Abstract
BACKGROUND: Physical activity, grip strength, sedentary behaviors, and sleep duration were found to be associated with risk of developing stroke and dementia. However, the combined influence of these factors on stroke and dementia remains unclear. OBJECTIVE: To investigate the combined influence of these multiple lifestyle and functional factors on risk of stroke and dementia and their subtypes and to investigate the potential interaction between combined factors and the apolipoprotein E gene ε4 allele (APOE ε4). METHODS: Data were obtained from the UK Biobank, including 474,983 participants. A score ranging from 0 to 4 was assigned based on adherence to healthy factors: meeting physical activity recommendations, grip strength above the sex-specific median, sleep duration of 7–8 h/day, and sedentary time < 6 h/day. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident stroke and dementia, adjusting for potential confounders. RESULTS: Over a median follow-up of 10.1 years, 4,992 incident strokes and 2,120 dementias were recorded. Compared with participants with 0–1 healthy factor, adjusted HRs (95% CIs) for total stroke were 0.85 (0.79–0.92), 0.71 (0.66–0.77), and 0.65 (0.59–0.72) for those with 2, 3, and 4 healthy factors, respectively (P-trend < 0.001). Similar inverse associations were observed for ischemic stroke and intracerebral hemorrhage but not subarachnoid hemorrhage. For dementia, HRs (95% CIs) were 0.74 (0.66–0.83), 0.64 (0.56–0.71), and 0.43 (0.39–0.51) across increasing numbers of healthy factors (P-trend < 0.001), with consistent results for Alzheimer’s disease and vascular dementia. All four factors independently predicted lower risk of all-cause stroke and all-cause dementia. For stroke subtypes, associations varied by factor. Regular physical activity and higher grip strength were both associated with lower risk of intracerebral hemorrhage, while none of the healthy factors had associations with subarachnoid hemorrhage. For dementia subtypes, all healthy factors, except for physical activity, were associated with a lower risk of both Alzheimer’s disease and vascular dementia. In addition, the association between combined healthy factors and total stroke or all-cause dementia was independent of APOE ε4 carrying status. CONCLUSIONS: The cumulative association of multiple healthy factors with reduced risk of stroke and dementia highlights the importance of adopting a lifestyle with more elements of healthy factors for the prevention of these neurological diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-025-25305-4.