Noninvasive neuroimaging provides evidence for deterioration of the glymphatic system in Parkinson's disease relative to essential tremor

Growing evidence has demonstrated dysfunction of the glymphatic system in α-synucleinopathy and related diseases. In this study, we aimed to use diffusion tensor image analysis along the perivascular space (DTI-ALPS) and MRI-visible enlarged perivascular spaces (EPVS) to evaluate glymphatic system function quantitatively and qualitatively and its relationship to clinical scores of disease severity in Parkinson's disease (PD) and essential tremor (ET).Overall, 124 patients with PD, 74 with ET, and 106 healthy controls (HC) were enrolled. Two trained neurologists performed quantitative calculations of ALPS on DTI and visual ratings of EPVS on T2-weighted images in the centrum semiovale (CSO), basal ganglia (BG), midbrain, and cerebellum.The ALPS index was lower in patients with PD than in patients with ET (p < 0.001) and HC (p < 0.001). Similarly, patients with PD showed a more severe EPVS burden in the CSO, BG, and midbrain compared to ET and HC. Moreover, the ALPS index was negatively correlated with disease severity in the PD subgroups; however, it did not differ within the ET subgroup. No differences in ALPS or EPVS were observed between the ET and HC groups.In conclusion, DTI-ALPS and EPVS both provide neuroimaging evidence of glymphatic system dysfunction in PD, which further supports that PD is an α-synucleinopathy disease, while ET is a cerebellar dysfunction-related disease.