Longitudinal Associations Between Cardiometabolic Risk Markers and Cognitive Function in Middle‐Aged and Older Adults: A Population‐Based Cohort Study

OBJECTIVES: Dementia and cardiometabolic diseases are both characterized by long prodromal phases, which may complicate the assessment of their temporal relationships. Associations between cardiometabolic risk markers and cognition remain inconsistent. We examined the associations between cardiometabolic risk markers and cognitive function in middle-aged and older adults. METHODS: A longitudinal analysis was conducted using data from a population-based cohort (2007-2014) of 1255 cognitively normal Koreans aged ≥ 50 years at baseline. Cardiometabolic risk markers and Korean Mini-Mental State Examination (K-MMSE) scores were repeatedly assessed through health examinations and interviewer-administered questionnaires. Multivariable linear regression (LR) and generalized estimating equation (GEE) models were used to investigate the associations between cardiometabolic risk markers and K-MMSE scores. RESULTS: After full adjustment for covariates, increases in the homeostasis model assessment of insulin resistance (HOMA-IR) and fasting insulin levels were associated with larger percent declines in K-MMSE scores and with lower K-MMSE scores in LR and GEE models (log-transformed HOMA-IR: β = -1.03, 95% CI: -1.87 to -0.20 for LR; β = -0.25, 95% CI: -0.41 to -0.08 for GEE). By age group, increases in HOMA-IR and blood pressure were associated with declines in K-MMSE scores among adults aged ≤ 65 years. By cognitive domain, increases in blood pressure were associated with declines in memory, while increases in HOMA-IR were marginally associated with declines in visuospatial ability (p = 0.052). High-density and low-density lipoprotein cholesterol levels were not significantly associated with cognitive function across all analyses. CONCLUSIONS: Our findings suggest that longitudinal increases in insulin resistance and blood pressure are associated with cognitive decline, particularly among middle-aged adults (≤ 65 years), and may differentially influence cognitive domains.