The role of cognitive and brain reserve in late-life depressive events

Background: Cognitive and brain reserve aim to explain individual differences in susceptibility to dementia and may also affect the risk of late-life depressive events. We assessed whether higher cognitive and brain reserve are associated with lower risk of a late-life depressive event. Methods: This study included 4509 participants from the population-based Rotterdam Study (mean age: 63.4 ± 10.2 years, 55 % women) between 2005 and 2019. Participants completed cognitive testing and brain-MRI at baseline. Cognitive reserve was defined as the common variance across cognitive tests, while adjusting for demographic factors and brain MRI-markers. Brain reserve was defined as total brain volume divided by intracranial volume. Depressive events (depressive symptoms/depressive syndrome/major depressive disorder) were repeatedly measured (follow-up: 6.6 ± 3.9 years) with validated questionnaires, clinical interviews, and follow-up of medical records. Hazard ratios (HR) with 95 % confidence intervals (CI) were estimated using Cox-regressions. Results: Higher cognitive (HR: 0.91/SD, 95%CI: 0.84; 1.00) and brain reserve (HR: 0.88/SD, 95%CI: 0.77; 1.00) were associated with a lower risk of a depressive event after adjustment for baseline depressive symptoms. These associations attenuated when participants with clinically relevant depressive symptoms at baseline were excluded (HR: 0.95/SD, 95%CI: 0.86; 1.05, HR: 0.89/SD, 95%CI: 0.76; 1.03, respectively). Limitations: No data was available on depression in early-life and the number of participants with major depressive disorder was relatively low (n = 105). Conclusions: Higher cognitive and brain reserve may be protective factors for late-life depressive events, particularly in those who have experienced clinical relevant depressive symptoms before. Further research is needed to determine whether cognitive and brain reserve could be used as targets for the prevention of late-life depression.