Front Aging Neurosci. 2026 Sep 28;18:1870150. doi: 10.3389/fnagi.2026.1870150. eCollection 2026.
ABSTRACT
INTRODUCTION: This study examined cross-sectional associations between ten-year American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) risk and plasma Alzheimer's disease (AD) biomarkers in relation to cognitive outcomes and to determine whether ASCVD risk modifies biomarker-cognition relationships.
METHODS: Baseline data were analyzed from cognitively unimpaired and mild cognitive impaired (MCI) participants enrolled in the Health and Aging Brain Study-Health Disparities (HABS-HD), a large, community-based cohort enriched for racial and ethnic diversity. Plasma biomarkers included amyloid-β42/40 (Aβ42/Aβ40), phosphorylated tau (p-tau181 and p-tau217), and neurofilament light (NfL). Ten-year ASCVD risk was calculated using pooled cohort equations. Multivariable logistic regression models examined associations of ten-year ASCVD risk and plasma biomarkers with MCI, while multivariable linear regression models evaluated associations with Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) Sum of Boxes scores. Separate models were constructed for Aβ42/40, p-tau217, p-tau181, NfL, and apolipoprotein (APOE) ε4 carrier status, and analyses were stratified by race and ethnicity. ASCVD × biomarker interaction terms were tested to evaluate effect modification.
RESULTS: Increased ten-year ASCVD risk was consistently associated with increased odds of MCI, ranging from OR = 2.62 (95% CI: 1.31-5.17) to OR = 4.22 (95% CI: 2.04-8.64), lower MMSE scores, ranging from β = -1.90 (95% CI: -2.62 to -1.18) to β = -2.56 (95% CI: -3.30 to -1.82), and increased CDR Sum of Boxes scores, ranging from β = 0.28 (95% CI: 0.09-0.46) to β = 0.39 (95% CI: 0.20-0.58). The ASCVD × p-tau181 interaction was significant for MCI (OR = 1.91; 95% CI: 1.26-2.95) and CDR Sum of Boxes (β = 0.27; 95% CI: 0.16-0.39). ASCVD associations with CDR Sum of Boxes ranged from β = 0.11 (95% CI: -0.08 to 0.30) to β = 0.24 (95% CI: 0.04-0.43) among non-Hispanic White participants, β = 0.80 (95% CI: 0.10-1.51) to β = 1.17 (95% CI: 0.49-1.86) among non-Hispanic Black participants, and β = 0.36 (95% CI: 0.08-0.65) to β = 0.52 (95% CI: 0.25-0.80) among Hispanic participants.
CONCLUSION: Greater ten-year ASCVD risk was consistently associated with cognitive impairment independent of plasma AD biomarkers, with evidence that p-tau181 modifies these associations and that their magnitude varies across racial and ethnic groups.
PMID:42865655 | PMC:PMC13655045 | DOI:10.3389/fnagi.2026.1870150