The role of Cognitive Reserve and depression on executive functions in older adults: a 10‐year longitudinal study

Abstract Background Cognitive reserve (CR) refers to the use of compensatory strategies related to executive functions (EFs) to reduce the negative effects of age‐related brain changes. Depression represents a risk factor for dementia, but little is known about its role in the association between CR and EFs. In the present study, we tested whether depression moderated the association between CR and EFs, and which variables among CR, depression and APOE‐e4 status (e4/non‐e4) predicted conversion to Cognitively Unimpaired‐Declining (CUD; Johnson et al., 2018) and Mild Cognitive Impairment (MCI) from a Cognitively Unimpaired‐Stable (CUS) baseline. Method 416 participants were selected from the Wisconsin Registry for Alzheimer’s Prevention. These were native English speakers, aged ≥50, CUS at baseline, and with no history of neurological or psychiatric disorders. Of these, 290 were still CUS, 97 were CUD and 29 had MCI at the 10‐year follow‐up visit. Depression was assessed with the 20‐item Center for Epidemiologic Studies Depression Scale (CES‐D). A standardized composite score from three tests (CFL, Digit Span, Letter‐Number sequencing) estimated EFs. Another composite score, based on the WRAT‐3 Reading subtest (a measure of literacy or premorbid abilities) and years of education estimated CR. A hierarchical linear regression was performed to evaluate the effect of CR and depression on EFs at follow‐up. Baseline demographic variables (age, gender, APOE‐e4) and diagnosis at follow‐up (CUS, CUD, MCI) were entered in Model 1, CR and depression in Model 2, and the CR*Depression interaction in Model 3. Moreover, a multinomial logistic regression was used to predict conversion to CUD and MCI from baseline. Result Model 3 added significantly onto Model 2 ( p = .024), indicating a moderation between CR and depression on EFs. Particularly, the beneficial effects of CR on EFs seem to be mitigated by increasing levels of depression. In the multinomial regression, depression predicted conversion to CUD from CUS while CR, depression and APOE‐e4 predicted conversion to MCI from CUS. Conclusion These findings support the hypothesis that CR, associated with EFs, may protect against cognitive aging, but also highlight the disruptive effect that depression has on long‐term cognitive health. Further studies may replicate these findings in clinical populations.