Abstract

To determine if cardiovascular risk factor (CVRF) burden is associated with Alzheimer's disease (AD) biomarkers and whether they synergistically associate with cognition. We cross-sectionally studied 1521 non-demented Mexican American (52%) and non-Hispanic White individuals aged ≥50 years. A composite score was calculated by averaging the z-scores of five cognitive tests. Plasma β-amyloid (Aβ) 42/40, total tau (t-tau), and neurofilament light (NfL) were assayed using Simoa. CVRF burden was assessed using the Framingham Risk Score (FRS). Compared to low FRS (< 10% risk), high FRS (≥ 20% risk) was independently associated with increased t-tau and NfL. High FRS was significantly associated with higher NfL only among Mexican American individuals. Intermediate or high FRS (vs. low FRS) were independently associated with lower cognition, and the association remained significant after adjusting for plasma biomarkers. Hypertension synergistically interacted with t-tau and NfL (p < 0.05). CVRFs play critical roles, both through independent and neurodegenerative pathways, on cognition.

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