Stroke and its diagnosis age on incidence dementia, and the mediating role of inflammation: A matched cohort study

Abstract Background We aimed to determine whether and to what extent the joint effect of stroke and age of stroke diagnosis on incident dementia, and to investigate whether inflammation indicators mediate the stroke-dementia relationship. Methods We conducted a nationwide, population-based, matched cohort analysis using data from the UK Biobank. The study examined a total of 13,712 individuals who had suffered a stroke (7,712 incident stroke, 6,000 prevalent stroke). Multivariable Cox proportional hazards models were employed to investigate the association between stroke and dementia risk. The relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and synergy index (SI) were calculated to measure the interaction on the additive scale. Longitudinal mediation analysis was conducted to assess the potential mediating effect of inflammation on the association between stroke and dementia, stratified by the age at stroke diagnosis. Competing risk models and propensity score matching were utilized in sensitivity analysis. Results: The median follow-up time was 4.76 years (range: 2.05-8.39) for the incident stroke cohort and 19.07 years (range: 15.87-23.97) for the prevalent stroke cohort. After stroke and non-stroke matching, younger patients exhibited a higher risk of post-stroke dementia compared to older patients, particularly in females and those with non-O blood type. For stroke survivors, older age at stroke onset was associated with higher risks of developing all-cause dementia (HR per 10-year increase, 3.41; 95% CI, 2.84-4.10), and 44%-47% of the combined risk was due to an additive interaction of stroke and its diagnosis age. Chronic inflammation mediated the stroke-dementia association, accounting for 5.4–5.8% of the overall impact in stroke survivors. Conclusion: In addition to confirming that stroke significantly elevates the risk of dementia and that an earlier age at stroke diagnosis augments dementia risk, our study underscores the joint effect of stroke and diagnosis age and inflammation may play a role in this relationship, advocating for early interventions and targeted therapeutic strategies for stroke survivors.