Yeh, Kai-JingKai-JingYehSun, Meng-JieMeng-JieSunSHIN-JOE YEHSUNG-CHUN TANGJENG-MIN CHIOUYEN-CHING KAREN CHENJEN-HAU CHEN2025-06-302025-06-302025-03-25https://scholars.lib.ntu.edu.tw/handle/123456789/730301Background Limited research has explored the intercorrelation between peripheral and central vascular factors on cognition incorporated longitudinal cognitive measures. Objective Explore associations between central and peripheral vascular factors and cognition. Methods This prospective cohort study recruited 516 older adults at baseline (2011–2013) with three follow-ups until 2019. Global and domain-specific cognition (memory, executive function, verbal fluency) were assessed biennially. The ankle-brachial index (ABI) and carotid intima-media thickness (CIMT) were the peripheral and central vascular markers. Generalized linear mixed models were utilized to explore the relationship between vascular factors and cognition adjusting for relevant covariates. Results Over time, one unit increment in the ABI was associated with decreased attention performance ( β ^  = −1.26). At baseline, one unit increase in CIMT (1 mm) was associated with better attention performance ( β ^  = 0.93) while the association decreased over time ( β ^  = −0.23). Over time, a unit increase in CIMT was associated with poor performance in global cognition ( β ^  = −0.52), memory ( β ^  = −0.21), executive function ( β ^  = −0.16), and verbal fluency ( β ^  = −0.15). These associations were particularly evident in APOE ε4 non-carriers, participants without lacunar infarct, and participants with hyperintensities. A significant interaction was found between lacunar infarct and CIMT on attention performance over time. Participants with both abnormal ABI (either low or high) and elevated CIMT showed the most pronounced decline in attention and memory domains, suggesting that the joint effect of these vascular markers affects cognitive performance. Conclusions Peripheral and central vascular factors differentially and jointly affect cognitive performance, emphasizing the importance of promoting vascular health to prevent dementia in the preclinical phase.[SDGs]SDG3journal article10.1177/13872877251319557