Post-cardiovascular disease healthy lifestyle, inflammation and metabolic biomarkers, and risk of dementia: a population-based longitudinal study

Background: Cardiovascular disease (CVD) is associated with an increased risk of dementia, but the impact of healthy lifestyle on post-CVD dementia remains unclear. Objectives: The aim of this study was to explore the association between post-CVD healthy lifestyle factors and risk of dementia. We further examined whether inflammation and metabolic biomarkers played a role in this association. Methods: This prospective cohort study included 77,324 dementia-free participants with prevalent CVD from the UK Biobank. We constructed the lifestyle score based on no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, adequate sleep duration, less sedentary behavior, and frequent social contact. Cox proportional hazard models were performed to examine the association of healthy lifestyle with risk of CVD-related dementia. Mediation models were fitted to investigate the underlying mechanisms driven by systemic inflammation, lipid profiles, liver/renal function, and blood pressure indices. Results: Over a median follow-up of 12.43 y, 1605 all-cause dementia (ACD) cases were documented, including 646 Alzheimer's dementia (AD) cases and 427 vascular dementia (VaD) cases. Healthy lifestyle scores were significantly associated with lower risk of dementia. The hazard ratios and 95% confidence intervals for the participants with 6-7 healthy lifestyle score were 0.50 (0.40, 0.62) for ACD, 0.80 (0.58, 1.10) for AD, and 0.30 (0.19, 0.48) for VaD, compared their counterpart with 0-1 score. Low-grade inflammatory markers and specific metabolic biomarkers were detected to significantly mediated the observed associations, explaining 1%similar to 11% of the associations of healthy lifestyle factors with dementia risk. Conclusions: Adherence to healthy lifestyle behaviors is significantly associated with a lower risk of dementia in individuals with CVD. The observed associations may be partly explained by a reduction in systemic inflammation and the promotion of metabolic balance.