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

INTRODUCTION: We 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. METHODS: In 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. RESULTS: First, 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. DISCUSSION: Higher AD-related genetic risk intensified deleterious effects of diabetes on neurocognitive slowing in nondemented aging beyond the independent influence of APOE.