Longitudinal Association of Mid-Life Ten Year Cardiovascular Disease Risk Score with Brain Biomarkers of Alzheimer's Disease, Neurodegeneration and White Matter Hyper Intensities in Cognitively Unimpaired Older Adults: Heart SCORE Brain Study

IntroductionAtherosclerotic cardiovascular disease (ASCVD) risk factors in mid-life have been associated with cognitive decline and late-life dementia. However, the role of these risk factors in preclinical Alzheimers disease (AD) pathophysiology remains elusive. We investigated whether mid-life 10-year pooled cohort equations (PCE) based ASCVD risk is associated with late-life amyloid, tau, neurodegeneration [AT(N)] measures and white matter hyperintensities (WMHI). MethodsParticipants 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 white matter hyperintensities (WMHIs). Mid-life PCE ASCVD risk was categorized as; borderline (5%-7.4%), intermediate (7.5%-<15%), or high ([&ge;]15%). Association of midlife ASCVD risk HR (5% CI) was assessed using logistic and linear regressions with A, T, or N and chi square beta coefficients for WMHI in latelife. ResultsOver a [~]16y follow up, in 135 participants (mean age 73y), A and T showed no significant association with mid-life ASCVD risk. Neurodegeneration had a graded association with mid-life ASCVD risk categories (ORASCVD high vs low risk% 6.98 [2.44-19.95]; p<0.05) driven by self-identified Black race and age. In a subset n=60, ASCVD risk score was also associated with WMHIs (({beta}=0.42 {+/-} 0.22; p=0.05) in a model adjusted for inflammation and education. ConclusionsIn this asymptomatic, diverse cohort, 10y ASCVD risk was predictive of late-life neurodegeneration and white matter hyperintensities but not amyloid or tau. These data suggest that ASCVD risk factors in midlife may lead to a state of vulnerability (through increased neurodegeneration and white matter hyperintensities) which may progress to cognitive decline and dementia. Further mechanistic studies are warranted to test this hypothesis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/24301752v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@3e2dbborg.highwire.dtl.DTLVardef@2c867borg.highwire.dtl.DTLVardef@13101a3org.highwire.dtl.DTLVardef@627e2c_HPS_FORMAT_FIGEXP M_FIG C_FIG