Coronary artery calcification reflects cognitive and cerebrovascular alterations in cognitively unimpaired adults

Coronary artery calcification (CAC) entails arterial wall hardening and lipid-rich plaques accumulation and may contribute to early cognitive decline. Its association with cognition, brain structure and function, Alzheimer’s disease, neurodegeneration, and inflammatory and lipid biomarkers remains unclear. We conducted a cross-sectional study of 278 cognitively unimpaired adults aged ≥ 50 years with absent (score = 0; n = 151) or high CAC (score ≥ 300; n = 127). Participants underwent cognitive testing, serum assays (Aβ42/40, pTau181, NfL, GFAP, inflammatory/lipid markers), and multimodal MRI (structural, resting-state and vessel encoded arterial spin labeling). High CAC was associated with lower general cognition, increased white matter hyperintensities, altered hippocampal and sensorimotor connectivity, and reduced perfusion in the inferior frontal gyrus pars opercularis. No group differences emerged in the serum biomarkers. These results reveal that high CAC is associated with cognitive and cerebrovascular changes independent of Alzheimer’s disease biomarker increase, suggesting vascular pathways in early brain aging.