Serum Creatinine Clearance and Cognitive Function in Older Adults: Mediating Effects of Systemic Inflammatory...

The association between renal dysfunction and cognitive decline in older adults has been increasingly recognized, although the underlying mechanisms remain poorly understood. This study explored the association between serum creatinine clearance (Ccr) and cognitive function, and evaluated whether the Systemic Inflammatory Response Index (SIRI) mediates this relationship.

We analyzed 2482 adults aged ≥ 60 years from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) using survey-weighted regression models. Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Memory Test, Animal Fluency Test (AFT), Digit Symbol Substitution Test (DSST), and global cognitive performance (Z-GCP). Associations among Ccr, SIRI, and cognitive outcomes were evaluated using regression models, subgroup and interaction analyses, restricted cubic splines, and mediation analysis with 10,000 bootstrap samples.

Higher Ccr was independently associated with better cognitive performance across all domains. In fully adjusted models, each unit increase in Ccr was significantly associated with higher cognitive scores (CERAD: β = 0.021, 95% CI: 0.010-0.032; AFT: β = 0.014, 95% CI: 0.003-0.025; DSST: β = 0.082, 95% CI: 0.029-0.134; Z-GCP: β = 0.003, 95% CI: 0.002-0.005; all p < 0.05). Participants in the highest Ccr tertile had better cognitive performance and lower odds of impairment, especially in CERAD, DSST, and Z-GCP (p-trend < 0.05). Receiver operating characteristic analysis showed moderate discriminative ability of Ccr for cognitive impairment (AUCs: 0.736-0.843), and restricted cubic spline analyses revealed significant nonlinear associations for CERAD and DSST domains (p for nonlinearity < 0.05). Subgroup analyses indicated effect modification by age, sex, diabetes, hypertension, and stroke (p-interaction < 0.05). Mediation analysis showed that SIRI partially mediated the association between Ccr and cognitive outcomes, accounting for 3%-6.6% of the mediated proportions in CERAD, DSST, and Z-GCP domains (all p < 0.05).

Ccr is independently associated with cognitive performance in older adults, particularly in the CERAD, DSST, and Z-GCP domains. Systemic inflammation, as indicated by the SIRI, partially mediates these associations.