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

J Neurol. 2023 May;270(5):2649-2658. doi: 10.1007/s00415-023-11594-5. Epub 2023 Mar 1.

Abstract

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 123I-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.

Keywords: Diffusion tensor image analysis along the perivascular space; Dopamine transporter imaging; Glymphatic system; Parkinson’s disease.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Humans
  • Male
  • Middle Aged
  • Neuroimaging
  • Parkinson Disease* / complications
  • Parkinson Disease* / diagnostic imaging
  • Tomography, Emission-Computed, Single-Photon