Late-Life Depression Linked to Increased Risk for Dementia

Fran Lowry

May 07, 2013

Late-life depression is associated with an increased risk for all-cause dementia, vascular dementia, and Alzheimer's disease, according to the results of a meta-analysis of 23 population-based, prospective cohort studies.

The analysis also showed that the risk for vascular dementia is significantly higher than the risk for Alzheimer's disease in older adults with late-life depression.

"Late-life depression is one of the most common psychiatric disorders in older adults," the authors, led by Breno S. Diniz, MD, PhD, from the University of Pittsburgh School of Medicine, in Pennsylvania, and the Federal University of Minais Gerais, Brazil, write.

"It is associated with significant functional impairment, variable treatment response, chronicity, high recurrence rates, and high rates of medical comorbidity and mortality."

The study is published in the May issue of the British Journal of Psychiatry.

High Risk for All Dementia Types

A previous meta-analysis of case-control and cohort studies found an association with incident Alzheimer's disease and depression, but it did not include studies of other dementia syndromes, such as vascular dementia or mixed dementias.

Moreover, recent studies have reported a significant association between these conditions, the authors note.

But to date, systematic evaluation of whether a depressive episode increases the risk for vascular dementia and other dementia syndromes in addition to Alzheimer's disease has been lacking.

Knowing whether this was so "could lead to better long-term predictive models and more rational preventive interventions," the authors write.

"This is of utmost importance given that the estimated number of cases of Alzheimer's disease attributable to depression is 781,000 (95% CI 506,000 - 1,078,000) and the prevention of 10 to 25% of depression cases may reduce the prevalence of Alzheimer's disease by 68,000 to 173,000 respectively."

The meta-analysis included 23 community-based prospective cohort studies with data on patients aged 50 years and older who were free of dementia at baseline.

The median follow-up interval for all-cause dementia and Alzheimer's disease studies was 5 years; for vascular dementia studies, the median follow-up interval was 6.1 years.

The total sample included in the pooled analysis for all-cause dementia was 49,612 participants, 5116 of whom had late-life depression.

Analyses for Alzheimer's disease were based on data from 28,746 participants, and of these, 3437 had late-life depression. Those for vascular dementia were based on data from 14,901 participants, 1801 of whom had late-life depression.

The analysis showed that individuals with late-life depression had a significantly higher risk for incident all-cause dementia, Alzheimer's disease, and vascular dementia compared with the elderly control participants.

Robust Evidence

For all-cause dementia, the pooled odds ratio (OR) was 1.85 (95% confidence interval [CI], 1.67 - 2.04; P < .001); for Alzheimer's disease, the OR was 1.65 (95% CI, 1.42 - 1.92; P < .001); and for vascular dementia, the OR was 2.52 (95% CI, 1.77 - 3.59; P < .001).

A subgroup analysis that took into account potential confounding variables such as age, education, sex, cognitive and functional performance, and biological status, including health status, vascular risk factors, hippocampal volume, and white matter lesions found that the strength of the association between late-life depression and the risk for all-cause dementia, Alzheimer's disease, and vascular dementia was reduced but was still significant.

There are several limitations to this meta-analysis, the authors point out.

First, they note, the studies that were included reported either the odds ratio or the hazard ratio for the association between late-life depression and dementia, and these measures are not interchangeable.

Also, depressive symptoms were measured with rating scales, using pre-established cutoff scores, and no structured interviews were used in the diagnosis. Additionally, the studies had follow-up intervals that varied from 1 to 17 years; some included only men or only women; and some included populations that were not randomly selected.

Limiting the search for appropriate studies to include in the meta-analysis to PubMed and Scopus databases could also be a limitation.

These limitations notwithstanding, the authors conclude that their study "provides robust evidence that depression is independently associated with an independent increased risk of Alzheimer's disease and vascular dementia in older adults."

They also stress their finding that the risk for vascular dementia appears to be significantly higher than the risk for Alzheimer's disease in these individuals.

The authors suggest that preventing depression while stimulating general healthy behaviors and lifestyles and reducing cardiovascular risk factors and other mental health–related problems should be considered in public health policies aimed at the prevention or possible delay of dementia syndromes in older adults.

They also call for new clinical trials to investigate the potential impact of prevention of depression on the risk for cognitive impairment and dementia in older adults.

This study was supported by the John Hartford Foundation, the University of Pittsburgh Medical Center Endowment in Geriatric Psychiatry, and the National Institutes of Health. Dr. Diniz reports financial relationships with Novartis and Pfizer. Other authors report financial relationships with Northstar Neuroscience, Medtronic, Fox Learning Systems, Bristol-Myers Squibb, Forest Laboratories, and Lilly.

Br J Psychiatry. 2013;202:329-335. Abstract

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