Objective: This study aimed to investigate the clinical relevance of glymphatic dysfunction in Parkinson’s disease (PD) by integrating the diffusion tensor imaging (DTI) analysis along the perivascular space (DTI-ALPS) index with dopaminergic and metabolic imaging biomarkers.

Background: The glymphatic system has recently been implicated in the clearance of neurotoxic proteins and may contribute to neurodegeneration in PD. However, the role of glymphatic dysfunction in the motor and cognitive manifestations of PD and its relationship with dopaminergic and metabolic neurodegeneration remain unclear.

Method: In this cross-sectional study, 190 patients with PD and 40 controls underwent brain MRI including DTI, ¹⁸F-FP-CIT PET, and ¹⁸F-FDG PET. Motor symptoms were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III, and cognitive function was evaluated with comprehensive neuropsychological testing. Associations between the DTI-ALPS index and clinical measures were examined using correlation analyses. Mediation and interaction analyses were performed to explore the relationships among glymphatic function, dopaminergic degeneration, metabolic alterations, and clinical manifestations.

Results: Patients with PD showed significantly lower DTI-ALPS indices compared with healthy controls (P = 0.024). The DTI-ALPS index was negatively correlated with UPDRS Part III total scores and was preferentially associated with bradykinesia and axial symptoms rather than tremor or rigidity. The index was also positively correlated with global cognitive performance and with visuospatial, memory, and executive domains. Mediation analyses revealed that cerebral metabolic alterations fully mediated the association between the DTI-ALPS index and motor severity, while putaminal dopaminergic depletion showed a synergistic interaction with reduced DTI-ALPS values in worsening motor symptoms. For cognitive function, the DTI-ALPS index was associated with cognitive impairment both directly and through serial mediation by reduced DAT-C SBR followed by elevated PDRP score.

Conclusion: These findings suggest that glymphatic dysfunction, reflected by a reduced DTI-ALPS index, may represent an upstream pathophysiological process in PD contributing to both motor and cognitive manifestations through interconnected PD-related neurodegenerative process.

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/dti-alps-index-and-its-association-with-dopamine-loss-brain-metabolism-and-motor-and-cognitive-manifestations-in-parkinsons-disease/