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

Article type: Research Article

Authors: Ma, Yanjun^{a; b; c} | Li, Chenglong^{a; b; c} | Hua, Rong^{a; b; c} | Yang, Chao^{d; e; f} | Xie, Wuxiang^{a; b; c; *} | Zhang, Luxia^{d; e; f; *}

Affiliations: [a] Heart and Vascular Health Research Center>, Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China | [b] PUCRI Heart and Vascular Health Research Center at Peking University Shougang Hospital, Beijing, China | [c] Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing, China | [d] National Institute of Health Data Science at Peking University, Beijing, China | [e] Advanced Institute of Information Technology, Peking University, Hangzhou, China | [f] Department of Medicine, Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China

Correspondence: [*] Correspondence to: Wuxiang Xie, PhD, Peking University Clinical Research Institute, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, 100034, Beijing, China. Tel.: +86 10 82805564 622; Fax: +86 10 62015547; E-mail: xiewuxiang@hsc.pku.edu.cn and Luxia Zhang, MD, National Institute of Health Data Science at Peking University, No.5 Yiheyuan Road Haidian District, 100191, Beijing, China. E-mail: zhanglx@bjmu.edu.cn

Abstract: Background:Studies on the association between cystatin C based estimated glomerular filtration rate (eGFRcys) and cognitive outcomes yielded inconsistent results. Objective:The present study aimed to examine the potential association of eGFRcys with subsequent cognitive decline rate. Methods: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. Results: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). Conclusion: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.

Keywords: Alzheimer’s disease, Cognitive decline, creatinine, cystatin, glomerular filtration rate

DOI: 10.3233/JAD-221162

Journal: Journal of Alzheimer's Disease, vol. 93, no. 2, pp. 459-469, 2023