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Review
. 2025 May;31(5):e70434.
doi: 10.1111/cns.70434.

Diffusion Tensor Imaging Along the Perivascular Space Is a Promising Imaging Method in Parkinson's Disease: A Systematic Review and Meta-Analysis Study

Kiarash Shirbandi  1 , Mostafa Jafari  2 , Fatemeh Mazaheri  3 , Marziyeh Tahmasbi  2
Affiliations
Review

Diffusion Tensor Imaging Along the Perivascular Space Is a Promising Imaging Method in Parkinson's Disease: A Systematic Review and Meta-Analysis Study

Kiarash Shirbandi et al. CNS Neurosci Ther. 2025 May.

Abstract

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 (I2, 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, I2: 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 (I2 = 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.

Keywords: ALPS index; Parkinson's disease; diffusion tensor imaging; glymphatic function.

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Conflict of interest statement

Transparency statement: The corresponding author Marziyeh Tahmasbi affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. The corresponding author Marziyeh Tahmasbi had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

All authors have read and verified the final version of the manuscript. The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
The PRISMA flow diagram for the study selection process.
FIGURE 2
FIGURE 2
Meta‐analysis of the overall ALPS index and its relation with cognitive functions in Parkinson's disease (PD) and healthy control (HC) groups: (A) Forest plot comparing the overall ALPS index between PD and HC groups, showing a significant difference (p < 0.001). (B) Prediction interval for future studies on the overall ALPS index (−0.720, −0.497). (C) Correlation between the overall ALPS index and UPDRS III, demonstrating a significant association (p = 0.01). (D) Forest plot showing the correlation between the overall ALPS index and MoCA. A weak and statistically non‐significant correlation was observed (r = 0.24, 95% CI: −0.32 to 0.68, p = 0.07), with considerable heterogeneity across studies (I 2 = 87.37, p < 0.001 for heterogeneity).
FIGURE 3
FIGURE 3
Publication bias and symmetry analysis for the overall ALPS‐index in PD and HC groups: (A) Doi plot showing no asymmetry (LFK = 0.46) between PD and HC groups. (B) Counter funnel plot indicating the absence of substantial publication bias for the overall ALPS index.
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