Cardiovascular health, genetic predisposition, and dementia risk among atherosclerotic cardiovascular disease patients

BACKGROUND: While optimal cardiovascular health (CVH) has been linked to a lower risk of dementia, few studies considered individuals' genetic background. We aimed to examine the interaction between CVH and genetic predisposition on dementia risk among individuals with atherosclerotic cardiovascular disease (ASCVD). METHODS: We included 30,818 ASCVD patients from the UK Biobank. CVH was assessed using Life's Essential 8, and genetic predisposition determined by a genetic risk score (GRS) incorporating 85 genetic variants. Cox proportional hazard models were used to estimate hazard ratios (HRs) for all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: Over a median follow-up of 13.5 years, 1,360 cases of all-cause dementia were identified, including 489 AD and 440 VaD cases. Higher CVH levels were associated with a reduced risk of all-cause dementia (HR for high vs. low CVH: 0.60; 95 % CI: 0.47-0.77) and VaD (HR for high vs. low CVH: 0.32; 95 % CI: 0.19-0.54), with a stronger association in individuals with lower GRS. Although the overall CVH score was not associated with the risk of dementia in individuals with high GRS, higher levels of sleep and glucose control were associated with a lower risk of VaD. CVH levels showed no association with the risk of AD. CONCLUSION: Higher CVH levels were associated with a lower risk of VaD, not AD, with a stronger association in individuals with low GRS. Improvements in specific LE8 components, particularly sleep health and blood glucose management, were associated with reduced VaD risk across various genetic risk strata.