BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome is an emerging clinical entity emphasizing the need for a holistic approach to patient care. The relationship between CKM syndrome and cognitive decline or dementia remains undetermined. METHODS: A total of 10 426 participants in the ARIC (Atherosclerosis Risk in Communities) study, classified into 4 CKM risk categories at baseline (visit 2: 1990-1992): low risk (≤5%), borderline risk (5%-7.4%), intermediate risk (7.5%-19.9%), and high risk (≥20%), were used to investigate the associations between CKM risk and cognitive decline or dementia using regression analysis. RESULTS: Elevated CKM risk level is significantly associated with increased risks of cognitive decline and dementia incidence. Each 1-unit increase in CKM risk level is linked to a 6% higher risk of dementia progression in the fully adjusted model. CONCLUSIONS: These findings highlight a strong association between CKM syndrome and cognitive decline or incident dementia, underscoring the importance of early interventions.