Association of type 2 diabetes treatment status with in vivo biomarkers of Alzheimer's disease

Abstract INTRODUCTION The association of type 2 diabetes (T2D) treatment with Alzheimer's disease (AD) is unclear. We examined T2D treatment status in relation to amyloid beta (Aβ) burden and AD‐related downstream processes. METHODS This cross‐sectional study included 546 cognitively unimpaired adults (mean age = 64.2 ± 3.2 years, 65% women), classified into normal glucose tolerance (NGT; hemoglobin A1c [HbA1c] < 5.7%), prediabetes/untreated T2D (HbA1c ≥ 5.7%), and treated T2D groups. Multiple regression analyses assessed group differences in Aβ ( 18 F‐florbetaben) and tau ( 18 F‐MK‐6240) positron emission tomography burden, magnetic resonance imaging–based AD signature cortical thickness, white matter hyperintensity (WMH) volume, and memory performance. RESULTS Compared to the NGT group, prediabetes/untreated T2D had greater anterior/posterior cingulate and superior parietal cortex Aβ burden, whereas treated T2D had lower cortical thickness and greater WMHs, independent of demographics and apolipoprotein E ε4 status. No group differences were found in tau or memory outcomes. DISCUSSION Prediabetes/untreated T2D, but not treated T2D, was associated with early Aβ deposition. Diabetes medications may mitigate brain Aβ burden.