Abstract

ObjectiveTo evaluate associations of Life's Essential 8 (LE8) score, the recently updated metric for promoting cardiovascular health (CVH), with the risk of incident dementia and its subtypes, cognition, and neuroimaging outcomes and to determine whether these associations differ among apolipoprotein E (APOE)-ε4 genotypes. DesignProspective cohort study. Setting and ParticipantsA total of 316,669 participants [mean (SD) age, 56.3 (8.1) years] without prior cardiovascular disease or dementia from the UK Biobank study at baseline survey (2006–2010) were enrolled. MethodsA modified version of the LE8 score was created (range: 0–100) and categorized into poor (0–49), intermediate (50–79), and optimal (80–100) CVH. Cox proportional hazard and multivariable linear regression models were used. ResultsDuring a median 12.6 years of follow-up, 4238 all-cause dementia cases including 1797 Alzheimer's disease and 939 vascular dementia (VaD) occurred. Individuals with optimal CVH had 44% (95% CI, 0.48–0.64) lower incident all-cause dementia risk and 71% (95% CI, 0.22–0.38) lower VaD risk compared with those who had poor CVH. A 10-point increment in LE8 was associated with higher fluid intelligence scores (β, 0.088; 95% CI, 0.073–0.102) and numeric memory scores (β, 0.054; 95% CI, 0.043–0.065), and was also associated with lower white matter hyperintensity volume (β, −0.673; 95% CI, −0.751 to −0.596), larger total brain volume (β, 77.93; 95% CI, 62.03–93.84), and hippocampal volume (β, 0.197; 95% CI, 0.106–0.288). In addition, the association between LE8 profiles and dementia diagnosis differed by APOE genotype (all P for interaction ≤ .001), and was more evident among APOE-ε4 noncarriers. Conclusions and ImplicationsIndividuals with a higher LE8 score experienced fewer dementia events (driven especially by incident VaD) and were associated with better neurocognitive brain health profiles. CVH optimization may be beneficial to the maintenance of brain health.

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