Objective: This study aimed to investigate the association between the diffusion tensor image (DTI) analysis along the perivascular space (ALPS) index, dopamine transporter (DAT) availability in the posterior putamen, and parkinsonian motor deficits in patients with Parkinson’s disease (PD).

Background: The glymphatic system is considered to play a key role in the accumulation of abnormal protein aggregates in neurodegenerative diseases, and glymphatic dysfunction may have a detrimental effect on neurodegenerative processes in PD.

Method: This study enrolled 207 patients with newly diagnosed PD who underwent brain MRI and ¹⁸F-FP-CIT PET. The DTI-ALPS index was used to assess glymphatic system function, and DAT availability in the posterior putamen was estimated. Motor function was assessed using the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III). Multiple linear regression and mediation analyses were performed to evaluate their associations.

Results: Multiple linear regression analysis showed that both DAT availability in the posterior putamen and DTI-ALPS index were negatively associated with baseline UPDRS-III scores after adjusting for age at symptom onset and sex as covariates. Mediation analyses showed that the DTI-ALPS index affected UPDRS-III scores both directly (β = −10.116) and indirectly via DAT availability in the posterior putamen (β = 2.509). When the DTI-ALPS index was located as a mediator, posterior putamen DAT availability affected UPDRS-III scores both directly (β = -5.494) and indirectly via DTI-ALPS index (β = 0.377). Furthermore, there was an interaction effect between the DTI-ALPS index and striatal DAT availability, and the DTI-ALPS index was significantly associated with parkinsonian motor deficits only when striatal dopamine depletion was severe.

Conclusion: These findings suggest that glymphatic dysfunction is associated with severe motor deficits in PD, together with nigrostriatal dopaminergic degeneration.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-of-glymphatic-flow-at-diffusion-tensor-image-with-motor-symptoms-and-striatal-dopamine-degeneration-in-parkinsons-disease/