Sex differential effects on the joint contribution of air pollution and biological aging on cognitive performance in individuals at risk of Alzheimer’s disease

Abstract

AbstractBackgroundAir pollution is associated with cognitive performance, risk for AD and may accelerate biological aging. Biological aging due to telomere shortening has been associated with cognitive impairment. However, few studies have looked at the link between air pollution, telomere length, and cognitive performance among sexes. In this study, we investigated the joint effect of sex, air pollution, and leukocyte telomere length (LTL), on cognitive performance in cognitively unimpaired (CU) individuals at risk of AD.MethodThe study included 1,472 middle‐aged CU adults with increased risk of AD from the ALFA study [Table 1]. Residential exposure to air pollutants including nitrogen dioxide (NO2) and particulate matter (PM2.5, PM10) was estimated by land use regression models. LTL was determined by qPCR from DNA extracted from peripheral blood leukocytes. LTL was residualized against chronological age and sex (rLTL). A cognitive battery was administered to assess verbal memory, psychomotor speed, visual processing and executive function. Further, episodic memory (EM), executive function and Preclinical Alzheimer Cognitive Composite (PACC) composites were calculated by averaging normalized raw scores of the subtests. Models were corrected by chronological age, years of education and APOE‐ε4 status. Sex‐specific effects were investigated by adjusting interaction models.ResultThere was no overall effect of neither rLTL nor air pollution on cognitive performance, but crossover interactions with sex were found. Exposure to higher levels of NO2 and PM2.5 were associated with worse EM only in men [Figure 1]. Three‐way interaction models revealed longer rLTL and lower levels of air pollution were associated with better performance on PACC (for PM2.5, PM10 and NO2) and EM (for PM10 and NO2) among men. In women, these associations were only observed at higher exposure levels of air pollution [Figure 2].ConclusionThe results show that lower levels of air pollution allow for the protective effect of rLTL on cognitive performance only in men for whom air pollution had a stronger negative impact. In women, the results show different mechanisms through which air pollution and rLTL affect cognitive performance. Further analyses will be conducted to gain insight into the observed effects.