Serum cystatin C and mild cognitive impairment: The mediating role of glucose homeostasis

Kai Li; Jing Xu; Meiduo Zhao; Jingtao Wu; Yayuan Mei; Quan Zhou; Jiaxin Zhao; Yanbing Li; Ming Yang; Qun Xu

doi:10.3389/fnagi.2023.1102762

Serum cystatin C and mild cognitive impairment: The mediating role of glucose homeostasis

Front Aging Neurosci. 2023 Mar 28:15:1102762. doi: 10.3389/fnagi.2023.1102762. eCollection 2023.

Authors

Kai Li^{1

2}, Jing Xu^{1

2}, Meiduo Zhao^{1

2}, Jingtao Wu^{1

2}, Yayuan Mei^{1

2}, Quan Zhou^{1

2}, Jiaxin Zhao^{1

2}, Yanbing Li^{1

2}, Ming Yang^{1

2}, Qun Xu^{1

2}

Affiliations

¹ Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
² Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Abstract

Background: This study explored the mediating role of glucose homeostasis indicators in the relationship between serum cystatin C and mild cognitive impairment (MCI).

Methods: The present study used a cross-sectional design and included 514 participants aged ≥50 years in Beijing, China. The Mini-Mental State Examination was used to assess cognitive function. Serum cystatin C and a comprehensive set of glucose homeostasis indicators were detected, including fasting blood glucose (FBG), glycosylated albumin percentage (GAP), glycated hemoglobin (HbAlc), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-β). Generalized linear models were used to investigate the associations among cystatin C, glucose homeostasis indicators, and cognitive function. Mediation analysis was conducted to explore potential mediator variables.

Results: In this study of 514 participants, 76 (14.8%) had MCI. Those with cystatin C levels ≥1.09 mg/L had a 1.98-fold higher risk of MCI than those with levels <1.09 mg/L (95% CI, 1.05-3.69). FBG, GAP, and HbA1c increased the risk of MCI, while HOMA-β decreased the risk. Notably, the associations between MCI risk and cystatin C or glucose homeostasis were only founded in diabetes patients. Serum cystatin C was found to be positively associated with HOMA-β (beta (95% CI): 0.20 [0.06, 0.34]), HOMA-IR (0.23 [0.09, 0.36]), and insulin (0.22 [0.09, 0.34]) levels. Moreover, HOMA-β was identified as playing a negative mediating role (proportion mediated: -16%) in the relationship between cystatin C and MCI.

Conclusion: Elevated levels of cystatin C are associated with an increased risk of MCI. The glucose homeostasis indicator, HOMA-β, plays a negative mediating role in the relationship between cystatin C and MCI risk.

Keywords: cystatin C; diabetes; glucose homeostasis; mild cognitive impairment; population-based study.

Grants and funding

This study was supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (grant no. 2022-JKCS-11), the CAMS Innovation Fund for Medical Sciences (grant no. 2022-I2M-JB-003), and the China prospective cohort study of air pollution and health effects in typical areas (grant no. MEE-EH-20190802).