History of depression as a risk factor for dementia: an updated review

Objective: This review updates an earlier meta-analysis of the data on history of depression as a risk factor for dementia. It also considers the available evidence on the hypotheses proposed to explain the association between history of depression and dementia. Method: A meta-analysis was carried out on results from seven case-control and six prospective studies. A qualitative review was carried out on the evidence related to the hypotheses to explain the association. Results: The meta-analysis found evidence to support an association from both case-control studies (estimated relative risk 2.01; 95% CI 1.16-3.50) and prospective studies (estimated relative risk 1.87; 95% CI 1.09-3.20). However, the evidence did not clearly support any one hypothesis explaining the association. The most likely contenders are: (i) depression can be an early prodrome of dementia, (ii) depression brings forward the clinical manifestation of dementing diseases, and (iii) depression leads to damage to the hippocampus through a glucocorticoid cascade. Conclusions: The possibility that history of depression is a risk factor for dementia needs to be taken seriously and explanations of the association need to be further researched.