Type 2 Diabetes Interacts With Alzheimer Disease Risk Factors to Predict Functional Decline

Objective: The current study examined the interactive effect of type 2 diabetes and Alzheimer disease (AD) risk factors on the rate of functional decline in cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative. Methods: Participants underwent annual assessments that included the Functional Activities Questionnaire, an informant-rated measure of everyday functioning. Multilevel modeling, controlling for demographic variables and ischemic risk, examined the interactive effects of diabetes status (diabetes, n=69; no diabetes, n=744) and AD risk factors in the prediction of 5-year longitudinal change in everyday functioning. One model was run for each AD risk factor, including: objectively-defined subtle cognitive decline (Obj-SCD), and genetic susceptibility [apolipoprotein E epsilon 4 (APOE epsilon 4) as well as cerebrospinal fluid beta-amyloid (A beta), total tau (tau), and hyperphosphorylated tau (p-tau). Results: The 3-way diabetesxAD risk factorxtime interaction predicted increased rates of functional decline in models that examined Obj-SCD, APOE epsilon 4, tau, and p-tau positivity, but not A beta positivity. Conclusions: Participants with both diabetes and at least 1 AD risk factor (ie, Obj-SCD, APOE epsilon 4, tau, and p-tau positivity) demonstrated faster functional decline compared with those without both risk factors (diabetes or AD). These findings have implications for early identification of, and perhaps earlier intervention for, diabetic individuals at risk for future functional difficulty.