Association of the serum creatinine-to-cystatin C ratio with low cognitive performance in middle-aged and older Chinese adults: cross-sectional and longitudinal findings from CHARLS

Abstract

Using data from the China Health and Retirement Longitudinal Study (CHARLS), this study examined the association of the serum creatinine-to-cystatin C ratio (CCR) with low cognitive performance and subsequent cognitive change among middle-aged and older Chinese adults. The cross-sectional analysis included 8,152 participants at baseline in 2011, and the longitudinal analysis included 5,506 participants with repeated cognitive assessments through 2020. Low cognitive performance was defined using age- and education-adjusted global cognitive-score residuals, while logistic regression, restricted cubic splines, sensitivity analyses, and linear mixed-effects models were applied. The prevalence of low cognitive performance declined from 23.6% in the lowest CCR quartile to 13.7% in the highest quartile (P < 0.001), with a nonlinear inverse association that was most pronounced at lower CCR values. Compared with the lowest quartile, the fully adjusted odds ratios for low cognitive performance were 0.75 (95% CI, 0.64–0.88), 0.64 (0.54–0.76), and 0.69 (0.57–0.82) for the second, third, and highest CCR quartiles, respectively. These findings remained robust across sensitivity analyses. Longitudinally, a 1-SD increase in baseline ln(CCR) was associated with a 0.044-point/year slower decline in global cognitive score (95% CI, 0.029–0.058; P < 0.001). Higher CCR was therefore associated with a lower likelihood of low cognitive performance and more favorable cognitive trajectories, suggesting that it may serve as a simple, accessible marker of vulnerability to adverse cognitive aging.