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

帕金森病颅内淋巴系统受损:基于非侵入性神经影像学的脑膜淋巴管和类淋巴系统联合研究

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Abstract

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. Based on Hoehn-Yahr (H-Y) scale and clinical symptoms, the patients were divided into two subgroups: early PD (ePD) and advanced PD (aPD), and three subtypes: tremor-dominant PD (tPD), rigid-akinetic PD (rPD), and mixed tremor-dominant and rigid-akinetic PD (t-rPD). All subjects underwent professional clinical assessments and non-invasive MRI examinations. The volume of meningeal lymphatic vessels (MLVs) and diffusion tensor imaging analysis along perivascular spaces (DTI-ALPS) indices were calculated. The differences in MLVs volume and DTI-ALPS indices between the PD group and the HC group were analyzed, as well as their correlations with clinical parameters. RESULTS: The MLVs volume ratios of whole brain, left hemisphere, and right hemisphere in the PD group were all higher than those in the HC group (p = 0.002, p = 0.001 and p = 0.005, respectively). The PD group demonstrated significantly lower DTI-ALPS index in comparison with the HC group (t = 3.587, p = 0.001). Pairwise comparisons further revealed that DTI-ALPS index in both HC and ePD groups was significantly higher than that in aPD group (p < 0.001 and p = 0.022, respectively). Correlation analysis revealed a negative association between DTI-ALPS index and H-Y scale in the PD group (r = - 0.371, p = 0.04), and the MLVs volume ratio in the HC group was positively correlated with age (r = 0.457, p = 0.01). Neither DTI-ALPS nor T-MLVV showed significant correlation between PD and HC groups. CONCLUSIONS: The changes of MLVs volume and DTI-ALPS index may elucidated the mechanisms underlying intracranial lymphatic circulation dysfunction in PD. The MLVs and the DTI-ALPS index may serve as objective neuroimaging indicators for assessing intracranial lymphatic function.

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