Objective: To investigate the activity and clinical significance of glymphatic system in Parkinson’s disease (PD) patients using diffusion MRI.

Background: Although much research on proteinopathies has focused on the mechanisms of production and degradation of the abnormally accumulated proteins, the mechanisms of their efflux out of the brain have recently attracted attention. The circulation of cerebrospinal fluid, including the perivascular space, has been proposed as a route for excretion of waste products in the brain and named the glymphatic system. However, since there is no established method to visualize and evaluate the glymphatic system in humans, it has not been fully investigated whether the function of the glymphatic system is impaired in patients with proteinopathies. Recently, a method has been reported that may allow noninvasive evaluation of the function of the glymphatic system in humans using MRI. Based on the hypothesis that water movement limited to the direction of the perivascular space can be used to evaluate the activity of the glymphatic system, diffusion tensor images of MRI is applied to assess the activity of the glymphatic system (Diffusion tensor imaging analysis along the perivascular space method: DTI-ALPS method).

Method: Head MRI (3.0T) was performed on 53 patients with PD (mean age 72.3 ± 7.3 years) and age-matched 23 healthy controls. DTI-ALPS method was used to evaluate an index for diffusivity along the direction of the perivascular space (ALPS index). We investigated the association between ALPS index and various symptoms including motor symptoms, cognitive function and sleep status.

Results: No significant difference in the ALPS index was found between all PD patients and HCs.  PD patients with cognitive impairment or sleep disturbances (PDSS-2 score ≥ 15) showed significantly lower diffusivity along the perivascular space shown as lower ALPS index compared to HCs. In PD patients, ALPS index exhibited significant negative correlations with severity of motor symptoms (γ=-0.54, p<0.0001). Additionally, significant positive correlations were observed between MoCA-J scores (ρ=0.33, p<0.05) and negative correlations with PDSS-2 scores (γ=-0.39, p<0.005).

Conclusion: Glymphatic system malfunction was suggested in PD patients with severe symptoms, cognitive impairment, or sleep disturbances.

References: [1] Taoka T, Masutani Y, Kawai H, Nakane T, Matsuoka K, Yasuno F, et al. Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer’s disease cases. Jpn J Radiol. 2017;35(4):172-8.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluation-of-glymphatic-system-function-in-parkinsons-disease-patients-using-diffusion-mri/