Abstract 16099: Life’s Essential 8 and Genetic Predisposition Predict Brain Volume Change, Mild Cognitive Impairment and Dementia Risk

Abstract

Introduction: Life’s Essential 8 (LE8) are the key measures for improving and maintaining cardiovascular health, as defined by the American Heart Association in 2022. The associations of LE8 with future brain volume change, mild cognitive decline (MCI), and dementia have been unclear. Hypothesis: We hypothesized that LE8 status might be related to future brain volume change, and predict risk of MCI and all-cause dementia. Apolipoprotein E (APOE) gene and polygenic risk score (PRS) may modify the association between them. Methods: We used cohort data from UK Biobank. LE8 was categorized into low (<50 score), moderate (50-79 score), and high (≥80 score) levels. Genetic predisposition was measured by APOE e4 carrier status and a polygenic risk score (PRS) calculated based on 39 non-APOE genetic variants. Linear regression models were used to analyze LE8 every 10-score increase and change of brain volume (total and hippocampus etc.). Cox regression models were used to estimate the hazard ratio (HR) and 95%CI on the association between LE8 and MCI and dementia. Results: We included 126,785 participants with a mean (SD) age of 56.0 (8.0) years and 53.5% were female. After a median of 13.0 years follow-up, we recorded 1797 (1.4%) people with MCI, and 1055 (0.8%) with dementia. Every 10-score increase of LE8 was related to 2826.11mm 3 increase in total brain volume, 8.41 and 12.04 mm 3 increase in left and right hippocampus volume respectively, while 393.41mm 3 decrease in ventricular cerebrospinal fluid volume (p values all <0.001). Compared to people with a low LE8, those with a high LE8 were associated with decreased risk of MCI (HR 0.54, 95% CI 0.44-0.68) and dementia (0.63, 0.47-0.85). Compared to people with high LE8 and no APOE e4 allele, those with low LE8 and one or two APOE e4 alleles were associated with increased risk of MCI (2.36, 1.69-3.29) and dementia (4.37, 2.86-6.68). The joint effects of LE8 and PRS showed that people with high LE8 and low PRS had lower risk of dementia. Conclusions: High LE8 was associated with increased total brain volume, hippocampus volume and decreased ventricular cerebrospinal fluid volume. Higher LE8 was also linked to reduced risk of MCI and dementia. There were joint effects between LE8 and APOE, PRS on MCI and dementia risk.