Glymphatic dysfunction predicts drooling severity in Parkinson’s disease

Drooling (Sialorrhea) is a prevalent and burdensome non-motor symptom in Parkinson’s disease (PD), yet its underlying mechanisms are not fully understood. The glymphatic system is implicated in the clearance of pathological α-synuclein, and its dysfunction may contribute to PD progression. This study aimed to investigate glymphatic system alterations in PD patients with drooling and their links to clinical biomarkers. We enrolled 72 PD patients, subdivided into 36 with drooling (PD-DR) and 36 without drooling (PD-NDR), alongside 38 age-matched healthy controls (HC). All participants underwent magnetic resonance imaging (MRI), and clinical assessments evaluated disease severity and drooling using standardized scales. MRI parameters, including the diffusion tensor image analysis along the perivascular space (DTI-ALPS), choroid plexus volume (CPV), and enlarged perivascular spaces (EPVS), were calculated. The PD-DR group showed significantly lower left ALPS-index (ALPS_L), right ALPS-index (ALPS_R), and average of the bilateral ALPS index (ALPS_BA) than the PD-NDR ( p = 0.032; p = 0.004; p = 0.004) and HC groups ( p < 0.001 for each comparison). Additionally, the PD-DR and PD-NDR groups exhibited significantly higher CPV relative to the total intracranial volume (CPV/TIV) compared to the HC group ( p < 0.001; p = 0.006). No significant differences were observed in EPVS/TIV among the PD-DR, PD-NDR, and HC groups (all p > 0.05). Lower ALPS indices correlated with greater disease severity and more severe drooling symptoms in both the PD-DR and PD groups. The receiver operating characteristic (ROC) curve analysis demonstrated that ALPS_BA best differentiated PD-DR from PD-NDR with an area under the ROC curve (AUC) of 0.725. The multivariate logistic regression analysis indicated that ALPS_BA was identified as an independent predictor for the occurrence of drooling in PD (OR and 95% CI, 0.063 [0.004–0.938], p = 0.045) Our findings may indirectly provide in vivo evidence of more pronounced glymphatic dysfunction in PD patients who exhibit drooling. The ALPS index correlates with symptom severity and may show promise as a novel imaging biomarker for predicting the occurrence and progression of drooling in PD, offering new insights into its pathophysiology.