ORIGINAL RESEARCH article
Front. Med.
Sec. Geriatric Medicine
The Left DTI-ALPS Index: A Potential Glymphatic Mediator of Cognitive and Motor Dysfunction in Parkinson's Disease
Provisionally accepted
Yanyan Li1,2
Jian Song1,2
Yuqing Zhao1,2
Zengru Lin1,2Xingduo Pan1,2Ming Li1,2Xiaoyan Zhou1,2Zhen Zhang1,2
Wei Wei1,2
Xiehua Xue1,2*- 1Fujian University of Traditional Chinese Medicine, Fuzhou, China
- 2The Affiliated Rehabilitation Hospital, Fuzhou, China
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Introduction: This study employed the Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) index to evaluate glymphatic function in patients with Parkinson's disease (PD) and investigated its association with cognitive and motor functions. Methods: Clinical data from the PD group (n=64) and the healthy control group (HC, n=30), matched for age, sex, and education years, were included. Based on Montreal Cognitive Assessment (MoCA) scale, PD patients were further categorized into subgroups. All participants underwent DTI scan and scale assessments. Results: Compared with the HC group, the PD group exhibited increased diffusivity of both the left projection (Dzzproj) and association fibers (Dzzassoc) along the z-axis (P<0.05) and a reduced left DTI-ALPS index (P<0.05). The left Dzzproj was negatively correlated with MoCA score (r=-0.299, P=0.024, q=0.048). The left Dzzassoc was negatively correlated with MoCA score (r=-0.280, P=0.035, q=0.035), and Movement Disorder Society-Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) score (r=0.333, P=0.011, q=0.022). The left DTI-ALPS index showed positive correlations with MoCA score (r=0.350, P=0.008, q=0.015) and a negative correlation with MDS-UPDRS III score (r=-0.322, P=0.015, q=0.015). Within the PD subgroup analysis, when compared to the HC group, and throughout the progression from PDCN to PDD, left Dzzproj, and left Dzzassoc all demonstrated a stepwise increasing trend. Conversely, the MoCA total score and the left DTI-ALPS index exhibited a stepwise decreasing trend. Mediation analysis revealed that the left DTI-ALPS index mediated the effect of MoCA scores on MDS-UPDRS III scores. Conclusion: Abnormalities in the left DTI-ALPS index and diffusivity reflect underlying glymphatic system (GS) dysfunction and white matter microstructural damage in PD patients. These neuropathological changes are significantly associated with, and collectively contribute to, the progression of motor and cognitive decline. Furthermore, the left DTI-ALPS index shows promise as a novel biomarker for identifying cognitive impairment in PD patients.
Keywords: Parkinson's disease, Diffusion Tensor Imaging Analysis Along thePerivascular Space (DTI-ALPS), magnetic resonance imaging (MRI), cognitivefunction, Motor function
Received: 28 Jul 2025; Accepted: 14 Nov 2025.
Copyright: © 2025 Li, Song, Zhao, Lin, Pan, Li, Zhou, Zhang, Wei and Xue. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiehua Xue, f110015@fjtcm.edu.cn
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