Associations between endothelial dysfunction, cognitive reserve, and cognitive function in dementia-free older adults: A population-based study

Background Current evidence has linked peripheral biomarkers of vascular endothelial dysfunction (ED) with cognitive impairment in older adults. Objective To investigate the associations of vascular ED with cognitive function while considering the potential influence of lifelong cognitive reserve (CR). Methods This population-based cross-sectional study included 1540 dementia-free participants who were aged ≥60 years and living in a rural area of China. Cognitive function was assessed using a neuropsychological test battery. A composite CR score was calculated by integrating education, occupational complexity, mental activity, and social support using a structural equation model. A composite ED score was calculated by averaging the z-scores of serum intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1). Data were analyzed using multiple general linear regression models. Results After controlling for multiple potential confounders, higher serum ICAM-1 levels and the composite ED score were significantly associated with lower z-scores in global cognition, verbal fluency, attention, and executive function (p < 0.05), but not with episodic memory z-score (p > 0.05). Higher serum VCAM-1 levels were significantly related with lower z-scores in global cognition, attention, and executive function (p < 0.05), but not with episodic memory or verbal fluency z-score (p > 0.05). There were no statistically significant interactions between ED biomarkers and lifelong CR on cognitive outcomes. Conclusions Vascular ED is associated with worse cognitive performance in dementia-free older adults, independent of lifelong CR.