Perivascular space fluid diffusivity predicts clinical deterioration in prodromal and early-stage Parkinson's disease

The glymphatic system is essential for clearing toxic proteins from the brain, and understanding its dysfunction in the early stages of Parkinson's disease (PD) may facilitate the development of disease-modifying therapies. This study aimed to evaluate alterations in glymphatic function and its correlation with disease progression in prodromal and early clinical stages of PD. Participants were categorized into three groups: prodromal PD (pPD), de novo PD (dnPD), and healthy controls (HCs), further divided by age. Glymphatic function was assessed using the ALPS index derived from diffusion tensor imaging. Results indicated that the ALPS index was significantly lower in older pPD and dnPD patients, correlating with various clinical symptoms. Longitudinal analysis revealed a decrease in the ALPS index over time in pPD patients who progressed to clinical PD, while it remained stable in non-converters. Additionally, the baseline ALPS index was predictive of the progression of both motor and non-motor symptoms in pPD patients. In dnPD patients, a lower baseline ALPS index predicted the progression of motor symptoms in the older subgroup. Overall, the ALPS index is reduced in the early stages of PD and may serve as a predictor for disease progression.