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

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.

To examine the individual and interactive associations of APOE and objectively-measured physical activity (PA) and sedentary activity with cognitive decline.

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.

There was an age dependent association between APOEɛ4 genotype and memory decline (page-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 APOEɛ4 association with fluid intelligence decline was 1.11 (95% CI 0.99 to 1.24), and there was no evidence for age interaction (page-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 APOEɛ4 regarding either of the cognitive decline measures (p > 0.63 for all).

This large-scale study using objectively measured PA did not find differential effects of PA on cognitive decline based on APOE genotype.