Summan Zahra, Scott French, Juan C. Arias, Madeline Ally, Haley Wiskoski, Cris Escareno, Emma Heitkamp, Franchell Vazquez, Madison Hillis, Gavin Culwell, Karthik Ainapurapu, Caronae Howell, Kevin Johnson, Deniz Karakay, Karthik Rayasam, Lindsay Taylor, Cody Kraemer, Luis R. León, Scott S. Berman, Federico Yanquez, Joshua Balderman, Joseph Sabat, Olivia Y. Hung, Layla C. Lucas, Edward J. Bedrick, Francesca Vitali, Raza Mushtaq, María I. Altbach, Theodore P. Trouard, Ali Bilgin, Eric M. Reiman, Gene E. Alexander, Craig Weinkauf
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.