Introduction: Cognitive reserve (CR) describes individual differences in susceptibility to brain damage that translates into varying dementia onsets and may also influence the occurrence of depressive symptoms. Within a population-based cohort of older people, we investigated two operationalizations of CR, residual- and activity-based approaches, in their association with the development of depressive symptoms.

Methods: We analyzed longitudinal data on 402 dementia- and depression-free adults aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) who underwent brain MRI at baseline. Residual-based reserve was derived by regressing episodic memory on a brain-integrity index incorporating six structural MRI markers. Activity-based reserve factored lifelong CR-enhancing experiences, including education, work complexity, social network, and leisure activities. Clinically relevant depressive symptoms were defined as a Montgomery–Åsberg Depression Rating Scale score >6. Cox hazard models were used to explore the association between both residual- and activity-based CR measures (categorized in tertiles) and incidence of depressive symptoms over a 15-year follow-up, while accounting for sociodemographic, clinical, behavioral factors, and brain integrity. Analyses for the activity-based measure were replicated in the full SNAC-K sample (N = 2709), further exploring depression diagnosis as additional outcome.

Results: Compared to low levels, higher levels of residual-based CR were associated with a lower hazard of depressive symptom onset in fully adjusted models (HR: .43, 95%CI .22, .84). While activity-based CR was not significantly associated with developing depressive symptoms in the MRI subsample (HRhigh .47, 95%CI .21, 1.04), it was in the full sample (HRhigh .52, 95%CI .39, .71). Activity-based CR was further associated with depression diagnoses in the full sample (HRhigh: .45, 95%CI .31, .65).

Discussion: Largely independent of its measurement, CR appears to influence depressive symptomatology in late life. Reserve-enhancing initiatives may be beneficial not only for cognitive but also for mental health in older people.