Glymphatic Dysfunction in Parkinson's Disease: A Systematic Review and Meta‐Analysis of Neuroimaging Studies

Abstract Background Parkinson's disease (PD) is a neurodegenerative disorder marked by motor and non‐motor symptoms. Impaired glymphatic clearance, which eliminates neurotoxic proteins, may contribute to PD pathogenesis. MRI techniques including Diffusion Tensor Imaging‐Along the Perivascular Space (DTI‐ALPS) and assessment of Enlarged Perivascular Spaces (EPVS) are used to evaluate glymphatic function. Objectives Assessment of glymphatic function in PD and its potential as an imaging biomarker. Methods A systematic search of Web of Science, Scopus, and PubMed was conducted on October 27, 2024, for observational MRI studies evaluating glymphatic function in PD. Meta‐analyses compared glymphatic indices between people with PD (PwPD) and healthy controls (HCs). Associations with clinical outcomes and participant characteristics were examined using effect‐direction plots and meta‐correlations. Results Thirty‐five studies involving 4224 PwPD and 1287 HCs were included. PwPD had lower DTI‐ALPS (SMD = −0.97; 95% CI: −1.42, −0.52; p < 0.01; I 2 = 91%; k = 15), higher EPVS numbers (SMD = 1.05; 95% CI: 0.37, 1.73; I 2 = 94%; k = 9), and higher EPVS volumes (SMD = 1.08; 95% CI: 0.67, 1.50; I 2 = 64%; k = 4) compared to HCs. Glymphatic dysfunction correlated with motor symptom severity (DTI‐ALPS: Z ‐correlation = −0.29; EPVS number: Z ‐correlation = 0.39). It was not associated with psychiatric symptoms and sex, while associations with global cognition and sleep disturbances were conflicting. Conclusions Glymphatic dysfunction is a prominent feature of PD and correlates with motor symptom severity, supporting its potential as a biomarker or potential therapeutic target. Variability in measurement techniques and inconsistent findings on non‐motor symptoms highlight the need for further research.