Supplementary Material for: Cystatin C and Risk of Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

<b><i>Introduction:</i></b> Cystatin C (Cys C) has been found as a novel biomarker of neurodegenerative diseases, such as dementia and Alzheimer’s disease. Published studies on the role of Cys C as a biomarker of mild cognitive impairment (MCI) have not been reviewed systematically. <b><i>Objective:</i></b> Present meta-analysis was performed to elucidate the association between Cys C and risk of MCI. <b><i>Methods:</i></b> A comprehensive search was performed in PubMed, EMBASE, Cochrane Library, Trip databases, Worldwide Science, and Google Scholar from January 1, 1950, to April 30, 2020. Standardized mean difference (SMD) with 95% confidence interval (CI) using fixed or random effect models were used to calculate summary estimates. Quality of evidence was also assessed using the Diagnostic Accuracy Quality Scale (DAQS) and grading quality of evidence and strength of recommendations approach. <b><i>Results:</i></b> In our meta-analysis, 12 studies with a total of 2,433 MCI patients and 1,034 controls were included. Our findings suggest a strong association between increased levels of Cys C and risk of MCI as compared to control subjects (SMD = 2.39, 95% CI = 0.22–4.57). Subgroup analysis based on ethnicity, a significant association for the high level of Cys C with the risk of MCI was observed in the Asian population (SMD = 1.63, 95% CI = 0.44–2.82) but not in the Caucasian population (SMD = 2.80, 95% CI = [−0.66]−6.26). <b><i>Conclusion:</i></b> Cys C was associated with MCI, and it could be considered as a predictor for the risk of cognitive impairment.