Diffusion–tensor MRI study of the relationship between glymphatic system asymmetry and onset lateralization in Parkinson’s disease

The characteristic asymmetric motor symptoms of Parkinson's disease (PD) may be associated with asymmetric deposition of α-synuclein. The impaired glymphatic system may promote pathological deposition of α-synuclein, leading to disease progression. The aim of this study was to investigate the function of the glymphatic system in PD patients with unilateral motor symptom onset using diffusion tensor image analysis along the perivascular spaces (DTI-ALPS) method, and to elucidate the relationship between glymphatic system asymmetry and the side of motor symptom onset. We conducted diffusion tensor imaging scans on 36 left-onset PD (LPD) patients, 27 right-onset PD (RPD) patients, and 49 healthy controls (HCs). Bilateral hemispheric ALPS indices were calculated to assess glymphatic function, and an asymmetry index (AI) was derived to quantify interhemispheric asymmetry in glymphatic function. Compared to HCs, RPD patients exhibited a significant reduction in the left ALPS index, while both left and right ALPS indices were significantly reduced in LPD patients. In both LPD patients and HCs, the right ALPS index was lower than the left, suggesting a natural leftward asymmetry. However, this asymmetry was diminished in RPD patients, as indicated by a lower AI. Moreover, in RPD patients, the Unified Parkinson's Disease Rating Scale Part III score showed a negative correlation with the left ALPS index and with AI. This study demonstrated that PD patients with lateralized motor symptom onset exhibit different patterns of glymphatic system function. The glymphatic system asymmetry may provide new insights into the mechanism underlying the lateralized onset of PD.