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 (ORASCVD 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.
Published Version
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