Abstract
IMPORTANCE: The American Heart Association introduced Life's Essential 8 (LE8) as a checklist of healthy lifestyle factors to help older individuals maintain and improve cardiovascular health and live longer. How LE8 can foster healthy brain aging and interact with genetic risk factors to render the aging brain less vulnerable to dementia is not well understood. OBJECTIVE: To investigate the impact of LE8 on the white matter brain aging and the moderating effects of the APOE4 allele. DESIGN SETTING AND PARTICIPANTS: This cross-sectional study uses genetic, imaging, and other health-related data collected in the UK Biobank cohort. Participants included non-pregnant whites with LE8 variables, diffusion tensor imaging data, and genetic data on APOE4 available, and excluded the extreme white matter hyperintensities. The baseline assessment was performed from 2006 to 2010. The diffusion tensor imaging data were collected since 2014. EXPOSURES: LE8 variables, encompassing diet, physical activity, smoking, sleep, body mass index, lipids, hemoglobin, and blood pressure. MAIN OUTCOMES AND MEASURES: The white matter brain age was predicted from regional fractional anisotropy measures derived from diffusion tensor imaging data using the random forest regression method. The outcome white matter brain age gap was calculated by subtracting individuals' chronological age from their predicted brain age. RESULTS: The analysis included 9,430 women and 9,387 men (mean age 55.45 [SD: 7.46] years). Higher LE8 scores were associated with lower white matter brain age gap, indicating delayed brain aging. The findings are consistent for each of the individual LE8 variables. The effect was stronger among non- APOE4 carriers (124 days younger per 10-point increase, 95% CI, 102 to 146 days; P<0.001) than APOE4 carriers (84 days younger per 10-point increase, 95% CI, 47 to 120 days; P<0.001). Notably, early middle-aged women with APOE4 showed significant interactions between LE8 scores and brain aging (P interaction = 0.048), not observed in men. CONCLUSIONS AND RELEVANCE: Adherence to LE8 is associated with delayed brain aging, moderated by genetic factors such as APOE4 . These findings highlight the potential of behavioral and lifestyle interventions in reducing dementia risk, emphasizing tailored prevention plans for those with different genetic predispositions to dementia and sex.