Abstract
INTRODUCTION: The relationship between peripheral vascular health, including endothelia, cognitive decline, and Alzheimer's disease (AD) dementia risk is unclear. METHODS: In this study, 2844 dementia-free Framingham Offspring participants (mean age 60.6 years, 53.2% women) had baseline brachial artery flow-mediated dilation (FMD%) and reactive hyperemia (RH). Participants were then followed for a median of 17 years for incident AD and underwent plasma biomarker testing and brain magnetic resonance imaging. RESULTS: FMD% (hazard ratio [HR] = 0.83, 95% confidence interval [CI] 0.76 to 0.91, p < 0.001) and RH (HR = 0.89, 95% CI 0.79 to 0.99, p = 0.049) were negatively associated with incident AD dementia after adjusting for confounders. Associations were stronger in individuals with elevated C-reactive protein. Poor vascular function correlated with higher plasma AD biomarkers, smaller brain volumes, greater white matter injury, and increased cerebral microbleeds. DISCUSSION: Poor FMD% and RH may serve as a prognostic biomarker for cerebrovascular pathology, including endothelial dysfunction in the AD brain.