Late-Life Depression, Mild Cognitive Impairment, and Dementia: Possible Continuum?

doi:10.1097/JGP.0b013e3181b0fa13

The American Journal of Geriatric Psychiatry

Volume 18, Issue 2, February 2010, Pages 98-116

https://doi.org/10.1097/JGP.0b013e3181b0fa13 Get rights and content

Clinical and epidemiologic research has focused on the identification of risk factors that may be modified in predementia syndromes, at a preclinical and early clinical stage of dementing disorders, with specific attention to the role of depression. Our goal was to provide an overview of these studies and more specifically to describe the prevalence and incidence of depression in individuals with mild cognitive impairment (MCI), the possible impact of depressive symptoms on incident MCI, or its progression to dementia and the possible mechanisms behind the observed associations. Prevalence and incidence of depressive symptoms or syndromes in MCI vary as a result of different diagnostic criteria and different sampling and assessment procedures. The prevalence of depression in individuals with MCI was higher in hospital-based studies (median: 44.3%, range: 9%–83%) than in population-based studies (median: 15.7%, range: 3%–63%), reflecting different referral patterns and selection criteria. Incidence of depressive symptoms varied from 11.7 to 26.6/100 person-years in hospital-based and population-based studies. For depressed normal subjects and depressed patients with MCI, the findings on increased risk of incident MCI or its progression to dementia were conflicting. These contrasting findings suggested that the length of the follow-up period, the study design, the sample population, and methodological differences may be central for detecting an association between baseline depression and subsequent development of MCI or its progression to dementia. Assuming that MCI may be the earliest identifiable clinical stage of dementia, depressive symptoms may be an early manifestation rather than a risk factor for dementia and Alzheimer disease, arguing that the underlying neuropathological condition that causes MCI or dementia also causes depressive symptoms. In this scenario, at least in certain subsets of elderly patients, late-life depression, MCI, and dementia could represent a possible clinical continuum.

Section snippets

Predementia Syndromes and MCI

Many different diagnostic criteria and terms have been proposed over the years to describe predementia syndromes in the elderly: age-associated memory impairment, aging-associated cognitive decline, cognitive impairment no dementia, and many others.1, 2 Furthermore, numerous rating scales for staging dementia include a specific preclinical phase of dementia, e.g., “questionable dementia” in Clinical Dementia Rating Scale (0.5).⁴ At present, MCI is a clinical label that includes nondemented aged

Prevalence of Depression in Patients With MCI

Depression has often been excluded from the definition of MCI, creating a bias in studies on the relationship of depression with predementia syndromes. However, research now indicates a high rate of cooccurrence between depression and MCI that seems to raise the risk for persistent cognitive impairment and dementia.¹³ Among population-based studies, in the Italian Longitudinal Study on Aging (ILSA), the diagnosis of MCI was associated with a high prevalence of depressive symptoms, with a higher

DEPRESSION AND RISK PREDEMENTIA SYNDROMES

Converging evidence suggests that late-onset depressive symptoms or syndromes often are a prodrome of cognitive decline. Recent history of depression is associated with increased incidence of AD.¹⁸ Individuals with late-life depression and transient cognitive impairment frequently develop AD or VaD within a few years after the onset of depression.¹³ Together, these observations suggest that some late-life depressive syndromes may be early manifestations of dementing disorders.⁵⁶ In contrast to

Depression and MCI: Shared Risk Factors or Confounding

At present, the mechanisms on the possible role of depression and depressive symptoms in the development of predementia syndromes or their progression to dementia are still under investigation. One possibility is that depression and predementia syndromes share the same risk factors or confounding. In fact, additional factors, genetic, environmental, or both may lead to the genesis of both MCI and depression (Fig. 1). Current etiological models of late-life depression and cognitive decline focus

CONCLUSIONS

Prevalence rates of depressive syndromes or symptoms vary widely among studies, as a result of different diagnostic criteria and operational definitions of depression (MDD versus depressive symptoms) and different sampling and assessment procedures. In fact, although hospital-based studies on MCI reported a higher prevalence of depressive symptoms (median value: 44.3%), population-based studies reported a prevalence of 3%–63.3% (median value: 15.7%) for depression among patients with MCI.

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View all citing articles on Scopus

This work was supported by the Italian Longitudinal Study on Aging (ILSA) (Italian National Research Council—CNR-Targeted Project on Ageing—grants 9400419PF40 and 95973PF40).

The CNR had no further role in study design; in the collection, analysis, and interpretation of data; in writing of the report; and in the decision to submit the paper for publication.

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Special ArticleLate-Life Depression, Mild Cognitive Impairment, and Dementia: Possible Continuum?

Section snippets

Predementia Syndromes and MCI

Prevalence of Depression in Patients With MCI

DEPRESSION AND RISK PREDEMENTIA SYNDROMES

Depression and MCI: Shared Risk Factors or Confounding

CONCLUSIONS

Am J Geriatr Psychiatry

Neurobiol Aging

Lancet

Lancet

Am J Geriatr Psychiatry

J Psychiatr Res

Biol Psychiatry

Eur Psychiatry

Biol Psychiatry

Clin Neurol Neurosurg

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

Am J Geriatr Psychiatry

Perspectives on depression, mild cognitive impairment, and cognitive decline

Arch Gen Psychiatry

A new clinical scale for the staging of dementia

Br J Psychiatry

Mild cognitive impairment: clinical characterization and outcome

Arch Neurol

Current concepts in mild cognitive decline

Arch Neurol

Mild cognitive impairment–beyond controversies, towards a consensus: report of the International Working Group on mild cognitive impairment

J Intern Med

Aging, memory, and mild cognitive impairment

Int Psychogeriatr

MCI Working Group of the European Consortium on Alzheimer's Disease (EADC): Mild cognitive impairment (MCI) in medical practice: a critical review of the concept and new diagnostic procedure report of the MCI Working Group of the European Consortium on Alzheimer's Disease

J Neurol Neurosurg Psychiatry

American Psychiatric Association Committee on Nomenclature and Statistics: Diagnostic and Statistical Manual of Mental Disorders

International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). Chapter V, categories F00–F99: Mental, Behavioural, and Developmental Disorders, Clinical Description and Diagnostic Guidelines

Contribution of depression to cognitive impairment and dementia in older adults

Neurologist

Overview of depression and psychosis in Alzheimer's disease

Am J Psychiatry

Psychomotor symptoms of depression

Am J Psychiatry

Pathways linking late-life depression to persistent cognitive impairment and dementia

Dialogues Clin Neurosci

Depression, antidepressants, and the shrinking hippocampus

Proc Natl Acad Sci USA

Structured Clinical Interview for DSM-IV Axis I Disorders (SCID I), Clinician Version, Administration Booklet

The importance of subsyndromal depression in older primary care patients: prevalence and associated functional disability

J Am Geriatr Soc

Depression without sadness: functional outcomes of nondysphoric depression in later life

J Am Geriatr Soc

Is the geriatric depression scale a reliable screening tool for depressive symptoms in elderly patients with cognitive impairment?

Int J Geriatr Psychiatry

The CES-D scale: a self-report depression scale for research in the general population

Appl Psychol Measurement

Screening for depression in the older adult: criterion validity of the 10-item Center for Epidemiological Studies Depression Scale (CES-D)

Arch Intern Med

Beck Depression Inventory-II Manual

The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia

Neurology

A rating scale for depression

J Neurol Neurosurg Psychiatry

A new depression scale designed to be sensitive to change

Br J Psychiatry

A comprehensive psychopathological rating scale

Acta Psychiatr Scand

Detecting anxiety and depression in general medical settings

BMJ

CERAD behavior rating scale for dementia

Int Psychogeriatr

Italian Longitudinal Study on Aging Working Group. Incident occurrence of depressive symptoms among patients with mild cognitive impairment—the Italian Longitudinal Study on Aging

Dement Geriatr Cogn Disord

Special Article
Late-Life Depression, Mild Cognitive Impairment, and Dementia: Possible Continuum?