REVIEW OF: Zhu Y et al, Age Ageing 2022;51(1):afab191

STUDY TYPE: Prospective cohort study

Depression in older adults (OAs) is correlated with dementia, but we don’t know exactly how. Does depression lead to the development of dementia? Or is it a prodromal condition in people who are fated to develop dementia? If depression causes dementia, we would be even more motivated to treat it aggressively in OAs.

Previous studies suggested that persistent or worsening depression is associated with cognitive decline. However, these studies were short term (<3 years), limiting our understanding about how the course of depression over many years may affect cognition.

To try and understand the connection, researchers combined data from two large cohort studies (one from the US and one from England) of community-dwelling adults 50 years and older. A total of 17,556 participants were followed over 18 years and evaluated for both depression and cognitive performance annually.

The results were in line with prior studies. There seemed to be a dose-response relationship between depression and cognitive decline. The “mild depressive symptoms” group had half the cognitive decline of the “worsening” and “persistent depressive symptoms” groups. The most interesting finding here is that even those with subclinical depression symptoms were at increased dementia risk.

The sample was heavily White and female, which limits generalizability. The very brief and slightly different executive function assessments between studies, and lack of evaluation or adjustment for genotypes such as apolipoprotein E that modify the association between depression and dementia, mean this study may be affected by information and confounding biases.

Carlat Take

You’d be forgiven for expecting big things of this study, with such a large cohort. It provides more evidence of a relationship between depression and cognitive decline, but doesn’t resolve whether depression is a prodrome versus an independent risk factor for dementia—it may well be both.