Type 2 Diabetes Moderates the Association Between Amyloid and 1-Year Change in Everyday Functioning in Older Veterans

Abstract

Background: Type 2 diabetes mellitus (T2DM) affects ∼25% of Veterans, a prevalence rate double that of the general population. T2DM is associated with greater dementia risk and has been shown to exacerbate the impact of Alzheimer’s disease (AD) risk factors on declines in daily functioning; however, there are few studies that investigate these patterns in older Veterans. Objective: This study sought to determine whether T2DM moderates the association between amyloid-β (Aβ) positron emission tomography (PET) and 1-year change in everyday functioning in older Veterans. Methods: One-hundred-ninety-eight predominately male Vietnam-Era Veterans without dementia from the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI) with (n = 74) and without (n = 124) T2DM completed Aβ PET imaging and everyday functioning measures, including the Clinical Dementia Rating–Sum of Boxes (CDR-SB) and Everyday Cognition (ECog). Linear mixed effects models tested the moderating role of T2DM on the association between Aβ PET and 1-year change in everyday functioning. Results: The 3-way T2DM×Aβ PET×time interaction was significant for CDR-SB (p < 0.001) as well as the Memory (p = 0.007) and Language (p = 0.011) subscales from the ECog. Greater amyloid burden was associated with greater increases in functional difficulties, but only in Veterans with T2DM. Conclusions: Higher Aβ was only associated with declines in everyday functioning over 1 year in Veterans with T2DM. Given that people with T2DM are more likely to have co-occurring cerebrovascular disease, the combination of multiple neuropathologies may result in faster declines. Future studies should examine how diabetes duration, severity, and medications impact these associations.