Abstract
INTRODUCTION: Asymptomatic extracranial carotid atherosclerotic disease (aECAD) has been associated with Alzheimer's disease (AD), but the earliest cognitive deficits in this hallmark vascular population are largely unknown. METHODS: A total of 182 participants 50-85 years of age with ≥2 vascular comorbidities with/without aECAD were evaluated prospectively using a neurocognitive battery and compared to vascular comorbidities, percent stenosis, apolipoprotein E (APOE) ε4 status, and plasma phosphorylated tau (p-tau217). Dementia, stroke < 6 months, and neurological disorders were exclusionary. RESULTS: aECAD was associated with significantly worse scores in processing speed (β = -0.19, p = 0.004) and executive function (β = -0.20, p = 0.009) domains after controlling for age, sex, education, race, and ethnicity. From these, a carotid cognitive index was created, which correlated with p-tau217 (β = -0.29, p < 0.001), accounting for demographics, vascular comorbidities, white matter lesions, and APOE ε4 status. DISCUSSION: These data identify specific cognitive deficits associated with carotid stenosis and build further impetus to understand how vascular-related cognitive deficits contrast and complement the classic memory deficits of AD.