Glymphatic system dysfunction in gliomas: A systematic review and meta-analysis of DTI-ALPS index

Abstract

Background: The glymphatic system's role in brain waste clearance is increasingly recognized in glioma pathophysiology. This study synthesizes evidence on DTI-ALPS index variations across glioma grades, molecular subtypes, and clinical outcomes to evaluate its diagnostic and prognostic utility. Methods: Following PRISMA 2020, major databases were searched up to December 20, 2025, for studies of adults with histologically confirmed gliomas who underwent DTI-ALPS assessment. Risk of bias was evaluated using ROBINS-E, and reporting quality using the STROBE checklist. Random-effects meta-analyses examined ALPS differences for six different outcome comparisons. Results: Fourteen studies were included. ROBINS-E revealed very high risk of bias in 14 of studies and some concerns in 64; mean STROBE compliance was 92.2. High-grade gliomas exhibited lower ALPS indices than low-grade tumors (MD=0.14, 95 CI: 0.11-0.16; I2=0). IDH wild-type gliomas showed lower ALPS indices than IDH-mutant tumors (MD=0.14, 95 CI: 0.10-0.18; I2=38). Multivariate Cox regression demonstrated that lower ALPS index is associated with worse overall survival (HR=0.73, 95 CI: 0.49-1.10; I2=57). Conclusion: DTI-ALPS index reliably detects glymphatic dysfunction in gliomas and provides prognostic information, supporting its use as a non-invasive biomarker for glioma assessment. However, methodological standardization and prospective multicenter studies are needed for clinical integration.