Physical Activity, APOE Genotype, and Cognitive Decline: Exploring Gene-Environment Interactions in the UK Biobank

Background: Apolipoprotein E (APOE) genotype affects the risk of Alzheimer's disease (AD) with inconclusive evidence on the opportunity to mitigate related adverse effects by lifestyle changes. Objective: To examine the individual and interactive associations of APOE and objectively-measured physical activity (PA) and sedentary activity with cognitive decline. Methods: We used data from middle-aged and older UK Biobank participants with repeat tests on visuospatial memory (n = 52,767) and fluid intelligence (n = 19,713), and who also took part in the accelerometer sub-study. PA and sedentary activity were assessed by a wrist-worn accelerometer over a seven-day period. Cognitive decline was defined as >1 standard deviation (SD) reduction in memory or fluid intelligence score, and the mean follow up from baseline was 5.8 years. Results: There was an age dependent association between APOE ϵ4 genotype and memory decline (p_{age-interaction} = 0.01), with the association only seen in participants who were >65 years (OR 1.33, 95% CI 1.11 to 1.24; for <65 years OR 1.06, 95% CI 0.99 to 1.14). The OR for the APOE ϵ4 association with fluid intelligence decline was 1.11 (95% CI 0.99 to 1.24), and there was no evidence for age interaction (p_{age-interaction} = 0.99). High PA and low sedentary activity were associated with reduced mean memory decline (p < 0.02 for both). There was no interaction between PA or sedentary activity with APOE ϵ4 regarding either of the cognitive decline measures (p > 0.63 for all). Conclusion: This large-scale study using objectively measured PA did not find differential effects of PA on cognitive decline based on APOE genotype.