Alzheimer's genetic risk intensifies neurocognitive slowing associated with diabetes in nondemented older adults

IntroductionWe examine interactive and intensification effects of type 2 diabetes (T2D) with APOE and an Alzheimer's disease genetic risk score (GRS) on neurocognitive speed performance and change in nondemented older adults.MethodsIn an accelerated longitudinal design, we used latent growth modeling to test moderators of level and change in a neurocognitive speed latent variable for 628 adults (baseline median age = 69.0) followed over 9 years. The GRS was compiled using the cumulative risk of APOE, CLU, CR1, and PICALM.ResultsFirst, T2D predicted slower speed performance at centering age (75). Second, no predictive effects were associated with APOE or GRS. Third, a significant interaction showed that high risk from both T2D and GRS was selectively associated with steeper longitudinal slowing than all comparison cross-domain risk groups.DiscussionHigher AD-related genetic risk intensified deleterious effects of diabetes on neurocognitive slowing in nondemented aging beyond the independent influence of APOE.