Sex Differences in the Association Between Vascular Risk Factors and Cognitive Decline: A UK Biobank Study

Background Age-related cognitive decline is accelerated by vascular risk factors for cerebral small vessel disease. However, the association of vascular risk factors with cerebral small vessel disease contributing to the sex differences in cognitive decline remains unclear. Objectives The purpose of this study was to evaluate sex differences in cognitive decline and the association between vascular risk factors and cognitive decline by sex. Methods We used data from the UK Biobank (>55 years of age; n = 19,067) to assess cognitive tests (executive function, processing speed, and memory) while adjusting for baseline measurements to examine how vascular risk factors affect cognition. A univariate regression analysis was used to assess sex differences at the first time point (2014). A repeated measure analysis with a mixed effect model was used to determine cognitive decline (between 2014 and 2019). Any significant interaction between vascular risk factors and sex was investigated. Results Females had lower scores in all three domains at the first cognitive tests (2014). We found a significant sex-by-time interaction over a 5-year period in matrix pattern completion (P = 0.03). After adjusting for vascular risk factors, this interaction was reduced (P = 0.08). High low-density lipoprotein, low education, and high blood pressure had a greater effect on the rate of cognitive decline in the executive function for females compared to males for the sex∗vascular risk factor interaction (P < 0.05). Conclusions The rate of cognitive decline did not differ significantly between males and females. However, the impact of several vascular risk factors was greater in females than in males, possibly explaining observed sex differences in rates of cognitive decline.