Association Between Serum Cystatin C and Cognitive Decline Independently from Creatinine: Evidence from Two Nationally Representative Aging Cohorts

Studies on the association between cystatin C based estimated glomerular filtration rate (eGFRcys) and cognitive outcomes yielded inconsistent results.The present study aimed to examine the potential association of eGFRcys with subsequent cognitive decline rate.A total of 11,503 community-based participants were involved in our analyses, including 5,837 (aged 72.9±6.3; 58.6% women) in the Health and Retirement Study (HRS) from the US and 5,666 (aged 58.1±9.2; 49.0% women) in the China Health and Retirement Longitudinal Study (CHARLS). The association of eGFRcys with subsequent cognitive decline rate was evaluated by linear mixed models.During 85,266 person-years of follow-up, both baseline elevated serum cystatin C (-0.048 standard deviation [SD]/year per mg/L; 95% confidence interval [CI], -0.060 to -0.036; p < 0.001) and decreased eGFRcys (0.026 SD/year per 30 mL/min/1.73m2; 95% CI, 0.020 to 0.032; p < 0.001) were associated with faster cognitive decline rate after full adjustment. Compared with those had eGFRcys ≥90 mL/min/1.73m2, participants with eGFRcys between 60 to 90 mL/min/1.73m2 (-0.012 SD/year; 95% CI, -0.020 to -0.004; p = 0.004) and those with eGFRcys <60 mL/min/1.73m2 (-0.048 SD/year; 95% CI, -0.058 to -0.039; p < 0.001) experienced statistically significantly faster cognitive decline after adjustment. The associations were independent from serum creatinine/eGFRcre (eGFR that was calculated from serum creatinine).Decreased eGFRcys are significantly associated with faster cognitive decline after full adjustment, independently from serum creatinine/eGFRcre. Serum cystatin C might be a risk factor or a prodromal biomarker of cognitive decline.