REVIEW OF: Wingo TS et al, Alzheimers Dement 2023;19(3);868–874.

STUDY TYPE: Prospective cohort study

We know that depression in late life doubles the risk for Alzheimer’s disease (AD). There’s also an association between dementia and depression diagnosed in early and middle life (Elser H et al, JAMA Neurol 2023;80(9):949–958). A recent, large, genome-wide association study found that depression and AD share a genetic basis (Harerimana NV et al, Biol Psychiatry 2022;92(1):25–33). However, establishing causality is challenging—does late life depression increase the risk for AD, or is depression an early sign of AD? This study attempted to find an answer.

Using a large database, researchers looked at the full genetic data of 6656 individuals of European ancestry who were 50 years or older and who had normal cognition. Their median age was 56 years at baseline, and 59% were women. The researchers assessed the participants’ cognitive function and depression every two years for about 16 years. They analyzed the subjects’ DNA for various genetic patterns that have been associated with a higher risk of AD, and from this data came up with these polygenic risk scores (PRS). 

Researchers found that people who were genetically more prone to AD, meaning they had a higher PRS, were also more likely to feel depressed after age 50. This finding held up even after adjusting for the genetic predisposition to depression, sex, age, and education. The association between AD and depression was not explained by the ApoE4 allele, which is the strongest genetic risk factor for AD. This suggests that genetic variations contributing to AD risk may also contribute to late-life depression risk.

The study focused on Europeans, so may not be generalizable to non-Europeans. The study also measured depression by self-report, which may miss cases. 

CARLAT TAKE

Depression after the age of 50 may be a possible indicator for AD, even many years before AD symptoms first appear. The risk of dementia varies with the presence or resolution of depression at different ages, although we don’t know how treating depression influences a patient’s risk for dementia. Regardless, it’s a good idea to keep a close eye on cognitive function in patients with depression in late life.