Is depression a risk factor for dementia or cognitive decline? A review

It is generally accepted that depression can be associated with significant cognitive deficits and that depression can be comorbid with dementia.

This review seeks to go further and ask whether depression earlier in life can be a risk factor for subsequent dementia or for cognitive decline.

A review was made of the epidemiological evidence from case-control and prospective studies that depression is a risk factor. The literature was also reviewed in relation to six hypotheses that might explain an association: (1) depression treatments are a risk factor for dementia, (2) dementia and depression share common risk factors, (3) depression is a prodrome of dementia, (4) depression is an early reaction to cognitive decline, (5) depression affects the threshold for manifesting dementia, and (6) depression is a causal factor in dementia.

A meta-analysis found that depression was associated with an increased risk of subsequent dementia in both case-control studies (95% CI for relative risk: 1.16-3.50) and prospective studies (95% CI: 1.08-3.20). There was little support for hypotheses 1 and 2. The other hypotheses have limited support, but warrant further research.

There is sufficient evidence to take seriously the possibility that depression is a risk factor for dementia and cognitive decline. Further work is needed to examine depression as a prodrome of vascular dementia, depression as an early reaction to perceived cognitive decline, the effects of depression on the threshold for manifesting dementia, and depression as a source of hippocampal damage through a glucocorticoid cascade.