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

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 15 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1102762

DOI=10.3389/fnagi.2023.1102762

ISSN=1663-4365

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 to 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.

Conclusions: 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.