Depression and risk of developing dementia


Depression is highly common throughout the life course and dementia is common in late life. Depression has been linked with dementia, and growing evidence implies that the timing of depression may be important in defining the nature of this association. In particular, earlier-life depression (or depressive symptoms) has consistently been associated with a more than twofold increase in dementia risk. By contrast, studies of late-life depression and dementia risk have been conflicting; most support an association, yet the nature of this association (for example, if depression is a prodrome or consequence of, or risk factor for dementia) remains unclear. The likely biological mechanisms linking depression to dementia include vascular disease, alterations in glucocorticoid steroid levels and hippocampal atrophy, increased deposition of amyloid-β plaques, inflammatory changes, and deficits of nerve growth factors. Treatment strategies for depression could interfere with these pathways and alter the risk of dementia. Given the projected increase in dementia incidence in the coming decades, understanding whether treatment for depression alone, or combined with other regimens, improves cognition is of critical importance. In this Review, we summarize and analyze current evidence linking late-life and earlier-life depression and dementia, and discuss the primary underlying mechanisms and implications for treatment.

Key Points

  • Depression is common throughout the life course, while dementia is very common in late life

  • Late-life depression or depressive symptoms may be associated with dementia, but inconsistencies across studies exist

  • Current research supports the association between earlier-life depression—or depressive symptoms—and dementia; however, more studies are needed to examine depression occurrence over the life course

  • Vascular disease, glucocorticoid steroid levels, hippocampal atrophy, increased deposition of amyloid-β plaques, inflammatory changes, and deficits of nerve growth factors or neurotrophins are likely to underlie depression and dementia

  • A patient presenting with early-life or late-life depression or depressive symptoms, especially if chronic, should be screened and monitored for cognitive deficits over the long term

  • Determining whether treatment of depression alone or combined with other regimens would delay or prevent dementia is critical

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Figure 1: Proposed predominant pathways linking depression to the onset of dementia.


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This work was supported by the National Institute of Mental Health (grant K01 MH079093 to A. L. Byers and R01 MH086498 to K. Yaffe) and the National Institute on Aging (grant K24 AG031155 to K. Yaffe).

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A. L. Byers researched data for, and wrote, the article. A. L. Byers and K. Yaffe made equal contributions to discussions, reviewing and editing the article.

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Correspondence to Amy L. Byers.

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Byers, A., Yaffe, K. Depression and risk of developing dementia. Nat Rev Neurol 7, 323–331 (2011).

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