APOE‐e4 Status Moderates Associations between Executive Function and Air Pollution Exposure in Older Men

Abstract

AbstractBackgroundAir pollution, which includes exposure to tiny particulate matter (PM2.5) and Nitrogen Dioxide (NO2) is a notable public health hazard. Exposure has adverse effects on multiple health outcomes as well as with increased risk of developing cognitive impairment and Alzheimer’s disease and related dementias. Although the primary cognitive focus in Alzheimer’s disease is memory, there is growing recognition of the importance of early executive function (EF) deficits as a risk indicator. In addition, there is some evidence of genetic susceptibility to pollution‐related cognitive decline. Few studies have strong measures of air pollution, EF, as well as APOE genotyping. We recently showed that APOE genotype was associated with significant decline in EF from middle to early old age among individuals who were cognitively unimpaired at baseline (Gustavson et al, 2022). Here we tested the hypothesis that the impact of air pollution on executive functions would be greater in APOE‐ε4+ carriers compared with APOE‐ε4‐ individuals.MethodWe examined associations between exposure in midlife and EF from midlife to early old age in ∼800 men from the Vietnam Era Twin Study of Aging. Measures included average PM2.5 and NO2 exposure in the three years prior to the time 1 (mean age 56; range 51‐61) assessment, and an executive function factor score at time 1 and time 2 (mean age 68; range 65‐72). GEE analyses adjusted for multiple health and lifestyle covariates, as well as the random effect of family.ResultCognitive performance declined over time from age 56 to age 68 (F = 439.38, p<0.0001). There were no main effects of air pollution on EF. Overall APOE‐ε4+ carriers had higher EF performance than non‐carriers (F = 5.43, p = 0.02). In addition, we found a significant PM2.5‐by‐APOE genotype interaction (F = 8.80, p = 0.003). Increased exposure to PM2.5 in midlife was related to lower executive function in APOE‐ε4 carriers, but not non‐carriers. The interaction with NO2 did not reach significance (F = 2.83, p = 0.09).ConclusionThese results indicate that midlife PM2.5 exposure in men is associated with poorer frontal‐executive function, and APOEε4 carriers are more susceptible to the deleterious effects of PM2.5.