The Association of Metabolic Syndrome and Its Components With Brain Volumes and Structural Connections: A Systematic Review and Meta-Analysis of Observational Studies Publisher



Soleymani Y ; Heshmat R ; Pourabbasi A
Source: Journal of Diabetes and Metabolic Disorders Published:2025

Abstract

Purpose: This systematic review and meta-analysis aimed to synthesize the current evidence on the associations of metabolic syndrome (MetS) and its components, central obesity, hypertension, dyslipidemia, and elevated fasting plasma glucose (FPG) with brain volumes and structural connectivities. Methods: We conducted a comprehensive literature search in major databases (PubMed, Web of Science, Scopus, and ScienceDirect) up to December 2024. Studies were included if they reported quantitative data on the association between MetS or its components and brain volumetric or white matter (WM) integrity outcomes in adults. Two independent reviewers screened titles, abstracts, and full texts, extracted data, and assessed study quality using established tools. Random-effects meta-analyses were performed to pool effect sizes (ESs) for key outcomes. Heterogeneity was assessed using I² statistics, and sensitivity analyses were conducted to evaluate the robustness of findings. Results: A total of 38 studies (n = 27 to 37395 participants) met the inclusion criteria. Central obesity and hypertension were robustly associated with reduced total brain volume and increased WM hyperintensity volume, respectively (n = 4677, ES = -0.15, 95% CI: -0.24, -0.05 and n = 36135, ES = 0.22, 95% CI: 0.13, 0.31, respectively). Hypertension also demonstrated a significant negative association with WM fractional anisotropy (FA) (n = 31167, ES = -0.20, 95% CI: -0.35, -0.05). Elevated FPG and low HDL cholesterol were linked to adverse brain changes, though the evidence was less consistent. High triglyceride levels did not consistently predict brain structural alterations. Heterogeneity was high for the analyses (I² >80%), and results remained significant in sensitivity analyses. Conclusions: MetS and its key components are associated with detrimental effects on brain structure and connectivity. These findings underscore the importance of early detection and management of metabolic risk factors for preserving brain health and reducing the risk of cognitive decline and dementia. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2025.