Glymphatic Function in Prodromal Parkinson's Disease: Associations With Symptoms, Gray Matter Volume, and...

Area of Science:

• Neuroimaging
• Neurodegenerative Diseases
• Cerebrospinal Fluid Dynamics

Background:

• Glymphatic system dysfunction is observed in Parkinson's disease (PD).
• The glymphatic system's status in prodromal PD (pPD) remains unclear.
• The diffusion tensor imaging along perivascular spaces (DTI-ALPS) index serves as an indirect measure of glymphatic function.

Purpose of the Study:

• To assess glymphatic-related changes in a pPD cohort using the DTI-ALPS index.
• To investigate the association between DTI-ALPS index and clinical symptoms in pPD.
• To explore the relationship between DTI-ALPS index and gray matter volume in pPD.
• To determine if DTI-ALPS index predicts phenoconversion risk in pPD.

Main Methods:

• Analysis of data from the Parkinson's Progression Marker Initiative (PPMI) cohort.
• Inclusion of 51 healthy controls (HC), 83 individuals with pPD, and 202 with de novo PD (dnPD).
• Cross-sectional comparison of DTI-ALPS index across groups and correlation with clinical/imaging data in pPD.
• Longitudinal assessment of DTI-ALPS index and phenoconversion risk using Kaplan-Meier and Cox regression over a ≥4-year follow-up.

Main Results:

• Significantly reduced DTI-ALPS index observed in pPD and dnPD compared to HC (p < 0.001).
• In pPD, lower DTI-ALPS index correlated with increased anxiety, elevated CSF p-tau and t-tau, and altered gray matter volumes (temporal pole, thalamus, occipital gyrus, posterior central gyrus).
• A decrease in DTI-ALPS index by one standard deviation increased the risk of phenoconversion to PD by 13% (adjusted HR = 0.87, p = 0.018).

Conclusions:

• Reduced DTI-ALPS index in pPD suggests potential glymphatic dysfunction.
• Altered glymphatic function in pPD is associated with an increased risk of phenoconversion.
• DTI-ALPS index correlates with clinical symptoms and structural brain changes in pPD.