Neuroimaging uncovers distinct relationships of glymphatic dysfunction and motor symptoms in Parkinson’s disease

Background Studies of glymphatic dysfunction in Parkinson’s disease (PD) patients have attracted much attention in recent years. However, the relationships between glymphatic dysfunction and clinical symptoms remains unclear. Objectives To determine whether the diffusion tensor image analysis along the perivascular space (DTI-ALPS) affect the severity and types of motor and non-motor symptoms in PD patients. Methods De novo PD patients and controls who performed both DTI and 123 I-DaTscan single photon emission computed tomography (SPECT) scanning were retrieved from the international multicenter Parkinson’s Progression Marker Initiative (PPMI) cohort. Glymphatic system was evaluated by the DTI-ALPS. Motor symptoms were assessed by Movement Disorders Society Unified Parkinson’s Disease Rating Scale III (MDS-UPDRS-III). The influence of glymphatic activity on motor and non-motor symptoms was explored by multivariate linear regression models. Results A total of 153 PD patients (mean age 60.97 ± 9.47 years; 99 male) and 67 normal controls (mean age 60.10 ± 10.562 years; 43 male) were included. The DTI-ALPS index of PD patients was significantly lower than normal controls ( Z = − 2.160, p = 0.031). MDS-UPDRS III score ( r = − 0.213, p = 0.008) and subscore for rigidity ( r = − 0.177, p = 0.029) were negatively correlated with DTI-ALPS index. The DTI-ALPS index was significantly associated with MDS-UPDRS-III score ( β = − 0.160, p = 0.048) and subscore for rigidity ( β = − 0.170, p = 0.041) after adjusting for putamen dopamine transporter availability and clinical factors. Conclusions Our results showed distinct relationships between glymphatic dysfunction and the severity and types of PD motor symptoms, suggesting the potential of DTI-ALPS index as a biomarker for PD motor symptoms.