Renal function and cognitive performance in older adults: a NHANES-based mediation analysis of methylmalonic acid as a marker of mitochondrial dysfunction.

Chronic kidney disease (CKD) is associated with cognitive impairment in older adults. Mitochondrial dysfunction (MD) is a key contributor to aging-related diseases, yet its potential role in mediating the relationship between renal function and cognitive function (CF) remains unclear. Therefore, we aimed to examine this association in older adults and to evaluate the mediating effect of MD. Our study analyzed data from the 2011-2014 National Health and Nutrition Examination Survey, including participants aged ≥60. CF was assessed using the Animal Fluency Test (AFT), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning Test, and the Digit Symbol Substitution Test (DSST). Multivariate linear regression models were used to explore the relationships between renal function and CF, CKD, and methylmalonic acid (MMA) levels, and CF. Mediation analysis was conducted to assess the role of MD, as reflected by serum MMA levels, in the link between renal function and cognitive impairment. A total of 2,437 participants aged ≥60 were included. Regression analysis showed a significant positive association between renal function and CF (β = 0.018, 95%CI: 0.013-0.024, p < 0.001). After adjusting for potential confounders, MMA levels mediated 13.33% of the relationship between renal function and CF. The indirect effect of renal function on CF via MMA was significant (β = 0.000949, 95%CI: 0.000419-0.002463, p = 0.002), as was the direct effect (β = 0.006165, 95%CI: 0.000271-0.010456, p = 0.034). This study identifies a potential link between CKD and CF in older US adults. MD, assessed by serum MMA levels, may partially mediate this relationship, with MMA potentially serving as a biomarker for cognitive impairment.