Abstract
BackgroundAlthough some studies examined the association of individual risk factors for cardiovascular-kidney-metabolic (CKM) syndrome (diabetes, chronic kidney disease, and stroke) with the risk of incident dementia, little is known about the impact of overall CKM health on dementia risk. This study investigated (1) the association between CKM syndrome and risk of incident dementia in 400,740 UK Biobank participants and (2) whether systemic inflammation mediated this association.MethodsThe association between CKM syndrome and the risk of dementia was assessed using Cox proportional hazards models. The mediating role of systemic inflammation markers was evaluated in 389,287 individuals.ResultsCompared with stage 0 CKM syndrome, stages 3 and 4 were significantly associated with an increased risk of dementia (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.14-1.59; HR, 1.80; 95% CI 1.57-2.07). A significant linear trend was observed between CKM syndrome stages and dementia risk. Stage 2 CKM syndrome with more than two risk factors for CKM significantly increased dementia risk (HR, 1.25; 95% CI 1.07-1.46). Advanced CKM syndrome was associated with an increased risk of dementia (HR, 1.62; 95% CI 1.53-1.71). Four systemic inflammation markers significantly mediated the association between CKM syndrome and the risk of dementia.ConclusionsHigher stages of CKM syndrome are associated with an increased risk of dementia, and systemic inflammation mediates this association. These results highlight the importance of early and comprehensive management of poor CKM health to reduce the risk of dementia.