Cardiovascular-Kidney-Metabolic Syndrome, Social Determinants of Health, and Dementia Risk: a prospective cohort study

Cardiovascular-kidney-metabolic (CKM) syndrome, characterized by pathophysiological interactions among metabolic risk factors, chronic kidney disease and the cardiovascular system, is a significant global health concern, particularly in populations with adverse social determinants of health (SDOH). However, the influence of CKM syndrome and the joint effects of SDOH on the risk of developing incident dementia has not been fully elucidated. Here, we examined these associations among 382569 individuals from the UK Biobank. We found that unfavorable SDOH and advanced CKM syndrome (stage 3-4) are independently associated with increased risks of incident all-cause dementia, Alzheimer’s disease and vascular dementia. Additionally, joint associations of CKM syndrome stages and SODH with incident dementia were observed. Individuals with ≥3 unfavorable SDOH and in CKM syndrome stage 4 exhibited the highest dementia risk, even after adjusting for APOE ε4 status. Our findings highlighted the importance of maintaining optimal CKM health and addressing unfavorable SODH in cognitive aging.