Abstract
Permutations of cerebrovascular pathologies (CVP) in persons with diabetes mellitus (DM) have not been comprehensively investigated. Here, we examine diverse postmortem CVP outcomes, including permutations of single or mixed CVP, in 2163 older adults with or without DM who were followed in longitudinal studies of aging. Annual clinical evaluations included data to classify DM status by medical history (DM diagnosis), direct medication inspection (anti-diabetic therapy), and hemoglobin A1C level (≥6.5 %). Upon death, neuropathological examinations were performed and included evaluation for CVP (considering vessel pathologies and brain infarcts) and Alzheimer's disease neuropathologic change (AD-NC). Among all participants [mean age, 89.49 ± 6.89 years (SD)], single CVP were more common than mixed CVP. Logistic regression was used to analyze the association of DM with CVP permutations, controlling for age at death, sex, education, and AD-NC, and revealed increased odds of microinfarcts alone (odds ratio, 1.56 [95 %CI, 1.03-2.35]) and mixed microinfarcts and macroinfarcts (odds ratio, 1.90 [95 %CI, 1.16-3.13]). These associations remained after adjusting for demographic factors and cohort or vascular comorbidities including stroke, heart disease, hypertension, claudication, smoking, and systolic blood pressure. Furthermore, after controlling for demographic factors as well as AD-NC and APOE type, mixed microinfarcts and macroinfarcts were associated with approximate threefold increased risk of dementia (odds ratio, 2.95 [95 %CI, 1.13-7.70]) in participants with DM. Evidence suggests that older adults living with DM have higher odds of microinfarcts and mixed microinfarcts and macroinfarcts in the absence of intracranial vessel pathologies that cannot be explained by vascular comorbidities, and in this population mixed microinfarcts and macroinfarcts are associated with higher odds of dementia.