Association of the endothelial activation and stress Index (EASIX) with cognitive function in United States older adults: Findings from NHANES 2011–2014

Background Cognitive decline poses a significant public health challenge in aging populations. Endothelial dysfunction is increasingly recognized as a key mechanism linking vascular pathology to cognitive impairment. The Endothelial Activation and Stress Index (EASIX), derived from routine laboratory measures, has been associated with vascular outcomes, but its relationship with cognitive function in the general aging population remains unexplored. Objective This study aimed to investigate the association between EASIX and cognitive performance among community-dwelling older adults. Methods We analyzed data from 2143 participants aged ≥60 from NHANES 2011–2014. EASIX was calculated as (creatinine × lactate dehydrogenase) / platelet count. Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease Word Learning (CERAD-WL) and Delayed Recall tests, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Survey-weighted linear and logistic regression models were employed to examine associations between EASIX and cognitive outcomes, adjusting for multiple covariates. Results Each unit increase in EASIX was significantly associated with lower scores on the DSST (β = –1.94, 95% CI: −2.79 to −1.10), AFT (β = –0.77, 95% CI: −1.04 to −0.50), and CERAD-WL (β = –0.53, 95% CI: −0.94 to −0.13). Higher EASIX was also associated with increased odds of cognitive dysfunction on AFT (OR = 1.22, 95% CI: 1.05–1.42) and DSST (OR = 1.66, 95% CI: 1.09–2.52). Associations remained robust in sensitivity analyses. Conclusions EASIX is independently associated with domain-specific cognitive decline in older adults, supporting its potential utility as an accessible biomarker of cognitive aging.