Depression and cognition: is there a bidirectional relationship?

The association between depression and cognition is well-established, but there is uncertainty regarding the direction of causation. We evaluated the relationship between depression and poor cognition in both directions.

We used population-based samples from the Health and Retirement Study (HRS, 2008-2020) and the Midlife in the United States (MIDUS, Waves 2 and 3) study. We used an incidence modeling approach, excluding individuals who exhibited the outcome of interest at the start of the survey interval to help mitigate potential reverse-causality. Adjustment for potential confounders included sociodemographic characteristics, alcohol consumption, and major health conditions.

In the fully-adjusted model for HRS, depression exhibited a significant effect on subsequent cognitive impairment two years later (OR = 1.28, 95% CI 1.12-1.46), whereas the effect of cognitive impairment on subsequent depression was weaker and not significant (OR = 1.10, 0.98-1.23). The pattern of results was similar in MIDUS. Depression was significantly associated with subsequent poor cognition approximately nine years later (OR = 2.01, 1.30-3.12), but poor cognition had no significant effect on subsequent depression (OR = 0.75, 0.93-1.43).

Our results suggest that depression may have an inverse causal effect on cognition, but we found little evidence that good cognitive function had a protective causal effect on depression.