Plasma p-tau181 moderates the association between ten-year atherosclerotic cardiovascular disease risk and mild cognitive impairment – HABS-HD

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.