Long-term depressive symptoms and midlife brain age

Background: Evidence suggests that depression may be a risk factor for dementia in older adults, but the link between depressive symptoms and brain health earlier in life is less understood. Our aim was to investigate the association between long-term depressive symptoms in young to mid-adulthood and a measure of brain age derived from structural MRI. Methods: From the Coronary Artery Risk Development in Young Adults study, we identified 649 participants (age 23–36 at baseline) with brain MRI and cognitive testing. Long-term depressive symptoms were measured with the Center for Epidemiological Studies Depression scale (CES–D) six times across 25 years and analyzed as time-weighted averages (TWA). Brain age was derived using previously validated high dimensional neuroimaging pattern analysis, quantifying individual differences in age-related atrophy. Elevated depressive symptoms were defined as CES-D ≥16. Linear regression was used to test the association between TWA depressive symptoms, brain aging, and cognition. Results: Each standard deviation (5-points) increment in TWA depression symptoms over 25 years was associated with one-year greater brain age (β: 1.14, 95 % confidence interval [CI]: 0.57 to 1.71). Participants with elevated TWA depressive symptoms had on average a 3-year greater brain age (β: 2.75, 95 % CI: 0.43 to 5.08). Moreover, elevated depressive symptoms were associated with higher odds of poor cognitive function in midlife (OR: 3.30, 95 % CI: 1.37 to 7.97). Limitations: Brain age was assessed at one time, limiting our ability to evaluate the temporality of depressive symptoms and brain aging. Conclusions: Elevated depressive symptoms in early adulthood may have implications for brain health as early as in midlife.