Impairment of the intracranial lymphatic system in Parkinson's disease: a combined study of the meningeal lymphatics vessels and glymphatic system based on noninvasive neuroimaging

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 development of PD. However, the underlying mechanisms remain inadequately elucidated. Methods: 31 PD patients and 31 age- and sex-matched healthy controls (HC) were recruited. The PD group was divided into early PD (ePD) and advanced PD (aPD) groups based on the Hoehn-Yahr (H-Y) scale. The PD group were divided into tremor-dominant PD (tPD), myotonic-dominant (mPD), and tremor-myotonic PD (t-mPD) subgroups according to clinical symptoms. All subjects 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 and correlations were observed among MLVs volume, DTI-ALPS index and various clinical parameters. Results： Both ePD and aPD groups demonstrated higher MLVs volume than in HC group ( p ＜0.001, p =0.019). For the DTI-ALPS index, PD group showed lower than HC group ( p =0.001). And the DTI-ALPS index in both HC and ePD groups were lower than the aPD group ( p ＜0.001, p =0.022). Correlation analysis revealed a negative association between DTI-ALPS index and H-Y scale in the PD group ( p =0.04), then the MLVs volume ratio in the HC group was positively correlated with age ( p =0.01). Conclusion： The changes of MLVs volume and DTI-ALPS index may elucidated the mechanisms underlying intracranial lymphatic circulation dysfunction in PD. The potential relationship between the DTI-ALPS index and MLVs volume warrants further in-depth investigation.