Vascular Risk Factors, Biological Aging, and Cognitive Performance in a National Sample of Older U.S. Adults

Abstract

Cardiovascular and cerebrovascular risk factors (CVRFs)-including hypertension, diabetes, heart disease, and stroke-are prevalent chronic conditions in older adults and major determinants of late-life cognitive decline. These conditions involve chronic inflammatory and metabolic processes that may accelerate biological aging, reflecting multisystem physiological decline beyond chronological age. We examined associations among CVRFs, accelerated biological aging, and cognitive performance and assessed whether biological aging mediates the association between CVRFs and cognitive performance overall and across race/ethnicity and sex. We analyzed data from 2,384 U.S. adults aged 60 years and older in the National Health and Nutrition Examination Survey 2011-2014. CVRFs were defined using clinical measurements and self-reported diagnoses. Biological aging was quantified using the PhenoAge algorithm derived from blood-based clinical biomarkers. Cognitive performance was assessed using composite scores of memory, executive function, and processing speed. Weighted linear regression and causal mediation analyses were conducted overall and stratified by race/ethnicity and sex. All CVRFs were associated with accelerated biological aging, with diabetes demonstrating the strongest association (0.76 SD higher PhenoAge acceleration; 95% CI: 0.67-0.85). CVRFs were associated with lower cognitive performance, with stroke showing the largest association (b = -0.317; 95% CI: -0.471 to -0.165). Accelerated biological aging mediated these associations, accounting for 88.5% of the diabetes association and 13.7%-27.2% for other CVRFs. Associations and mediation effects varied across racial/ethnic and sex groups, with mediation more consistent among Non-Hispanic Whites and females. Accelerated biological aging represents an important link between cardiometabolic risk to cognitive performance in older adults.