Soluble receptor of advanced glycation end product as a biomarker in neurocognitive and neuropsychiatric disorders: A meta‐analysis of controlled studies

Abstract Background & Objectives Currently, there is a significant focus on the decrease of soluble receptor of advanced glycation end products (sRAGE) in neurocognitive and neuropsychiatric disorders. sRAGE plays a decoy role against the inflammatory response of advanced glycation end products (AGE), which has led to increased interest in its role in these disorders. This meta‐analysis aimed to investigate the significant differences in sRAGE levels between neurocognitive and neuropsychiatric disorders compared to control groups. Method A systematic review was conducted using the PUBMED, Scopus and Embase databases up to October 2023. Two reviewers assessed agreement for selecting papers based on titles and abstracts, with kappa used to measure agreement and finally publications were scanned according to controlled studies. Effect sizes were calculated as weighted mean differences (WMD) and pooled using a random effects model. Heterogeneity was assessed using I 2 , followed by subgroup analysis and meta‐regression tests. Quality assessment was performed using the Newcastle‐Ottawa Quality Assessment Scale. Results In total, 16 studies were included in the present meta‐analysis. Subjects with neurocognitive ( n = 1444) and neuropsychiatric ( n = 444) disorders had lower sRAGE levels in case–control (WMD: −0.21, 95% CI: −0.33, −0.10; p <.001) and cross‐sectional (WMD: −0.29, 95% CI = −0.44, −0.13, p <.001) studies with high heterogeneity and no publication bias. In subgroup analysis, subjects with cognitive impairment (WMD: −0.87, 95% CI: −1.61, −0.13, p =.000), and age >50 years (WMD: −0.39, 95% CI: −0.74, −0.05, p =.000), had lower sRAGE levels in case–control studies. Also, dementia patients (WMD: −0.41, 95% CI: −0.72, −0.10, p =.014) with age >50 years (WMD: −0.33, 95% CI: −0.54, −0.13, p = 0.000) and in Asian countries (WMD: −0.28, 95% CI: −0.42, −0.13, p =.141) had lower sRAGE levels in cross‐sectional studies. Conclusion This meta‐analysis revealed a significant reduction in sRAGE in neurocognitive and neuropsychiatric disorders particularly in Asians and moderate age.