Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis
Ownby RL, Crocco E, Acevedo A, John V, Loewenstein D;
Commented by , 25 Jul 2006
Background
Results from a number of studies suggest that a history of depression may increase the risk for developing Alzheimer disease (AD) later in life. No recent systematic review of the issue has been published.
Method
An electronic bibliographic search of MEDLINE, PsychLit, EMBASE, and BIOSIS using terms related to depression and AD and reviewed reference lists of articles were performed. Only studies with data contrasting depressed vs nondepressed patients who did and did not later develop AD were included. Studies that related continuous measures of depression and cognitive status were excluded.
Numerical data were independently extracted by 3 reviewers. They also rated studies on a scale that assessed quality indicators for observational studies. Data on the interval between observation of depression and the diagnosis of AD were collected when available.
Results
Meta-analytic evaluation with random-effects models resulted in pooled odds ratios of 2.03 (95% confidence interval, 1.73-2.38) for case-control and of 1.90 (95% confidence interval, 1.55-2.33) for cohort studies. Findings of increased risk were robust to sensitivity analyses. Interval between diagnoses of depression and AD was positively related to increased risk of developing AD, suggesting that rather than a prodrome, depression may be a risk factor for AD.
Professor Kessing's comments
The authors conclude that a history of depression is an independent risk factor for later developing AD. The analyses seem to be correctly performed and the finding is of great importance. Thus, they strengthen the conclusion from a recent meeting by the National Institute of Mental Health, National Institute on Aging and National Institute of Neurological Disorders and Stroke that a major important focus for future research is to understand the interrelation between depression and memory disorders (ref. 1).
One recent postmortem study that compared the brains of AD patients with and without a lifetime history of depression found that brains of patients with AD with a lifetime history of depression showed significantly higher levels of both plaque and tangle formation within the hippocampus (ref. 2). However, the more precise nature of the aetiology is unclear, e.g. it is unclear whether the risk of dementia increases with the number of depressions (ref. 3).
References
1. Steffens DC, Otey E, Alexopoulos GS, Butters MA, Cuthbert B, Ganguli M, et al. Perspectives on depression, mild cognitive impairment, and cognitive decline. Archives of General Psychiatry 2006;63 (2); 130-138
2. Rapp MA, Schnaider-Beeri M, Grossman HT, Sano M, Perl DP, Purohit DP, et al. Increased hippocampal plaques and tangles in patients with Alzheimer disease with a lifetime history of major depression. Archives of General Psychiatry 2006;63 (2); 161-167
3. Kessing LV, Andersen PK. Does the risk of developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder?. Journal of Neurology, Neurosurgery and Psychiatry 2004; 75 (12); 1662-1666