biostudies-literatureFeng LNIBIB NIH HHSNIDA NIH HHSNIMH NIH HHSNINDS NIH HHSNIH HHS105723https://www.ebi.ac.uk/biostudies/studies/S-EPMC12242590biostudies-literatureUnknown115<h4>Background</h4>The American Heart Association introduced Life's Essential 8 (LE8) to promote cardiovascular health and longevity. However, its impact on brain ageing and interactions with genetic risk factors of dementia, such as APOE4, remains unclear. This study investigates the relationship between LE8 and white matter brain ageing and evaluates the moderating effects of the APOE4 allele.<h4>Methods</h4>This cross-sectional study utilized data from the UK Biobank, including genetic, neuroimaging, and health-related data from touchscreen questionnaires, physical examinations, and biological samples. Participants were non-pregnant whites with LE8 variables, diffusion tensor imaging (DTI) data, and APOE4 genetic information available, excluding those with extreme white matter hyperintensities. Regional fractional anisotropy measures from DTI data were used to predict white matter brain age via random forest regression. The white matter brain age gap (BAG) was calculated by subtracting chronological age from predicted brain age.<h4>Findings</h4>The analysis included 18,817 participants (9430 women and 9387 men; mean age 55.45 years [SD: 7.46]). Higher LE8 scores were associated with a lower white matter BAG, indicating delayed brain ageing. The effect was more pronounced in non-APOE4 carriers (124 days younger per 10-point increase, 95% CI: 102-146 days; p < 0.001) compared to APOE4 carriers (84 days younger per 10-point increase, 95% CI: 47-120 days; p < 0.001). Potential interaction between APOE4 and LE8 on brain ageing was observed for some age and sex groups but with only borderline significance, further investigation in larger and more targeted studies is needed to validate the finding.<h4>Interpretation</h4>Adherence to LE8 is associated with delayed brain ageing, with genetic factors such as APOE4 potentially moderating this effect in specific age and sex groups. The overall benefit from a healthier lifestyle in individuals' brain ageing across genetic, sex, and age groups underscore the importance and broad applicability of behavioural lifestyle interventions in promoting brain health.<h4>Funding</h4>US National Institute of Health, University of Maryland, Montgomery County of Maryland.EBioMedicineAdherence to life's essential 8 is associated with delayed white matter aging.PMC12242590U01 MH108148S10 OD023696R01 NS114628RF1 NS114628DP1 DA048968RF1 MH123163R01 EB015611K01 DA059603Ke HPan YChen JLei DKYLee HLiu SChen CMa TYe ZKochunov PHong LEFeng LNguyen TTShenassa ELi YMcCoy RGLiang MThompson PMCanida TChen SMitchell BDfalseAdherence to life's essential 8 is associated with delayed white matter aging.<h4>Background</h4>The American Heart Association introduced Life's Essential 8 (LE8) to promote cardiovascular health and longevity. However, its impact on brain ageing and interactions with genetic risk factors of dementia, such as APOE4, remains unclear. This study investigates the relationship between LE8 and white matter brain ageing and evaluates the moderating effects of the APOE4 allele.<h4>Methods</h4>This cross-sectional study utilized data from the UK Biobank, including genetic, neuroimaging, and health-related data from touchscreen questionnaires, physical examinations, and biological samples. Participants were non-pregnant whites with LE8 variables, diffusion tensor imaging (DTI) data, and APOE4 genetic information available, excluding those with extreme white matter hyperintensities. Regional fractional anisotropy measures from DTI data were used to predict white matter brain age via random forest regression. The white matter brain age gap (BAG) was calculated by subtracting chronological age from predicted brain age.<h4>Findings</h4>The analysis included 18,817 participants (9430 women and 9387 men; mean age 55.45 years [SD: 7.46]). Higher LE8 scores were associated with a lower white matter BAG, indicating delayed brain ageing. The effect was more pronounced in non-APOE4 carriers (124 days younger per 10-point increase, 95% CI: 102-146 days; p < 0.001) compared to APOE4 carriers (84 days younger per 10-point increase, 95% CI: 47-120 days; p < 0.001). Potential interaction between APOE4 and LE8 on brain ageing was observed for some age and sex groups but with only borderline significance, further investigation in larger and more targeted studies is needed to validate the finding.<h4>Interpretation</h4>Adherence to LE8 is associated with delayed brain ageing, with genetic factors such as APOE4 potentially moderating this effect in specific age and sex groups. The overall benefit from a healthier lifestyle in individuals' brain ageing across genetic, sex, and age groups underscore the importance and broad applicability of behavioural lifestyle interventions in promoting brain health.<h4>Funding</h4>US National Institute of Health, University of Maryland, Montgomery County of Maryland.2025-01-01T00:00:00Z2025 May2025-08-27T03:07:03.498Z2025-08-27T03:07:03.498ZS-EPMC122425904028002510.1016/j.ebiom.2025.105723