Provisional Diagnostic Criteria for Depression of Alzheimer Disease: Rationale and Background

doi:10.1097/00019442-200203000-00004

The American Journal of Geriatric Psychiatry

Volume 10, Issue 2, March–April 2002, Pages 129-141

https://doi.org/10.1097/00019442-200203000-00004 Get rights and content

This review provides the rationale and background for the development of diagnostic criteria for depression of Alzheimer disease (AD), including risk factors and neurobiological correlates, epidemiology, and clinical characteristics, along with course, assessment, treatment, economics, a description of the criteria, and future research directions. Overall, there is substantial research to suggest that the depression that may co-occur with AD is different from other depressive disorders. Further research is needed to better define core symptoms, clinical course, and efficacy of treatments.

Section snippets

What Is Known About Possible Neurobiological Correlates or Risk Factors?

There is ample evidence that the neuropathology of AD plays a role in the development of depression. Depression in AD has been associated with a variety of neurochemical abnormalities, including the selective loss of noradrenergic cells in the locus ceruleus3, 4, 5, 6, 7 and loss of dorsal raphe serotonergic nuclei.⁷ Apoptotic processes that occur as a function of AD may also play a part in the loss of aminergic nuclei, affecting mood.⁸ Also, there may be susceptibility genes common to both

“Uncomplicated” Alzheimer Disease

Transient mood symptoms in individuals with “uncomplicated” AD usually can be distinguished from more persistent symptomatology. By describing persistent depression, the provisional diagnostic criteria help to distinguish transient moods from more extensive states that characterize a depressive disorder. The criteria, however, do not require specific duration and intensity thresholds for each symptom.

The diagnostic criteria have been constructed with the recognition that there is overlap of

WHAT METHODS OFASSESSMENT CAN BE USED?

Several approaches can be used to measure depression of AD. Rating scales that assess mood and behavioral symptoms in individuals with dementia include the BEHAVE-AD,⁸⁵ the Columbia University Scale for the Psychopathology of AD,⁸⁶ the CERAD Behavior Rating Scale for Dementia,45, 46 and the Neuropsychiatric Inventory.⁸⁷ These instruments have been used both in clinical trials and population-based studies.⁸⁴ The Hamilton Rating Scale for Depression (Ham-D) has been used in numerous clinical

WHAT CONSTITUTES SAFE AND EFFECTIVE TREATMENT OF DEMENTIA WITH DEPRESSION? WHAT ARE THE INDICATIONS AND CONTRAINDICATIONS FOR SPECIFIC TREATMENTS?

Open intervention studies of individuals with AD have long established that those with behavioral symptoms, including depression, showed a different response to treatment than patients with MDD.¹⁰⁸ There are several expert recommendations for the treatment of depression in the context of AD or other dementias.109, 110, 111 Although there are 11 published systematic controlled trials, they are quite hetrogeneous in their designs and do not provide strong support for specific treatment

WHAT ARE THE ECONOMIC CONSIDERATIONS OF TREATMENT? WHAT ARE THE POTENTIAL CONSEQUENCES OF NOT TREATING THIS SYNDROME?

A number of studies in the United States and Europe have assessed costs associated with late-life depression and dementia as separate disorders. Total healthcare costs have been found to be significantly increased in depressed older adults, as compared with nondepressed control subjects.¹²⁰ Medicare beneficiaries with AD had almost twice the per-capita health care costs of Medicare beneficiaries in general.¹²¹ Healthcare costs are significantly associated with the severity of dementia.122, 123,

WHAT ARE THE PROPOSED CRITERIA AND HOW WERE THEY DEVELOPED?

The National Institute of Mental Health organized a workshop to facilitate the development of criteria, using methods similar to those used in the DSM (apart from field trials). A team of 21 investigators who had expertise in both dementia and late-life depression research was asked to participate. Before beginning the process of criteria development, the group created a website that provided for the distribution of review articles.

Alternative processes to developing diagnostic criteria through

WHAT ARE THE MOST PROMISING QUESTIONS FOR FUTURE RESEARCH?

A key reason for developing the provisional diagnostic criteria of depression of AD is to better understand and define the nature of the depression syndrome that accompanies AD. The following issues and questions were considered important:

SUMMARY AND CONCLUSIONS

There are findings from multiple domains that provide evidence to support the diagnostic concept of depression of AD. Depression, although not completely characterized, is common in AD. Individuals with both AD and depression are distinguishable both from cognitively intact depressed elderly persons and from other individuals with AD. Also, the heterogeneity of AD's pathophysiology and age at presentation suggests that variations in clinical presentation should be expected, which adds support

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The authors thank the following people who participated in the Workshop: George S. Alexopoulos, M.D. (Cornell University), John C. Breitner, M.D. (Johns Hopkins University), Martha L. Bruce, Ph.D. (Cornell University), Eric D. Caine, M.D. (Rochester University), Jeffrey L. Cummings, M.D. (University of California, Los Angeles), Davangere P. Devanand, M.D. (Columbia University), Dilip V. Jeste, M.D. (University of California, San Diego), K. Ranga Rama Krishnan, M.D. (Duke University), Constantine G. Lyketsos, M.D. (Johns Hopkins University), Jeffrey M. Lyness, M.D. (Rochester University), Peter V. Rabins, M.D. (Johns Hopkins University), Charles F. Reynolds III, M.D. (University of Pittsburgh), Barry W. Rovner, M.D. (Thomas Jefferson), David C. Steffens, M.D. (Duke University), Pierre N. Tariot, M.D. (Rochester University), Jürgen Unutzer, M.D., M.P.H. (University of California, Los Angeles).

We also thank the three anonymous reviewers for their thoughtful and thorough comments.

Dr. Katz is at the Section of Geriatric Psychiatry, University of Pennsylvania, VISN 4 MIRECC, Philadelphia VA Medical Center (NIMH grants P30 MH52129 and R37 MII51247); Dr. Meyers is at the Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, the Leonard Davis School of Gerontology, University of Southern California.

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Special ArticleProvisional Diagnostic Criteria for Depression of Alzheimer Disease: Rationale and Background

Section snippets

What Is Known About Possible Neurobiological Correlates or Risk Factors?

“Uncomplicated” Alzheimer Disease

WHAT METHODS OFASSESSMENT CAN BE USED?

WHAT CONSTITUTES SAFE AND EFFECTIVE TREATMENT OF DEMENTIA WITH DEPRESSION? WHAT ARE THE INDICATIONS AND CONTRAINDICATIONS FOR SPECIFIC TREATMENTS?

WHAT ARE THE ECONOMIC CONSIDERATIONS OF TREATMENT? WHAT ARE THE POTENTIAL CONSEQUENCES OF NOT TREATING THIS SYNDROME?

WHAT ARE THE PROPOSED CRITERIA AND HOW WERE THEY DEVELOPED?

WHAT ARE THE MOST PROMISING QUESTIONS FOR FUTURE RESEARCH?

SUMMARY AND CONCLUSIONS

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Psychiatr Clin North Am

J Affect Disord

Biol Psychiatry

Am J Geriatr Psychiatry

Am J Psychiatry

Biol Psychiatry

Diagnostic and Statistical Manual of Mental Disorders

The neuropathology of aminergic nuclei in Alzheimer's disease

Ann Neurol

Neuropathology of aminergic nuclei in Alzheimer disease

Prog Clin Biol Res

Neurochemical correlates of major depression in primary dementia

Arch Neurol

Biological correlates of clinical heterogeneity in primary dementia

Neuropsychopahrmacology

Clinical and neuropathological correlates of depression in Alzheimer's disease

Psychol Med

Neurobiology of major depression in Alzheimer's disease

Int Psychogeriatr

Do susceptibility loci contribute to the expression of more than one mental disorder? a view from the genetics of Alzheimer's disease

Mol Psychiatry

Psychiatric diagnosis as reified measurement

J Health Soc Behav

Comment to Mirowsky and Ross

J Health Soc Behav

A comparison of self-report and clinical diagnostic interviews for depression

Arch Gen Psychiatry

A comparison of diagnostic interviews for depression in the Stirling County Study

Arch Gen Psychiatry

Limitations of diagnostic criteria and assessment instruments for mental disorders

Arch Gen Psychiatry

Diagnosis and need for treatment are not the same

Arch Gen Psychiatry

Problems in defining clinical significance in epidemiologic studies

Arch Gen Psychiatry

Depressive symptoms in Alzheimer disease: assessment and determinants

Alzheimer Dis Assoc Disord

Epidemiology of Alzheimer's disease

Epidemiol Rev

Prevalence of Alzheimer's disease in a retirement community

Am J Epidemiol

Prevalence of Alzheimer's disease in a community population of older persons: higher than previously reported

JAMA

Alzheimer's disease in the National Academy of Sciences-National Research Council Registry of Aging Twin Veterans, III: detection of cases, longitudinal results, and observations on twin concordance

Arch Neurol

Impaired insight in Alzheimer disease: association with cognitive deficits, psychiatric symptoms, and behavioral disturbances

Neuropsychiatry Neuropsychol Behav Neurol

The psychiatric symptoms of Alzheimer's disease

J Am Geriatr Soc

Symptoms of “depression” in dementia of the Alzheimer type

Alzheimer Dis Assoc Disord

Differences between patient and family assessments of depression in Alzheimer's disease

Am J Psychiatry

Dementia, awareness, and depression

Int J Geriatr Psychiatry

Depression, insight, and personality changes in Alzheimer's disease and vascular dementia

J Geriatr Psychiatry Neurol

The relationship of cognitive and functional impairment to depressive features in Alzheimer's disease and other dementias

J Neuropsychiatry Clin Neurosci

Prevalence and correlates of dysthymia and major depression among patients with Alzheimer's disease

Am J Psychiatry

Prevalence of depression in Alzheimer's disease and validity of Research Diagnostic Criteria

Special Article
Provisional Diagnostic Criteria for Depression of Alzheimer Disease: Rationale and Background