Can Cognitive Reserve Moderate the Association Between Brain Structure and Later-Life Behavioural Symptoms?

Introduction Cognitive reserve (CR) buffers against cognitive manifestations of neurodegenerative disease; little is known about CR and neuropsychiatric symptoms (NPS). We investigated CR moderation on the relationship between AD-related cortical changes and NPS. Methods Cross-sectional data from 455 participants in COMPASS-ND were analyzed. CR score (CRS) was operationalized from education, occupation, and mentally stimulating activities; NPS were assessed using the Mild Behavioral Impairment Checklist. Logistic regression modelled the relationship between hippocampal volume/entorhinal thickness and NPS. A volume/thickness*CRS interaction term was included to assess effect modification. All models adjusted for age, sex, and cognition. Results CR moderated the relationship between hippocampal volume and NPS (B = −3.39, 95% CI: [−6.04, −0.84], P = .01), with greater impact at lower CR. A weaker but non-significant interaction effect was observed with lower entorhinal thickness. Discussion Greater CR may mitigate NPS associated with lower hippocampal volume, independent of cognition, suggesting CR may preserve cognition and behaviour.