Atherosclerotic cardiovascular disease risk is associated with AT(N)V neuroimaging biomarkers and cognitive impairment in the health and aging brain study–health disparities cohort

Abstract

Cardiovascular risk is increasingly recognized as relevant to cognitive aging and dementia-related brain changes, yet its relationship to multimodal neuroimaging biomarkers of amyloid, tau, neurodegeneration, and vascular injury (AT(N)-V) remains incompletely understood in racially and ethnically diverse cohorts. We examined whether ten-year atherosclerotic cardiovascular disease (ASCVD) risk was associated with AT(N)-V neuroimaging biomarkers and cognitive domain scores. This cross-sectional study included 1,626 Health and Aging Brain Study–Health Disparities (HABS-HD) participants without cardiovascular disease or dementia who had amyloid positron emission tomography (PET) imaging linked to visit 1. Ten-year ASCVD risk was estimated using the Pooled Cohort Equations and modeled continuously. Neuroimaging outcomes included global florbetaben amyloid PET standardized uptake value ratio (SUVR), medial temporal lobe (MTL) PI-2620 tau PET SUVR, cortical thickness, hippocampal volume, and white matter hyperintensity (WMH) volume. Cognitive domain outcomes included memory, executive function, processing speed, and language. Multivariable linear regression models accounted for apolipoprotein E ( APOE ) ε4 status, relevant neuroimaging biomarkers, and imaging scanner/protocol covariates as appropriate, with Holm adjustment for multiple comparisons. Amyloid-status-stratified analyses were also conducted using a global amyloid PET SUVR threshold of 1.08. Increasing ten-year ASCVD risk was associated with increasing global amyloid and MTL tau PET SUVR, smaller cortical thickness, smaller hippocampal volume, and increased WMH volume. Increasing ten-year ASCVD risk was also associated with lower memory, executive function, processing speed, and language scores after accounting for APOE ε4 status, amyloid burden, neurodegeneration, vascular injury, and scanner covariates. Associations between ten-year ASCVD risk and structural and vascular injury markers were observed in both amyloid-positive and amyloid-negative participants, whereas associations with amyloid and MTL tau PET were modest and statistically significant only among amyloid-negative participants. In this diverse HABS-HD sample, increasing ten-year ASCVD risk was associated with greater AT(N)-V biomarker burden and poorer cognitive performance across multiple domains. These cross-sectional findings suggest that ten-year ASCVD risk may serve as a marker of co-occurring cardiovascular and brain health burden, but they do not establish causality or temporal direction.