Associations between lifestyle, genetic risk for Alzheimer's disease, and longitudinal brain atrophy in the UK Biobank (N = 3265).

INTRODUCTION: The associations of modifiable daily lifestyle variables (e.g., smoking, diet, alcohol intake, sedentary behavior, and physical activity) with structural brain atrophy, and interaction with apolipoprotein E (APOE) ε4 genetic risk, remain unclear. METHODS: Among 3265 UK Biobank participants with repeated magnetic resonance imaging (MRI) data (mean follow-up 2.6 years), we assessed the relations between lifestyle, APOE ε4 genotype, and volumetric changes in 15 structural brain phenotypes, using linear regression. RESULTS: APOE ε4 presence showed greater atrophy by 25.1 mm3 in the left hippocampus (β: -0.115 standard deviations, 95% confidence interval [CI] [-0.192, -0.039] and 187.7 mm3 in frontal pole gray matter (β: -0.112, 95% CI [-0.186, -0.039]) (q < 0.05). Unfavorable lifestyle accelerated left hippocampal atrophy, and smoking increased white matter hyperintensity volumes (q > 0.05). No interactions were observed. DISCUSSION: Our study reinforces the independent effect of APOE ε4 on longitudinal brain atrophy. Lifestyle may help preserve structural brain health, and our findings provide no evidence this varies by APOE ε4 genotype.