Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101473265 Publication Model: Print Cited Medium: Internet ISSN: 1755-5949 (Electronic) Linking ISSN: 17555930 NLM ISO Abbreviation: CNS Neurosci Ther Subsets: MEDLINE

Parkinson Disease*/diagnostic imaging , Diffusion Tensor Imaging*/methods , Glymphatic System*/diagnostic imaging, Humans ; Cross-Sectional Studies

Introduction: Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder that primarily affects motor functions. Recently, a diffusion tensor imaging technique called DTI along the perivascular space (DTI-ALPS) has gained attention as a noninvasive biomarker for glymphatic function. This systematic review and meta-analysis aimed to evaluate the potential and implications of the DTI-ALPS index for diagnosing PD.
Methods: This study followed the PRISMA 2020 statement. Eligible cohort and cross-sectional studies measured the ALPS index in PD patients versus non-PD participants. Web of Science, Medline, Scopus, Embase, Cochrane, PROSPERO, and ICTRP databases were explored until November 14, 2024. Two researchers independently screened studies, extracted data, and assessed the risk of bias using the Newcastle-Ottawa Scale (NOS). The meta-analysis used a random effects model (REM), assessing heterogeneity (I ² , Q-test) and publication bias (Egger's test, trim&fill plot). The certainty of the evidence was evaluated using the GRADE approach.
Results: This meta-analysis of 11 studies, involving 1462 patients (855 PD, 607 non-PD of both genders), yielded significant findings. The overall ALPS index differed substantially between PD and non-PD groups (SMD: -0.61, 95% CI: -0.72, -0.50, p < 0.001). Additionally, a significant negative correlation emerged between the ALPS index and Unified PD Rating Scale III (UPDRS III) (r = -0.40, (95% CI: -0.59, -0.18, I ² : 89.81, p < 0.001)), indicating glymphatic dysfunction's impact on cognitive decline. However, a weak and statistically non-significant correlation was observed between the ALPS index and Montreal Cognitive Assessment (MoCA) (r = 0.24, 95% CI: -0.32 to 0.68), with high heterogeneity across studies (I ²  = 87.37, p < 0.001 for heterogeneity). Publication bias risk was low for the overall ALPS index.
Conclusion: These findings highlight the potential of DTI-ALPS as a noninvasive biomarker for PD diagnosis and progression monitoring. Further studies are warranted to explore its applicability in differentiating PD from other neurodegenerative disorders.
(© 2025 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)