data from the patient, and maximizing compliance with somatic therapy can be an effective component of the overall treatment program for VLOSLP. A recommended therapeutic stance toward the patient’s delusional belief is “respectful disagreement,” wherein the therapist does not claim to share the patient’s false belief but avoids confrontation or argument with its content. Psychotic patients usually realize that others do not agree with their beliefs, and they may become suspicious and distrustful of the treating professional who does. However, open disagreement invites the patient to incorporate the therapist into the delusion, thereby thwarting ef-

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forts to establish a mutually respectful, trusting relationship. Although some elderly patients are capable of a degree of detachment from their delusions and can gain insight into their defensive function, insight-oriented psychotherapeutic approaches are usually discouraged in favor of approaches that focus on more dynamically superficial content, such as conscious concerns and feelings. In this regard, psychotic patients often refuse to cooperate with treatment aimed at the delusions or hallucinations per se, in which case the therapy should be aimed at the accompanying anxiety, fear, sleeplessness, or anhedonia. Group therapy is generally of little value in the acute phase of psychotic illness, although some patients can use the group situation to initiate social contact with other patients and appear to benefit indirectly. Family therapy may be extremely useful, particularly in situations in which family members have been alienated by psychotic behavior. Although sessions without the patient can be productive, inviting the patient to participate each time may avoid exacerbating feelings of mistrust and paranoia. Work with family members focuses on education about the patient’s condition, the natural history and prognosis of the disorder, and details of the treatment plan; the family therapist also attempts to enlist family support for the inpatient and outpatient components of the treatment plan. Psychopharmacotherapy Controlled studies are lacking, but Alexopoulos et al. (2004) surveyed 52 “American experts on treatment of older adults.” The experts’ first-line recommendation for late-life schizophrenia was risperidone (1.25–3.5 mg/day). “Quetiapine (100–300 mg/day), olanzapine (7.5–15 mg/day), and aripiprazole (15–30 mg/day) were high second-line [choices]” (p. 5). Consistent with these recommendations, several open studies have shown risperidone (Davidson et al. 2000; Madhusoodanan et al. 1999) and olanzapine (Madhusoodanan et al. 2000) to be effective and well tolerated in elderly patients with psychoses. These agents’ main advantages over the typical antipsychotic medications are their relative lack of extrapyramidal side effects, somewhat greater efficacy for negative symptoms of schizophrenia, and somewhat lower propensity to impair cognition. Acute side effects of risperidone and olanzapine are usually limited to sedation and orthostatic hypotension, and olanzapine has anticholinergic effects that are usually well tolerated in therapeutic dosage

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ranges. However, long-term side effects of significant weight gain, insulin resistance and diabetes, and dyslipidemia are seen in varying degrees of severity with all of the atypical antipsychotic agents. Accordingly, the experts surveyed by Alexopoulos et al. (2004) would avoid clozapine, olanzapine, and conventional antipsychotics (especially low- and mid-potency) for patients with diabetes, dyslipidemia, or obesity. Moreover, Alexopoulos et al. stated the following: Quetiapine is first line for a patient with Parkinson’s disease. Clozapine, ziprasidone, and conventional antipsychotics (especially low- and midpotency) should be avoided in patients with QTc prolongation or congestive heart failure. For patients with cognitive impairment, constipation, diabetes, diabetic neuropathy, dyslipidemia, xerophthalmia, and xerostomia, the experts prefer risperidone, with quetiapine high second line. (p. 5)

Of the typical antipsychotic agents, low-dose, high-potency medications such as haloperidol and fluphenazine still have a role in VLOSLP, particularly in patients whose symptoms are nonresponsive to the atypical agents or who cannot tolerate the tendency of these agents to stimulate weight gain. Acute side effects to be anticipated with typical agents include sedation, akathisia, akinesia, and cogwheel rigidity. Adjunctive treatment with lorazepam or other short-acting benzodiazepines often allows the total dosage of neuroleptic to be reduced below levels that cause these side effects. One or two doses of an antiparkinsonian agent such as benztropine or trihexyphenidyl hydrochloride may be useful for diagnostic purposes when akathisia is suspected, but longterm administration of anticholinergic agents should be avoided whenever possible because of the increased susceptibility of elderly patients to memory impairment, confusion, and anticholinergic delirium. Alternatively, clonazepam, which produces no extrapyramidal side effects, may be effective in controlling agitation and hallucinations but is typically less effective than neuroleptic medications in reversing thought disorder and delusions. A typical starting dosage of clonazepam is 0.5 mg administered orally three times a day, which can be increased up to threefold. At these dosages, side effects are usually limited to sedation, but the risk of blood dyscrasia necessitates a pretreatment complete blood count followed by periodic retesting. Dosages of atypical and typical antipsychotic medications required to achieve symptom remission in VLOSLP typically range around 33%–100%

Antipsychotic drugs, dose equivalences, and side-effect profiles

Drug Typical agents Chlorpromazine Thioridazineb,c Perphenazine Trifluoperazine Thiothixene Haloperidol Fluphenazine Atypical agents Risperidone Clozapined Olanzapine Quetiapine Ziprasidonec Aripiprazole

Equivalent dose (mg/day)

Sedation

Anticholinergic effects

Extrapyramidal effectsa

Hypotensive effects

100 100 8 5 5 2 2

+++ +++ ++ + + + +

++ +++ 0/+ + 0/+ 0 0/+

++ + +++ ++ ++ +++ +++

+++ (im) ++ + + ++ 0/+ +

1.5 100 5 75 40 15

+ +++ ++ + ++ +

0 +++ ++ + + 0

+ 0/+ 0/+ 0/+ 0/+ 0/+

+ ++ + + + +

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Table 7–11.

Table 7–11.

Antipsychotic drugs, dose equivalences, and side-effect profiles (continued)

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Note. 0/+ =absent or very weak effect; += weak effect; ++= moderate effect; +++= strong effect; im=intramuscular. aInclude acute dystonia, pseudoparkinsonism, akathisia, and perioral tremor (“rabbit syndrome”). bMaximal dosage is 800 mg/day; higher dosages may cause pigmentary retinopathy. c Causes increase in QT/QTc interval; is contraindicated in patients with preexisting QTc interval>500 msec or various forms of cardiac illness. dHypersalivation is common, especially at night. Source. Adapted from Wise MG, Rundell JR: “Delirium (Acute Confusional States) and Dementia,” in Concise Guide to Consultation Psychiatry, 2nd Edition. Washington, DC, American Psychiatric Press, 1994, p. 41. Copyright © 1994, American Psychiatric Press. Used with permission.

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of the recommended dosage for schizophrenic adults. An effective dosage titration approach is to prescribe one-third to one-half the adult dosage on a standing basis and to add a similar dosage on an as-needed basis once or twice a day for agitation, hallucinations, or delusion-driven behavior (e.g., the patient will not eat because the food “comes from the toilet” or “is poisoned”). Because delusional thought content may persist for weeks or months after delusions are no longer driving the patient’s affect and behavior, it is usually impractical to use delusional thought content per se as a target symptom of acute therapy. After acute symptoms subside, dosages can be gradually reduced until symptom breakthrough occurs, at which point the dosage is increased slightly and maintained. Table 7–11 presents dose equivalences and relative side-effect potencies of the commonly prescribed atypical and typical antipsychotic medications.

References Alexopoulos GS, Streim J, Carpenter D, et al: Using antipsychotic agents in older patients. J Clin Psychiatry 65 (suppl 2):5–99, 2004 American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition. Washington, DC, American Psychiatric Association, 1980 American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, Revised. Washington, DC, American Psychiatric Association, 1987 American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Washington, DC, American Psychiatric Association, 1994 American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000 Andersen SL, Teicher MH: Serotonin laterality in amygdala predicts performance in the elevated plus maze in rats. Neuroreport 10:3497–3500, 1999 Arnold OH: Schizophrenia—a disturbance of signal interaction between the entorhinal cortex and the dentate gyrus? the contribution of experimental dibenamine psychosis to the pathogenesis of schizophrenia: a hypothesis. Neuropsychobiology 40:21–32, 1999 Barak Y, Aizenberg D, Mirecki I, et al: Very late-onset schizophrenia-like psychosis: clinical and imaging characteristics in comparison with elderly patients with schizophrenia. J Nerv Ment Dis 190:733–736, 2002

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Barlow DH, Gorman JM, Shear MK, et al: Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: a randomized controlled trial. JAMA 283:2529–2536, 2000 Beck AT, Epstein N, Brown G, et al: An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol 56:893–897, 1988 Beck JG, Stanley MA, Zebb BJ: Characteristics of generalized anxiety disorder in older adults: a descriptive study. Behav Res Ther 34:225–234, 1996 Beck AT, Baruch E, Balter JM, et al: A new instrument for measuring insight: the Beck Cognitive Insight Scale. Schizophr Res 68:319–329, 2004 Beekman AT, de Beurs E, van Balkom AJ, et al: Anxiety and depression in later life: co-occurrence and communality of risk factors. Am J Psychiatry 157:89–95, 2000 Bernstein DA, Borkovec TD: Progressive Relaxation Training: A Manual for the Helping Professions. Champaign, IL, Research Press, 1973 Blazer D, George LK, Hughes D: The epidemiology of anxiety disorders: an age comparison, in Anxiety in the Elderly: Treatment and Research. Edited by Salzman C, Lebowitz BD. New York, Springer, 1991, pp 17–30 Calkin PA, Kunik ME, Orengo CA, et al: Tolerability of clonazepam in demented and non-demented geropsychiatric patients. Int J Geriatr Psychiatry 12:745–749, 1997 Carmin CN, Pollard CA, Gillock KL: Assessment of anxiety disorders in the elderly, in Handbook of Assessment in Clinical Gerontology. Edited by Lichtenberg P. New York, Wiley, 1999, pp 59–90 Carmin CN, Wiegartz PS, Yunus U, et al: Treatment of late-onset OCD following basal ganglia infarct. Depress Anxiety 15:87–90, 2002 Chung MC, Werrett J, Easthope Y, et al: Coping with post-traumatic stress: young, middle-aged and elderly comparisons. Int J Geriatr Psychiatry 19:333–343, 2004 Cottraux J, Note I, Albuisson E, et al: Cognitive behavior therapy versus supportive therapy in social phobia: a randomized controlled trial. Psychother Psychosom 69:137–146, 2000 Crist DA, Rickard HC, Prentice-Dunn S, et al: The Relaxation Inventory: self-report scales of relaxation training effects. J Pers Assess 53:716–726, 1989 Davidson M, Harvey PD, Vervarcke J, et al: A long-term, multicenter, open-label study of risperidone in elderly patients with psychosis. On behalf of the Risperidone Working Group. Int J Geriatr Psychiatry 15:506–514, 2000 Dwork AJ, Susser ES, Keilp JG, et al: Senile degeneration and cognitive impairment in chronic schizophrenia. Am J Psychiatry 155:1536–1543, 1998 Eysenck H: Stress, disease, and personality: the ‘inoculation’ effect, in Stress Research. Edited by Cooper CJ. New York, Wiley, 1983, pp 121–146

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Gelowitz DL, Kokkinidis L: Enhanced amygdala kindling after electrical stimulation of the ventral tegmental area: implications for fear and anxiety. J Neurosci 19:RC41, 1999 Glenthøj BY, Hemmingsen R: Dopaminergic sensitization: implications for the pathogenesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 21:23–46, 1997 Goldberg RJ: The use of buspirone in geriatric patients. Journal of Clinical Psychiatry Monograph Series 12:31–36, 1994 Granholm E, McQuaid JR, McClure FS, et al: A randomized, controlled trial of cognitive behavioral social skills training for middle-aged and older outpatients with chronic schizophrenia. Am J Psychiatry 162:520–529, 2005 Gross C, Zhuang X, Stark K, et al: Serotonin-1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature 416:396–400, 2002 Gurian BS, Miner JH: Clinical presentation of anxiety in the elderly, in Anxiety in the Elderly: Treatment and Research. Edited by Salzman C, Lebowitz BD. New York, Springer, 1991, pp 31–44 Hamilton M: The assessment of anxiety states by rating. Br J Med Psychol 32:50–55, 1959 Harrison PJ: The neuropathology of schizophrenia: a critical review of the data and their interpretation. Brain 122 (pt 4):593–624, 1999 Heaton RK, Gladsjo JA, Palmer BW, et al: Stability and course of neuropsychological deficits in schizophrenia. Arch Gen Psychiatry 58:24–32, 2001 Hegel MT, Unützer J, Tang L, et al: Impact of comorbid panic and posttraumatic stress disorder on outcomes of collaborative care for late-life depression in primary care. Am J Geriatr Psychiatry 13:48–58, 2005 Heuzenroeder L, Donnelly M, Haby MM, et al: Cost-effectiveness of psychological and pharmacological interventions for generalized anxiety disorder and panic disorder. Aust N Z J Psychiatry 38:602–612, 2004 Hirsch SR, Das I, Garey LJ, et al: A pivotal role for glutamate in the pathogenesis of schizophrenia, and its cognitive dysfunction. Pharmacol Biochem Behav 56:797– 802, 1997 Hommer D, Skolnick P, Paul D: The benzodiazepine/GABA receptor complex and anxiety, in Psychopharmacology: The Third Generation of Progress. Edited by Meltzer H. New York, Raven, 1987, pp 977–983 Hopko DR, Stanley MA, Reas DL, et al: Assessing worry in older adults: confirmatory factor analysis of the Penn State Worry Questionnaire and psychometric properties of an abbreviated model. Psychol Assess 15:173–183, 2003

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Howard R, Rabins PV, Seeman MV, et al: Late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: an international consensus. The International LateOnset Schizophrenia Group. Am J Psychiatry 157:172–178, 2000 Khan A, Leventhal RM, Khan S, et al: Suicide risk in patients with anxiety disorders: a meta-analysis of the FDA database. J Affect Disord 68:183–190, 2002 Kohn R, Westlake RJ, Rasmussen SA, et al: Clinical features of obsessive-compulsive disorder in elderly patients. Am J Geriatr Psychiatry 5:211–215, 1997 Krasucki C, Howard R, Mann A: The relationship between anxiety disorders and age. Int J Geriatr Psychiatry 13:79–99, 1998 Lenze EJ, Mulsant BH, Shear MK, et al: Comorbid anxiety disorders in depressed elderly patients. Am J Psychiatry 157:722–728, 2000 Lenze EJ, Mulsant BH, Mohlman J, et al: Generalized anxiety disorder in late life: lifetime course and comorbidity with major depressive disorder. Am J Geriatr Psychiatry 13:77–80, 2005a Lenze EJ, Mulsant BH, Shear MK, et al: Efficacy and tolerability of citalopram in the treatment of late-life anxiety disorders: results from an 8-week randomized, placebo-controlled trial. Am J Psychiatry 162:146–150, 2005b Le Roux H, Gatz M, Wetherell JL: Age at onset of generalized anxiety disorder in older adults. Am J Geriatr Psychiatry 13:23–30, 2005 Leuchter AF, Spar JE: The late-onset psychoses: clinical and diagnostic features. J Nerv Ment Dis 173:488–494, 1985 Lyons J, McClendon O: Changes in PTSD symptomatology as a function of aging. Nova-Psy Newsletter 8:13–18, 1990 Madhusoodanan S, Brecher M, Brenner R, et al: Risperidone in the treatment of elderly patients with psychotic disorders [published erratum appears in Am J Geriatr Psychiatry 7:268, 1999]. Am J Geriatr Psychiatry 7:132–138, 1999 Madhusoodanan S, Brenner R, Suresh P, et al: Efficacy and tolerability of olanzapine in elderly patients with psychotic disorders: a prospective study. Ann Clin Psychiatry 12:11–18, 2000 Mazeh D, Zemishlani C, Aizenberg D, et al: Patients with very-late-onset schizophrenia-like psychosis: a follow-up study. Am J Geriatr Psychiatry 13:417–419, 2005 Mohlman J: Psychosocial treatment of late-life generalized anxiety disorder: current status and future directions. Clin Psychol Rev 24:149–169, 2004 Morinigo A, Blanco M, Labrador J, et al: Risperidone for resistant anxiety in elderly persons. Am J Geriatr Psychiatry 13:81–82, 2005 Palmer BW, Bondi MW, Twamley EW, et al: Are late-onset schizophrenia spectrum disorders neurodegenerative conditions? annual rates of change on two dementia measures. J Neuropsychiatry Clin Neurosci 15:45–52, 2003

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Pedrelli P, McQuaid JR, Granholm E, et al: Measuring cognitive insight in middleaged and older patients with psychotic disorders. Schizophr Res 71:297–305, 2004 Philpot MP, Banerjee S: Obsessive-compulsive disorder in the elderly. Behav Neurol 11:117–121, 1998 Rabins PV, Lavrisha M: Long-term follow-up and phenomenologic differences distinguish among late-onset schizophrenia, late-life depression, and progressive dementia. Am J Geriatr Psychiatry 11:589–594, 2003 Rector NA, Beck AT: Cognitive therapy for schizophrenia: from conceptualization to intervention. Can J Psychiatry 47:39–48, 2002 Redmond DJ: Studies of the nucleus locus coeruleus in monkeys and hypotheses for neuropsychopharmacology, in Psychopharmacology: The Third Generation of Progress. Edited by Meltzer H. New York, Raven, 1987, pp 967–975 Reeves SJ, Sauer J, Stewart R, et al: Increased first-contact rates for very-late-onset schizophrenia-like psychosis in African- and Caribbean-born elders. Br J Psychiatry 179:172–174, 2001 Regier DA, Boyd JH, Burke JJ, et al: One-month prevalence of mental disorders in the United States: based on five Epidemiologic Catchment Area sites. Arch Gen Psychiatry 45:977–986, 1988 Riecher-Rossler A, Hafner H, Hafner-Ranabauer W, et al: Late-onset schizophrenia versus paranoid psychoses: a valid diagnostic distinction? Am J Geriatr Psychiatry 11:595–604, 2003 Ritchie K, Artero S, Beluche I, et al: Prevalence of DSM-IV psychiatric disorder in the French elderly population. Br J Psychiatry 184:147–152, 2004 Rodriguez-Ferrera S, Vassilas CA, Haque S: Older people with schizophrenia: a community study in a rural catchment area. Int J Geriatr Psychiatry 19:1181–1187, 2004 Schwartz DA: A review of the “paranoid” concept. Arch Gen Psychiatry 4:349–361, 1963 Scogin F, Rickard HC, Keith S, et al: Progressive and imaginal relaxation training for elderly persons with subjective anxiety. Psychol Aging 7:419–424, 1992 Sheikh JI, Lauderdale SA, Cassidy EL: Efficacy of sertraline for panic disorder in older adults: a preliminary open-label trial (letter). Am J Geriatr Psychiatry 12:230, 2004a Sheikh JI, Swales PJ, Carlson EB, et al: Aging and panic disorder: phenomenology, comorbidity, and risk factors. Am J Geriatr Psychiatry 12:102–109, 2004b Simpson HB, Gorfinkle KS, Liebowitz MR: Cognitive-behavioral therapy as an adjunct to serotonin reuptake inhibitors in obsessive-compulsive disorder: an open trial. J Clin Psychiatry 60:584–590, 1999

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Sinoff G, Werner P: Anxiety disorder and accompanying subjective memory loss in the elderly as a predictor of future cognitive decline. Int J Geriatr Psychiatry 18:951–959, 2003 Spar JE, Ford CV, Liston EH: Bipolar affective disorder in aged patients. J Clin Psychiatry 40:504–507, 1979 Spielberger C, Gorsuch R, Lushene R: State-Trait Anxiety Inventory. Palo Alto, CA, Consulting Psychologists Press, 1970 Steffens DC, McQuoid DR: Impact of symptoms of generalized anxiety disorder on the course of late-life depression. Am J Geriatr Psychiatry 13:40–47, 2005 Sunderland T, Lawlor BA, Martinez RA, et al: Anxiety in the elderly: neurobiological and clinical interface, in Anxiety in the Elderly: Treatment and Research. Edited by Salzman C, Lebowitz BD. New York, Springer, 1991, pp 105–129 Tarrier N: Cognitive behaviour therapy for schizophrenia—a review of development, evidence and implementation. Psychother Psychosom 74:136–144, 2005 Turkington D, Dudley R, Warman DM, et al: Cognitive-behavioral therapy for schizophrenia: a review. J Psychiatr Pract 10:5–16, 2004 van Os J, Howard R, Takei N, et al: Increasing age is a risk factor for psychosis in the elderly. Soc Psychiatry Psychiatr Epidemiol 30:161–164, 1995 Webster J, Grossberg GT: Late-life onset of psychotic symptoms. Am J Geriatr Psychiatry 6:196–202, 1998 Weiss AP, Jenike MA: Late-onset obsessive-compulsive disorder: a case series. J Neuropsychiatry Clin Neurosci 12:265–268, 2000 Wetherell JL, Gatz M, Craske MG: Treatment of generalized anxiety disorder in older adults. J Consult Clin Psychol 71:31–40, 2003a Wetherell JL, Le Roux H, Gatz M: DSM-IV criteria for generalized anxiety disorder in older adults: distinguishing the worried from the well. Psychol Aging 18:622– 627, 2003b Wisocki PA, Handen B, Morse C: The Worry Scale as a measure of anxiety among home bound and community active elderly. Behavior Therapist 9:91–95, 1986 World Health Organization: International Classification of Diseases, 9th Revision, Clinical Modification. Ann Arbor, MI, Commission on Professional and Hospital Activities, 1978

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8 Other Common Mental Disorders of the Elderly Insomnia Assessment In addition to conducting thorough interviews of the patient and a sleep partner, procedures that can be useful in establishing a diagnosis of insomnia include sleep diaries, rating scales that assess sleep behaviors and related issues, and physiological measures such as polysomnography. Trevorrow (1999) has provided recommendations of topics to cover in a sleep assessment interview (Table 8–1) and a description of sleep questionnaires and rating scales.

Differential Diagnosis Almost half of the 29 million Americans age 65 and older complain of inadequate amount or quality of sleep (Monane 1992). The differential diagnosis of insomnia in the elderly includes the conditions listed below. Normal Aging Changes In general, with advancing age, sleep becomes more fragmented, more time is required to fall asleep, more awakenings occur, relatively less deep (Stage IV) sleep is experienced, and people tend to spend more time in bed. The subjective impression produced by these changes is unsatisfying sleep, which may be reported as insomnia; it is not uncommon for elderly hospitalized patients to report not sleeping at all, despite nursing observations of 6–8 hours of apparent sleep, complete with snoring. 313

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Table 8–1. Areas to consider in a sleep assessment interview Nature of the complaint—what the problem is and when it occurs (e.g., sleep onset, sleep maintenance, early-morning wake-up, daytime fatigue, nightmares) Current sleep-wake schedule History of sleep complaint (transient disturbance vs. long-standing complaint) Symptoms of sleep disorders that may not be initially volunteered (e.g., restless legs, periodic limb movements, narcolepsy, gastroesophageal reflux, parasomnias, disruption of sleep-wake schedule) Symptoms of sleep-disordered breathing (disturbed breathing at night, complaints of snoring, headache on waking, partner sleeps in another room) Daytime states, routines, activities (sleepiness, fatigue, functioning, mood, activities, satisfaction with daily routines) Naps (frequency, time of day, length) Sleep hygiene (daytime activity, exercise, sleep environment, activity in bed, diet, use of stimulants or depressants; see Table 8–3) History of professional treatment of the sleep complaint and a review of what the patient has tried to remedy the sleep problem Medical or physical problems Use of prescription and nonprescription drugs Psychiatric history and mental status review (symptoms of depression, anxiety, thought disorder, other psychological maladjustment) Stressful circumstances (currently and when sleep problems began) Information about antecedents, consequences, secondary gains, precipitating factors, perpetuating factors Source. Adapted from Trevorrow T: “Assessing Sleep Functioning in Older Adults,” in Handbook of Assessment in Clinical Gerontology. Edited by Lichtenberg P. New York, Wiley, 1999, pp. 331–350. Copyright © 1999 John Wiley & Sons, Inc. Reprinted with permission of John Wiley & Sons, Inc.

Insomnia Associated With Axis I Psychiatric Illness Sleep disturbance is associated with almost all of the major syndromes discussed in this book, including anxiety disorders, mood disorders, dementia and delirium, psychosis, and adjustment disorder. The normal disruptions in mental life caused by stressful or grief-producing situations must be added to this list.

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Insomnia Associated With Physical Illness Physical conditions associated with pain (e.g., arthritis), with difficulty breathing (e.g., congestive heart failure or chronic obstructive pulmonary disease), or with immobility (e.g., stroke or Parkinson’s disease) can severely disturb sleep. Frequent awakenings also may be associated with urinary obstruction secondary to prostatism or chronic urinary tract infection. Sleep apnea has been found in about 30%–40% of elderly patients evaluated in sleep laboratories and is typically associated with obesity and snoring. Nocturnal myoclonus, usually manifested as leg twitches and jerks, is diagnosed somewhat less frequently and may be observed without using sophisticated electronic equipment. Muscle movements that cause brief awakenings are most likely to be indicative of this condition. Substance-Induced Insomnia Sympathomimetic agents (including decongestants and bronchodilators), methylxanthine derivatives (such as theophylline and aminophylline), psychostimulants, certain antidepressants (fluoxetine, bupropion, higher doses of mirtazapine), and medications containing caffeine (as well as caffeinecontaining beverages such as coffee and many cola drinks) can interfere with sleep, particularly if they are ingested late in the evening. Also, experimental and clinical evidence indicates that most, if not all, hypnotic medications can produce sleep disturbance after prolonged use (sometimes in as little as 3 weeks of nightly ingestion) or during the acute withdrawal phase after repeated ingestion (the so-called rebound effect). Primary Insomnia When the causes of insomnia listed above have been ruled out, the proper diagnosis is primary insomnia. DSM-IV-TR (American Psychiatric Association 2000) diagnostic criteria for primary insomnia are summarized in Table 8–2.

Treatment—General and Behavioral Interventions In light of the differential diagnosis of insomnia described earlier in this section, it is important whenever possible to treat mental and physical illness and to adjust the type, dosage, and timing of medications that can cause insomnia before prescribing hypnotic agents. Of the physical illnesses that can disturb sleep, it is particularly important to identify and treat breathing-related sleep disorder because taking sedative-hypnotic drugs can exacerbate this condition and create a

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Table 8–2. Summary of DSM-IV-TR diagnostic criteria for primary insomnia A.

The predominant complaint is difficulty initiating or maintaining sleep, or nonrestorative sleep, for at least 1 month. B. The sleep disturbance (or associated daytime fatigue) causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. C. The sleep disturbance does not occur exclusively during the course of narcolepsy, breathing-related sleep disorder, circadian rhythm sleep disorder, or a parasomnia. D. The disturbance does not occur exclusively during the course of another mental disorder. E. The disturbance is not due to the direct physiological effects of a substance or a general medical condition. Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

potentially lethal situation. Similarly, optimization of sleep hygiene should always be attempted before hypnotic agents are prescribed for other than occasional use. Table 8–3 lists the features regarded by The International Classification of Sleep Disorders (American Sleep Disorders Association 1997) as diagnostic of inadequate sleep hygiene. Interventions as simple as systematically restricting time spent in bed and providing education about normal variability in sleep patterns and age-related changes have been effective in increasing sleep efficiency and reducing daytime sleepiness in older patients with insomnia (Riedel et al. 1995). Modifying thoughts about “good” and “poor” sleep (e.g., 8 hours of sleep per night is not necessary for everyone) is an example of a cognitive-behavioral intervention that may also be useful in treating insomnia in old age (Morin et al. 1993). A recent state-of-the-science conference (National Institutes of Health 2005) on the manifestations and management of chronic insomnia in adults concluded that a cognitive-behavioral treatment package is “as effective as prescription medications are for brief treatment of chronic insomnia” (p. 8) and that “beneficial effects of CBT [cognitive-behavioral therapy], in contrast to those produced by medications, may last well beyond the termination of treatment” (p. 8). However, the review also pointed out that few clinicians are trained in the use of CBT for chronic insomnia.

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Table 8–3. Features of inadequate sleep hygiene 1. Daytime napping at least two times each week 2. Having variable wake-up times or bedtimes 3. Experiencing frequent periods (two to three times per week) of extended amounts of time spent in bed 4. Routinely using products containing alcohol, tobacco, or caffeine in the period preceding bedtime 5. Scheduling exercise too close to bedtime 6. Engaging in exciting or emotionally upsetting activities too close to bedtime 7. Frequently using the bed for nonsleep-related activities (e.g., television watching, reading, studying, snacking) 8. Sleeping on an uncomfortable bed (e.g., poor mattress, inadequate blankets) 9. Allowing the bedroom to be too bright, too stuffy, too cluttered, too hot, too cold, or in some way not conducive to sleep 10. Performing activities demanding high levels of concentration shortly before bed 11. Allowing mental activities, such as thinking, planning, and reminiscing, to occur in bed Source. Adapted from American Sleep Disorders Association: The International Classification of Sleep Disorders: Diagnostic and Coding Manual, Revised. Rochester, MN, American Sleep Disorders Association, 1997.

Treatment—Psychopharmacotherapy Benzodiazepine anxiolytic and hypnotic medications and the nonbenzodiazepine medications zolpidem, zaleplon, and eszopiclone (see Table 8–4) are the drugs of choice for elderly patients with primary insomnia. Benzodiazepine Hypnotics Although Table 8–4 includes only three benzodiazepines that are specifically marketed for inducing sleep, all agents of this class have hypnotic activity and are essentially interchangeable, even though minor interindividual differences in susceptibility to one or more of their effects are the rule. For occasional use, almost any of the available agents are effective, but most elderly patients will experience less morning “hangover” with the short-acting agents, such as temazepam, lorazepam, or oxazepam, than with the long-acting agents, such as diazepam or flurazepam. In this regard, alprazolam is intermediate in duration of action and in desirability, whereas triazolam is very

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Table 8–4. Sedative-hypnotics, with dosage and duration of action Generic name (trade name) Benzodiazepine hypnotics Flurazepam (Dalmane) Temazepam (Restoril)a Triazolam (Halcion) Benzodiazepine anxiolytics Lorazepam (Ativan)a Oxazepam (Serax)a Diazepam (Valium) Alprazolam (Xanax) Barbiturates Pentobarbital (Nembutal) Secobarbital (Seconal) Others Chloral hydrate (many) Glutethimide (Doriden) Methyprylon (Noludar) Zolpidem (Ambien)a Zaleplon (Sonata)a Eszopiclone (Lunesta)a

Dose (mg)

15–30 15–30 0.125–0.250

Duration of action

Long Short Ultrashort

0.5–2 15–30 2.5–5 0.5–1

Short Short Long Intermediate

50–100 50–500

Intermediate Intermediate

500–1,000 25–250 100–200 5–10 5–10 1–2

Intermediate Intermediate Intermediate Short Ultrashort Short

a

Agents recommended for use in elderly persons.

short acting but should be avoided because of its propensity to cause ataxia, paradoxical agitation, and mild but sometimes disturbing amnesia in some elderly patients. For long-term use, the short-acting agents named above (temazepam, lorazepam, or oxazepam) are much preferred over long-acting agents (diazepam or flurazepam) because of the risk with the latter of building up potentially intoxicating blood levels of very long-acting active metabolites. The following case is illustrative: A 76-year-old woman was admitted to the hospital for evaluation of mental cloudiness and lethargy. Comprehensive medical and neurological workup failed to identify a cause of her symptoms, and the fact that she had started taking 5 mg of diazepam per night for sleep about 2 months before admission

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was initially ignored. Subsequent consultation with a geriatric psychopharmacologist led to discontinuation of the diazepam and rapid amelioration of her symptoms.

Because benzodiazepine hypnotic agents begin to lose effectiveness after several weeks of nightly ingestion, it is important to provide detailed instructions on their use, with emphasis on the advantages of irregular administration. Some clinicians attempt to avoid the development of tolerance by prescribing two or three different benzodiazepines concurrently, with instructions to the patient to alternate between the medications weekly. Although this approach has been successful in certain instances, no formal research data supporting this practice have yet been published. Nonbenzodiazepine Hypnotics Three nonbenzodiazepine agents have been shown to be safe and effective for elderly patients with primary insomnia: zolpidem (Shaw et al. 1992), zaleplon (Hedner et al. 2000), and eszopiclone (R. Rosenberg et al. 2005; Zammit et al. 2004). Each agent produces sleep by selectively binding to the γ-aminobutyric acid (GABA)A1 receptor, and each is comparable to benzodiazepine hypnotics in terms of efficacy but produces somewhat less next-day drowsiness and cognitive impairment. The nonbenzodiazepine agents, particularly eszopiclone, may be effective for longer than a few weeks, but definitive data have not yet been published. Zolpidem has a half-life of about 2 hours, has no active metabolites, and does not accumulate during repeated administration. It has little anxiolytic or anticonvulsant effect and causes few side effects beyond mild dizziness and nausea. Studies of its effects on sleep architecture are equivocal, with some reporting minor increases in delta sleep. One study (Girault et al. 1996) suggested that zolpidem is safe to administer to patients with chronic obstructive pulmonary disease. Zaleplon has a half-life of about 1 hour and also has no active metabolites to accumulate. It is as effective as zolpidem and produces even less next-day psychomotor impairment, although this may be largely because of its more rapid elimination. Controlled studies have not identified any side effects in excess of those produced by placebo, and “rebound” insomnia after the drug has been eliminated has not been observed. Neither zolpidem nor zaleplon has consistently shown sleep maintenance efficacy, as measured by wake time

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after sleep onset, unlike the newest entry in the nonbenzodiazepine hypnotic category, eszopiclone, which is a single-isomer cyclopyrrolone agent. Eszopiclone is rapidly absorbed, with a time to peak concentration of approximately 1 hour and a half-life of 5–6 hours. It has been shown to produce improvement in all four domains of insomnia—including sleep onset, sleep maintenance, sleep duration, and restorative sleep—and studies in the elderly suggest that it is safe and effective at dosages up to 2 mg/night. Trazodone Trazodone is not marketed as a hypnotic, but in low doses (i.e., 50–75 mg) it is well tolerated and effective in inducing sleep and has the theoretical advantage over several of the agents listed above of maintaining or actually increasing delta sleep (Stages III and IV) (Scharf and Sachais 1990), which some sleep researchers believe are the most refreshing stages of sleep. It has been shown to be an effective hypnotic in patients with selective serotonin reuptake inhibitor–induced insomnia (Kaynak et al. 2004). However, trazodone, like the benzodiazepine hypnotics, is associated with next-day somnolence and mild impairment on some measures of cognitive function. It should also be noted that insomnia remains an “off-label” (i.e., not approved by the U.S. Food and Drug Administration), although widely recognized, indication for use of trazodone.

Alcohol Abuse and Dependence Epidemiology The prevalence of alcohol abuse and dependence in community-dwelling elderly persons ranges from 2% to 4% (Adams and Cox 1995) when DSMIII (American Psychiatric Association 1980) criteria are used; less strict criteria lead to higher estimates. Among primary care patients, the prevalence is 8%–15% (Oslin 2004), and surveys of hospitalized elderly persons and those in nursing homes have produced prevalence estimates from 8% to around 50% (Johnson 2000). As the elderly population increases in the next decade, the absolute number of older people with substance abuse problems will rise, and because the currently middle-aged cohort has an increased incidence of substance abuse, the frequency of problems among elderly persons is expected to increase as well. The trend is already occurring: Grant et al. (2004) con-

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trasted alcohol abuse prevalence rates from two comparable national surveys, one done in 1991–1992 and the other in 2001–2002, and found a 4.8-fold increase in the rate of alcohol abuse in people age 65 and older, from 0.25% in 1991–1992 to 1.21% in 2001–2002. All studies find that men are much more likely to be problem drinkers than are women, and several patterns of relation to age at onset have been identified. Most elderly alcoholic patients began drinking in young adulthood, but a significant proportion (up to 30%) do not develop a problem with alcohol until late life.

Risk Factors Risk factors for development of alcohol abuse or dependency in late life have been difficult to pin down, but one survey (Moos et al. 2005) found that increased health problems in elderly individuals predicted reduced alcohol consumption but more drinking problems. The authors stated, “Older adults with several health problems who consume more alcohol are at elevated risk for drinking problems and should be targeted for brief interventions to help them curtail their drinking” (p. 49).

Diagnostic Criteria DSM-IV-TR distinguishes substance (alcohol) dependence, which is defined in Table 8–5, from the generally less severe syndrome of substance (alcohol) abuse, which is defined in Table 8–6.

Associated Psychiatric Conditions Besides intoxication and withdrawal, the major mental syndromes associated with alcohol abuse and dependence in the elderly are cognitive impairment and depression. Cognitive impairment severe enough to meet DSM-IV-TR criteria for dementia is common in active elderly drinkers but typically resolves during the first few weeks of abstinence as the acute effects of intoxication, poor nutrition, compromised liver function, and alcohol-induced mood changes diminish. The proper diagnosis of cognitive deficits that persist in the sober elderly alcoholic person may be challenging, but in clinical practice, these deficits are often attributed to varying combinations of age-associated memory impairment, Korsakoff-type amnesia (i.e., isolated short-term mem-

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Table 8–5. Summary of DSM-IV-TR criteria for substance dependence A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period: (1) tolerance, as defined by either of the following: (a) a need for markedly increased amounts of the substance to achieve intoxication or desired effect (b) markedly diminished effect with continued use of the same amount of the substance (2) withdrawal, as manifested by either of the following: (a) the characteristic withdrawal syndrome for the substance (b) the same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms (3) the substance is often taken in larger amounts or over a longer period than was intended (4) there is a persistent desire or unsuccessful efforts to cut down or control substance use (5) a great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects (6) important social, occupational, or recreational activities are given up or reduced because of substance use (7) the substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

ory deficit), and underlying focal or diffuse vascular and/or degenerative brain disease. Oslin and colleagues (1998) reviewed the literature on this topic and proposed a set of research diagnostic criteria for “alcohol-related dementia” (see Table 8–7), which they then validated in a later study of 192 institutionalized veterans (Oslin and Cary 2003). The 10.1% of the veterans with dementia who met criteria for alcohol-related dementia were younger (mean age=66.8 years) than those with Alzheimer’s disease, vascular dementia, or mixed dementia (mean age= 74.7, 74.3, and 73.2 years, respectively)

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Table 8–6. Summary of DSM-IV-TR criteria for substance abuse A.

B.

A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period: (1) recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (2) recurrent substance use in situations in which it is physically hazardous (3) recurrent substance-related legal problems (4) continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance The symptoms have never met the criteria for substance dependence for this class of substance.

Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

and, unlike subjects with Alzheimer’s disease, vascular dementia, or mixed dementia, did not show declines in cognitive or physical functioning over a 24month follow-up period, during which they were abstinent from alcohol. The relation between depressive symptoms and syndromes and alcohol use and abuse is similarly complex. However, it is well established that depressive symptoms are usually self-limited and spontaneously resolve if the elderly individual is able to abstain for 3–4 weeks; persistent depressive symptoms should be regarded as not directly related to the alcohol problem. Factors that predict persistent depression include poor social support, major life problems (both of which may be indirect effects of alcohol abuse), a history of depression or suicidality, and a family history of depression (Atkinson 1999).

Assessment Accurate histories of alcohol use in adults can often be augmented by embedding alcohol-related questions in the context of a general interview about health behaviors. Several short questionnaires—for example, the CAGE Questionnaire (Buchsbaum et al. 1992), the Michigan Alcoholism Screening Test—Geriatric Version (Blow et al. 1992), the Alcohol Use Disorders Identification Test (AUDIT; Saunders et al. 1993), and the five-item AUDIT-5

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Table 8–7. Classification of probable alcohol-related dementia (ARD) A.

Criteria for the clinical diagnosis of probable ARD include the following: 1. A clinical diagnosis of dementia at least 60 days after the last exposure to alcohol 2. Significant alcohol use, as defined by a minimum average of 35 standard drinks per week for men, and 28 for women, for a period greater than 5 years. The period of significant alcohol use must occur within 3 years of the initial onset of cognitive deficits. B. The diagnosis of ARD is supported by the presence of any of the following: 1. Alcohol-related hepatic, pancreatic, gastrointestinal, cardiovascular, or renal disease; that is, other end-organ damage 2. Ataxia or peripheral sensory polyneuropathy (not attributable to other specific causes) 3. Beyond 60 days of abstinence, the cognitive impairment stabilizes or improves. 4. After 60 days of abstinence, any neuroimaging evidence of ventricular or sulcal dilatation improves. 5. Neuroimaging evidence of cerebellar atrophy, especially of the vermis C. The following clinical features cast doubt on the diagnosis of ARD: 1. The presence of language impairment, especially dysnomia or anomia 2. The presence of focal neurological signs or symptoms (except ataxia or peripheral sensory polyneuropathy) 3. Neuroimaging evidence of cortical or subcortical infarction, subdural hematoma, or other focal brain pathology 4. Elevated Hachinski Ischemia Scale score D. Clinical features that neither are supportive nor cast doubt on the diagnosis of ARD include 1. Neuroimaging evidence of cortical atrophy 2. The presence of periventricular or deep white-matter lesions on neuroimaging, in the absence of focal infarct(s) Source. Adapted from Oslin and Cary 2003; Oslin et al. 1998.

(Philpot et al. 2003)—have been used to screen for problematic alcohol use. Conigliaro and colleagues (2000) found each of these instruments to have shortcomings when used in an elderly primary care population, and O’Connell et al. (2004) reported that the CAGE Questionnaire “performed poorly

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in psychiatric populations” but were more enthusiastic about the AUDIT-5, which, they stated, “may prove more useful in older people with psychiatric illness.”

Treatment—Brief Counseling and Psychotherapy Simple advice and counseling provided by primary care physicians have been shown to be effective in reducing problem drinking among high-risk (i.e., heavy-drinking) older adults (Fleming et al. 1999). In this study, two 10- to 15-minute counseling sessions resulted in a 34% reduction in 7-day alcohol use, 74% reduction in mean number of binge-drinking episodes, and 62% reduction in the percentage of patients drinking more than 21 drinks per week in the intervention group compared with the control group. The research literature generally suggests that treatment of established alcohol abuse and dependence in the elderly follows principles appropriate for young and middleaged adults and depends on the severity of the problem, the financial and social resources of the patient, and the patient’s motivation. Combinations of individual and group counseling, treatment of associated physical and mental conditions, and referral to outpatient, partial hospital, and inpatient programs can be expected to result in outcomes as good as or better than in younger individuals.

Treatment—Pharmacology Oslin and associates (1997) studied a group of older veterans ages 50–70 years in a double-blind, placebo-controlled randomized trial of naltrexone (50 mg/ day). The results were similar to those found with middle-aged adults: no improvement was seen in total abstinence, but half as many naltrexone-treated subjects relapsed to significant drinking compared with those who received placebo. The medication was well tolerated and had few side effects beyond nausea and dizziness. Acamprosate (calcium acetylhomotaurinate) is the newest pharmacological agent approved for the treatment of alcoholism. It is a derivative of the essential amino acid taurine and is structurally similar to GABA. Acamprosate is believed to enhance GABA neurotransmission and interfere with glutamate action at the N-methyl-D-aspartate receptor. Bouza and colleagues (2004) reviewed the research literature, which does not include any studies in the elderly, and concluded that acamprosate was effective as adjuvant treatment

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for alcohol dependence in adults and “appears to be especially useful in a therapeutic approach targeted at achieving abstinence” (p. 811). Side effects are minimal and include diarrhea, headaches, nausea, and pruritus. Disulfiram is the best-studied agent for promoting abstinence but is seldom used in elderly patients because of the risks of serious adverse reactions.

Other Psychoactive Substance Abuse and Dependence Epidemiology Abuse and dependence (as defined in DSM-IV-TR) involving substances other than alcohol appear to be quite rare in elderly individuals, but a prospective, blinded observational study of patients age 60 years or older who presented to a large urban emergency department over a 6-month period found that 2% of these patients had positive urine test results for cocaine (Rivers et al. 2004). Cocaine-positive patients were older, more frequently male, and more than five times as likely to have alcohol or drug abuse diagnoses as those with negative urine test results. This rate is three times higher than the 0.6% rate for all illicit drug use in this age group estimated by the National Household Survey on Drug Abuse (Substance Abuse and Mental Health Services Administration 2001) and suggests that official surveys may underestimate the actual prevalence of illicit drug use among the elderly. More typical findings emerged from a study of 100 elderly patients hospitalized for substance abuse: female sex was a risk factor for drug dependence, almost all cases involved sedative-hypnotics (primarily benzodiazepines), and physical health problems involving chronic pain were common (Finlayson and Davis 1994). This extreme version of a pattern of misuse has been termed nonmedical use and is defined as use of pain relievers, tranquilizers, stimulants, or sedatives that were not prescribed for the individual, or use of the drug only for the experience or feeling it caused (Zarba et al. 2005). According to a study by Zarba et al. (2005), such use among those 65 or older declines in comparison to those ages 50–64, but the likelihood increases among those who smoke cigarettes and drink alcohol and is highest among older Americans who smoke, drink, and use cannabis. The authors interpreted this finding as “carrying habits into old age” because the association between cannabis use and other drug

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abuse is also seen in young people. Other studies suggest that drug misuse could affect as many as 14%–25% of elderly outpatients seen in psychiatric settings (Jinks and Raschko 1990; Whitcup and Miller 1987). Medications that are not in themselves psychoactive, and therefore not usually thought of as abusable, may pose problems when they are combined with addicting substances. In this regard, acetaminophen-containing compounds, such as hydrocodone bitartrate–acetaminophen preparations. are of particular concern because of renal (Elseviers and De Broe 1998) and hepatic (McClain et al. 1999) toxicity. Hepatic damage from long-term use may be severe; one author of this book (J.E.S.) has consulted on several cases in which liver transplantation was necessitated by addiction to opioid-acetaminophen preparations.

Common Patterns of Abuse Table 8–8 lists drugs that are abused or misused by elderly patients and that should be inquired about in any suspect cases. In addition to simple overuse or underuse of prescribed and over-the-counter drugs, the clinician should inquire about timing of drug ingestions, because significant problems could arise from combining several agents in the following list: • • •

Benzodiazepine anxiolytics and antihistamines (additive sedation) Narcotic analgesics and antihistamines (additive sedation, constipation) Decongestants and caffeine (additive stimulation)

Distinguishing Use From Abuse Distinguishing use from abuse is difficult in any age group, but it is particularly challenging in elderly patients, which may partially explain why so many cases—more than 95% in one study (McInnes and Powell 1994)—are overlooked by physicians. Several of the factors discussed earlier regarding the negative effects of alcohol apply here as well: 1) adverse consequences of medication misuse such as falls, burns, generalized weakness, and sleep disturbance may be misattributed to other medical conditions or may not be reported because of age-related memory impairment exacerbated by the effects of the abused substance itself; 2) obvious mental status changes due to medication abuse (e.g., somnolence, depression, poor attention and concentration) may be ascribed to other causes (age, vascular or degenerative dementia, functional

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Table 8–8. Psychoactive substances abused by elderly patients Cold preparations containing anticholinergic antihistamines Chlorpheniramine Diphenhydramine Cold preparations containing stimulating sympathomimetics Ephedrine Phenylephrine Phenylpropanolamine Pseudoephedrine Narcotic analgesics Codeine Oxycodone Propoxyphene Nonnarcotic analgesics Acetaminophen Aspirin Other nonsteroidal anti-inflammatory agents Over-the-counter products containing caffeine or alcohol Sedative-hypnotics Barbiturates Benzodiazepines Chloral hydrate Over-the-counter antihistamines

mood disorder); and 3) other negative consequences of substance abuse may be disregarded entirely (e.g., symptom breakthrough caused by skipped doses of medications prescribed for chronic physical illness, such as congestive heart failure) or may be recognized but inappropriately considered an acceptable side effect of or adverse reaction to an otherwise effective medication regimen.

Treatment The key to treatment of substance abuse in elderly patients is preventing the problem in the first place; Table 8–9 lists factors that Juergens (1994) recommends physicians consider before prescribing potentially addictive medica-

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tions to elderly patients. Recognition of the existence of a substance abuse problem and the necessity of its treatment is also important: Brennan and colleagues (2001) found that fewer than 25% of elderly Medicare beneficiaries whose substance abuse had been identified in the hospital obtained outpatient treatment in the 4 years following hospital discharge. These researchers suggest that treating professionals need to take an active role in follow-up with these patients. Once substance abuse or dependence has been identified and acknowledged, the specific approach is dictated by clinical circumstances. Detoxification in the hospital is often the first step and should be considered whenever drug effects are obvious and the precise identity of the drugs and their dosages cannot be reliably ascertained. After detoxification, communitybased programs that incorporate home visits, individual and family counseling, recommendations for medication changes, and involvement in a peer support or education group have been shown to be effective (Brymer and Rusnell 2000) in reducing misuse of prescription medications. The clinician should attempt to enlist the spouse, other family members, the patient’s other physicians, and, when possible, the local pharmacist to help maintain surveillance and control of availability of substances. Sponsors of nursing homes and administrators at retirement hotels are often willing and able to assist in this manner as well, and a firm therapeutic alliance with the patient, in the context of which are discussed the patient’s fears that his or her real or imagined symptoms will go untreated if abused substances are not available, can be extremely important and may in itself obviate the need for specific intervention.

Sexual Dysfunction Sexual Dysfunction Versus Normal Aging Changes In general, the diagnosis of sexual dysfunction is based on reduced function in one or more of the first three phases of the sexual response cycle: 1. The desire phase (DSM-IV-TR hypoactive sexual desire disorder) 2. The excitement phase (DSM-IV-TR male erectile disorder, female sexual arousal disorder) 3. Orgasm (DSM-IV-TR male or female orgasmic disorder)

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Table 8–9. Factors to consider before prescribing potentially addictive substances for elderly patients Do the diagnosis, distress, and disability warrant the drug use? Have appropriate nonpharmacological therapies been used when indicated? Have pharmacological agents with less potential for long-term problems and dependence been used if appropriate (e.g., buspirone hydrochloride for anxiety or nonopioid analgesics for pain)? Is the drug yielding an acceptable therapeutic response with use of appropriate doses (often lower in elderly than in younger patients), and, if not, have the diagnosis and treatment been reconsidered? Has the patient had other drug or alcohol dependence or abuse problems in the past (a major relative contraindication to use of addictive drugs)? Do any findings suggest addiction to the prescribed drug (e.g., hoarding of drugs, uncontrolled dose escalation, or obtaining drugs from multiple physicians)? Is other drug-related impairment evident (e.g., memory or psychomotor disturbance)? Can a family member or significant other confirm the effectiveness of the drug as well as the absence of impairment and addiction? Would tapering the dose of the drug (after an appropriate trial) help determine whether problems are related to the drug or whether further treatment is needed? Source. Adapted from Juergens SM: “Prescription Drug Dependence Among Elderly Persons.” Mayo Clinic Proceedings 69:1215–1217, 1994.

Because normal aging is associated with reduced function in all three areas, particularly in men, diagnosis of the above sexual dysfunctions in elderly patients requires that the clinician take normal aging changes into account. The Massachusetts Male Aging Study found that the probability of complete erectile dysfunction tripled from 5% to 15%, and that of moderate erectile dysfunction doubled from 17% to 34%, between ages 40 and 70 years. The probability of minimal erectile dysfunction was constant at 17% throughout the age range, however (Levine 2000). This study also surveyed changes in male sexual activity over a 9-year follow-up period. The investigators reported consistent declines in frequency of intercourse, frequency of erections, sexual desire, and satisfaction with sex in all age groups, but the largest declines were in men ages 60–70 at entry into the study (Araujo et al. 2004). Similar results were found in the Global Study of Sexual Attitudes and Behaviors (Laumann et al. 2005). These data indicated that as men age, they should expect that sexual desire will gradually diminish, sexual arousal will take more time and more stimulation, erections

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will be softer and not last as long, ejaculation may be diminished in vigor, and orgasm may not occur during every episode of intercourse. Because of the natural lengthening of the plateau phase of arousal, premature ejaculation is somewhat less likely to occur late in life but can occur in men at any age. Despite these age-related changes, in one survey, almost 74% of the married men older than 60 reported being sexually active, with the percentage declining to 43% in men older than 75 (Diokno et al. 1990). Women may notice several changes with advancing age: reduced desire for sex, less vaginal lubrication (which can contribute to the development of the sexual pain disorders dyspareunia and vaginismus), reduced clitoral and breast sensitivity, and reduced intensity of the muscular phase of orgasm (due to reduced perineal muscle tone). The ability to have orgasm per se is more inconsistently affected, with some reporting increased ease of orgasm with age. Despite these possible problems, the Global Study of Sexual Attitudes and Behaviors found that increased age among women was not reliably associated with any sexual dysfunction except lubrication difficulties (Laumann et al. 2005). This relative “immunity” to age-related problems notwithstanding, the reported prevalence of sexual activity in older women is somewhat lower than in elderly men and appears to be influenced more by the availability of a secure partner (Mooradian and Greiff 1990).

Sexual Dysfunction and Physical Illness One of the most common causes of physiological erectile dysfunction in men is prostate surgery. Perineal prostatectomy is the most likely cause of impotence, followed by retropubic prostatectomy and transurethral prostatectomy. Nevertheless, about two-thirds of men remain potent after retropubic procedures. Erectile dysfunction is also strongly associated with hypertension, hyperlipidemia, diabetes mellitus, ischemic heart disease, peripheral vascular disease, and several other conditions, almost all of which increase in prevalence with age. Seftel et al. (2004) analyzed medical records of more than 272,000 men with erectile dysfunction and found that more than 60% of those ages 65–85 had hypertension, more than 50% had hyperlipidemia, about 25% had diabetes, and 6% had depression. About 13% had the triad of hypertension, hyperlipidemia, and diabetes. The authors concluded that “ED [erectile dysfunction] is a pathophysiological event that shares common

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etiological factors with hypertension, hyperlipidemia, diabetes and depression” (p. 2344) and advised physicians to view erectile dysfunction as a clinical marker for detecting and treating these conditions at an early stage.

Sexual Dysfunction and Medications The worst drug offenders vis-à-vis sexual dysfunction appear to be antihypertensive medications, particularly guanethidine, methyldopa, clonidine, and the β-blockers, all of which can impair erectile and ejaculatory function. Psychopharmacological agents, including cyclic antidepressants and neuroleptics, also have been implicated in erectile and ejaculatory dysfunction, and selective serotonin reuptake inhibitors (see Chapter 4, “Mood Disorders—Treatment”), monoamine oxidase inhibitors, and venlafaxine can also cause anorgasmia in men and women. Sexual side effects of psychopharmacological agents are common in patients with severe mental illness and are a major cause of noncompliance; often, patients are reluctant to discuss these side effects with their doctors (K.P. Rosenberg et al. 2003). Trazodone has been reported in a relatively small number of patients to cause painful and prolonged erection (priapism) that can require surgical reduction and result in permanent damage. (Adverse medication effects are discussed more fully in Chapter 4.) Whether age is a risk factor for these adverse effects is not clear, but a complete sexual history should address the potential contribution of these agents, and dosage adjustment or replacement should be attempted before more specific therapy is prescribed.

Treatment Adjustment of offending medications, treatment of underlying physical and mental illnesses, and optimization of general health are the treatments of first choice for diminished libido and anorgasmia in elderly men and women. When these steps are ineffective, treatment with testosterone may be effective. According to a review by Bolour and Braunstein (2005), testosterone therapy in the low-dose regimens is efficacious for the treatment of low libido in postmenopausal women who are adequately estrogenized. Clinical studies support the idea that androgens stimulate sexual desire and satisfaction and demonstrate improved sexual enjoyment and well being in women who switched from estrogen alone to estrogen–androgen therapy. (p. 406)

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The results of testosterone therapy in elderly men are somewhat more complex. Studies in men with hypogonadism (Steidle et al. 2003) and erectile dysfunction (Jain et al. 2000) have shown improvements in libido and erectile function with testosterone therapy, but Gray et al. (2005), studying healthy elderly men with experimentally manipulated testosterone levels, found improved libido only in subjects who received high doses of testosterone and who were sexually active at the beginning of the study. Total testosterone levels were significantly correlated with changes in overall sexual function, waking erections, and libido but not correlated with changes in spontaneous erections, intercourse frequency, or masturbation frequency. The authors concluded “that testosterone supplementation in older men can dose-dependently improve...libido and erectile function” (p. 3845). Testosterone therapy for sexual dysfunction is not without risks, especially in men with incipient prostate cancer, and is probably not within the range of expertise of the typical geriatric psychiatrist. Treatment of erectile dysfunction has been revolutionized by the phosphodiesterase-5 inhibitors, including sildenafil, vardenafil, and tadalafil. All seem to be safe and generally effective in elderly men (Salonia et al. 2005). Hypogonadism, cigarette smoking, and more severe erectile dysfunction at baseline predict a poor response to sildenafil (Park et al. 2005), but testosterone replacement enhances the response, at least in diabetic men (Kalinchenko et al. 2003), and is likely to be effective in hypogonadal men as well. Smoking cessation, although not studied, is another promising approach to suboptimal response to sildenafil and probably vardenafil and tadalafil as well. In addition to the precautions listed by the manufacturers, recent reports of the new onset of nonarteritic anterior ischemic optic neuropathy (NAION), a type of blindness in men taking phosphodiesterase-5 inhibitors, warrant additional caution in those with preexisting NAION. Other risk factors are thought to include tightly bundled nerves and blood vessels in the back of the eye (which are apparently detectable via ophthalmoscopic examination), high blood pressure, high cholesterol, and diabetes, all conditions common among elderly men. Second-line treatment options for erectile dysfunction include intracavernosal self-injection, a procedure that was the most common medical therapy for erectile dysfunction before the approval of sildenafil. The patient injects a vasoactive drug, such as alprostadil or prostaglandin E1, directly into the penis to relax cavernous and arterial smooth muscle. Although response rates of up to

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85% have been reported, the rate of treatment discontinuation is high, and side effects include prolonged erection, penile pain, penile fibrosis, and hematoma or ecchymosis. Because of the high dropout rate, a transurethral preparation of alprostadil was developed that does not require needle injections into the penis. In the medicated urethral system for erection, the patient uses a polypropylene applicator to insert a semisolid pellet containing alprostadil into the urethra. The medicated urethral system for erection produced erections sufficient for intercourse in 65.9% of patients, and efficacy was similar regardless of age or the cause of erectile dysfunction. The most common complaint was mild penile pain, which was reported after 10.8% of alprostadil administrations in the home setting and by 32.7% of men (Padma-Nathan et al. 1997). The third-line intervention for treatment-resistant erectile dysfunction is surgical implantation of a penile prosthesis. The three types of implants are semirigid, positionable, and multicomponent inflatable. Each has advantages and disadvantages, and consultation with a urologist experienced with these devices is recommended. Treatment of erectile dysfunction is summarized in Table 8–10.

Psychiatric Illness Related to a General Medical Condition Personality Change Due to a General Medical Condition Although personality changes are common in Alzheimer’s disease and vascular dementia and nearly universal in frontotemporal dementia, personality change due to a general medical condition as defined in DSM-IV-TR is relatively rare. DSM-IV-TR criteria for this syndrome are summarized in Table 8–11; note that the presence of delirium or dementia rules out this condition. Koponen et al. (2002) diagnosed definite organic personality syndrome (by DSM-III-R [American Psychiatric Association 1987] criteria) in 9 of 60 patients evaluated an average of 30 years after sustaining head trauma; another 5 had “subclinical” organic personality syndrome. Definite personality disorder that would have met DSM-IV-TR’s broader criteria for personality change due to a general medical condition was diagnosed in another 14, for an inclusive total of 28 of 60, or 47% of the sample. This prevalence is similar to that reported by other investigators (Franulic et al. 2000).

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Table 8–10.

Assessment and treatment of erectile dysfunction

I. Diagnostic process A. Sexual, medical, and psychosocial history B. Physical examination C. Laboratory tests II. Consultation with patient and partner A. Review findings B. Determine patient and partner preferences C. Educate about erectile dysfunction III. Initial intervention A. Change or discontinue offending medications B. Replace hormones C. Modify lifestyle D. Corrective surgery IV. First-line therapy, if above is ineffective A. Oral agents (sildenafil, vardenafil, tadalafil) B. Vacuum constriction devices C. Couples therapy V. Second-line therapy, if above is ineffective A. Intraurethral alprostadil B. Intracavernosal self-injection (alprostadil, prostaglandin E1) VI. Third-line therapy, if above is ineffective A. Surgical prosthesis Source. Adapted from Process of Care Consensus Panel: “Position Paper: The Process of Care Model for Evaluation and Treatment of Erectile Dysfunction.” International Journal of Impotence Research 11:59–74, 1999.

Personality change due to a general medical condition without cognitive impairment (per DSM-IV-TR) has also been described in Sydenham’s chorea and in two prefrontal disconnection syndromes: 1) orbitofrontal syndrome, in which limbic structures and orbital prefrontal cortex are damaged by, for example, trauma, stroke, or tumor, and in which irritability, disinhibition, and mood elevation are common; and 2) anterior cingulate syndrome, in which the circuit connecting the anterior cingulate gyrus and ventral striatum is involved, and in which apathy is common (Mega and Cummings 1994). Although orbitofrontal syndromes may be classified as without cognitive def-

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Table 8–11. Summary of DSM-IV-TR diagnostic criteria for personality change due to a general medical condition A.

A persistent personality disturbance that represents a change from the individual’s previous characteristic personality pattern. B. There is evidence from the history, physical examination, or laboratory findings that the disturbance is the direct physiological consequence of a general medical condition. C. The disturbance is not better accounted for by another mental disorder. D. The disturbance does not occur exclusively during the course of a delirium. E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. Source. Adapted from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000. Copyright © 2000, American Psychiatric Association. Used with permission.

icit by DSM-IV-TR criteria, impairments in everyday executive functions are common (e.g., poor planning, monitoring, or completion of complex tasks), reflecting the lability, impulsivity, and distractibility that characterize this disorder. These deficits may be less apparent on structured neurological or neuropsychological examination than in natural problem-solving situations. If midline brain structures are involved (orbitomedial frontal syndrome), memory deficits and problems with inhibition may be observed on careful testing. Beneficial effects of behavioral interventions have been reported in some patients with frontal lobe impairment; retraining of cognitive strategies is emphasized in mildly impaired patients, whereas altering the environment to reduce the need for self-initiation is emphasized in more severely impaired patients (Sohlberg et al. 1993). In general, however, treatment of personality change due to a general medical condition is aimed at amelioration of the specific medical condition judged to be causative in each case.

Psychotic Disorder Due to a General Medical Condition Many general medical conditions have been identified as being capable of causing hallucinations or delusions. A review by Plotkin (1989) suggested that the most likely general medical causes of delusions in elderly patients are cerebral lesions associated with stroke or trauma, particularly if the temporal lobe and limbic structures are affected. Pearlson (2000) argued that multiple infarctions

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that do not necessarily cause dementia (“multi-infarct disease”) are associated with late-life onset of schizophrenia. Whether this syndrome should be thought of as a psychotic disorder secondary to a general medical condition or as lateonset schizophrenia cannot be determined from the available data. Some specific delusion-like false beliefs also have been observed in patients with damage to the occipital lobe (denial of blindness) and parietal lobe (denial of hemiparesis). Blindness and deafness have been associated with visual and auditory hallucinations, and complex partial seizures have been associated with olfactory hallucinations and delusions. Psychosis has been reported as a consequence of vitamin B12 deficiency, meningioma, and antiretroviral therapy. Alcoholic hallucinosis is a specific syndrome that occurs within 2–3 days after termination of drinking. In this syndrome, frightening auditory or visual, sometimes tactile, hallucinations occur in an otherwise clear sensorium and are typically accompanied by persecutory delusions. The differential diagnosis of psychotic disorder due to a general medical condition includes functional psychosis, dementia, and delirium. In most cases, a complete medical evaluation will identify the general medical condition judged to be etiologically related to the disturbance, allowing functional psychosis to be ruled out. In dementia, cognitive disturbance will be present, and in delirium, prominent deficits in attention and concentration, occasional frank clouding of consciousness, and variable cognitive disturbance will be seen. Inasmuch as sensory deficits have been cited as contributing factors in the development of functional psychosis in elderly patients, the correct diagnosis of psychosis with sensory loss may be difficult to establish with confidence. Treatment of psychotic disorder due to a general medical condition is very similar to treatment of mood disorder due to a general medical condition; that is, potential endogenous causes are appropriately treated, and then therapy for residual symptoms is administered according to the guidelines for treatment of functional psychosis described in Chapter 7 (“Anxiety Disorders and Late-Onset Psychosis”).

Chronic Pain Half of the community-dwelling elderly and 60%–80% of those living in nursing homes have been reported to have persistent pain complaints (Schneider 2005); these complaints can be exacerbated by depression and

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anxiety and can be applied consciously or unconsciously as a means to gain attention and care. Therefore, proper management of chronic pain entails assessment and manipulation of social support networks, recognition and treatment of associated depressive and anxiety syndromes, physical therapy, and pharmacological management (Schneider 2005). Acetaminophen and tramadol, nonsteroidal anti-inflammatory drugs (NSAIDs, particularly the selective cyclooxygenase-2 [COX-2] inhibitors), topical agents, and opioids are the mainstay of pharmacological treatment of chronic pain. Tramadol is a weak agonist of the mu opiate receptor and is indicated for treatment of moderate to moderately severe pain. It has weak opiate-like effects, blocks reuptake of norepinephrine and serotonin, may have antidepressant properties (Rojas-Corrales et al. 2002), and has been reported to produce serotonin syndrome in combination with selective serotonin reuptake inhibitors. Some clinicians are reluctant to prescribe chronic opioids because of the fear of addiction, despite evidence that the great majority of individuals who take opioids chronically for pain do not become addicted to these drugs (even though physical dependency may develop) and evidence that increased age is associated with reduced rate of development of tolerance to opioid medications (Buntin-Mushock et al. 2005). Duloxetine, a mixed norepinephrine and serotonin reuptake blocker, has been approved for the treatment of chronic pain due to diabetic neuropathy, and evidence indicates that other mixed norepinephrine- and serotonin-enhancing agents are also effective for neuropathic pain (Bomholt et al. 2005). Some elderly patients can also benefit from behaviorally oriented pain management training, including relaxation techniques (e.g., Ersek et al. 2003). Patients with no significant memory problems, with some insight into the synergistic effects of mood state on pain, are good candidates for such interventions. It is not surprising that evidence suggests that elderly patients manage chronic pain quite well with available agents and that chronic pain is not a major determinant of the use of medical services (Cook and Thomas 1994). However, when chronic pain is combined with depression, use of medical services is increased, and persistent limitations in activities because of pain are likely (Moosey and Gallagher 2004). Treatment of chronic pain in patients with dementia poses several problems, not the least of which is the challenge of assessing pain and its response to treatment when the patient is unable to

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provide reliable information about the pain. Several visual analogue scales have been shown to be useful in this situation (Pautex et al. 2005), and Rubey (2005) provides a good overview of chronic pain management in elderly patients with dementia.

Influence of Aging on Disorders of Early Onset Mood Disorders As described in Chapter 3 (“Mood Disorders—Diagnosis”), some differences in presentation of unipolar major depression in late life have been reported. Elderly patients with bipolar disorder have been reported to have generally less severe symptoms and less religiosity (Broadhead and Jacoby 1990), more frequent and longer episodes, and more rapid cycling (Cutler and Post 1982) compared with younger bipolar patients. However, Sajatovic et al. (2005) found few differences in clinical characteristics between elderly patients with early-onset and elderly patients with late-onset (i.e., after age 50) bipolar disorder, except that those with late-onset bipolar disorder were 2.8 times more likely to be female.

Schizophrenia Positive symptoms tend to diminish in aging schizophrenic patients, whereas negative symptoms are more variable. Patients with schizophrenia have more age-related decline in cognitive function than do age-matched control subjects but much less than do patients with Alzheimer’s disease (Friedman et al. 2001). Bowie et al. (2005) reported that verbal productivity declines with age and is correlated with worsening in Mini-Mental State Examination scores. Kosmidis et al. (2005) used a word-list-generating task to distinguish phonemic word fluency from semantic word fluency (semantic=generate words in a category—e.g., animals; phonemic= generate words starting with a particular letter—e.g., f) and found that the decline in elderly schizophrenic patients was in phonemic and not semantic fluency. Bowie et al. (2005) concluded that “thought disorder does not appear to ‘burn out’ in chronic schizophrenia” (p. 794). Some geriatric patients with schizophrenia may lose the skills necessary to report symptoms, leading to the impression that their clinical status is improving, but the trend among elderly schizophrenic patients seems to be toward improved social adaptation (Cohen et al. 2000).

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Personality Disorders Agronin and Maletta (2000) reviewed the literature on personality disorders in late life and found not more than “several dozen articles”; most were crosssectional prevalence studies in community and treatment populations that used variable diagnostic criteria and inconsistent methodology, thereby allowing few reliable generalizations. Studies that used structured interviews suggested that the prevalence of personality disorders tends to decline with age in community-dwelling subjects. However, personality disorders are as prevalent among elderly patients in geropsychiatric inpatient units as in a young adult comparison sample (Ames and Molinari 1994; Molinari et al. 1994). Studies typically report a higher prevalence of DSM-IV-TR Cluster C personality disorders (avoidant, dependent, and obsessive-compulsive) among older adults than either Cluster A disorders (paranoid, schizoid, and schizotypal) or Cluster B disorders (antisocial, borderline, histrionic, and narcissistic) (Kunik et al. 1994). Personality disorder as a comorbid condition appears to be significantly more common in patients hospitalized for depression than in those hospitalized for disorders of cognition (Kunik et al. 1994), and older depressed patients with personality disorder have more persistent declines in function and quality of life despite treatment (Abrams et al. 2001). Regarding the natural history of personality disorders, Agronin and Maletta (2000) found that published studies generally agreed with the prognostic scheme proposed by Solomon (1981), which claimed that individuals with PD [personality disorder] characterized by affective and behavioral lability (antisocial, borderline, histrionic, narcissistic, avoidant, and dependent) demonstrate less impulsivity and aggression and have a tendency to improve in late life, but with depression and hypochondriasis as common endpoints. On the other hand, individuals with PD characterized by overcontrol of affect and impulses (obsessive-compulsive, paranoid, schizoid, and schizotypal) either remain the same or worsen in late life, and demonstrate persistent characteristics of rigidity and suspiciousness. (p. 7)

A study by Engels et al. (2003), which found that “community residents in the oldest age group reported more schizoid and more obsessive-compulsive characteristics compared to one or more of the younger age groups (and)…older mental health patients showed more schizoid disorder characteristics and fewer high-energy disorder characteristics compared to one or

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more of the younger patient groups” (p. 447), provided further support for Solomon’s scheme. For an excellent overview of the effects of personality factors on mental disorders in later life, see Seidlitz (2001).

References Abrams RC, Alexopoulos GS, Spielman LA, et al: Personality disorder symptoms predict declines in global functioning and quality of life in elderly depressed patients. Am J Geriatr Psychiatry 9:67–71, 2001 Adams WL, Cox NS: Epidemiology of problem drinking among elderly people. Int J Addict 30:1693–1716, 1995 Agronin ME, Maletta G: Personality disorders in late life: understanding and overcoming the gap in research. Am J Geriatr Psychiatry 8:4–18, 2000 American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition. Washington, DC, American Psychiatric Association, 1980 American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, Revised. Washington, DC, American Psychiatric Association, 1987 American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000 American Sleep Disorders Association: The International Classification of Sleep Disorders: Diagnostic and Coding Manual, Revised. Rochester, MN, American Sleep Disorders Association, 1997 Ames A, Molinari V: Prevalence of personality disorders in community-living elderly. J Geriatr Psychiatry Neurol 7:189–194, 1994 Araujo AB, Mohr BA, McKinlay JB: Changes in sexual function in middle-aged and older men: longitudinal data from the Massachusetts Male Aging Study. J Am Geriatr Soc 52:1502–1509, 2004 Atkinson R: Depression, alcoholism and ageing: a brief review. Int J Geriatr Psychiatry 14:905–910, 1999 Blow FC, Brower KJ, Schulenberg JE, et al: The Michigan Alcoholism Screening Test— Geriatric Version (MAST-G): a new elderly specific screening instrument. Alcohol Clin Exp Res 16:1029–1034, 1992 Bolour S, Braunstein G: Testosterone therapy in women: a review. Int J Impot Res 17:399–408, 2005 Bomholt SF, Mikkelsen JD, Blackburn-Munro G: Antinociceptive effects of the antidepressants amitriptyline, duloxetine, mirtazapine and citalopram in animal models of acute, persistent and neuropathic pain. Neuropharmacology 48:252–263, 2005

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Bouza C, Angeles M, Munoz A, et al: Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: a systematic review. Addiction 99:811– 828, 2004 Bowie CR, Tsapelas I, Friedman J, et al: The longitudinal course of thought disorder in geriatric patients with chronic schizophrenia. Am J Psychiatry 162:793–795, 2005 Brennan PL, Kagay CR, Geppert JJ, et al: Predictors and outcomes of outpatient mental health care: a 4-year prospective study of elderly Medicare patients with substance use disorders. Med Care 39:39–49, 2001 Broadhead J, Jacoby R: Mania in old age: a first prospective study. Int J Geriatr Psychiatry 5:215–222, 1990 Brymer C, Rusnell I: Reducing substance dependence in elderly people: the side effects program. Can J Clin Pharmacol 7:161–166, 2000 Buchsbaum DG, Buchanan RG, Welsh J, et al: Screening for drinking disorders in the elderly using the CAGE Questionnaire. J Am Geriatr Soc 40:662–665, 1992 Buntin-Mushock C, Phillip L, Moriyama K, et al: Age-dependent opioid escalation in chronic pain patients. Anesth Analg 100:1740–1745, 2005 Cohen CI, Cohen GD, Blank K, et al: Schizophrenia and older adults: an overview: directions for research and policy. Am J Geriatr Psychiatry 8:19–28, 2000 Conigliaro J, Kraemer K, McNeil M: Screening and identification of older adults with alcohol problems in primary care. J Geriatr Psychiatry Neurol 13:106–114, 2000 Cook AJ, Thomas MR: Pain and the use of health services among the elderly. J Aging Health 6:155–172, 1994 Cutler NR, Post RM: Life course of illness in untreated manic-depressive patients. Compr Psychiatry 23:101–115, 1982 Diokno AC, Brown MB, Herzog AR: Sexual function in the elderly. Arch Intern Med 150:197–200, 1990 Elseviers MM, De Broe ME: Analgesic abuse in the elderly: renal sequelae and management. Drugs Aging 12:391–400, 1998 Engels GI, Duijsens IJ, Haringsma R, et al: Personality disorders in the elderly compared to four younger age groups: a cross-sectional study of community residents and mental health patients. J Personal Disord 17:447–459, 2003 Ersek M, Turner JA, McCurry SM, et al: Efficacy of a self-management group intervention for elderly persons with chronic pain. Clin J Pain 19:156–167, 2003 Finlayson RE, Davis LJ Jr: Prescription drug dependence in the elderly population: demographic and clinical features of 100 inpatients. Mayo Clin Proc 69:1137– 1145, 1994

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Fleming MF, Manwell LB, Barry KL, et al: Brief physician advice for alcohol problems in older adults: a randomized community-based trial. J Fam Pract 48:378–384, 1999 Franulic A, Horta E, Maturana R, et al: Organic personality disorder after traumatic brain injury: cognitive, anatomic and psychosocial factors: a 6 month follow-up. Brain Inj 14:431–439, 2000 Friedman JI, Harvey PD, Coleman T, et al: Six-year follow-up study of cognitive and functional status across the lifespan in schizophrenia: a comparison with Alzheimer’s disease and normal aging. Am J Psychiatry 158:1441–1448, 2001 Girault C, Muir JF, Mihaltan F, et al: Effects of repeated administration of zolpidem on sleep, diurnal and nocturnal respiratory function, vigilance, and physical performance in patients with COPD. Chest 110:1203–1211, 1996 Grant BF, Dawson DA, Stinson FS, et al: The 12-month prevalence and trends in DSM-IV alcohol abuse and dependence: United States, 1991–1992 and 2001– 2002. Drug Alcohol Depend 74:223–234, 2004 Gray PB, Singh AB, Woodhouse LJ, et al: Dose-dependent effects of testosterone on sexual function, mood, and visuospatial cognition in older men. J Clin Endocrinol Metab 90:3838–3846, 2005 Hedner J, Yaeche R, Emilien G, et al: Zaleplon shortens subjective sleep latency and improves subjective sleep quality in elderly patients with insomnia. The Zaleplon Clinical Investigator Study Group. Int J Geriatr Psychiatry 15:704–712, 2000 Jain P, Rademaker AW, McVary KT: Testosterone supplementation for erectile dysfunction: results of a meta-analysis. J Urol 164:371–375, 2000 Jinks MJ, Raschko RR: A profile of alcohol and prescription drug abuse in a high-risk community-based elderly population. DICP 24:971–975, 1990 Johnson I: Alcohol problems in old age: a review of recent epidemiological research. Int J Geriatr Psychiatry 15:575–581, 2000 Juergens SM: Prescription drug dependence among elderly persons. Mayo Clin Proc 69:1215–1217, 1994 Kalinchenko SY, Kozlov GI, Gontcharov NP, et al: Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone. Aging Male 6:94–99, 2003 Kaynak H, Kaynak D, Gozukirmizi E, et al: The effects of trazodone on sleep in patients treated with stimulant antidepressants. Sleep Med 5:15–20, 2004 Koponen S, Taiminen T, Portin R, et al: Axis I and II psychiatric disorders after traumatic brain injury: a 30-year follow-up study. Am J Psychiatry 159:1315–1321, 2002 Kosmidis MH, Bozikas VP, Vlahou CH, et al: Verbal fluency in institutionalized patients with schizophrenia: age-related performance decline. Psychiatry Res 134:233–240, 2005

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Kunik ME, Mulsant BH, Rifai AH, et al: Diagnostic rate of comorbid personality disorder in elderly psychiatric inpatients. Am J Psychiatry 151:603–605, 1994 Laumann EO, Nicolosi A, Glasser DB, et al: Sexual problems among women and men aged 40–80 y: prevalence and correlates identified in the Global Study of Sexual Attitudes and Behaviors. GSSAB Investigators’ Group. Int J Impot Res 17:39– 57, 2005 Levine LA: Diagnosis and treatment of erectile dysfunction. Am J Med 109 (suppl 9A):3S–12S, 2000 McClain CJ, Price S, Barve S, et al: Acetaminophen hepatotoxicity: an update. Curr Gastroenterol Rep 1:42–49, 1999 McInnes E, Powell J: Drug and alcohol referrals: are elderly substance abuse diagnoses and referrals being missed? BMJ 308:444–446, 1994 Mega MS, Cummings JL: Frontal-subcortical circuits and neuropsychiatric disorders (comments). J Neuropsychiatry Clin Neurosci 6:358–370, 1994 Molinari V, Ames A, Essa M: Prevalence of personality disorders in two geropsychiatric inpatient units. J Geriatr Psychiatry Neurol 7:209–215, 1994 Monane M: Insomnia in the elderly. J Clin Psychiatry 53(suppl):23–28, 1992 Mooradian AD, Greiff V: Sexuality in older women. Arch Intern Med 150:1033–1038, 1990 Moos RH, Brennan PL, Schutte KK, et al: Older adults’ health and changes in latelife drinking patterns. Aging Ment Health 9:49–59, 2005 Moosey JM, Gallagher RM: The longitudinal occurrence and impact of comorbid chronic pain and chronic depression over two years in continuing care retirement community residents. Pain Med 5:335–348, 2004 Morin CM, Kowatch RA, Barry T, et al: Cognitive-behavior therapy for late-life insomnia. J Consult Clin Psychol 61:137–146, 1993 National Institutes of Health: NIH State-of-the-Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults (final statement). August 18, 2005. Available at http://consensus.nih.gov/2005/ 2005InsomniaSOS026html.htm. Accessed September 25, 2005. O’Connell H, Chin AV, Hamilton F, et al: A systematic review of the utility of selfreport alcohol screening instruments in the elderly. Int J Geriatr Psychiatry 19:1074–1086, 2004 Oslin DW: Late-life alcoholism: issues relevant to the geriatric psychiatrist. Am J Geriatr Psychiatry 12:571–583, 2004 Oslin DW, Cary MS: Alcohol-related dementia: validation of diagnostic criteria. Am J Geriatr Psychiatry 11:441–447, 2003 Oslin D, Liberto JG, O’Brien J, et al: Naltrexone as an adjunctive treatment for older patients with alcohol dependence. Am J Geriatr Psychiatry 5:324–332, 1997

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Oslin D, Atkinson RM, Smith DM, et al: Alcohol related dementia: proposed clinical criteria. Int J Geriatr Psychiatry 13:203–212, 1998 Padma-Nathan H, Hellstrom WJ, Kaiser FE, et al, for the Medicated Urethral System for Erection (MUSE) Study Group: Treatment of men with erectile dysfunction with transurethral alprostadil. N Engl J Med 336:1–7, 1997 Park K, Ku JH, Kim SW, et al: Risk factors in predicting a poor response to sildenafil citrate in elderly men with erectile dysfunction. BJU Int 95:366–370, 2005 Pautex S, Herrmann F, Le Lous P, et al: Feasibility and reliability of four pain selfassessment scales and correlation with an observational rating scale in hospitalized elderly demented patients. J Gerontol A Biol Sci Med Sci 60:524–529, 2005 Pearlson GD: Late-life–onset psychoses, in The American Psychiatric Press Textbook of Geriatric Neuropsychiatry. Edited by Coffey CE, Cummings JL. Washington, DC, American Psychiatric Press, 2000, pp 329–346 Philpot M, Pearson N, Petratou V, et al: Screening for problem drinking in older people referred to a mental health service: a comparison of CAGE and AUDIT. Aging Ment Health 7:171–175, 2003 Plotkin DA: Organic delusional syndrome and organic hallucinosis, in Treatments of Psychiatric Disorders: A Task Force Report of the American Psychiatric Association. Washington, DC, American Psychiatric Association, 1989, pp 831–839 Riedel BW, Lichstein KL, Dwyer WO: Sleep compression and sleep education for older insomniacs: self-help versus therapist guidance. Psychol Aging 10:54–63, 1995 Rivers E, Shirazi E, Aurora T, et al: Cocaine use in elder patients presenting to an inner-city emergency department. Acad Emerg Med 1:874–877, 2004 Rojas-Corrales MO, Berrocoso E, Gibert-Rahola J, et al: Antidepressant-like effects of tramadol and other central analgesics with activity on monoamines reuptake, in helpless rats. Life Sci 72:143–152, 2002 Rosenberg KP, Bleiberg KL, Koscis J, et al: Survey of sexual side effects among severely mentally ill patients taking psychotropic medications: impact on compliance. J Sex Marital Ther 29:289–296, 2003 Rosenberg R, Caron J, Roth T, et al: An assessment of the efficacy and safety of eszopiclone in the treatment of transient insomnia in healthy adults. Sleep Med 6:15– 22, 2005 Rubey RN: Treatment of chronic pain in persons with dementia: an overview. Am J Alzheimers Dis Other Demen 20:12–20, 2005 Sajatovic M, Bingham CR, Campbell EA, et al: Bipolar disorder in older adult inpatients. J Nerv Ment Dis 193:417–419, 2005 Salonia A, Briganti A, Montorsi P, et al: Safety and tolerability of oral erectile dysfunction treatments in the elderly. Drugs Aging 22:323–338, 2005

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Saunders JB, Aasland OG, Babor TF, et al: Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons With Harmful Alcohol Consumption—II. Addiction 89:791–804, 1993 Scharf MB, Sachais BA: Sleep laboratory evaluation of the effects and efficacy of trazodone in depressed insomniac patients. J Clin Psychiatry 51(suppl):13–17, 1990 Schneider JP: Chronic pain management in older adults: with coxibs under fire, what now? Geriatrics 60:26–28, 30–31, 2005 Seftel AD, Sun P, Swindle R: The prevalence of hypertension, hyperlipidemia, diabetes mellitus and depression in men with erectile dysfunction. J Urol 171:2341–2345, 2004 Seidlitz L: Personality factors in mental disorders of later life. Am J Geriatr Psychiatry 9:8–21, 2001 Shaw SH, Curson H, Coquelin JP: A double-blind, comparative study of zolpidem and placebo in the treatment of insomnia in elderly psychiatric in-patients. J Int Med Res 20:150–161, 1992 Sohlberg MM, Mateer CA, Stuss DT: Contemporary approaches to the management of executive control dysfunction. J Head Trauma Rehabil 8:45–58, 1993 Solomon K: Personality disorders in the elderly, in Personality Disorders, Diagnosis, and Management. Edited by Lion JR. Baltimore, MD, Williams & Wilkins, 1981, pp 310–338 Steidle C, Schwartz S, Jacoby K, et al: AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab 88:2673–2681, 2003 Substance Abuse and Mental Health Services Administration: Illicit drug use, in National Household Survey on Drug Abuse, 2001. Available at: http:// oas.samhsa.gov/nhsda/2k1nhsda/vol1/chapter2.htm#2.age. Accessed February 28, 2006. Trevorrow T: Assessing sleep functioning in older adults, in Handbook of Assessment in Clinical Gerontology. Edited by Lichtenberg P. New York, Wiley, 1999, pp 331–350 Whitcup SM, Miller F: Unrecognized drug dependence in psychiatrically hospitalized elderly patients. J Am Geriatr Soc 35:297–301, 1987 Zammit GK, McNabb LJ, Caron J, et al: Efficacy and safety of eszopiclone across 6weeks of treatment for primary insomnia. Curr Med Res Opin 20:1979–1991, 2004 Zarba A, Storr CL, Wagner FA: Carrying habits into old age: prescription drug use without medical advice by older American adults. J Am Geriatr Soc 53:170–171, 2005

9 Competency and Related Forensic Issues

The issue of competency arises in many contexts involving cognitively im-

paired elderly individuals. Health care providers may question the patient’s ability to give informed consent for medical treatment or to make end-of-life decisions regarding resuscitation and life support. Attorneys may become concerned about future challenges to the provisions of wills, gifts, and trusts, and concerned friends or relatives may recommend that durable powers of attorney be executed or may contemplate guardianship or conservatorship. In this chapter, we address the specific social contexts in which the geriatric psychiatrist is most likely to perform a contemporaneous or retrospective evaluation of competency. The chapter covers decisional competency, undue influence, competency to care for oneself and manage one’s finances, expert consultation and testimony on competency, determination of competency to drive, and elder abuse. We first discuss decisional competency, or the ability to make an acceptably rational and self-interested single decision at a particular point in time. The main types of decisional competency are 1) to give informed consent for medical care, 347

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2) to execute an advance directive, 3) to give informed consent for enrollment in a research study, 4) to enter into (and be held accountable for) a contract (contractual capacity), and 5) to execute a will (testamentary capacity) or trust. Next we discuss functional competency, or the ability to provide self-care (provide oneself with food, clothing, shelter, and medical care) and manage one’s finances. Functional competency entails multiple types of decisional capacity but adds the requirement of executive function, including motivation, prioritization, planning, and execution of goal-oriented sequences of behavior over time. (Note: For purposes of illustration and discussion, this chapter refers to California law. Because statutory and governing case laws differ considerably from state to state, readers are strongly urged to check the law applicable to their jurisdiction.)

Decisional Competency Competency to Give Informed Consent for Medical Care Four components of decisional competency in the medical setting were distinguished by Appelbaum and Grisso (1988) and have been accepted by most authors. The four components involve the ability to 1. 2. 3. 4.

Communicate a choice Understand relevant information Appreciate the situation and its consequences Manipulate information rationally (i.e., “to reach conclusions that are logically consistent with the starting premises. This requires both weighing the risks and benefits of a single option and the usually more complex process of weighing multiple options simultaneously.” [p. 1636])

Decisional competency is only one of three equally important components of informed consent for medical care. The President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (1982) concluded that the patient must be provided with appropriate information about the recommended medical intervention (the categories of information required by California law are listed in Table 9–1) and that the consent must be given voluntarily—that is, it cannot be a result of coercion or threats (discussed in “Undue Influence: The Question of Voluntariness” later in this chapter).

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Table 9–1. Requirements of informed consent: what patients must be told about a proposed treatment The nature and seriousness of the illness, disorder, or defect that the person has The nature of the medical treatment that is being recommended by the person’s health care providers The probable degree and duration of any benefits and risks of any medical intervention that is being recommended by the person’s health care providers and the consequences of lack of treatment The nature, risks, and benefits of any reasonable alternatives Source. Adapted from Cal. Prob. Code §813.

Informed consent is generally not required for the great majority of medical interventions, which are performed on the basis of “simple consent,” usually obtained at the time a patient engages a new physician or during the admission process (the “Terms and Conditions of Admission” typically include simple consent). Simple consent similarly requires that the patient be competent and that the consent be voluntary but does not require the provision of a predetermined body of information to the patient by the physician. Neither informed nor simple consent is required in an emergent situation, in which significant harm would come to a patient (or to others, in the case of a violent patient) if the intervention were delayed so that consent could be obtained. Under these circumstances, the principle of implied consent applies: that is, the physician may perform the intervention to which a reasonable, self-interested patient would consent, given the opportunity. Similarly, if the patient is unconscious or otherwise incompetent to participate in the consent process, and no substitute decision maker (e.g., guardian or conservator, attorney-in-fact for health care, or, in some jurisdictions, next of kin) or advance directive is available, the physician may administer appropriate emergency treatment until the patient is able to consent. In California, a nonemergent situation in which no competent decision maker is available requires a specific court order for medical intervention (Cal Prob. Code §3201).

Competency to Execute an Advance Directive Advance directives are legal instruments intended to ensure that appropriate decisions regarding medical care are made when a patient becomes incompetent to give informed consent. The Patient Self-Determination Act of 1990

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(P.L. 101-508), which became federal law on December 1, 1991, mandates that hospitals, nursing homes, and other health care organizations provide information to patients about availability and use of these instruments. There are generally two types of advance directives: proxy directives, such as the durable power of attorney for health care or health care proxy, and instruction directives, such as the living will. Durable power of attorney for health care allows an individual (the principal) to authorize another person, usually a family member or spouse (the attorney-in-fact or agent), to give or withhold consent for medical care for the principal if the principal becomes incompetent. Legally defined, a durable power of attorney is a power of attorney by which a principal designates another his attorney in fact and the writing contains the words, “This power of attorney shall not be affected by disability of the principal,” or “This power of attorney shall become effective upon the disability or incapacity of the principal” or similar words showing the intent of the principal that the authority conferred shall be exercisable notwithstanding the principal’s subsequent disability or incapacity. (Uniform Durable Power of Attorney Act 1983, p. 3960)

Some states have enacted similar laws creating the health care proxy. A living will is a document that is created by an individual when he or she is of sound mind, specifying the limits of care to be given by health care providers if the individual “cannot make or communicate a choice regarding a particular health care decision.” The version available through the American Medical Association directs the attending physician to withhold or withdraw treatment “when the treatment will not give me a meaningful quality of life” and provides a choice of three levels of quality of life, including “permanent unconsciousness,” “some consciousness and in an irreversible condition of complete, or nearly complete, loss of ability to think or communicate with others,” and “no more than some ability to think or communicate with others, and the likely risks and burdens of treatment outweigh the expected benefits.” It also has a section in which the individual can specify particular treatments that he or she does not want, as well as particular preferences regarding treatment and the end of his or her life (e.g., the preference to die at home), and a section containing instructions regarding organ donation. There are clear advantages and disadvantages to both types of directives. A proxy has much more flexibility than an “instructive” has, and a proxy can

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respond to circumstances that may not have been anticipated by the principal. Conversely, a proxy also can betray the trust of the principal by making decisions that the principal would not have endorsed. In some states, a living will and durable power of attorney for health care or health care proxy can be combined, resulting in an instrument that requires the attorney-in-fact or proxy to follow the provisions of the living will and authorizes the exercise of his or her judgment in circumstances not covered by the will. Because advance directives are intended to be executed when the principal is competent to give or withhold consent for medical care, one might think that the standard for competency to execute an advance directive would be the same as the standard for competency to consent to medical care. Yet California law states, “A natural person having the capacity to contract may execute a power of attorney” (Cal. Prob. Code §4120). However, different standards for competency to execute an advance directive may obtain in other states. In a similar vein, the powers of the attorney-in-fact differ from state to state. California law prohibits the attorney-in-fact from consenting to placement in a mental health treatment facility, convulsive treatment, psychosurgery, sterilization, or abortion (Cal. Prob. Code §4722) and also prohibits the attorney-in-fact from consenting to health care or consenting to the withholding or withdrawal of health care “necessary to keep the principal alive, if the principal objects to the health care or to the withholding or withdrawal of the health care. In such a case, the case is governed by the law that would apply if there were no durable power of attorney for health care” (Cal. Prob. Code §4724). This section appears to reflect the will of the California legislature that individuals retain the authority to make end-of-life decisions, even if they are incompetent to make other medical decisions. Much has been written about the question of which rules should govern the decisions of substitute decision makers such as attorneys-in-fact. The prevailing view is known as the doctrine of “substituted judgment,” according to which the substitute decision maker should act, as much as possible, in accordance with the wishes, values, and goals of the principal. The alternative “best interests” approach calls on the substitute decision maker to perform an “objective assessment of the burdens and benefits for this patient” as the basis for his or her decision (Fellows 1998, p. 924). The court in a New Jersey case (In re Conroy 1985) spelled out a three-step protocol for analyzing the patient’s

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wishes: First, consider any statements or other directives made by the patient. If these are not conclusive, then attempt to deduce the patient’s wishes from his or her more generally held values, religious beliefs, and so on. Finally, if these steps leave the issue in doubt, revert to what a person in the patient’s situation might reasonably choose.

Competency to Consent to Enrollment in a Research Study The considerations discussed earlier regarding competency to consent to medical care generally apply to competency to consent to enrollment in a study. Before an investigator can claim to have secured informed consent, the subject must have been supplied with appropriate information, voluntary consent must have been obtained, and the subject must have been considered competent. In 1982, the President’s Commission clearly spelled out the disclosures required under ordinary circumstances (Table 9–2), and in 1996, the U.S. Food and Drug Administration published an “exception to informed consent” rule intended to govern research conducted in medically emergent circumstances. In 1998, the National Bioethics Advisory Commission (created by President Clinton in 1995) issued a lengthy report, with 21 recommendations, entitled, “Research Involving Persons With Mental Disorders That May Affect Decisionmaking Capacity,” but few recommendations were adopted, and the Code of Federal Regulations now includes minimal language aimed at protection of cognitively impaired subjects. Specifically, Title 45 (Public Welfare), Part 46 (Protection of Human Subjects), section 46.111 (criteria for Institutional Review Board [IRB] Approval of Research), (a) 3 states, “Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons,” whereas section (b) states, “When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects” (italics added; original available at http://www.hhs.gov/ ohrp/humansubjects/guidance/45cfr46.htm#46.111).

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Table 9–2. Disclosures required for research subjects The fact that research is being performed and the purposes of the research Reasonably foreseeable risks, reasonably expected benefits, and appropriate alternatives A statement about the maintenance of confidentiality An explanation about possible compensation if injury occurs, in cases of research involving more than minimal risk Information about how the subject can have pertinent questions answered A statement about voluntary participation, indicating that refusal to participate involves no penalties or loss of benefits Source. President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research 1982.

Competency to Enter Into a Contract or Make a Gift The traditional view of contract versus property law distinguishes between the “future orientation” of contracts and the “present orientation” of a gift, but competency to enter into a contract and competency to give a gift during one’s lifetime (inter vivos) are treated as essentially the same in contemporary legal literature (Meiklejohn 1988–1989). Geriatric psychiatrists are likely to confront the issue of contractual capacity in two situations: 1) when an individual who has entered into a contract or made a gift (the grantor) attempts to escape responsibility for the future performance demanded by the contract, or to retrieve assets already transferred per the terms of the contract or gift, on the basis of the claim that he or she lacked contractual competency at the time; and 2) when the establishment of a conservatorship of estate (discussed in “Competency to Care for Oneself and Manage One’s Finances” later in this chapter) is under contemplation by a court because a proposed conservatee is thought to be unable, on the basis of mental incapacity, to manage his or her finances or resist fraud or undue influence. Although courts have the authority to grant exceptions in specific cases, the establishment of a conservatorship generally creates an irrebuttable presumption that the conservatee lacks contractual and donative (but not testamentary) capacity (although California, oddly, allows conservatees to marry). Definitions of contractual capacity vary widely by jurisdiction. Restatement of the Law Second, Contracts 2d (American Law Institute 1981) provides as follows:

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A person incurs only voidable contractual duties by entering into a transaction if by reason of mental illness or defect (a) he is unable to understand in a reasonable manner the nature and consequences of the transaction, or (b) he is unable to act in a reasonable manner in relation to the transaction and the other party has reason to know of his condition. (p. 41)

California law states, “A person entirely without understanding has no power to make a contract of any kind” (Cal. Civ. Code §38) and “A conveyance or other contract made by a person of unsound mind, but not entirely without understanding, made before his incapacity has been judicially determined, is subject to rescission” (Cal. Civ. Code §39). The vagueness of these sections is partially remedied by the next section: “A rebuttable presumption affecting the burden of proof that a person is of unsound mind shall exist if the person is substantially unable to manage his or her own financial resources or resist fraud or undue influence” (Cal. Civ. Code §39). This statute provides a partial remedy for situations in which an individual, typically elderly and cognitively impaired, who qualifies for but has not (yet) been provided a conservator of estate has entered into an unwise contract (e.g., for unneeded home improvements) because of impaired judgment. If it can be proved that a conservatorship could have been established, the usual assumption that every adult is competent for all legal purposes is reversed, and the other party to the contract must prove that the elderly individual possessed contractual capacity (Hankin 1995). When a claim of contractual or donative incompetency is adjudicated, courts tend to give substantial weight to facts besides the degree of mental impairment of the grantor, such as the substantive fairness (i.e., the terms of the contract or gift, as opposed to the procedural fairness) of the transaction in question. In other words, the fact that the grantor agreed to an obviously bad deal may be regarded as evidence supporting the claim that the grantor was incompetent.

Competency to Make a Will Most states define testamentary capacity as the capacity to “understand the nature of the testamentary act, understand and recollect the nature and situation of his or her property, and remember and understand his or her relations to his or her living descendants, spouse, and parents, and those whose interests are

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affected by the will.” Some states require only one or two of these criteria to be met, and many states require that “the testator [be] also free of…delusions or hallucinations [that] result in the person’s devising his or her property in a way which, except for the existence of the delusions or hallucinations, he or she would not have done” (Cal. Prob. Code §6100.5). In general, if lack of testamentary capacity is proved, the entire will or codicil (modification to an existing will) is invalid. Testamentary capacity is generally recognized as “only a modest level of competence (‘the weakest class of sound minds’)” (Estate of Rosen 1982), and legal presumptions relating to this competency have traditionally also helped to set the bar fairly low. Besides the general presumption that the testator was competent at the time the will was executed, it has also been stated that “when one has a mental disorder in which there are lucid periods, it is presumed that his will has been made during a time of lucidity” (Estate of Goetz 1967). The trend of more recent cases, however, has been toward increasing recognition that at least in the case of progressive illnesses, such as Alzheimer’s disease and vascular dementia, once testamentary capacity has been lost, it is unlikely to return, even for brief periods. Despite the fact that testamentary capacity is a low standard, wills are vulnerable to challenge if an aggrieved party can produce any evidence of mental impairment in the testator, and a medical record containing the mere diagnosis of a neuropsychiatric illness is almost always enough, all things else being equal, to encourage contestants to proceed. Although it is common knowledge among psychiatrists that a diagnosis alone does not imply any particular level of intellectual function or automatically determine the presence or absence of any type of competency, many judges, attorneys, and juries are not in possession of this insight and may need to be educated through expert testimony. In many will contests, the allegation that the testator lacked testamentary capacity at the time the will was executed is accompanied by the allegation that the will, or parts of it, is the product of undue influence. Because testamentary capacity is such a low standard, and because prospective evaluation of the testator is rarely performed (and if it is, it is almost always at the request of a competent testator or of his or her anticipated beneficiaries), it is usually very difficult to prove that a testator did not possess testamentary capacity at the precise moment that the contested will was signed (executed). Accordingly, allegation of undue influence often proves to be the stronger case for the contestant. Any part of a will that is proved to be a result of undue influence is overturned, but the remainder remains valid if the will

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without the influenced provisions still makes sense and the testator otherwise had testamentary capacity. Undue influence is discussed later in this chapter.

Competency to Execute a Trust Trusts are increasingly popular instruments with which to determine the disposition of one’s assets after death, and to that extent, a trust serves the same function as a will, and the relatively low standard for testamentary capacity should apply. But even if that standard did apply, the testamentary standard of understanding the nature of the testamentary act would almost always require more intact intellectual function for a trust than that required for a will because trusts are generally more complicated than wills, with more, and more detailed, provisions. Moreover, a will is simply a piece of paper with a set of instructions, whereas a trust is a more abstract entity that requires relatively intact higher intellectual functions to grasp. Some courts have differentiated the standards of competency for trusts and wills on the basis of the fact that establishing a trust entails a step in addition to merely signing a set of instructions: the creator of the trust must also transfer his or her property to the trust. This act would seem to require contractual or donative capacity, which is widely but not universally regarded as a higher level of competency than mere testamentary capacity. (For example, in Citizen’s National Bank v. Pearson [1978], the court stated, “Greater mental capacity is required to make a deed than is required to execute a will.”) Another path to the same conclusion is the argument that because the trustee is endowed with the authority to enter into contracts involving the trust assets, the creator of the trust (who is usually the trustee) should possess contractual capacity.

Assessing Decisional Competency Clinical Interview The cornerstone of the assessment of decisional capacity is the clinical interview with the subject. This interview should include discussion of the social, economic, and, if appropriate, medical circumstances surrounding the decision at issue (i.e., who is affected by the decision, and how that party is affected); how the subject arrived at the decision, including discussion of the role of other parties (especially those affected by the decision); and what alternatives to the decision the subject recognizes. For example, the discussion of a proposed trust amendment should include inquiry about what assets are entailed; how the

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trustee(s), successor trustees, and beneficiaries were selected; and what events and considerations led to the decision to amend the trust. The discussion of a proposed medical intervention should cover the risks and benefits of the proposed intervention and the most reasonable alternatives and should include inquiries of the subject that allow her or him to paraphrase and manipulate the information provided and ask whatever questions that arise. By the end of this discussion, it should be clear to the examiner whether the subject has the requisite understanding and appreciation of the consequences of the decision for the subject and all others affected, the extent to which the decision was influenced by interactions with others, how the decision comports with previously held values and goals, and whether delusional thinking affected the decision. The conclusion that the subject is or is not competent to make the decision at issue then depends on what the examiner regards as evidence of minimally acceptable ability to “understand and appreciate,” “recall and recollect,” and so forth. That is, does the examiner require that the subject produce key information from memory, either spontaneously or in response to inquiry, or is the ability merely to recognize information acceptable (e.g., a description of a parcel of real property or of a proposed surgical procedure)? What level of detail is acceptable? How much error is acceptable? This interrater variability in threshold accounts, in part, for the often observed lack of agreement between examiners in published studies of decisional competency (e.g., Marson et al. 1997; Vellinga et al. 2004) and for the fact that equally qualified experts often provide conflicting opinions under oath. Tests of Cognitive Function To help mitigate the effects of the interrater variables described earlier, the examiner is advised to administer a battery of standardized tests of cognitive function along with the clinical interview. Impairment in other domains of mental function (e.g., abnormal mood, anxiety, thought disorder) can, in principle, negatively affect competency, but cognitive ability is the most consistent correlate of decisional competence (Palmer et al. 2005), and scores on tests of cognitive function provide support for the examiner’s conclusions and allow the cross-examining attorney and the trier of fact to place the expert’s opinion in something approximating an “objective” context. One author of this book (J.E.S.) routinely administers a Folstein Mini-Mental State Examination (MMSE), a 12-item Boston Naming Test, general information items from the Wechsler Adult Intelligence Scale, tests of remote memory (list the presidents,

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describe key news events such as “What happened on 9/11/01?” and “What was unusual about the 2000 presidential election?”), and tests of frontal executive function, including similarities, word-list generation, proverb interpretation, alternating design copying, and clock drawing. When indicated, this battery is augmented with a “shopping list” test of new learning, tests of verbal comprehension, and other more focused tests as indicated. Standardized Tests of Decisional Competency The literature on competency generally agrees that standardized tests have had a limited role in competency determination, in part because of their inability to adjust to unique situational factors, including the consequences of the decision at issue. As Grisso and Appelbaum (1998) indicated, the threshold for competence should be adjusted according to the degree of harm associated with the subject’s choice. For example, a lower level of understanding would be acceptable when a patient is consenting to a medical procedure with a high benefit-risk ratio, as compared with one that has a low ratio. Similarly, a lower threshold for concluding that a testator has the ability to “understand and recollect the nature and situation of his or her property” would be appropriate if there is only one natural heir, the testator had no previous intention to leave the estate to anyone else, and the testator now intends to leave his or her estate entirely to that heir, as compared with a situation in which a will contest is likely. Several of the more recently developed standardized tests of competency allow the rater to adjust the threshold and may be useful as adjuncts to the clinical interview. They include the MacArthur Competence Assessment Tool—Treatment (Grisso et al. 1997) and the Competence Assessment Tool for Psychiatric Advance Directives (Srebnik et al. 2004). These instruments assess a patient’s capacity for understanding, appreciation, and reasoning by providing a body of information and then requiring the patient to respond to questions about that information. The result is several subscale scores that can be incorporated into a competency determination.

Undue Influence: The Question of Voluntariness As mentioned earlier, the question of undue influence is commonly raised in conjunction with a claim of lack of testamentary capacity and in connection with contested wills, contracts, and gifts. Susceptibility to undue influence is

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also one of the criteria for establishment of a conservatorship of estate in California and some other states, and the underlying question of voluntariness is also relevant to the issue of informed consent for medical care. Yet undue influence is a complex and poorly defined legal concept at best. In the legal literature, the question of undue influence tends to be reduced to the “will substitution test”—that is, was the testator’s mind so controlled by another person that his or her will is actually the will of another person? Depending on the situation, this “will substitution” may require an element of “coercion, compulsion, or restraint,” as in the testamentary context, or, with regard to contracts, merely consist 1) in the use, by one in whom a confidence is reposed by another, or who holds a real or apparent authority over him, of such confidence or authority for the purpose of obtaining an unfair advantage over him; 2) in taking an unfair advantage of another’s weakness of mind; or, 3) in taking a grossly oppressive and unfair advantage of another’s necessities or distress. (Cal. Civ. Code §1575)

In some jurisdictions, the mere existence of a confidential and trusting relationship, such as that between an elderly patient with psychiatric illness and his or her primary caregiver, may be enough to shift the burden of proof to the recipient, who then must prove that undue influence did not occur. The presumption of undue influence is strengthened if the donor is mentally weak; a diagnosis of mental illness or retardation is generally adequate to support this claim, and in some cases, even evidence that the donor is passive or manipulable will suffice. The presumption of undue influence is also strengthened if the recipient is a clerical, church, or spiritual adviser who fails to ascertain that a donor has received competent and independent advice; if the recipient actively procures the gift or bequest; or if the recipient unduly benefits from the gift or bequest. A somewhat weaker set of factors are widely regarded as indicia (i.e., they serve to strengthen a claim of undue influence but do not, by themselves, establish a presumption) of undue influence in a testamentary context. These include “unnatural provisions in the will, provisions in the will that are inconsistent with prior or subsequent expressions of the testator’s intentions, and a relationship between the testator and the beneficiary that created an opportunity to control the testamentary act” (Spar and Garb 1992, p. 170). A diagnosis of psychiatric illness in the allegedly influenced party will generally support a

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claim of undue influence, but such a diagnosis is rarely more than just one consideration of many. Singer (1992) identified six additional factors that “are prominent in undue influence situations.” They are the production of isolation, the creation of the ‘siege mentality,’ the fostering of dependence, the creation of powerlessness, the use of fear and deception, and keeping the victim unaware of the manipulative program put into place to influence and control the person and to obtain the signing of documents which benefit the manipulators at the cost of the signer. (p. 8)

These factors notwithstanding, it is important to remember that influence, even that which is clearly coercive, is not undue if it does not change the preexisting disposition of the testator. That is, if the bequest or gift would have been made anyway, absent the influence, then no undue influence has occurred. Obviously, knowledge of the testator’s long-term wishes and intentions is critical to the establishment of this defense. Geriatric psychiatrists are likely to become involved in undue influence evaluations in the clinical setting when an individual is believed by friends or family members to be vulnerable to exploitation and a conservatorship or guardianship of estate is under consideration. A typical situation involves an elderly divorced or widowed person with vascular or Alzheimer’s dementia who has fallen under the sway of a much younger individual who has gradually taken over many caregiving functions and, in some cases, has even become romantically involved with the elderly person. Particularly if there is no close family, or if preexisting family dynamics are distant or conflictful, it may be an easy matter for the younger person to create several of the circumstances listed by Singer (1992). Naïve family members may exacerbate the situation by opposing the relationship or by suggesting that mental impairment is present, both of which responses may facilitate the creation of the siege mentality. Inappropriate gifts, excessive payments for services rendered, new trusts and wills, and even late-life marriages are typical results of this situation, especially if the patient has substantial assets.

Competency to Care for Oneself and Manage One’s Finances Laws exist in all 50 states and the District of Columbia providing for the appointment by a court of a guardian or conservator for persons found in-

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competent to care for themselves or manage their finances. Criteria vary for appointment of a conservator of a person (this conservator is called a guardian in many states) and conservator of an estate (both conservator roles may be assumed by the same person). This competency may be regarded as a form of decisional capacity, at least in those states that use the Uniform Probate Code (e.g., Alaska, Colorado, Montana), which defines an incapacitated individual as someone who is “impaired by reason of mental illness, mental deficiency, physical illness or disability, chronic use of drugs, chronic intoxication, or other cause (except minority) to the extent that he lacks sufficient understanding or capacity to make or communicate responsible decisions concerning his person or which cause has so impaired the person's judgment that he is incapable of realizing and making a rational decision with respect to his need for treatment” (for an example, see http://data.opi.state.mt.us/bills/mca/72/5/ 72-5-101.htm). However, in California, “a conservator of the person may be appointed for a person who is unable to provide properly for his or her personal needs for physical health, food, clothing, or shelter” (Cal. Prob. Code §1801a), and “a conservator of the estate may be appointed for a person who is substantially unable to manage his or her own financial resources or resist fraud or undue influence” (Cal. Prob. Code §1801b). Functional criteria such as these subsume simple decisional capacity and, as mentioned earlier, add the requirements of sustained motivation, judgment, and other executive functions. Other than at the extremes of cognitive function (i.e., a perfectly normal individual or one with severe, end-stage dementia), everyday function is difficult to predict from an office interview. Accordingly, the evaluation of the need for a conservator of a person and/or an estate in California typically includes interviewing individuals familiar with the proposed conservatee’s everyday level of function; given that such informants are subject to bias and may themselves not be perfectly reliable (Wadley et al. 2003), multiple sources are desirable. In addition to this ancillary information, measures of frontal executive function are also more critical in the assessment of these “downstream” functions than are the simpler tests of language, memory, and comprehension that are typically used in the assessment of decisional capacity (Brekke et al. 1997; Chen et al. 1998). In general, the powers of the conservator of person and the conservator of estate are quite broad: the conservator of person has the power to make decisions regarding place of residence and administration of medical care, and the

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conservator of estate has the power to manage property, assets, and income (this includes the power to enter into contractual arrangements on behalf of the principal). In California, the conservator of person can consent to medical care, but not over the objection of the conservatee, unless the court has granted general or specific medical power—that is, the power to consent to all medical care (general power) or to consent to a specific treatment (specific power) even over the objection of the conservatee. The establishment of a conservator of estate automatically renders the conservatee legally incompetent to contract or to transfer property but does not establish lack of testamentary capacity (i.e., the conservatee can still execute a will). Conservatorship and guardianship are clearly radical solutions to the competency problems occasioned by psychiatric and other illnesses. The process of appointment of a guardian or conservator is often demeaning and embarrassing to the conservatee, and disagreement over the need for conservatorship and the motivations of those who support or resist it may lead to long-lasting intrafamilial conflict and resentment. The appointment is also expensive and time-consuming. In response to these shortcomings, most states have provision for limited conservatorship and guardianship, wherein only some of the powers discussed earlier are granted to the conservator, and the rest remain with the conservatee, as determined by the court on a case-bycase basis. But even this approach is costly and demeaning to the patient and, despite court oversight, is sometimes conducive to fiduciary and even physical abuse by guardians. And the process of adjudication of conservatorship and guardianship itself has been criticized. Guardianship petitions often recite minimal facts in support of the claim of incompetence; often, in fact, they simply restate the circular and conclusory language of the statutory definitions of incompetency. … Far too often, [courts] are satisfied with only a perfunctory assessment of the alleged incompetent’s mental capacity.…Typically, evidence is limited to a brief letter from a physician stating that the patient is incompetent. A complete psychiatric evaluation and formal mental status exam are rarely included. (Rosoff and Gottlieb 1987, pp. 15–16)

As if to document this claim, Armstrong (2000) has collected a series of cases that poignantly illustrate the consequences of abuse of the conservatorship system. Clearly, alternatives to conservatorship and guardianship are desirable, and fortunately several are available (Table 9–3).

Table 9–3. Surrogate decision-makers available to older persons in California (may vary in other states) Capacity necessary to establish

Survives Powers of agent incapacity or conservator

Powers retained by individual

Risks and recourse

Personal decisionmaking Yes

Living will

Contractual

Yes

Probate conservatorship of person (guardianship)

None

Yes

Makes medical May revoke DPAHC decisions when as long as competent, principal cannota may refuse medical care despite agent’s consent Specifies certain Not applicable limits of care

Agent may not make “substituted judgment”; court is recourse

May not anticipate all situations, may not reflect changed values Conservator may not respect May refuse medical May determine care, civil commitment conservatee’s values and residence, make wishes; court is recourse (psychiatric medical decisions hospitalization), certain treatments

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Contractual Durable power of attorney for health care (DPAHC)

363

Capacity necessary to establish

Survives Powers of agent incapacity or conservator

Powers retained by individual

Risks and recourse

Personal decisionmaking (continued) None Probate conservatorship of person with general medical powers

Yes

Probate conservatorship for persons with dementia

None

Yes

Mental health conservatorship of person

None

Yes

Conservator may not respect May refuse civil May determine conservatee’s values and commitment residence, make wishes; court is recourse (psychiatric medical decisions hospitalization), certain treatments (e.g., psychosurgery, abortion, sterilization) Conservator may not respect May refuse civil May determine conservatee’s values and commitment residence, make wishes; court is recourse (psychiatric medical decisions hospitalization), certain treatments May refuse physical but Conservator may not respect May consent to conservatee’s values and mental health care not mental health care wishes; court is recourse (including civil only, including commitment). civil commitment

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Table 9–3. Surrogate decision-makers available to older persons in California (may vary in other states) (continued)

Table 9–3. Surrogate decision-makers available to older persons in California (may vary in other states) (continued) Capacity necessary to establish

Survives Powers of agent incapacity or conservator

Powers retained by individual

Risks and recourse

Financial decisionmaking Contractual

No

Durable power of attorney

Contractual

Yes

Personal trusts

Contractual to establish, testamentary to modifyb None

Yes

None

Yes

Probate conservatorship of estate Mental health conservatorship of estate

Principal must monitor use of funds: court is recourse No oversight of use of funds (“a license to steal”) since principal is incompetent: court is recourse Trustee (if not the settlor) Trustee can manage May modify as long as may not respect settlor’s trust assets competent; some are values and wishes: court is revocable recourse May expend funds, May marry Variably reliable court contract oversight, yet court is only recourse May expend funds, May contest most powers Variably reliable court contract of conservator of estate oversight, yet court is only recourse

Typically is a “springing power” that comes into effect after the principal becomes incompetent. (J.E.S.) opinion.

bAuthor

365

a

Yes

May expend funds, May revoke as long as contract competent May expend funds, May revoke as long as contract when competent principal cannota

Competency and Related Forensic Issues

Power of attorney

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Expert Consultation and Testimony on Competency Geriatric psychiatrists are particularly qualified to provide expert forensic consultation and testimony regarding questions of competency and susceptibility to undue influence. Accordingly, geriatric psychiatrists need to be familiar with local statutes and case laws defining the various forms of competency. The psychiatric expert may be asked to perform a contemporaneous evaluation of an individual’s competency or susceptibility to undue influence or to state an opinion on the competency and susceptibility to undue influence of an individual who has since died. Guidelines for such evaluations in the testamentary context have been published previously (Spar and Garb 1992) and are applicable to each of the forms of decisional competency discussed in this chapter but are not reviewed here. However, two revisions to those guidelines are suggested. First, it is recommended that the medical expert avoid testifying on the issue of undue influence per se, simply because undue influence is a complex finding that requires the judgment that a particular benefit is “undue” or “unfair,” a judgment that does not require medical expertise and is therefore not a proper part of expert testimony. In this regard, the only “expert” on the issue of undue influence per se is the trier of fact, who hears all of the admissible evidence. Rather, medical expert testimony should be restricted to the question of the presence and severity of mental impairment and how the patient’s vulnerability to influence, persuasion, manipulation, being taken advantage of, and so on is or would have been affected by that impairment. If circumstances permit, testimony on whether particular decisions made by the impaired individual are the direct result of such manipulation and persuasion also may be justified and may be permitted. The second revision is based on Rule 703 of the Federal Rules of Evidence, which states, in part, that the facts or data in the particular case upon which an expert bases an opinion or inference may be those perceived by or made known to the expert at or before the hearing. If of a type reasonably relied upon by experts in the particular field in forming opinions or inferences upon the subject, the facts or data need not be admissible in evidence in order for the opinion or inference to be admitted.

Rule 703 particularly applies when the psychiatrist’s expert opinion is based on retrospective evaluation, which always depends on information derived from

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sources other than the testator. Here it may be prudent to elicit testimony on direct examination that clinical assessment and diagnosis of psychiatric illness in the elderly are commonly reliant on information from sources (such as spouses, relatives, caregivers, and medical records) other than direct examination of the patient, especially if the patient is severely cognitively impaired, uncooperative, mute, or catatonic. This explanation may be important testimony if the court is inclined to believe, as some clearly are, that retrospective evaluation is not part of reasonable clinical practice, is therefore not “protected” by Rule 703, and is of highly questionable probative value. Anticipating and correcting this misperception can be of great value in preserving the proper weight of expert testimony. However it is performed, the expert role is substantially different from the role of clinician, and somewhat different ethical principles pertain. The clinician’s obligation to act in the best interests of the patient is replaced by the consultant’s mandate to provide an honest and objective opinion and, in the testimonial context, to express that opinion in a convincing manner. Because the two obligations can easily conflict, it is usually not recommended for one individual to assume both roles for the same patient.

Competency to Drive The fraction of the American population that drives is rapidly aging, and it is estimated that by the year 2024, one in four drivers in the United States will be older than 65. Motor vehicle injuries are the leading cause of injury-related deaths among drivers ages 65- to 74-years old and are the second leading cause (after falls) among drivers ages 75- to 84-years old. Older drivers have a higher fatality rate per mile driven than any other age group except drivers under age 25. By age 80, male and female drivers are, respectively, 4 and 3.1 times more likely than 20-year-olds to die as a result of a motor vehicle crash. On the basis of estimated annual travel, the fatality rate for drivers 85 years and older is 9 times higher than the rate for drivers ages 25–69 years old (Wang et al. 2003). Multiple age-related factors are likely to contribute to this phenomenon, including declining visual and auditory acuity, effects of physical and neuropsychiatric illnesses and their treatments, and declining decisional competence resulting from slowing of cognitive processes and reaction time and deficits in attention, concentration, and visuospatial and executive functions.

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Available data are not adequate to determine the precise contribution of each of these factors, but some generalizations are possible. Dementia clearly increases the risk of crashing, even in the early stages of illness. Dubinsky et al. (2000) reviewed the literature on behalf of the American Academy of Neurology and concluded that drivers with early Alzheimer’s disease (MMSE score between 19 and 25 or Clinical Dementia Rating [CDR; Morris 1993] score of 1.0) had a relative crash risk “greater than our society tolerates for any group of drivers,” and those with a CDR score of 0.5 (approximately corresponding to an MMSE score of 25, according to Reisberg et al. [1994]) “have an increased risk of accidents similar to that which society accepts for 16 to 19 year old drivers and for those drivers intoxicated with alcohol at a (blood alcohol concentration) <0.08%” (p. 5). Dubinsky et al. issued a “practice parameter” stating that individuals with Alzheimer’s disease whose CDR score is 1.0 or greater should not drive, and those with a CDR score of 0.5 should be referred for a driving performance evaluation by a qualified examiner and should be reassessed every 6 months. Several investigators have examined the ability of various off-road assessment tools to predict on-road driving ability of cognitively impaired elders. Performance on tests of executive function, including mazes (Ott et al. 2003), the Trail Making Test Part B (Uc et al. 2005), and clock drawing (Freund et al. 2004), correlates with driving abilities in individuals with dementia, as does performance on tests of visual attention and visuoperception. In particular, a measure called the Useful Field of View (UFOV), which refers to the area of the visual field in which information can be rapidly extracted without eye and head movements, appears to be of value in this context. Three component functions contribute to the UFOV: speed of visual processing, ability to divide attention, and ability to distinguish target from background; impairments in each of these functions can result in diminished UFOV (Ball 1997; Ball et al. 1993). Reger et al. (2004) conducted a meta-analysis of the literature correlating neuropsychological test performance with driving ability and found that in studies that included a control group, the relation between cognitive measures and on-road or nonroad driving measures was significant for all reported domains, with mean correlations ranging from 0.35 to 0.65. In studies without a control group, measures of visuospatial abilities were the best predictors. In a study published since that review, the Driving Scenes test, which is part of the new Neuropsychological Assessment Battery (Stern and

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White 2003), was examined for its predictive value. It uses color drawings of a road scene from the perspective of sitting behind the steering wheel of the car and correctly classified 66% of the subjects into the three driving safety categories of “safe,” “marginal,” and “unsafe.” It may have advantages over the other tests discussed here in ease and convenience of administration and acceptableness to older adult examinees. Physicians who make judgments about patients’ driving based on clinical data appear to be comparably accurate at predicting the on-road performance of patients with dementia. Ott et al. (2005) found that physician accuracy (percentage of correct classifications) in categorizing patients as safe or unsafe (as subsequently determined by on-road testing) ranged from 62% to 78%, with the accuracy of the general practitioners ranging from 62% to 64% and that of the dementia specialists ranging from 72% to 78%. Participating physicians based their predictions on almost 20 clinical variables, but those whose predictions were most accurate placed more weight on duration of dementia, measures of dementia severity (CDR and MMSE scores), and specific tests of visuospatial ability, praxis, and executive function. In a similar study by Brown et al. (2005), the single physician rater was an experienced neurologist and specialist in dementia. His judgments, based on an extensive clinical interview that included specific questions about any recent history of driving problems, and the tests included in his diagnostic dementia evaluation were 74% accurate in predicting which patients would be classified as safe, marginal, or unsafe after an on-road driving test. In this study, the physician was more accurate than either a family member “informant” or the patient in predicting driving safety. Subjects with very mild dementia (CDR score=0.5) or mild dementia (CRD score=1.0) did not differ significantly in driving performance, but both groups were significantly worse than control subjects without dementia. On-road evaluation remains the gold standard for assessing the safety of drivers with dementia. Fitten et al. (1995) found that subjects with dementia not only performed significantly more poorly on a driving test than did control subjects but also committed more serious driving errors, particularly during the more complex stages of the course. A. R. Dobbs (1997) studied cognitively impaired seniors who were all still driving and observed three types of driving errors. The most serious errors, which “could have resulted in a crash had the driving instructor not taken control of the vehicle or the

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traffic adjusted” (p. 10), were made almost exclusively by subjects with dementia, and three of the four control subjects who made errors of this type were subsequently determined, on the basis of cognitive testing, to have dementia or other cognitive impairments. In this study, 25% of the subjects with dementia showed driving competence within the range of the normal drivers. Dobbs concluded that diminished driving competence among subjects with dementia is most likely to be picked up by a test protocol (course and scoring procedure) that focuses on the very serious errors that were most discriminating in the experimental situation. Uc and colleagues (2005) studied subjects with mild Alzheimer’s disease (average MMSE score= 26; average age = 76.1 years) using several measures of cognitive function, the UFOV, and visual acuity and then had subjects drive along a 1-mile stretch of four-lane divided highway. The task was to identify and verbally report traffic signs and restaurants along the route. Subjects with Alzheimer’s disease identified a significantly smaller percentage of restaurant and traffic signs than did neurologically normal control subjects and made significantly more at-fault driving errors. Older drivers are at risk for other medical conditions that can impair driving ability. McCloskey et al. (1994) found that retinal disorders, macular degeneration, myopia and presbyopia, and monocular vision, which all would seem likely to increase crash risk, in fact did not. Glaucoma, however, was associated with an increased relative risk (odds ratio) of 1.5. Foley et al. (1995) found that having cataracts severe enough to preclude reading a newspaper or recognizing a friend across the street was associated with a relative risk of only 0.9, which did not reach statistical significance, and McCloskey et al. (1994) found that hearing impairment did not increase crash risk, but wearing a hearing aid while driving increased the risk of crashing by a relative risk of 1.9. Koepsell et al. (1994) looked at stroke; coronary disease, including heart attack, angina, and coronary surgery; chronic obstructive pulmonary disease; cancer; asthma; osteoarthritis; rheumatoid arthritis; and diabetes and found that only coronary disease in general (odds ratio=1.4) and diabetes (odds ratio=2.6) were associated with increased crash risk. Certain medications, as expected, are also important contributors to crash risk. Ray et al. (1992) found that current use of benzodiazepines was statistically significantly associated with injurious crashes among older drivers in Tennessee, at a relative risk of 1.5, whereas current use of cyclic antidepres-

Competency and Related Forensic Issues 371

sants was associated with a twofold increased risk. Foley et al. (1995) reported the surprising finding that the use of opioids or antihistamines was not associated with increased crash risk but use of nonsteroidal anti-inflammatory agents was (relative risk =1.4). Despite the evidence that dementia is a major contributor to crash risk, as of this writing, few states have laws mandating that physicians report drivers with dementia or other neuropsychiatric conditions that could impair driving. In 2002, only 28 states had laws providing immunity for breach of confidentiality for physicians who report medically unfit drivers. Responding to evidence that a patient has become a dangerous driver may be fraught with conflicts for the physician. A physician’s official report to authorities of the patient’s impairment may result in an angry patient who chooses another physician. Conversely, and more seriously, a physician’s decision not to report impairment may result in adverse legal consequences for the physician. Physicians practicing in states with laws mandating reporting of impaired drivers would seem somewhat better off in this regard, as would physicians in states that do not provide immunity for a breach of confidentiality. But every physician has the right and the obligation to attempt to convince dangerously impaired drivers to stop driving, even if these admonitions are not always effective. B.M. Dobbs (1997) found that 26% of the patients evaluated as unsafe to drive continued to do so despite being instructed by their physician to stop. Even here, though, there are conflicts of obligation, because many patients perceive the loss of “the right to drive” as an intolerable deprivation of autonomy and freedom, and the physician is obligated to protect the patient from that loss whenever it is reasonable to do so. But the physician is also obliged to protect the patient and others from the possible consequences of the patient’s impairment. Improvements in the ability to predict dangerous driving on the basis of office evaluations are likely to exacerbate this aspect of the physician’s dilemma.

Elder Abuse Epidemiological and clinical studies suggest that for every 100 older adults, between 2 and 10 individuals are victims of abuse (Lachs and Pillemer 2004). These figures may well be underestimates, because most cases are likely to go undetected. In the National Elder Abuse Incidence Study, for example, 84%

372 Clinical Manual of Geriatric Psychiatry

of the cases were not reported to adult protective service agencies (Administration on Aging 1998). Elder abuse can occur in several forms, including the following generally recognized categories: • • • • •

Physical—acts done to cause physical pain or injury Psychological—acts done to cause emotional pain or injury Sexual assault Material exploitation—including misappropriation of money or possessions Neglect—failure to meet the needs of a dependent person

Neglect is by far the most commonly identified condition, including many cases of self-neglect. In a study (Pavlik et al. 2001) of all allegations of neglect in the state of Texas in 1997, 51% reflected general neglect (85% selfneglect, 14% neglect by others) and 21% involved medical neglect, with the remainder involving physical abuse, including sexual abuse (12%), exploitation (8%), and emotional abuse (6%). The risk of abuse increases sharply with age. In the Texas study, for example, rates of reported elder abuse doubled with each 10-year increase in age (Pavlik et al. 2001). Other factors that increase an older person’s risk for abuse include dementia or other forms of cognitive deficit and a shared living situation, especially within a socially isolated family. Perpetrators of elder mistreatment often have mental illness or alcohol abuse and may be dependent on the abused person for material support (Lachs and Pillemer 2004). In about 9 of every 10 cases of elder abuse, perpetrators are family members, and two-thirds of perpetrators are adult children or spouses (Administration on Aging 1998). The American Medical Association (1992) guidelines on elder abuse suggest routine screening for family violence of all outpatients, and several screening tools have been developed (for a review, see Fulmer et al. 2004). However, practitioner surveys continue to indicate that physicians rarely do formal screening for elder abuse and often do not inquire about this topic at all. After reviewing the domestic violence literature, the U.S. Preventive Services Task Force (2004) declined to endorse routine screening for elder abuse, in part because there have been no systematic investigations of the effectiveness of interventions for older adults who have been victims of mistreatment. Nonetheless, there is widespread recognition

Competency and Related Forensic Issues 373

that all health care professionals need to be alert to the possibility of elder abuse and to adopt methods for its detection in the United States and worldwide (Bonnie and Wallace 2002; World Health Organization 2002). In their tutorial for physicians, Lachs and Pillemer (2004) emphasize the need for in-depth but flexible examinations when elder abuse is suspected, given the diverse forms and circumstances that may give rise to concern. In the context of a comprehensive geriatric assessment, direct inquiries about abuse and neglect are recommended, in addition to functional, cognitive, physical, and social assessment. Psychiatrists and other physicians must be able to differentiate normal aging changes and symptoms of disease from signs of mistreatment and must be alert to both their own biases and those of patients and family members with regard to acknowledging mistreatment. Many older patients are reluctant to divulge abuse, and those with cognitive impairment may be unable to recall or report their experiences. In most cases, it is recommended that the patient be interviewed separately from caregivers or family members whenever abuse is suspected. A home interview can also yield valuable information. Interventions for abused older adults need to be tailored to the symptoms and situation. Medication to reduce agitation in an older person with dementia may help to control triggers for abuse by a caregiver, or in the case of a mentally ill perpetrator, treatment focused on the abuser may have the greatest effect. Excellent case examples illustrating issues in intervention can be found in a recent edited volume by Anetzberger (2004). The National Center on Elder Abuse (http://www.elderabusecenter.org/) provides links to bibliographies on detection and management of elder abuse, as well as state-specific guidelines for case substantiation and reporting requirements. Bergeron (2004) provides a thoughtful and practical discussion of obligation to report issues for mental health professionals.

References Administration on Aging: The National Elder Abuse Incident Study. Prepared by the National Center on Elder Abuse in collaboration with Westat. Final Report, September 1998. Available at http://www.aoa.gov/eldfam/Elder_Rights/ Elder_Abuse/AbuseReport_Full.pdf. Accessed September 25, 2005.

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American Law Institute: Restatement of the Law Second, Contracts 2d. St. Paul, MN, American Law Institute, 1981 American Medical Association: Diagnostic and Treatment Guidelines on Elder Abuse and Neglect. Chicago, IL, American Medical Association, 1992 Anetzberger G (ed): The Clinical Management of Elder Abuse. Binghamton, NY, Haworth, 2004 Appelbaum PS, Grisso T: Assessing patients’ capacities to consent to treatment [published erratum appears in N Engl J Med 320:748, 1989]. N Engl J Med 319:1635– 1638, 1988 Armstrong DG: Retirement Nightmare: How to Save Yourself From Your Heirs and Protectors. Amherst, NY, Prometheus Books, 2000 Ball K: Attentional problems and older drivers. Alzheimer Dis Assoc Disord 11 (suppl 1):42–47, 1997 Ball K, Owsley C, Sloane ME, et al: Visual attention problems as predictor of vehicle crashes in older drivers. Invest Opthalmol Vis Sci 34:3110–3123, 1993 Bergeron L: Clinical assessment and the obligation to report, in Health Consequences of Abuse in the Family. Edited by Kendall-Tackett K. Washington, DC, American Psychological Association, 2004, pp 109–128 Bonnie R, Wallace R (eds): Elder Abuse: Abuse, Neglect, and Exploitation in an Aging America. Washington, DC, National Academy Press, 2002 Brekke JS, Raine A, Ansel M, et al: Neuropsychological and psychophysiological correlates of psychosocial functioning in schizophrenia. Schizophr Bull 23:19–28, 1997 Brown LB, Ott BR, Papandonatos GD, et al: Prediction of on-road driving performance in patients with early Alzheimer’s disease. J Am Geriatr Soc 53:94–98, 2005 Cal Civ Code §38. Available at http://leginfo.public.ca.gov/calaw.html. Accessed March 8, 2006. Cal Civ Code §39. Available at http://leginfo.public.ca.gov/calaw.html. Accessed March 8, 2006. Cal Civ Code §1575. Available at http://leginfo.public.ca.gov/calaw.html. Accessed March 8, 2006. Cal Prob Code §813. Available at http://leginfo.public.ca.gov/calaw.html. Accessed March 8, 2006. Cal Prob Code §1801a. Available at http://leginfo.public.ca.gov/calaw.html. Accessed March 8, 2006. Cal Prob Code §1801b. Available at http://leginfo.public.ca.gov/calaw.html. Accessed March 8, 2006. Cal Prob Code §3201. Available at http://leginfo.public.ca.gov/calaw.html. Accessed March 8, 2006.

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Cal Prob Code §4120. Available at http://leginfo.public.ca.gov/calaw.html. Accessed March 8, 2006. Cal Prob Code §4722 Cal Prob Code §4724 Cal Prob Code §6100.5. Available at http://leginfo.public.ca.gov/calaw.html. Accessed March 8, 2006. Chen ST, Sultzer DL, Hinkin CH, et al: Executive dysfunction in Alzheimer’s disease: association with neuropsychiatric symptoms and functional impairment. J Neuropsychiatry Clin Neurosci 10:426–432, 1998 Citizen’s National Bank v Pearson, 67 III App 3d 457 43N55 (1978) Dobbs AR: Evaluating the driving competence of dementia patients. Alzheimer Dis Assoc Disord 11 (suppl 1):8–12, 1997 Dobbs BM: Driving and dementia: consequences of evaluation and de-licensing. Paper presented at the 50th annual scientific meeting of the Gerontological Society of America, Cincinnati, OH, November 14–18, 1997 Dubinsky RM, Stein AC, Lyons K: Practice parameter: risk of driving and Alzheimer’s disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 54:2205–2211, 2000 Estate of Goetz, 253 Cal App 2d 107 1 (1967) Estate of Rosen, 447 A2d 1220, 1222 (Me 1982) Federal Rules of Evidence. Available at http://judiciary.house.gov/media/pdfs/printers/ 109th/evid2005.pdf. Accessed March 8, 2006. Fellows LK: Competency and consent in dementia. J Am Geriatr Soc 46:922–926, 1998 Fitten LJ, Perryman KM, Wilkinson CJ, et al: Alzheimer and vascular dementias and driving: a prospective road and laboratory study. JAMA 273:1360–1365, 1995 Foley DJ, Wallace RB, Eberhard J: Risk factors for motor vehicle crashes among older drivers in a rural community. J Am Geriatr Soc 43:776–781, 1995 Freund B, Gravenstein S, Ferris R, et al: Clock Drawing Test tracks progression of driving performance in cognitively impaired older adults: case comparisons. Clinical Geriatrics 12:33–36, 2004 Fulmer T, Guadano L, Dyer C, et al: Progress in elder abuse assessment instruments. J Am Geriatr Soc 52:297–304, 2004 Grisso T, Appelbaum PS: Assessing Competence to Consent to Treatment: A Guide for Physicians and Other Health Professionals. New York, Oxford University Press, 1998 Grisso T, Appelbaum PS, Hill-Fotouhi C: The MacCAT-T: a clinical tool to assess patients’ capacities to make treatment decisions. Psychiatr Serv 48:1415–1419, 1997 Hankin MB: A brief introduction to the Due Process in Competence Determinations Act: a statement of legislative intent. California Trusts and Estates Quarterly 1:36– 50, 1995

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In re Conroy, 9N24A1 (1985) Koepsell TD, Wolf ME, McCloskey L, et al: Medical conditions and motor vehicle injuries in older adults. J Am Geriatr Soc 42:695–700, 1994 Lachs MS, Pillemer K: Elder abuse. Lancet 364:1263–1271, 2004 Marson DC, McInturff B, Hawkins L, et al: Consistency of physician judgments of capacity to consent in mild Alzheimer’s disease. J Am Geriatr Soc 45:453–457, 1997 McCloskey LW, Koepsell TD, Wolf ME, et al: Motor vehicle collision injuries and sensory impairments of older drivers. Age Ageing 23:267–273, 1994 Meiklejohn AM: Contractual and donative capacity. Case West Reserve Law Rev 39:307–387, 1988–1989 Morris JC: The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 43:2412–2414, 1993 Ott BR, Heindel WC, Whelihan WM, et al: Maze test performance and reported driving ability in early dementia. J Geriatr Psychiatry Neurol 16:151–155, 2003 Ott BR, Anthony D, Papandonatos GD, et al: Clinician assessment of the driving competence of patients with dementia. J Am Geriatr Soc 53:829–833, 2005 Palmer BW, Dunn LB, Appelbaum PS, et al: Assessment of capacity to consent to research among older persons with schizophrenia, Alzheimer disease, or diabetes mellitus: comparison of a 3-item questionnaire with a comprehensive standardized capacity instrument. Arch Gen Psychiatry 62:726–733, 2005 Patient Self-Determination Act of 1990, Pub. L. No. 101-508, §4206 and 4751, 104 Stat. 1388, 1388-115, and 1388-204 [classified respectively at 42 USC 1395cc(t) (Medicare) and 1396a(w) (Medicaid)] (1991) Pavlik VN, Hyman DJ, Festa NA, et al: Quantifying the problem of abuse and neglect in adults—analysis of a statewide database. J Am Geriatr Soc 49:45–48, 2001 President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research: Making Health Care Decisions, Vol 1: A Report on the Ethical and Legal Implications of Informed Consent in the Patient-Practitioner Relationship. Washington, DC, U.S. Government Printing Office, 1982 Ray WA, Fought RL, Decker MD: Psychoactive drugs and the risk of injurious motor vehicle crashes in elderly drivers. Am J Epidemiol 136:873–883, 1992 Reger MA, Welsh RK, Watson GS, et al: The relationship between neuropsychological functioning and driving ability in dementia: a meta-analysis. Neuropsychology 18:85–93, 2004 Reisberg B, Sclan SG, Franssen E, et al: Dementia staging in chronic care populations. Alzheimer Dis Assoc Disord 8 (suppl 1):S188–S205, 1994 Rosoff AJ, Gottlieb GL: Preserving personal autonomy for the elderly. competency, guardianship, and Alzheimer’s disease. J Leg Med 8:1–47, 1987

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Singer M: Undue influence and written documents: psychological aspects. Journal of Questioned Document Examination 1:4–13, 1992 Spar JE, Garb AS: Assessing competency to make a will. Am J Psychiatry 149:169– 174, 1992 Srebnik D, Appelbaum PS, Russo J: Assessing competence to complete psychiatric advance directives with the Competence Assessment Tool for Psychiatric Advance Directives. Compr Psychiatry 45:239–245, 2004 Stern RA, White T: Neuropsychological Assessment Battery. Lutz, FL, Psychological Assessment Resources, 2003 Uc EY, Rizzo M, Anderson SW, et al: Driver landmark and traffic sign identification in early Alzheimer’s disease. J Neurol Neurosurg Psychiatry 76:764–768, 2005 Uniform Durable Power of Attorney Act, §1 8U2 (1983). Available at: http:// www.legis.state.wi.us/statutes/1983/83stat0243.pdf. Accessed February 28, 2006. Also available from the National Conference of Commissioners on Uniform State Laws, 211 E. Ontario Street, Suite 1300, Chicago, IL 60611. U.S. Food and Drug Administration: Protection of human subjects: informed consent, 61 Federal Register 51498 (1996) U.S. Preventive Services Task Force: Screening for family and intimate partner violence: recommendation statement. Rockville, MD, Agency for Healthcare Research and Quality, March 2004. Available at: http//:www.ahrq.gov/clinic/ 3rduspstf/famviolence/famviolrs.htm. Accessed February 28, 2006. Vellinga A, Smit JH, Van Leeuwen E, et al: Competence to consent to treatment of geriatric patients: judgments of physicians, family members and the vignette method. Int J Geriatr Psychiatry 19:645–654, 2004 Wadley VG, Harrell LE, Marson DC: Self- and informant report of financial abilities in patients with Alzheimer’s disease: reliable and valid? J Am Geriatr Soc 51: 1621–1626, 2003 Wang CC, Kosinski CJ, Schwartzberg JG, et al: Safety and the older driver: an overview, in Physicians Guide to Assessing and Counseling Older Drivers. Washington, DC, National Highway Traffic Safety Administration, 2003. Available at: http://www.nhtsa.gov/people/injury/olddrive/OlderDriversBook/pages/ Chapter1.html#Anchor-33096). Accessed February 28, 2006. Wilber KH, Reynolds SL: Rethinking alternatives to guardianship. Gerontologist 35:248–257, 1995 World Health Organization: World report on violence and health. Geneva, World Health Organization, 2002. Available at: http://www.who.int/ violence_injury_prevention/violence/world_report/en. Accessed February 28, 2006.

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Geriatric Depression Scale Choose the best answer for how you felt over the past week. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30.

Are you basically satisfied with your life? Have you dropped many of your activities and interests? Do you feel that your life is empty? Do you often get bored? Are you hopeful about the future? Are you bothered by thoughts you can’t get out of your head? Are you in good spirits most of the time? Are you afraid that something bad is going to happen to you? Do you feel happy most of the time? Do you often feel helpless? Do you often get restless and fidgety? Do you prefer to stay home, rather than going out and doing new things? Do you frequently worry about the future? Do you feel you have more problems with memory than most? Do you think it is wonderful to be alive now? Do you often feel downhearted and blue? Do you feel pretty worthless the way you are now? Do you worry a lot about the past? Do you find life very exciting? Is it hard for you to get started on new projects? Do you feel full of energy? Do you feel that your situation is hopeless? Do you think that most people are better off than you are? Do you frequently get upset over little things? Do you frequently feel like crying? Do you have trouble concentrating? Do you enjoy getting up in the morning? Do you prefer to avoid social gatherings? Is it easy for you to make decisions? Is your mind as clear as it used to be?

yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no yes/no

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Geriatric Depression Scale (continued) Critical responses: “yes”: Items 2, 3, 4, 6, 8, 10, 11, 12, 13, 14, 16, 17, 18, 20, 22, 23, 24, 25, 26, 28 “no”: Items 1, 5, 7, 9, 15, 19, 21, 27, 29, 30 Scores ≥ 11 raise a question of depression. Source. Yesavage J, Brink T, Rose T, et al.: “Development and Validation of a Geriatric Depression Screening Scale: A Preliminary Report.” Journal of Psychiatric Research 17:37–49, 1983. See also Yesavage JA: “The Use of Self-Rating Depression Scales in the Elderly,” in Handbook for Clinical Memory Assessment of Older Adults. Edited by Poon L. Washington, DC, American Psychological Association, 1986, pp. 213–217.

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Six-Item Orientation-Memory-Concentration Test Item What year is it now? What month is it now? Repeat this phrase after me: “John Brown, 42 Market Street, Chicago” About what time is it? Count backward from 20 to 1 Say the months in reverse order Repeat the memory phrase

Maximum error

Weight Score

1 1

×4 ×3

= _____ = _____

1 2 2 5

×3 ×2 ×2 ×2

= _____ = _____ = _____ = _____

Total

= _____

Note. One point is scored for each incorrect response and then multiplied by the weighing factor. Total weighted error scores > 10 suggest cognitive impairment. Source. Adapted from Katzman R, Brown T, Fuld P, et al.: “Validation of a Short OrientationMemory-Concentration Test of Cognitive Impairment.” American Journal of Psychiatry 140:734– 739, 1983. Copyright 1983, American Psychiatric Association. Used with permission.

Note. ATT= attention; CALC= calculation; COMP= comprehension; CONST= construction; JUD= judgment; LOC = level of consciousness; MEM= memory; NAM= naming; ORI= orientation; REP= repetition; SIM= similarities. Source. Adapted from Northern California Neurobehavioral Group: Manual for Cognistat (The Neurobehavioral Cognitive Status Examination). Fairfax, CA, Northern California Neurobehavioral Group, 1995, p. 12. Used with permission.

Appendix: Clinical Assessment Instruments

Cognistat profile of an 82-year-old woman with probable Alzheimer’s disease.

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Instrumental Activities of Daily Living (IADL) Scale A. Ability to use the telephone Does not answer the telephone at all Answers telephone but does not dial Dials a few well-known numbers Operates telephone on own initiative

1 2 3 4

B. Shopping Completely unable to shop Needs to be accompanied on any shopping trip Shops independently for small purchases Takes care of all shopping needs independently

1 2 3 4

C. Food preparation Needs to have meals prepared and served Heats and serves prepared meals, or prepares meals but does not maintain an adequate diet Prepares adequate meals if supplied with ingredients Plans, prepares, and serves adequate meals independently

1 2 3 4

D. Housekeeping Unable to participate in any housekeeping tasks Needs help with all home maintenance tasks Performs light daily tasks such as dishwashing Maintains house alone or with occasional assistance

1 2 3 4

E. Laundry All laundry must be done by others Launders a few small items Does most small items, depends on others for large items Does personal laundry completely

1 2 3 4

F. Mode of transportation Does not travel at all Travel limited to taxi or automobile with assistance of another Travels on public transportation when assisted or accompanied by another Travels independently on public transportation, taxi, or drives own car

1 2 3 4

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Instrumental Activities of Daily Living (IADL) Scale (continued) G. Responsibility for own medications Is not capable of dispensing own medication Takes responsibility if medication is prepared in advance in separate dosages Takes independent responsibility but occasionally forgets a dosage Is responsible for taking medication in correct dosages at correct times H. Ability to handle finances Incapable of handling money Manages day-to-day purchases but needs help with banking, major purchases, etc. Manages financial matters independently but, on occasion, has forgotten to pay a bill or has been overdrawn in bank account Manages financial matters independently, collects and keeps track of income I.

J.

Ability to perform household repairs or chores Unable to do even simple household repairs or chores Can only do very simple tasks such as hanging a picture or mowing the lawn With some help and direction can do moderately difficult household repairs such as fixing a leaky faucet Is able to independently perform most household chores or repairs Skill in driving an automobile Is unable to drive an automobile Drives when someone is present to give directions, drives poorly, or drives very slowly and cautiously Drives alone but has some tendency to get lost or has occasional driving problems Drives alone, has good sense of direction, and good driving skills

1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4

Note. Items can be rated as “not applicable” for persons who have never performed a particular activity (e.g., driving a car) or who have no opportunity to perform a particular activity. Source. Reprinted from Lawton MP, Brody EM: “Assessment of Older People: Self-Maintaining and Instrumental Activities of Daily Living.” The Gerontologist 9:179–186, 1969. Copyright ©The Gerontological Society of America. Reproduced by permission of the publisher.

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Revised Memory and Behavior Problems Checklist Instructions The following is a list of problems patients sometimes have. Please indicate if any of these problems have occurred during the past week. If so, how much has this bothered or upset you when it happened? Please rate the frequency of the problem and your reaction to it by circling a number from 0 to 9 for both frequency and reaction. Frequency ratings 0=never occurred 1=not in the past week 2=1 to 2 times in the past week 3=3 to 6 times in the past week 4=daily or more often 9=don’t know/not applicable Reaction ratings 0=not at all 1=a little 2=moderately 3=very much 4=extremely 9=don’t know/not applicable

1. Asking the same question over and over 2. Trouble remembering recent events (e.g., items in the newspaper or on TV) 3. Trouble remembering significant past events 4. Losing or misplacing things 5. Forgetting what day it is 6. Starting, but not finishing things 7. Difficulty concentrating on a task 8. Destroying property 9. Doing things that embarrass you 10. Waking you or other family members up at night 11. Talking loudly and rapidly 12. Appears anxious or worried

Frequency

Reaction

012349

012349

012349 012349 012349 012349 012349 012349 012349 012349 012349 012349 012349

012349 012349 012349 012349 012349 012349 012349 012349 012349 012349 012349

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Revised Memory and Behavior Problems Checklist (continued)

13. Engaging in behavior that is potentially dangerous to self or others 14. Threats to hurt oneself 15. Threats to hurt others 16. Aggressive to others verbally 17. Appears sad or depressed 18. Expressing feelings of hopelessness or sadness about the future (e.g., “Nothing worthwhile ever happens,” “I never do anything right”) 19. Crying and tearfulness 20. Commenting about death of self or others (e.g., “Life isn’t worth living,” “I’d be better off dead”) 21. Talking about feeling lonely 22. Comments about feeling worthless or being a burden to others 23. Comments about feeling like a failure or about not having worthwhile accomplishments in life 24. Arguing, irritability, and/or complaining

Frequency

Reaction

012349 012349 012349 012349 012349

012349 012349 012349 012349 012349

012349 012349

012349 012349

012349 012349

012349 012349

012349

012349

012349 012349

012349 012349

Source. Adapted from Teri L, Truax P, Logsdon R, et al.: “Assessment of Behavior Problems in Dementia: The Revised Memory and Behavior Problems Checklist.” Psychology and Aging 7:622–631, 1992. Used with permission.

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Items Rated on the Neuropsychiatric Inventory Item

N/A

Delusions Hallucinations Agitation Depression/dysphoria Anxiety Euphoria/elation Apathy/indifference Disinhibition Irritability/lability Aberrant motor behavior Nighttime behavior Appetite/eating change

X X X X X X X X X X X X

Absent 0 0 0 0 0 0 0 0 0 0 0 0

Frequency 1234 1234 1234 1234 1234 1234 1234 1234 1234 1234 1234 1234

Severity 123 123 123 123 123 123 123 123 123 123 123 123

Note. N/A =not applicable (e.g., caregiver does not appear to understand the item, or response misleading for any reason). Frequency: 1= less than once/week; 2 =about once/week; 3 =several times/week but less than daily; 4= daily or continuously. Severity: 1= mild; 2 =moderate; 3 =severe. Source. Reprinted from Cummings JL, Mega M, Gray K, et al.: “The Neuropsychiatric Inventory: Comprehensive Assessment of Psychopathology in Dementia.” Neurology 44:2308–2314, 1994. Used with permission.

Index Page numbers printed in boldface type refer to tables or figures.

Abbreviated cognitive screens, 181–183 Abraham, Karl, 108, 115 Acamprosate, 325–326 Accidents, and motor vehicles, 367– 368 Acetaminophen, 327, 328, 338 Acetazolamide, 78 Acetylcholinesterase, 207 Acquired immunodeficiency syndrome (AIDS), and dementia, 249 Activated or hyperactive subtype, of delirium, 258 Activities of daily life Alzheimer’s disease and, 202 cognitive changes of normal aging and, 32–34 rating scales and, 183–184, 384– 385 Acute treatment, for bipolar disorder, 163–165 Adjustment anxiety and, 276–277 bereavement and, 69 Advance directives, and competency, 349–352 African Americans. See Black Americans

Age and aging. See also Age of onset; Older adults; Very old people biological factors in, 48–61 conceptual issues in, 21–23 delirium and, 262 diversity in patterns of, 12–15 elder abuse and, 372 general trends in, 25–28 increase in older adults as percentage of population, 1–2 influence on mental disorders of early onset, 339–341 Mini-Mental State Examination and, 180 personality and emotional changes in, 38–43 prevalence of Alzheimer’s disease by, 193 processing resource model of cognitive abilities and, 23–38 psychosis and, 294 sexual dysfunction and, 329–331 sleep and advancing, 313 social context of, 43–48 Age-associated memory impairment (AAMI), 35–36, 37

389

390 Clinical Manual of Geriatric Psychiatry

Age of onset. See also Age and aging; Early onset; Late onset Alzheimer’s disease and, 192 anxiety disorders and, 278 bipolar disorder and, 113 dysthymic disorder and, 91, 92 frontotemporal dementia and, 231 major depression and, 83 psychopharmacotherapy for depression and, 147 Agitated Behavior in Dementia scale, 217–218 Agitation psychopharmacotherapy for Alzheimer’s disease and, 214, 216–218, 220 vascular dementia and, 246 AIDS dementia complex, 249 Alcohol and alcohol abuse. See also Substance abuse assessment of, 323–325 associated psychiatric conditions and, 321–323 delirium and withdrawal from, 263 diagnosis of, 321 epidemiology of, 320–321 risk factors for, 321 substance-induced dementia and, 254–255 symptoms of depression induced by, 78 treatment of, 325–326 Alcohol Use Disorders Identification Test (AUDIT), 323–324

Alprazolam anxiety disorders and, 291, 292 insomnia and, 317, 318 Alprostadil, 334 Alternative approaches, to treatment of depression, 161–162 Alzheimer’s Association, 213 Alzheimer’s disease clinical presentation of, 197, 199 Cognistat profile and, 383 competency to drive and, 368, 370 dementia and, 88, 239–240, 250 depression and, 73–74, 90 diagnosis of, 195–205, 198–199 differential diagnosis of, 205–206, 250 epidemiology of, 7, 192–195 frontotemporal dementia and, 232, 234, 236 genetics of, 208 Mini-Mental State Examination and, 178–179 neurobiochemistry of, 207–208 neuropathology of, 206–207 psychopharmacotherapy for, 213– 220 psychosocial theory of, 208–210 psychotherapy for caregivers, 210– 213 Alzheimer’s Disease Assessment Scale, 213, 241 American Academy of Neurology, 368 American Medical Association, 350, 372 Amitriptyline, 134

Index

Amnestic disorders, and Alzheimer’s disease, 205 Amnestic mild cognitive impairment, 36 Amoxapine, 138 Amphetamines, and depression, 137, 153 Amyloid precursor protein (APP), and Alzheimer’s disease, 206 Analgesics. See also Narcotic analgesics; Nonsteroidal anti-inflammatory agents substance abuse and, 327, 328 symptoms of depression induced by, 78 Animal models, for pathogenesis of anxiety disorders, 287 Animal Naming task, 174, 175, 181– 182 Anorexia, and depression, 90 Anterior cingulate syndrome, 335 Anticholinergic agents anxiety symptoms and, 277 delirium and, 263–264 Anticholinergic effects, of tricyclic antidepressants, 149 Anticipatory anxiety, and panic attacks, 281 Anticonvulsants Alzheimer’s disease and, 218 cytochrome P450 system and, 140 Antidepressants. See also Selective serotonin reuptake inhibitors; Tricyclic antidepressants advantages and disadvantages of, 136–137

391

Alzheimer’s disease and, 219 anxiety disorders and, 292 anxiety symptoms induced by, 277 automobile driving and, 370–371 cytochrome P450 system and, 140– 141 dosages of, 148 management of side effects of, 148– 149 predictors of response to, 147 receptor affinities of, 134–135 sexual dysfunctions and, 332 treatment resistance and, 153–155 Antiepileptic agents, and depression, 78 Antihistamines Alzheimer’s disease and, 219 drug-drug interactions and, 139 medication-induced mental disorders and, 56 substance abuse and, 327, 328 Antihypertensive agents sexual dysfunction and, 332 symptoms of depression induced by, 78 Antioxidants, and Alzheimer’s disease, 194 Antiparkinsonian agents medication-induced mental disorders and, 56 psychosis and, 303 Antipsychotics. See also Atypical antipsychotics anxiety disorders and, 292 bipolar disorder and, 163 cytochrome P450 system and, 140 delirium and, 264

392 Clinical Manual of Geriatric Psychiatry

Antipsychotics (continued) dementia with Lewy bodies and, 241 late-onset psychosis and, 303–306 psychotic depression and, 156 sexual dysfunctions and, 332 symptoms of depression induced by, 78 vascular dementia and, 248 Anxiety Alzheimer’s disease and, 218 mood disorder with, 283, 285 schizophrenia with, 285–286 Anxiety disorders autonomic and psychomotor features of, 275 clinical presentation of, 274 diagnosis of, 276–286 epidemiology of, 273–274 laboratory evaluation of, 276 pathogenesis of, 286–288 rating scales for, 274–276 treatment of, 288–293 Anxiolytic agents Alzheimer’s disease and, 218 symptoms of depression and, 78 Apathy, and Alzheimer’s disease, 219 APOE4, and Alzheimer’s disease, 192– 193, 205 Appetite, and major depression, 83 Aripiprazole Alzheimer’s disease and, 216, 220 dementia with Lewy bodies and, 241 psychosis and, 304

Arteriosclerosis, and vascular dementia, 191, 246 Asparaginase, 79 Aspirin, 328 Assessment. See also Diagnosis of alcohol abuse or dependency, 323–325 of competency, 356–358 elder abuse and, 373 of erectile dysfunction, 335 of insomnia, 313, 314 of suicidality in elderly, 105–106, 107 Attorney-in-fact, 350, 351 Atypical antipsychotics. See also Antipsychotics Alzheimer’s disease and, 216–217 dementia with Lewy bodies and, 241 psychosis and, 302–303, 304 AUDIT-5 (five-item Alcohol Use Disorders Identification Test), 323–324 Auditory acuity, and normal aging, 24 Augmentation, of antidepressants, 154– 155 Automobiles. See Driving Baclofen, 79 Barbiturates delirium and withdrawal from, 263 substance abuse and, 328 symptoms of depression induced by, 79 Beck Anxiety Inventory, 275–276 Beck Cognitive Insight Scale, 301

Index

Beck Depression Inventory (BDI), 100, 101, 103 Beck Depression Inventory for Primary Care (BDI-PC), 102, 105 Beck Hopelessness Scale, 106 Behavior. See also Agitation; Behavior therapy complications of vascular dementia and, 248 interventions for insomnia, 315– 316 major depression and regression of, 90–91 Behaviorally oriented pain management training, 338 Behavior Pathology in Alzheimer’s Disease Rating Scale (BEHAVEAD), 217–218 Behavior therapy. See also Cognitivebehavioral therapy Alzheimer’s disease and, 216 anxiety disorders and, 288–290 geriatric depression and, 128 late-onset psychosis and, 300–302 Benzodiazepines Alzheimer’s disease and, 216, 219 anxiety disorders and, 290–292, 291 competency to drive and, 370 delirium and withdrawal from, 263 insomnia and, 317–319 psychosis and, 303 substance abuse and, 326, 327, 328 symptoms of depression induced by, 78

393

Bereavement depression compared to “normal,” 68–70 loss and, 80, 108 widowhood and, 46–47 Bibliotherapies, for depression, 161– 162 Biology, of aging, 48–61. See also Genetics; Neurobiological theories Bipolar disorder. See also Hypomania; Mania aging and early-onset, 339 clinical presentation of, 113 epidemiology of, 111, 113 pathogenesis and theories of, 115– 116 psychopharmacotherapy for, 157, 163–166 treatment of, 162–163 Black Americans caregivers for dementia patients and, 211, 212 patterns of health and aging in, 12– 14 poverty rates and, 45 Blessed Information Memory Concentration Test, 183 β-Blockers medication-induced mental disorders and, 56 substance-induced mood disorder and, 77 symptoms of depression induced by, 78 Boston Naming Test (BNT), 188, 357

394 Clinical Manual of Geriatric Psychiatry

Braak’s criteria, for Alzheimer’s disease, 195, 196 Brief dynamic therapy, for geriatric depression, 130 Bronchodilators anxiety symptoms induced by, 277 medication-induced mental disorders and, 56 Bupropion advantages and disadvantages of, 136 depression and, 138, 143–144, 148 receptor affinities of, 134 Buspirone, 292 Caffeine anxiety and, 277 substance abuse and, 327, 328 CAGE Questionnaire, 323–325 Calcium channel blockers, and symptoms of depression, 78 California, and laws on competency, 348, 349, 351, 354, 361, 362, 363–365 California Verbal Learning Test (CVLT), 187 Cannabis, 326–327 Capacity. See also Competency contracts and, 351 testamentary, 354–356 Carbamazepine, and bipolar disorder, 164–165, 166 Cardiovascular system, and biological aging, 52. See also Heart disease; Stroke; Vascular disorders; Vascular lesions

Caregivers psychotherapy for dementia and, 210–213 relief after death of patient, 69–70 resources for, 228 social context of aging and, 48 Case examples of biology of aging, 51 of insomnia, 318–319 of major depression, 85–86 of psychotic depression, 84 Category fluency measures, 181–182 Center for Epidemiologic Studies Depression Scale, 69–70, 90, 93 Cerebrovascular disease. See also Stroke dementia with Lewy bodies and, 237 vascular dementia and, 242, 245 Chemotherapeutic agents, and symptoms of depression, 78–79 China, older adults as percentage of population of, 2 Chloral hydrate, 318, 328 Chlordiazepoxide, 291 Chlorpheniramine, 328 Chlorpromazine, 304 Choline acetyltransferase, and Alzheimer’s disease, 207 Cholinesterase inhibitors Alzheimer’s disease and, 213, 214, 215, 218 delirium and, 263, 264 dementia due to general medical conditions and, 253 dementia with Lewy bodies and, 240–241

Index

substance-induced persisting dementia and, 254 vascular dementia and, 247 Chronic illness, and major depression, 71–72. See also Medical conditions Chronic pain, 337–339 Cimetidine, 79 Citalopram anxiety disorders and, 292 depression and, 139, 143, 148 receptor affinities of, 134 Clinical Dementia Rating (CDR), 368 Clinical Global Impression (CGI), 160 Clinical implications. See also Treatment of biology of aging, 50–61 of cognitive change in aging, 34–35 of personality and emotional changes in aging, 42–43 Clinical interview, and assessment of competency, 356–357 Clinical presentation of age-associated memory impairment, 37 of Alzheimer’s disease, 197, 199 of anxiety disorders, 274 of bipolar disorder, 113 of delirium, 257 of dementia with Lewy bodies, 238 of frontotemporal dementia, 231 of psychosis, 294, 296 of social context of aging, 48 of vascular dementia, 243 Clock Drawing Test, 176, 182, 368

395

Clonazepam pharmacological properties of, 291 psychosis and, 303 Clonidine, 78 Clorazepate, pharmacological properties of, 291 Clozapine, and late-onset psychosis, 303, 304 Cocaine, 326 Code of Federal Regulations, 352 Codeine substance abuse and, 328 symptoms of depression induced by, 78 Cognistat, 175, 383 Cognitive Abilities Screening Instrument (CASI), 174, 175, 181 Cognitive and behavioral theories, of depression, 108–109 Cognitive-behavioral therapy. See also Behavior therapy for anxiety disorders, 288–289 for geriatric depression, 128–129 for insomnia, 316 for late-onset psychosis, 300–302 Cognitive impairment. See also Executive functions; Learning; Memory aging effects on performance and, 26–27 alcohol abuse or dependency and, 321–323 competency assessment and, 357– 358 delirium and, 262

396 Clinical Manual of Geriatric Psychiatry

Cognitive impairment (continued) depression and, 83, 87–91, 128, 147 evaluation of Alzheimer’s disease and, 200–201, 202 late-onset psychosis and, 297 processing resource model of, 23–38 psychopharmacotherapy for Alzheimer’s disease and, 213– 220 risk of in older adults, 7 standardized measures for rating, 174–183 variables of in normal aging, 29 vascular dementia and, 243, 247– 248 Cohen-Mansfield Agitation Inventory, 217–218 Cohort effects, on cognition in normal aging, 29 Combined treatment, for geriatric depression, 132, 155 Community-based programs, for substance abuse, 329 Comorbidity, of psychiatric disorders alcohol abuse or dependency and, 321–323 diagnosis and treatment of depression and, 129 personality disorders and, 340 Competence Assessment Tool for Psychiatric Advance Directives, 358 Competency advance directives and, 349–352 assessment of, 356–358

caring for oneself and management of finances, 360–362 contracts and gifts, 353–354 definition of, 347–348 driving and, 367–371 enrollment in research studies and, 352, 353 informed consent for medical care and, 348–349, 349 surrogate decision-makers and, 363–365 trusts and, 356 wills and, 354–356 Compliance, with treatment for depression, 131–132 Complicated grief, 70, 71 Computed tomography, in diagnosis of Alzheimer’s disease, 198, 201, 250 of delirium, 261 of dementias, 185, 250–252 dementia with Lewy bodies, 237 frontotemporal dementia, 234 vascular dementia, 245 of depression, 97 of hypomania or mania, 116 Computers. See Web sites Confusion Assessment Method (CAM) algorithm, 258–259, 260 Congestive heart failure, 72 Conservators and conservatorship, 361–362, 363–365 Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word List Learning, 188, 195, 196–197, 203 Continuity, in personality, 39

Index

Contracts, and competency, 351, 353– 354, 359 Contraindications, for tricyclic antidepressants, 138 Control, and emotional changes during aging, 41, 42 Controlled Oral Word Association Test (COWAT), 188 Coping, and emotional changes during aging, 40–42 Cornell Scale for Depression in Dementia, 101, 104–105 Costs, of health care for older adults, 5– 6 Counseling, and alcohol abuse and dependency, 325 Creutzfeldt-Jakob disease, and dementia, 252 Cross-sectional view, of aging, 22 Culture access to mental health services and, 14 caregivers for dementia patients and, 213 Cytochrome P450 system, and psychotropic medications, 138, 139, 140–141, 142, 143, 144 Death, leading causes of in older adults, 3. See also Mortality Decisional competency, 347–348 Decongestants anxiety symptoms induced by, 277 medication-induced mental disorders and, 56 substance abuse and, 327

397

Delirium Alzheimer’s disease and, 206 diagnostic criteria for, 258 differential diagnosis of, 259, 261– 262 epidemiology of, 256–257 laboratory evaluation of, 259–260, 261 mental status examination and, 257–259 pathogenesis of, 262 patient history and clinical presentation of, 257 prognosis in, 264 psychosis and, 298, 337 treatment of, 263–264 vascular dementia and, 246 Delirium Rating Scale, 258, 259 Delis-Kaplan Executive Function System, 234 Delusions and delusional disorder Alzheimer’s disease and, 197, 199 diagnostic criteria for, 296 late-onset psychosis and, 299, 306 psychotic depression and, 84 psychotic disorder due to a general medical condition and, 336 Dementia. See also Dementia due to general medical conditions; Dementia with Lewy bodies; Frontotemporal dementia; Mixed dementia; Reversible dementia; Substance-induced persisting dementia; Vascular dementia alcohol-related, 322, 324 Alzheimer’s disease and, 205

398 Clinical Manual of Geriatric Psychiatry

Dementia (continued) chronic pain and, 338–339 competency to drive and, 368, 369– 370, 371 delirium and, 259, 261–262 diagnosis of, 173–186, 187–189 differentiation of common forms, 250–252 etiologies of, 186, 190–191 major depression and, 89 mild cognitive impairment and progression to, 36–38 psychosis and, 337 psychotherapy for caregivers, 210– 213 resources for caregivers, 228 Dementia due to general medical conditions, 249–254 Dementia with Lewy bodies, 235, 237– 241 Dementia Rating Scale (DRS), 174, 176, 178 Dementia syndrome of depression (DSD), 87–88 Depression. See also Major depression aging and early-onset, 339 alcohol abuse or dependency and, 323 Alzheimer’s disease and, 218–219 chronic pain and, 338 complementary and alternative approaches to treatment of, 161–162 dementia and, 89 experimental therapies for, 159–160

importance of in older adults, 7–8, 67 laboratory evaluation of, 95–96, 97 medical conditions and, 70–76 minor or subthreshold forms of, 92– 93, 94–95 normal grief and, 68–70 personality disorders and, 340 problems in diagnosis and treatment of, 129 psychological tests for, 96–97 psychopharmacotherapy for, 132– 156, 218–219 psychotherapy for, 127–130 rating scales and, 97–105 theories of, 107–110 undertreatment of, 67–68 Depressive personality disorder, 95 Depressive pseudodementia, 87 Desipramine, and depression, 134, 146 Detoxification, and substance abuse, 329 Developmental optimism, 38 Dexamethasone, and depression, 79, 96 Diagnosis. See also Assessment; Differential diagnosis; DSM-IVTR; Rating scales; Underrecognition of age-related cognitive change and mild cognitive impairment, 35–38 of alcohol abuse or dependency, 321 of Alzheimer’s disease, 195–197, 198–199 of anxiety disorders, 276–286

Index

biological aging and guidelines for, 55 of delirium, 258 of dementia with Lewy bodies, 237– 238 of dementia with unspecified cause, 173–186 of depression due to a general medical condition, 70–76 of depressive personality disorder, 95 of dysthymic disorder, 91–92 of frontotemporal dementia, 229, 230–231 of hypomania and mania, 110–117 of major depression, 80–91, 129 of minor depression, 92–95 of mixed mood disorder, 117 of substance-induced mood disorder, 76–80 of vascular dementia, 241–242, 243 Diazepam insomnia and, 318 pharmacological properties of, 291 Differential diagnosis. See also Diagnosis Alzheimer’s disease and, 205–206 delirium and, 259, 261–262 dementia with Lewy bodies and, 240 frontotemporal dementia and, 234, 236 insomnia and, 313–315 normal grief and bereavement, 68– 70

399

psychosis and, 298, 337 vascular dementia and, 245–246 Differential vulnerability hypothesis, for posttraumatic stress disorder, 281–283 Digoxin, 79 Diphenhydramine Alzheimer’s disease and, 219 substance abuse and, 328 Direct Assessment of Functioning Scale, 184 Disability, rates of in older adults, 3–4 Disulfiram, 79 Divalproex, and bipolar disorder, 164, 165, 166 Diversity, in patterns of health and aging, 12–15 Doctor-patient relationship, and agerelated cognitive changes, 34 Donepezil Alzheimer’s disease and, 213, 215, 218 delirium and, 263, 264 dementia with Lewy bodies and, 240–241 vascular dementia and, 247 Dosage. See also Psychopharmacotherapy of antidepressants for geriatric depression, 148 of antipsychotics for Alzheimer’s disease, 217 for bipolar disorder, 163 for late-onset psychosis, 303– 306 of carbamazepine, 164

400 Clinical Manual of Geriatric Psychiatry

Dosage (continued) of lamotrigine, 165 of monoamine oxidase inhibitors, 152 Double depression, 91 Doxepin, 134 Driving cognitive changes of aging and, 33 competency to, 367–371 Drop-out rates, from treatment for depression, 131–132 Drug-drug interactions monoamine oxidase inhibitors and, 139, 152–153, 155 selective serotonin reuptake inhibitors and, 139, 155 DSM-III-R, and late-onset psychosis, 293 DSM-IV-TR. See also Diagnosis age-related cognitive changes and, 35, 36 alcohol abuse or dependency and, 321, 322 Alzheimer’s disease and, 195, 196, 203 anxiety disorders and, 274, 279 delirium and, 257, 258 delusional disorder and, 296 dementia due to general medical conditions and, 249 depression due to a medical condition and, 68 depressive personality disorder and, 95 dysthymic disorder and, 91 insomnia and, 316

major depression and, 82, 85 mania and hypomania in, 114–115, 117 minor depressive disorder and, 94–95 obsessive-compulsive disorder and, 282 panic disorder and, 281, 283 personality change due to a general medical condition and, 336 phobias and, 280 posttraumatic stress disorder and, 284–285 psychiatric illness related to a general medical condition and, 334 psychosis and, 293 schizophrenia and, 286, 295 substance abuse and, 322, 323 substance-induced mood disorder and, 76 vascular dementia and, 242, 243 Duloxetine advantages and disadvantages of, 136, 145 chronic pain and, 338 receptor affinities of, 134 Durable power of attorney for health care (DPAHC), 363 Dysthymic disorder, 91–92 Early onset. See also Age of onset influence of aging on disorders of, 339–341 of major depression, 83 Economics. See Costs; Financial decision making; Financial status

Index

Education. See also Learning cognition in normal aging and, 29 Mini-Mental State Examination and, 180 social context of aging and, 43–45, 44 treatment of depression and, 161– 162 Elder abuse, 371–373 Electrocardiogram in laboratory evaluation of delirium, 261 of dementia, 185 lithium and, 165, 166 tricyclic antidepressants and, 145 Electroconvulsive therapy (ECT) major depression and, 157–159 manic episodes following, 111, 114, 117 psychotic depression and, 156 Electroencephalogram diagnosis of Alzheimer’s disease, 198, 201 Creutzfeldt-Jakob disease, 252 delirium, 261 dementia with Lewy bodies, 237 frontotemporal dementia, 230 in laboratory evaluation of dementia, 185 Emotions, and changes in normal aging, 40–42 Endocrine disorders, and dementia, 190 Endocrine system, and biological aging, 53

401

Ephedrine, 328 Epidemiologic Catchment Area (ECA) Study, 6, 92, 111, 273 Epidemiology of alcohol abuse and dependency, 320–321 of Alzheimer’s disease, 192–195 of anxiety disorders, 273–274 of bipolar disorder, 111, 113 of delirium, 256–257 of dementia with Lewy bodies, 237 of frontotemporal dementia, 229 of major depression, 80 of substance abuse, 326–327 of vascular dementia, 241 Erectile dysfunction (ED), 330, 331– 332, 333, 334, 335 Escitalopram, and depression, 139, 148 Estrogen, and Alzheimer’s disease, 194 Eszopiclone, and insomnia, 318, 319, 320 Etiology, of dementia, 186, 190–191. See also Pathogenesis and pathology Executive functions. See also Cognitive impairment aging effects on cognitive performance and, 27, 32 competency assessment and, 358 Executive Interview, 232 Exercise, and treatment of depression, 161 Experimental therapies, for depression, 159–160 Explicit memory, 30

402 Clinical Manual of Geriatric Psychiatry

Family. See also Caregivers grandparents and, 48 legal issue of undue influence and, 360 marriage and, 45–47 social context of aging and, 47–48 substance abuse and, 329 Family history, of frontotemporal dementia, 231. See also Genetics Family therapy dementia caregivers and, 211–212 geriatric depression and, 130 late-onset psychosis and, 302 Fatality rate, for older drivers, 367. See also Mortality Fatigue, and depression, 83 Feeling Good (Burns 1999), 162 Filter hypothesis, for schizophrenia, 300 Financial decision making, and legal surrogates, 365 Financial status, and social context of aging, 43–45 Fluoxetine depression and, 139, 142 receptor affinities of, 134 Fluphenazine, and psychosis, 303, 304 Flurazepam, 318 Fluvoxamine, and depression, 139, 142 Food and Drug Administration (FDA), 216–217, 248, 352 Freud, Sigmund, 108 Friendship, and social context of aging, 47–48 Frontal Assessment Battery (FAB), 232 Frontal Behavioral Inventory, 232–233

Frontal lobe hypothesis, and neuropsychological model of normal aging, 25 Frontal Systems Behavior Scale, 232 Frontotemporal dementia, 229–235, 236 Functional competency, 348 Functional magnetic resonance imaging (fMRI), and Alzheimer’s disease, 203, 204 Galantamine Alzheimer’s disease and, 213, 215 vascular dementia and, 247 Gastrointestinal system, and biological aging, 52 Gender, and cognition in normal aging, 14, 29. See also Women Generalized anxiety disorder autonomic and psychomotor features of, 275 diagnosis of, 277–278, 279 prevalence of, 273 treatment of, 289, 290, 292 Genetics. See also Family history Alzheimer’s disease and, 192–193, 208 biological aging and, 49–50 cognition in normal aging and, 29 personality and, 39 pharmacogenetics and, 58 Genitourinary system, and biological aging, 53 Geriatric Depression Scale (GDS), 75, 100, 101, 103, 380–381 Geriatric Mental State Schedule, 75

Index

Gifts, and competency, 353–354 Gingko biloba, and Alzheimer’s disease, 214 Global Study of Sexual Attitudes and Behaviors, 330, 331 Glutethimide, 318 Grandparents, and caregiving, 48 Grief. See Bereavement; Complicated grief Group therapy geriatric depression and, 130, 161 late-onset psychosis and, 302 Guanethidine, and depression, 78 Guardians and guardianship, 361–362, 363 Guidelines for diagnostic process with older adults, 55 for treatment of older adults, 55–61 Hallucinations late-onset psychosis and, 296 psychotic depression and, 84 psychotic disorder due to a general medical condition and, 336 Haloperidol Alzheimer’s disease and, 217, 220 bipolar disorder and, 163 delirium and, 264 psychosis and, 303, 304 symptoms of depression induced by, 78 Hamilton Anxiety Rating Scale, 274– 275 Hamilton Rating Scale for Depression (Ham-D), 81, 101, 104, 132, 160

403

Hasegawa Dementia Scale, 181 Hayflick phenomenon, 49 Head injury dementia and, 251, 253 secondary mania and, 112 Health, personality and perceptions of, 40. See also Health care; Medical conditions; Public health Health care. See also Hospitalization; Insurance; Medical evaluation; Medicare; Nursing homes; Primary care physicians informed consent and, 348–349, 349 overview of for older adults, 3–6 Health and Retirement Study, 7 Heart disease, and depression, 72–73 Heavy metals, and dementia, 191 Heterogeneity, in patterns of aging, 22– 23 Highly active antiretroviral therapy (HAART), 249 Hispanic Americans caregivers for dementia patients and, 211, 212–213 Mini-Mental State Examination and, 181 patterns of health and aging in, 12– 14 poverty rates and, 45 HIV dementia, 249, 250 Home visits, and geriatric depression, 128 Hormone replacement therapy, and Alzheimer’s disease, 194

404 Clinical Manual of Geriatric Psychiatry

Hospitalization anorexia and depression, 90 rates of for older adults, 3 Huntington’s disease, and dementia, 251, 253 Hypertension caution with lithium and, 165–166 and side effects of monoamine oxidase inhibitors, 152 tricyclic antidepressants, 149 Hypnotic agents. See also Benzodiazepines; Sedativehypnotics Alzheimer’s disease and, 219 insomnia and, 319–320 Hypochondriasis, and major depression, 86 Hypomania. See also Bipolar disorder diagnosis of, 110–117 psychosis and, 298 treatment of, 162 Imipramine, 134 Immunological system, and biological aging, 54 IMPACT (Improving MoodPromoting Access to Collaborative Treatment) project, 105, 131 Implicit memory, 30 Implied consent, 349 Incidental recall, 30 Infectious diseases dementia and, 190 secondary mania and, 112

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), 184 Informed consent, for medical care, 348–349, 349 Inoculation hypothesis, for posttraumatic stress disorder, 281– 283 Insight-oriented psychotherapy, for late-onset psychosis, 302 Insomnia. See also Sleep disturbance Alzheimer’s disease and, 219 assessment of, 313, 314 diagnostic criteria for, 316 differential diagnosis of, 313–315 sleep hygiene and, 316, 317 treatment of, 315–320 Institutional Review Board (IRB), 352 Instruction directives, 350 Instrumental Activities of Daily Living (IADL) Scale, 184, 384–385 Insurance, and barriers to geriatric mental health care, 11–12. See also Medicare Intelligence, and aging effects on cognitive performance, 26 International Classification of Sleep Disorders, The (American Sleep Disorders Association 1997), 316 International Late-Onset Schizophrenia Group, 294 Internet. See Web sites Interpersonal psychotherapy, for geriatric depression, 129–130 Intracavernosal self-injection, 333–334 Isotretinoin, 79

Index

Japan, and Hasegawa Dementia Scale, 181 Keep Your Brain Young (McKhann and Albert 2002), 31 Knowledge, needed for effective work with elderly patients, 15 Korsakoff ’s syndrome, 205, 254, 255 Korsakoff-type anemia, 321–322 Kraepelin, Emil, 115 Laboratory evaluation. See also Medical evaluation of Alzheimer’s disease, 203 of anxiety disorders, 276 of delirium, 259–260, 261 of dementia of unspecified type, 185 of depression, 95–96, 97, 147 of frontotemporal dementia, 234 of hypomania and mania, 116 of vascular dementia, 245 Lamotrigine bipolar depression and, 157 bipolar disorder and, 164, 165 Language aging effects on cognitive performance and, 26 evaluation of Alzheimer’s disease and, 202 Mini-Mental State Examination and, 179, 181 Late onset. See also Age of onset of major depression, 83 of psychosis, 293–306

405

Learned helplessness, and depression, 108–109 Learning. See also Cognitive impairment; Education cognition in normal aging and, 30– 31, 33–34 psychotherapy for depression and, 128 Learning Throughout Life (National Retired Teachers Association et al. 2004), 31 Legal issues caring for oneself and management of finances, 360–362 competency and, 347–358 driving and, 367–371 elder abuse and, 371–373 surrogate decision-makers and, 360–362, 363–365 undue influence and, 358–360 Levodopa, 79 Levonorgestrel implant, 79 Lewis, Sir Aubrey, 110 Lewy bodies, 240 dementia with, 235, 237–241 Life expectancy, 1–2, 12 Lifestyle modifications, for treatment of depression, 161 List-learning tasks, and Alzheimer’s disease, 203 Lithium advantages and disadvantages of, 137 Alzheimer’s disease and, 216, 219 augmentation of antidepressants, 154–155

406 Clinical Manual of Geriatric Psychiatry

Lithium (continued) bipolar depression and, 157 bipolar disorder and, 163–166 Liver damage, and acetaminophen, 327 Living will, 350, 363 Longitudinal Aging Study Amsterdam, 72 Longitudinal view, of aging, 22 Long-term management, of bipolar disorder, 165 Long-term memory, 30 Lorazepam Alzheimer’s disease and, 217 anxiety disorders and, 290, 291 delirium and, 263, 264 insomnia and, 318 psychosis and, 303 Loss, and depression, 80, 108. See also Bereavement MacArthur Competence Assessment Tool—Treatment, 358 Magnetic resonance imaging (MRI) and Alzheimer’s disease, 203, 204 and other dementias, 252 dementia with Lewy bodies, 237 frontotemporal dementia, 234 vascular dementia, 245 Maintenance treatment, with antidepressants, 156 Major depression. See also Depression chronic illness and, 71–72 diagnosis of, 80–91 electroconvulsive therapy for, 157– 159

Major depressive disorder, in partial remission, 92 Management, of chronic pain, 338 Mania. See also Bipolar disorder diagnosis of, 110–117 psychosis and, 298 treatment of, 162 MAOIs. See Monoamine oxidase inhibitors Maprotiline, 138 Marriage, and social context of aging, 45–47 Masked depression, 85–87 Massachusetts Male Aging Study, 330 MCMI-III (Millon Clinical Multiaxial Inventory–III), 98 Medical conditions. See also Health; Health care; Neurological disorders anxiety and, 277 delirium and, 257, 258 dementia and, 190–191, 249–254 depression due to, 70–76 diagnosis and treatment of depression and, 129 insomnia and, 315 mania due to, 111, 112–113 psychiatric illness due to, 334–337 psychotherapy for depression and, 128 psychotic disorder due to, 336–337 sexual dysfunction and, 331–332 Medical evaluation. See also Laboratory evaluation; Neurological examination

Index

dementia with Lewy bodies and, 239 frontotemporal dementia and, 230– 231, 233 lithium therapy for bipolar disorder and, 165–166 vascular dementia and, 243–244 Medicare, 5, 11, 329 Medications. See also Anticonvulsants; Antiepileptic agents; Antihistamines; Antihypertensive agents; Antiparkinsonian agents; Overdose; Psychopharmacotherapy; Steroids; Treatment; Withdrawal anxiety symptoms produced by, 277 cognitive changes of aging and monitoring of, 33 competency to drive and, 370–371 dementia induced by, 191 depression symptoms induced by, 78–79 diagnosis and treatment of depression and, 129 guidelines for older adults and, 55– 61 insomnia and, 315 prescription of potentially addictive substances and, 330 sexual dysfunction and, 332 signs and symptoms of mental disorder induced by, 56 Mefloquine, 79 Memantine Alzheimer’s disease and, 208, 213– 214, 215 vascular dementia and, 247

407

Memory. See also Cognitive impairment; Working memory aging effects on cognitive performance and, 26–27, 28, 30–32 Alzheimer’s disease and, 202 clinical presentation of loss in old age, 37 electroconvulsive therapy and, 159 psychotherapy for depression and, 128 Memory and Behavior Problems Checklist, 212 Memory Impairment Screen (MIS), 177, 183 Memory Prescription, The (Small 2004), 31 Memory training, for Alzheimer’s disease, 209 Mental activity, and cognition in normal aging, 29 Mental disorders. See also Age of onset; Comorbidity; Diagnosis; Psychiatric illness related to a general medical condition; Treatment influence of aging on disorders of early onset, 339–341 medication-induced signs and symptoms of, 56 overview of in older adults, 6–8, 9 prevalence of for minority groups, 13–14 underrecognition of in older adults, 10

408 Clinical Manual of Geriatric Psychiatry

Mental health care, barriers to geriatric, 8–12 Mental health professionals. See also Psychiatrists barriers to geriatric mental health care and, 11 working effectively with older adults, 15–16 Mentally disabled persons, and competency, 352 Mental status examination. See also Mini-Mental State Examination (MMSE) Alzheimer’s disease and, 202 caution in interpretation of, 34 delirium and, 257–259 dementia of unspecified cause and, 173–174, 175–177 vascular dementia and, 243 Meperidine, and depression, 78, 152 Metabolic disturbances, and mania, 112 Methyldopa, 78 Methylphenidate advantages and disadvantages of, 137 Alzheimer’s disease and, 219 depression and, 153 Methylsergide, 79 Methyprylon, 318 Metoclopramide, 79 Metronidazole, 79 Meyer, Adolf, 110 Michigan Alcoholism Screening Test— Geriatric Version, 323–324 Mild cognitive impairment, 35–38

Mild decline, 25 Millon Clinical Multiaxial Inventory– III (MCMI-III), 98 Mini-Cog, 174, 177, 182 Mini-Mental State Examination (MMSE) cognitive impairment and, 174, 175, 178–181, 357 depression and, 74, 88 frontotemporal dementia and, 232 sample items from, 179 schizophrenia and, 339 Minnesota Multiphasic Personality Inventory–2 (MMPI-2), 98 Minor depression, 92–95 Mirtazapine advantages and disadvantages of, 136 depression and, 138, 144 receptor affinities of, 134 Mixed dementia, 248–249 Mixed episode, of hypomania and mania, 117 Mixed mood disorder, 117 MMSE. See Mini-Mental State Examination MMPI-2 (Minnesota Multiphasic Personality Inventory–2), 98 Mnemonic training, 31 Moclobemide depression and, 150, 151, 152, 155 frontotemporal dementia and, 235 Modafinil Alzheimer’s disease and, 219 depression and, 153

Index

Moderate decline, 25 Modified Ischemic Score, and vascular dementia, 244 Molindone, 78 Monoamine oxidase inhibitors (MAOIs) advantages and disadvantages of, 137 bipolar depression and, 157 depression and, 149–153, 154 drug-drug interactions and, 139, 152–153, 155 sexual dysfunction and, 332 Mood disorders. See also Bipolar disorder; Depression; Mixed mood disorder influence of aging on early-onset, 339 mood disorder with anxiety and, 283, 285 treatment of vascular dementia and, 248 Mood stabilizers. See also Lithium Alzheimer’s disease and, 219 bipolar disorder and, 166 Morale, and emotional changes in aging, 41 Mortality. See also Death; Fatality rate delirium and rates of posthospitalization, 263 poststroke depression and, 73 Musculoskeletal system, and biological aging, 54 Myocardial infarction, and depression, 72

409

Naltrexone, 325 Narcotic analgesics medication-induced mental disorders and, 56 substance abuse and, 328 symptoms of depression induced by, 78 National Bioethics Advisory Commission, 352 National Center on Elder Abuse, 373 National Elder Abuse Incidence Study, 371–372 National Household Survey on Drug Abuse, 326 National Institute on Aging and Ronald and Nancy Reagan Institute of the Alzheimer’s Association criteria, for Alzheimer’s disease, 196 National Institute of Neurological and Communicative Disorders and Stroke (NINCDS), 195, 198– 199, 203 National Institutes of Health, 109 Neglect, and elder abuse, 372 NEO Five-Factor Inventory (NEOFFI), 98 Neoplasms, and mania, 112 Nervous system, and biological aging, 53 Neurobehavioral Cognitive Status Examination (NCSE), 174, 175 Neurobiochemistry, of Alzheimer’s disease, 207–208. See also Neurotransmitters

410 Clinical Manual of Geriatric Psychiatry

Neurobiological theories. See also Neuropsychology; Neurotransmitters of anxiety disorders, 286–288 of bipolar disorder, 116 of depression, 109–110 of psychosis, 299–300 Neurofibrillary tangles, and Alzheimer’s disease, 206 Neuroleptics. See Antipsychotics; Atypical antipsychotics Neurological disorders. See also Neuropathology dementia and, 190 secondary mania and, 113 Neurological examination for dementia with Lewy bodies, 239 for vascular dementia, 243–244 Neuropathology, of Alzheimer’s disease, 195–197, 206–207 Neuropsychiatric Inventory (NPI), 74, 184–185, 212, 233, 388 Neuropsychological Assessment Battery, 368–369 Neuropsychological tests. See also Neuropsychology; Rating scales for Alzheimer’s disease, 202–203 for dementia with Lewy bodies, 239–240 for dementia of unspecified cause, 186, 187–189 for frontotemporal dementia, 233– 234, 236 for psychosis, 296–297 for vascular dementia, 244–245

Neuropsychology, and cognitive changes in aging, 24–25. See also Neurobiological theories; Neuropsychological tests; Neurotransmitters Neuroticism, and depression, 110 Neurotransmitters. See also Neurobiochemistry; Neurobiological theories anxiety disorders and, 286–288 bipolar disorder and, 116 depression and, 109–110 New Jersey, and In re Conroy case, 351– 352 Nocturnal myoclonus, 315 Nonamnestic mild cognitive impairment, 36 Nonarteritic anterior ischemic optic neuropathy (NAION), 333 Nonbenzodiazepine hypnotics, 319– 320 Nonresponse, to antidepressants, 154 Nonsteroidal anti-inflammatory agents (NSAIDs). See also Analgesics Alzheimer’s disease and, 193–194, 214 caution with lithium and, 165–166 chronic pain and, 338 competency to drive and, 371 substance abuse and, 328 symptoms of depression induced by, 78 Noradrenergic system, and anxiety disorders, 286–287 Normative fallacy, 67

Index

Nortriptyline depression and, 145–146, 148 receptor affinities of, 134 NSAIDs. See Nonsteroidal antiinflammatory agents Nursing homes barriers to geriatric mental health care and, 9 health care for older adults and, 4–5 substance abuse and, 329 Nutritional disorders, and dementia, 190–191 Obesity, in older adults, 3 Object Memory Evaluation, 188 Obsessive-compulsive disorder diagnosis of, 279–281, 282 prevalence of, 273 treatment of, 289–290, 292, 293 Olanzapine Alzheimer’s disease and, 216, 217, 220 bipolar disorder and, 163 delirium and, 264 psychosis and, 302–303, 304 vascular dementia and, 248 Older adults. See also Age and aging; Very old people barriers to mental health care for, 8– 12 definition of, 21–22 health and functioning of, 3–6 increase in population of, 1–2 mental disorders in later life and, 6– 8, 9 working effectively with, 15–16

411

Omnibus Budget Reconciliation Act (1987), 8 Opioids, and chronic pain, 338 Optimistic and supportive attitude, and treatment of older adults, 61 Oral contraceptives, and symptoms of depression, 79 Orbitofrontal syndrome, 335–336 Organ systems, and biological aging, 52–54 Orientation-Memory-Concentration Test (OMCT), 174, 177, 183, 382 Overdose, and medication guidelines for older adults, 61 Oxazepam anxiety disorders and, 290, 291 insomnia and, 318 Oxycodone, 328 Pain. See Chronic pain Panic disorder and panic attack autonomic and psychomotor features of, 275 diagnosis of, 281, 283 prevalence of, 273 treatment of, 292–293 Parkinsonism, and dementia with Lewy bodies, 237, 238, 239 Parkinson’s disease dementia and, 251, 253 depression and, 76 Paroxetine depression and, 139, 142 frontotemporal dementia and, 235 receptor affinities of, 134

412 Clinical Manual of Geriatric Psychiatry

Patchiness, of cognitive deficits in vascular dementia, 243 Pathogenesis and pathology. See also Etiology anxiety disorders and, 286–288 bipolar disorder and, 115–116 delirium and, 262 dementia with Lewy bodies and, 240 frontotemporal dementia, 234–235 psychosis and, 298–300 vascular dementia and, 246–247 Patient Health Questionnaire (PHQ9), 102, 105 Patient history Alzheimer’s disease and, 199–202 delirium and, 257 dementia with Lewy bodies and, 238 frontotemporal dementia and, 231 general dementia and, 173 vascular dementia and, 242 Patient Self-Determination Act of 1990, 349–350 Penile prosthesis, 334 Penn State Worry Questionnaire, 276 Pension programs, and financial status, 45 Pentobarbital, and insomnia, 318 Perceptual changes, in normal aging, 24 Perphenazine, 304 Personality changes of in normal aging, 38–43 cognition in normal aging and, 29

psychiatric illness related to a general medical condition and, 334–336 Personality disorders, influence of aging on early-onset forms of, 340–341 Personal qualities, for effective work with elderly patients, 16 Pharmacokinetic and psychodynamic changes, and medications for older adults, 57–58 Phencyclidine, and psychosis, 300 Phenelzine, and depression, 150, 152 Phenothiazines, 78 Phenylephrine, 328 Phenylpropanolamine, 328 Phobias diagnosis of, 278–279 prevalence of, 273 Phosphodiesterase-5 inhibitors, 333 Physical examination. See Medical evaluation Physicians. See Primary care physicians Physostigmine, and delirium, 263, 264 Pick’s disease, and dementia, 252 Pittsburgh Compound-B (PIB), 204 Population, increase of older adults as percentage of, 1–2 Positron emission tomography (PET) and Alzheimer’s disease, 201, 203, 204, 250 and dementia, 185 and dementia with Lewy bodies, 237 and Parkinson’s disease, 251 Poststroke depression, 73

Index

Posttraumatic stress disorder (PTSD), 281–283, 284–285 Poverty, among elderly, 45 Power of attorney, 350, 363, 365 Prednisone, 79 President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (1982), 348 Pretreatment evaluation, for lithium therapy, 165–166 Prevalence. See also Epidemiology of age-associated memory impairment, 35 of alcohol abuse and dependency, 320–321 of Alzheimer’s disease, 7, 193 of anxiety disorders, 273 of delirium, 256–257 of frontotemporal dementia, 229 of major depression, 80 Prevention, of vascular dementia, 247 Primary aging, 49, 50, 52–54 Primary care physicians. See also Health care alcohol abuse and, 325 assessment of suicidality and, 106 barriers to geriatric mental health care and, 10–11 competency to drive and, 369, 371 elder abuse and, 372–373 Primary dysthymia, 91 Primary insomnia, 315, 316 Probable Alzheimer’s disease, 198–199, 203

413

Probate, and surrogate decision-makers, 363–365 Problem-solving therapy, for geriatric depression, 128 Problem Solving Treatment in Primary Care (PST-PC), 131 Processing speed, and cognitive abilities, 23, 27 Professional approaches, for effective work with elderly patients, 16 Prognosis, for elderly patients with delirium, 264 Progressive nonfluent aphasia, 231 Propentofylline, and vascular dementia, 247–248 Propoxyphene, 328 Propranolol, 78 Prospective memory, 30 Protective factors for Alzheimer’s disease, 192–195 for suicidality, 107 Proxy directives, 350–351 Pseudodelirium, 262 Psychiatric illness related to a general medical condition, 334–337 Psychiatrists. See also Mental health professionals barriers to geriatric mental health care and, 11 working effectively with older adults, 15–16 Psychodynamic theories of anxiety disorders, 286 of bipolar disorder, 115 of depression, 108 of psychosis, 298–299

414 Clinical Manual of Geriatric Psychiatry

Psychological tests, and depression, 96– 97. See also Neuropsychological tests Psychopharmacotherapy. See also Antidepressants; Antipsychotics; Anxiolytic agents; Augmentation; Benzodiazepines; Beta-blockers; Dosage; Drug-drug interactions; Maintenance treatment; Medications; Monoamine oxidase inhibitors; Mood stabilizers; Psychostimulants; Sedativehypnotics; Selective serotonin reuptake inhibitors; Side effects; Treatment for alcohol abuse or dependency, 325–326 for Alzheimer’s disease, 213–220 for anxiety disorders, 290–293 for bipolar depression, 157 for bipolar disorder, 163–166 for delirium, 263–264 electroconvulsive therapy and, 158 for geriatric depression, 132–156 for insomnia, 317–320 for late-onset psychosis, 302–306 for psychotic depression, 156 Psychosis. See also Psychotic depression; Psychotic disorder due to a general medical condition; Schizophrenia clinical presentation of, 294, 296 differential diagnosis of, 298, 337 epidemiology of, 293–294 medications for agitation in Alzheimer’s disease and, 220

neuropsychological tests for, 296– 297 pathogenesis of, 298–300 risk factors for, 294 subsyndromal depression and, 93 treatment of, 248, 300–306 vascular dementia and, 248 Psychosocial theory, of Alzheimer’s disease, 208–210 Psychosocial therapy for anxiety disorders, 288–290 for bipolar disorder, 162–163 for late-onset psychosis, 300–302 Psychostimulants advantages and disadvantages of, 137 Alzheimer’s disease and, 219 anxiety symptoms induced by, 277 depression and, 153 Psychotherapy. See also Cognitivebehavioral therapy; Family therapy; Group therapy; Psychosocial therapy; Supportive therapy; Treatment age-related cognitive changes and, 34–35 for alcohol abuse or dependency, 325 for Alzheimer’s disease, 210 for dementia caregivers, 210–213 for geriatric depression, 127–130 guidelines for treatment of older adults and, 56 research on for depression, 130–132 Psychotic depression, 83–85, 156

Index

Psychotic disorder due to a general medical condition, 336–337 PTSD (posttraumatic stress disorder), 281–283, 284–285 Public health, and depression in later life, 67 Quality of life, and anxiety disorders, 274 Quetiapine Alzheimer’s disease and, 216, 217, 220 dementia with Lewy bodies and, 241 psychosis and, 303, 304 Race, and diversity in patterns of health and aging, 12–14, 29. See also Black Americans; Hispanic Americans Ranitidine hydrochloride, 79 Rating scales. See also Neuropsychological tests; Standardized tests for activities of daily living, 184 for anxiety disorders, 274 for cognitive impairment, 174–183 for depression, 97–105 for frontotemporal dementia, 232– 233 Recent memory, 30 Recovery phase, of bereavement, 69 Referrals, for geriatric mental health care, 10 Relaxation training, for obsessivecompulsive disorder, 290

415

Religion, and social context of aging, 48 Reminiscence therapy for Alzheimer’s disease, 209 for geriatric depression, 130 Remote memory, 30, 357–358 Repetitive transcranial magnetic stimulation (rTMS), and depression, 159 Research competency to enroll in studies, 352, 353 on psychotherapy for geriatric depression, 130–132 Reserpine, 78 Resources for Enhancing Alzheimer’s Caregiver health (REACH), 211, 212 Respiratory system, and biological aging, 52 Restatement of the Law Second, Contracts 2d (American Law Institute 1981), 353–354 Reversible dementia, 255–256 Revised Memory and Behavior Problems Checklist, 386–387 Revised NEO Personality Inventory (NEO-PI-R), 98 Risk factors for alcohol abuse or dependency, 321 for Alzheimer’s disease, 192–195 for major depression, 80 for suicidality, 106, 107 for vascular dementia, 242

416 Clinical Manual of Geriatric Psychiatry

Risperidone Alzheimer’s disease and, 216, 217, 220 anxiety disorders and, 292 bipolar disorder and, 163 psychosis and, 302, 304 vascular dementia and, 248 Rivastigmine Alzheimer’s disease and, 215, 218 dementia with Lewy bodies and, 241 frontotemporal dementia and, 235 vascular dementia and, 247 Rorschach Inkblot Test, 99, 285–286 St. John’s wort, and depression, 161 Schizoid disorder, 340–341 Schizophrenia. See also Psychosis aging and early-onset, 339 anxiety and, 285–286 diagnostic criteria for, 295 Screening instruments, for frontotemporal dementia, 232– 233. See also Rating scales Seattle Longitudinal Study, 22 Secobarbital, 318 Secondary aging, 49 Secondary dysthymia, 91 Sedative-hypnotics. See also Hypnotic agents insomnia and, 318 substance abuse and, 326, 328 symptoms of depression induced by, 78 Seizure disorders, and secondary mania, 112

Selective serotonin reuptake inhibitors (SSRIs) Alzheimer’s disease and, 219 anxiety disorders and, 293 bipolar depression and, 157 geriatric depression and, 133, 136, 138–145, 148 heart disease and, 72 sexual dysfunction and, 332 Selegiline Alzheimer’s disease and, 214 depression and, 150, 151, 152 Self-help materials Alzheimer’s disease and, 213 depression and, 161 memory function in old age and, 31–32 Self-report scales, for depression, 100, 104–105 Semantic dementia, 231 Senile plaques, and Alzheimer’s disease, 206 Sensory changes. See also Visual acuity normal aging and, 24, 54 treatment of depression and, 128 Serotonin system, and pathogenesis of anxiety disorders, 288 Sertraline anxiety disorders and, 292–293 depression and, 139, 142, 148 receptor affinities of, 134 Setting, for treatment of older adults, 58–59 Sexual dysfunction, 329–334 Short-term memory, 28

Index

Sibling relationships, and social context of aging, 47 Side effects, of medications antidepressants for geriatric depression and, 148–149 antipsychotics and atypical antipsychotics, 304–305 guidelines for treatment of older adults and, 60 lithium and, 166 monoamine oxidase inhibitors and, 152 Sildenafil, 333 Simple consent, 349 Single photon emission computed tomography (SPECT) and Alzheimer’s disease, 201, 203– 204, 250 and dementia with Lewy bodies, 237 and frontotemporal dementia, 234 Situational anxiety, 276 Six-Item Orientation-MemoryConcentration Test, 174, 177, 183, 382 Sleep disturbance. See also Insomnia dementia with Lewy bodies and, 237 major depression and, 83 sleep apnea, 315 Sleep evaluation, and depression, 96 Social clock, 39 Social context, of aging, 43–48 Social Security, 21, 43–44, 45 Somatic complaints, and major depression, 83, 85

417

Somatization disorder, 86 Somnolent or hypoactive subtype, of delirium, 258 Space-occupying lesions, and dementia, 191 Specific phobia, 280 Spielberger State-Trait Anxiety Inventory, 274, 275 Stage theories, of personality, 39–40 Standardized tests, of decisional competency, 358. See also Rating scales Statins, and Alzheimer’s disease, 194–195 Steroids, and medication-induced mental disorders and, 56, 79 Stroke depression following, 73 vascular dementia and, 242 Substance abuse. See also Alcohol and alcohol abuse common patterns of, 327 diagnostic criteria for, 322, 323 distinguishing substance use from, 327–328 epidemiology of, 326–327 prescription of potentially addictive substances and, 330 substance-induced mood disorder and, 77 treatment of, 328–329 Substance-induced insomnia, 315 Substance-induced mania, 111, 112 Substance-induced mood disorder, 76– 80 Substance-induced persisting dementia, 254–255

418 Clinical Manual of Geriatric Psychiatry

Substitute decision makers, 350, 351– 352 Substituted judgment, doctrine of, 350 Subthreshold depression, 92–95 Suicide and suicidality anxiety disorders and, 274, 278 assessment of in elderly, 105–106, 107 Supportive therapy for Alzheimer’s disease, 210 for late-onset psychosis, 301–302 Surrogate decision-makers, 363–365 Sydenham’s chorea, 335 Sympathomimetics, and anxiety, 277 Systemic disorders, and dementia, 191 Tacrine, 213 Tadalafil, 333 Target symptoms, and treatment of older adults, 59 Tau-positive pathology, of frontotemporal dementia, 235 Telomeric shortening, 49–50 Temazepam insomnia and, 318 pharmacological properties of, 291 Testamentary capacity, 354–356 Testosterone, and treatment of sexual dysfunction, 332–333 Texas, and elder abuse, 372 Texas Medication Algorithm Project, 156 Thematic Apperception Test (TAT), 99, 285–286

Theophylline, and electroconvulsive therapy, 158 Thiazide diuretics, and depression, 78 Thioridazine, 217, 304 Thiothixene, 304 Thyroid function, and depression, 96 Time course, of normal grief, 69 Tocopherol forms, and Alzheimer’s disease, 194 Toxins, and dementia, 191 Trail Making Test (TMT), 189, 368 Tramadol, 338 Tranylcypromine, and depression, 150– 151, 152 Trazodone advantages and disadvantages of, 136 Alzheimer’s disease and, 216, 217, 220 depression and, 138, 146 frontotemporal dementia and, 235 insomnia and, 320 receptor affinities of, 134 sexual dysfunction and, 332 Treatment, of mental disorders in older adults. See also Clinical implications; Combined treatment; Compliance; Medications; Psychopharmacotherapy; Psychotherapy; Undertreatment of anxiety disorders, 288–293 of bipolar disorder, 162–166 of delirium, 263–264 of dementia with Lewy bodies, 240– 241

Index

of erectile dysfunction, 335 of frontotemporal dementia, 235 guidelines for, 55–61 of hypomania and mania, 162 of insomnia, 315–320 of late-onset psychosis, 300–306 of psychotic disorder due to a medical condition, 337 of sexual dysfunction, 332–334, 335 of substance abuse, 328–329 of vascular dementia, 247–248 Treatment resistance, and antidepressants, 153–155 Triazolam, and insomnia, 317–318 Tricyclic antidepressants (TCAs). See also Antidepressants advantages and disadvantages of, 136 bipolar depression and, 157 geriatric depression and, 133, 138, 145–146, 149, 154 psychotic depression and, 156 Trifluoperazine, 304 Triiodothyronine, and augmentation of antidepressants, 155 Trusts, and competency, 356, 365 Twin studies, of Alzheimer’s disease, 208 Underrecognition, of mental health problems in older adults, 10 Undertreatment, mental health problems in older adults, 60, 67–68 Undue influence, and question of voluntariness, 358–360

419

Uniform Probate Code, 361 U.S. Preventive Services Task Force, 105, 372 Useful Field of View (UFOV), 368 Vagus nerve stimulation, and depression, 160 Valproate, and Alzheimer’s disease, 220 Valproic acid, and Alzheimer’s disease, 218, 219 Vardenafil, 333 Vascular dementia clinical presentation of, 243 depression and, 73–74 diagnosis of, 241–242, 243 differential diagnosis of, 245–246, 250 epidemiology of, 241 laboratory evaluation of, 245 neuropsychological tests and, 244– 245 pathogenesis of, 246–247 patient history in, 242 physical and neurological examinations for, 243–244 prevention of, 247 treatment of, 247–248 Vascular depression, 74–76, 109 Vascular disorders, and dementia, 191 Vascular lesions, and mania, 112 Venlafaxine advantages and disadvantages of, 136 depression and, 138, 144, 148 receptor affinities of, 134 sexual dysfunction and, 332

420 Clinical Manual of Geriatric Psychiatry

Very-late-onset schizophrenia-like psychosis (VLOSLP), 294, 296, 297, 298, 301, 303 Very old people (85 years and older). See also Age and aging definition of “old-old” and, 21 as percentage of population, 1 Veterans Affairs, 73 Visual acuity, and normal aging, 24, 368 Visuospatial ability, and aging effects on cognitive performance, 27 Vitamin B deficiency, and dementia, 256 Vitamin C, and Alzheimer’s disease, 194 Vitamin E, and Alzheimer’s disease, 194, 214 Voluntariness, and undue influence, 358–360 Voluntary consent, 352 Web sites, for information on Alzheimer’s disease, 213 on elder abuse, 373 Wechsler Adult Intelligence Scale, 28, 187, 357 Wechsler Memory Scale, 187 Widowhood, and social context of aging, 45–47 Wills, and competency, 354–356. See also Living will Will substitution test, and undue influence, 359 Wisconsin Card Sorting Test, 189

Withdrawal, from medications anxiety and, 277 delirium and, 263 guidelines for treatment of older adults and, 61 Women diversity in patterns of health and aging, 14–15, 29 employment trends for, 44 personality changes during aging and, 39 poststroke depression in, 73 poverty and, 45 social context of aging and, 48 vascular depression and, 75 very-late-onset schizophrenia-like psychosis and, 294 widowhood and, 45–47 Women’s Health Initiative Memory Study, 194 Word List Learning, and Alzheimer’s disease, 203 Work, and social context of aging, 43– 45 Working memory, 23–24, 28 Worry Scale, 274, 275 Xanthine derivatives, and anxiety, 277 Zaleplon, and insomnia, 318, 319–320 Ziprasidone bipolar disorder and, 163 dementia with Lewy bodies and, 241 psychosis and, 303, 304 Zolpidem, and insomnia, 318, 319–320