Abstract: Objective To explore the association between left ventricular ejection fraction (LVEF) and brain structure as well as cognitive impairment in stroke-free older adults. Methods A total of 389 stroke-free older adults undergoing health examinations were retrospectively enrolled. Participants were divided into cognitive impairment group (n=138) and non-cognitive impairment group (n=251) based on their Mini-Mental State Examination (MMSE) scores. Whole-brain morphological analysis was conducted utilizing the Computational Anatomy Toolbox 12 (CAT12). After adjusting for relevant confounding factors, restricted cubic splines (RCS) were used to examine the potential nonlinear relationship between LVEF and cognitive impairment. Binary logistic regression was then employed to quantify their independent association, and mediation analysis was conducted to assess the mediating roles of gray matter volume (GMV) and white matter volume (WMV). Results RCS analysis revealed nonlinear associations between LVEF and WMV, and between cognitive scores and WMV, with linear relationships observed for all other variables. Logistic regression analysis indicated that LVEF (OR=0.951, 95%CI: 0.915－0.989, P=0.012), GMV (OR=0.989, 95%CI: 0.983－0.995, P<0.001), WMV (OR=0.991, 95%CI: 0.986－0.996, P=0.001), cortical thickness (OR=0.121, 95%CI: 0.019－0.760, P=0.024) and white matter hyperintensity volume (WMHV) (OR=1.051, 95%CI: 1.010－1.094, P=0.014) were associated with the risk of cognitive impairment. Mediation analysis showed that GMV (accounting for 16.8%) and WMV (significant only when LVEF<60%, accounting for 17.92%) partially mediated the association between LVEF and cognitive impairment. Conclusions In stroke-free older adults, reduced LVEF is significantly associated with cognitive impairment, and brain structural changes play a partial mediating role in this association.

Key words: cognitive function, left ventricular ejection fraction, brain volume, stroke-free older adults, mediation analysis