Abstract
BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) risk factors in mid-life are associated with cognitive decline and late-life dementia. However, the role of these risk factors in Alzheimer's disease (AD) pathology remains elusive. OBJECTIVE: We investigated the association of mid-life 10-year ASCVD risk with late-life amyloid, tau, neurodegeneration [AT(N)] measures and white matter hyperintensities (WMHs). METHODS: Participants enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study between 2003-2005 (mid-life) and underwent brain MRI and PET scans in 2018-2022 (age >65 years, late-life) to detect and quantify amyloid (A, PiB-PET) and tau (T, Flortaucipir (FTP) PET) deposition, cortical thickness (N) and WMHs. Mid-life ASCVD risk was categorized as; borderline (5%-7.4%), intermediate (7.5%-<15%), or high (≥15%). Association of mid-life ASCVD risk HR (95% CI) was assessed using logistic and linear regressions with A, T, or N and chi square beta coefficients for WMH in late life. RESULTS: Over a ∼16 years follow up, in 135 participants (mean age 73 years), mid-life ASCVD risk categories had a graded association with neurodegeneration (OR(ASCVD high vs low risk%) 6.98 [2.44-19.95]; p < 0.05) driven primarily by self-identified Black race and age, while none with A and T. ASCVD risk score was also associated with WMHs ((β=0.42 ± 0.22; p = 0.05). CONCLUSIONS: In this asymptomatic, diverse cohort, 10-year ASCVD risk was predictive of late-life neurodegeneration and WMHs but not amyloid or tau. Further mechanistic studies can elucidate whether midlife ASCVD risk factors associated neurodegeneration initiates brain vulnerability leading to AD in late life.