Abstract 10806: Ten Year Atherosclerotic Cardiovascular Disease Risk in Mid Life Predicts Late-Life Amyloid and Tau Deposition on Brain Imaging

Abstract

Introduction: Risk factors of ASCVD have been associated with Alzheimer’s disease (AD) dementia. This association may be mediated by arteriosclerosis (ART), which have been implicated in incident dementia. However, the relationships among ASCVD risk factors, ART, and AD brain biomarkers (amyloid and tau) remains elusive. We investigated the association of the mid-life 10y ASCVD risk and subclinical ASCVD with late-life AD pathology. Methods: Participants >65y enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study between 2003-2005 (mid-life) underwent brain PET scans in 2018-2020 (late-life) to detect and quantify AD-specific amyloid [Pittsburgh Compound B (PiB)] and tau deposition. Mid-life 10-year ASCVD risk was categorized as borderline (5%-7.4%), intermediate (7.5%-14.9%), or high (≥15%). Logistic regression was used to calculate OR (95% CI) for association of late-life cortical amyloid and tau with mid-life ASCVD risk and marker of ART (vascular stiffness). Results: In 135 participants (mean age ~79y), global tau uptake had a graded association with increasing mid-life ASCVD risk categories (OR ASCVD high vs low risk% 11.00 [2.82-47.49]; p<0.05 ) while no significant association was found with PiB uptake on PET (Table) after mean 16y follow up. In fully adjusted models, Tau uptake was mainly driven by Black race ( OR 10.07 [3.25-36.39] ) and age ( OR 1.24 [1.10-1.41] ); all p<0.05. Midlife vascular stiffness showed a trend of association with late-life PiB retention (OR 1.76 [0.71-4.30]; p 0.05) but not with Tau . Conclusions: In an asymptomatic middle-aged biracial cohort, 10y ASCVD risk was predictive of late-life tau deposition but not amyloid. Vascular stiffness did not independently predict AD pathology. A simple mid-life ASCVD risk calculation may predict late-life AD risk. Further mechanistic studies are warranted to elucidate the race-related differences in the links between ASCVD risk and Alzheimer’s disease.