Impairment of the intracranial lymphatic system in Parkinson's disease: a initial study of the meningeal lymphatics and glymphatic system based on multi-parameter magnetic resonance imaging

Background: The role of intracranial lymphatic circulation in Parkinson's disease (PD) causes more and more concerns nowadays. The drainage function of meningeal lymphatic vessels (MLVs) and the clearance capability of the glymphatic system have been demonstrated to associate with onset and progression of PD. However, the underlying mechanisms remain inadequately elucidated. Methods: 31 PD patients and 31 age- and sex-matched healthy controls (HC) were recruited for this study. The PD group was divided into early PD (ePD) and advanced PD (aPD) subgroups based on the Hoehn-Yahr (H-Y) staging. Meanwhile, the PD patients were subdivided into tremor-dominant, rigidity-dominant, and tremor-rigidity subgroups according to clinical symptoms. All participants underwent specialized clinical assessments and noninvasive MRI examinations. The volume of MLVs and the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index were calculated. The differences been or inter groups and subgroups were analyzed. Furthermore, we also investigated the correlations between the MLVs volume ratio, the DTI-ALPS index, and various clinical parameters. Results： Both ePD and aPD groups demonstrated significantly higher MLVs volume ratios than in HC group ( p ＜0.001, p =0.019). For the DTI-ALPS index, PD group showed lower index value than HC group (t=3.587, p =0.001). And the DTI-ALPS index in both HC and ePD groups were lower than that in the aPD group (( p ＜0.001, p =0.022). Correlation analysis revealed a negative association between DTI-ALPS index and H-Y staging in PD group, then the MLVs volume ratio in the HC group was positively correlated with age. Conclusion： MLVs volume ratios and DTI-ALPS index based on noninvasive MRI have the potential to disclose dysfunction of glymphatic system, that may contribute to the onset and progression of PD. Furthermore, the degree of impairment in the glymphatic system's clearance function is closely associated with the severity of the disease. The potential relationship between the DTI-ALPS index and MLVs volume ratios warrants further in-depth investigation.