PRACTICE GUIDELINE FOR THE Treatment of Patients With ...

PRACTICE GUIDELINE FOR THE

Treatment of Patients With

Alzheimer's Disease and

Other Dementias

Second Edition

WORK GROUP ON ALZHEIMER'S DISEASE AND OTHER DEMENTIAS Peter V. Rabins, M.D., M.P.H., Chair Deborah Blacker, M.D., Sc.D. Barry W. Rovner, M.D. Teresa Rummans, M.D. Lon S. Schneider, M.D. Pierre N. Tariot, M.D. David M. Blass, M.D., Consultant

STEERING COMMITTEE ON PRACTICE GUIDELINES John S. McIntyre, M.D., Chair Sara C. Charles, M.D., Vice-Chair Daniel J. Anzia, M.D. Ian A. Cook, M.D. Molly T. Finnerty, M.D. Bradley R. Johnson, M.D. James E. Nininger, M.D. Barbara Schneidman, M.D. Paul Summergrad, M.D. Sherwyn M. Woods, M.D., Ph.D.

AREA AND COMPONENT LIAISONS Joseph Berger, M.D. (Area I) C. Deborah Cross, M.D. (Area II) Harry A. Brandt, M.D. (Area III) Philip M. Margolis, M.D. (Area IV) John P. D. Shemo, M.D. (Area V) Barton J. Blinder, M.D. (Area VI) David L. Duncan, M.D. (Area VII) Mary Ann Barnovitz, M.D. Anthony J. Carino, M.D. Zachary Z. Freyberg, M.D., Ph.D. Sheila Hafter Gray, M.D. Tina Tonnu, M.D.

Copyright 2010, American Psychiatric Association. APA makes this practice guideline freely available to promote its dissemination and use; however, copyright protections are enforced in full. No part of this guideline may be reproduced except as permitted under Sections 107 and 108 of U.S. Copyright Act. For permission for reuse, visit APPI Permissions & Licensing Center at .

STAFF Robert Kunkle, M.A., Senior Program Manager Amy B. Albert, B.A., Project Manager Thomas J. Craig, M.D., M.P.H., Director, Dept. of Quality Improvement and Psychiatric Services Darrel A. Regier, M.D., M.P.H., Director, Division of Research

MEDICAL EDITOR Laura J. Fochtmann, M.D.

This practice guideline was approved in July 2007 and published in October 2007.

A guideline watch, summarizing significant developments in the scientific literature since publication of this guideline, may be available in the Psychiatric Practice section of the APA Web site at .

The Work Group on Alzheimer's Disease and Other Dementias reports the following potentially competing interests for the period January 2003 to December 2006: Dr. Rabins has received speaking fees from Pfizer, AstraZeneca, Janssen, Eli Lilly and Company, Forest Pharmaceuticals, Inc., and Wyeth Pharmaceuticals. Dr. Blacker reports no competing interests. Dr. Rovner has served on speakers bureaus for Pfizer and Forest Pharmaceuticals, Inc. Dr. Rummans has received a research grant from the Linse Bock Foundation. Dr. Schneider has received research or other grants from Abbott Laboratories, AstraZeneca, Forest Pharmaceuticals, Inc., Johnson & Johnson, Eli Lilly and Company, Novartis, Pfizer, and Myriad. Dr. Schneider has served on speakers bureaus or performed other work relating to continuing medical education for Abbott Laboratories, AstraZeneca, Forest Pharmaceuticals, Eli Lilly and Company, Solvay, Bristol-Myers Squibb, and Lundbeck. Dr. Schneider has served on advisory panels for Abbott Laboratories, AstraZeneca, Forest Pharmaceuticals, Inc., Johnson & Johnson, Eli Lilly and Company, and Novartis. Dr. Tariot has received consulting fees from Memory Pharmaceuticals Corp. and Novartis; consulting fees and research support from Abbott Laboratories, Bristol-Myers Squibb, Eisai Inc., GlaxoSmithKline, Janssen, Eli Lilly and Company, Merck and Company, Myriad, Pfizer, Sanofi-Synth?labo, Dr. Willmar Schwabe Pharmaceuticals, and Takeda Pharmaceuticals North America, Inc.; educational fees from Lundbeck; consulting fees, research support, and educational fees from AstraZeneca, Eisai Inc., Forest Pharmaceuticals, Inc., and Pfizer; and research support from Elan Corporation, Mitsubishi Pharma Corporation, Neurochem, Inc., Ono Pharmaceuticals Co., Ltd., and Wyeth Pharmaceuticals. Dr. Tariot has received other research support from the National Institute of Aging, the National Institute of Mental Health, the Alzheimer's Association, the Arizona Department of Health Services, and the Institute for Mental Health Research. Dr. Tariot has served on speakers bureaus for AstraZeneca, Eisai Inc., Forest Pharmaceuticals, Inc., and Pfizer, Inc. Dr. Blass reports no competing interests. The Executive Committee on Practice Guidelines has reviewed this guideline and found no evidence of influence from these relationships.

Copyright 2010, American Psychiatric Association. APA makes this practice guideline freely available to promote its dissemination and use; however, copyright protections are enforced in full. No part of this guideline may be reproduced except as permitted under Sections 107 and 108 of U.S. Copyright Act. For permission for reuse, visit APPI Permissions & Licensing Center at .

CONTENTS

STATEMENT OF INTENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

OVERVIEW OF GUIDELINE DEVELOPMENT PROCESS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

GUIDE TO USING THIS PRACTICE GUIDELINE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

PART A: TREATMENT RECOMMENDATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

I. EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 A. Coding System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 B. General Treatment Principles and Alternatives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 1. Psychiatric Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2. Specific Psychotherapies and Other Psychosocial Treatments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 3. Special Concerns Regarding Somatic Treatments for Elderly Patients and Patients With Dementia. . . . . . . . . . . . 12 4. Treatment of Cognitive Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 5. Treatment of Psychosis and Agitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 6. Treatment of Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 7. Treatment of Sleep Disturbances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 8. Special Issues for Long-Term Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

II. FORMULATION AND IMPLEMENTATION OF A TREATMENT PLAN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 A. Determining the Site of Treatment and Frequency of Visits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 B. Psychiatric Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 1. Establish and Maintain an Alliance With the Patient and the Family . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 2. Perform a Diagnostic Evaluation and Refer the Patient for Any Needed General Medical Care . . . . . . . . . . . . . . . 15 a. General Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 b. Neuropsychological Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 c. Neuroimaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 d. Biomarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 e. Genetic Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3. Assess and Monitor Psychiatric Status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 4. Monitor and Enhance the Safety of the Patient and Others . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 a. Suicidal Ideation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 b. Agitation and Aggression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 c. Supervision . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 d. Falls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 e. Abuse and Neglect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 f. Wandering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 5. Advise the Patient and Family Concerning Driving (and Other Activities That Put Other People at Risk) . . . . . . . . 20

Copyright 2010, American Psychiatric Association. APA makes this practice guideline freely available to promote its dissemination and use; however, copyright protections are enforced in full. No part of this guideline may be reproduced except as permitted under Sections 107 and 108 of U.S. Copyright Act. For permission for reuse, visit APPI Permissions & Licensing Center at .

6. Provide Education and Support to Patients and Families . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 a. Educate the Patient and Family About the Illness and Available Treatments . . . . . . . . . . . . . . . . . . . . . . 22 b. Refer the Family to Appropriate Sources of Care and Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 c. Watch for Signs of Caregiver Distress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 d. Support Families During Decisions About Institutionalization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

7. Advise the Family to Address Financial and Legal Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 C. Development and Implementation of a Stage-Specific Treatment Plan . . . . . . . . . . . . . . . . . . . . . . . . . . .24

1. Mildly Impaired Patients. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 2. Moderately Impaired Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 3. Severely and Profoundly Impaired Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 4. Implementation of Psychosocial Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 5. Implementation of Pharmacological Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

a. Treatments for Cognitive and Functional Losses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 b. Treatments for Psychosis and Agitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 c. Treatments for Depression and Related Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 d. Treatments for Sleep Disturbance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

III. SPECIFIC CLINICAL FEATURES INFLUENCING THE TREATMENT PLAN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .37 A. Demographic and Social Factors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .37 1. Age. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 2. Gender . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 3. Ethnic and Cultural Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 4. Other Demographic and Psychosocial Factors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 B. Co-occurring Conditions and Other Dementias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .38 1. General Medical Conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 2. Delirium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 3. Parkinson's Disease Spectrum Illnesses (Including Parkinson's Disease and Dementia With Lewy Bodies). . . . . . . 39 4. Cerebrovascular Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 5. Frontotemporal Dementia Spectrum Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 C. Site-Specific Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .40 1. Home Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 2. Day Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 3. Long-Term Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 4. Inpatient General Medical or Surgical Services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 5. General Psychiatric Inpatient Units . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

PART B: BACKGROUND INFORMATION AND REVIEW OF AVAILABLE EVIDENCE . . . . . . . . . . . . . . . 42

IV. DISEASE DEFINITION, NATURAL HISTORY, AND EPIDEMIOLOGY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .42 A. Definition of Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .42 B. Associated Features. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43 C. Differential Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43 D. Prevalence and Course . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .44 E. Staging of Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .44 F. Specific Dementias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .45 1. Dementia of the Alzheimer's Type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 2. Mild Cognitive Impairment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 3. Vascular Dementia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

Copyright 2010, American Psychiatric Association. APA makes this practice guideline freely available to promote its dissemination and use; however, copyright protections are enforced in full. No part of this guideline may be reproduced except as permitted under Sections 107 and 108 of U.S. Copyright Act. For permission for reuse, visit APPI Permissions & Licensing Center at .

4. Dementia of Parkinson's Disease and Dementia With Lewy Bodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 5. Dementia Due to Frontotemporal Dementia Spectrum Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 6. Other Progressive Dementing Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 7. Dementia Due to Other Causes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 V. REVIEW OF AVAILABLE EVIDENCE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 A. Specific Psychotherapies/Psychosocial Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 1. Behavior-Oriented Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 2. Emotion-Oriented Approaches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 3. Cognition-Oriented Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 4. Stimulation-Oriented Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 B. Somatic Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 1. Treatments for Cognitive and Functional Losses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

a. Cholinesterase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 b. Memantine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 c. Vitamin E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 d. Other Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 2. Treatments for Psychosis and Agitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 a. Antipsychotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 b. Benzodiazepines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 c. Anticonvulsants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 d. Other Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 3. Treatments for Depression and Related Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 a. Antidepressants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 b. Electroconvulsive Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 4. Treatments for Sleep Disturbance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 PART C: FUTURE RESEARCH NEEDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 INDIVIDUALS AND ORGANIZATIONS THAT SUBMITTED COMMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 REFERENCES. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

Copyright 2010, American Psychiatric Association. APA makes this practice guideline freely available to promote its dissemination and use; however, copyright protections are enforced in full. No part of this guideline may be reproduced except as permitted under Sections 107 and 108 of U.S. Copyright Act. For permission for reuse, visit APPI Permissions & Licensing Center at .

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