Association Between Glymphatic Dysfunction and Anxiety in Parkinson’s Disease: Insights from DTI-ALPS and Choroid Plexus Volume

Purpose: To explore glymphatic system function in Parkinson's disease (PD) patients with anxiety using multimodal imaging: diffusion tensor image analysis along the perivascular space (DTI-ALPS), enlarged perivascular space (EPVS) number, and choroid plexus volume (CPV). Patients and Methods: In this prospective observational study, 64 PD patients (34 with anxiety [PD-A] and 30 without anxiety [PD-NA]) and 42 healthy controls (HC) were recruited. All participants underwent clinical assessments for anxiety, depression, cognition, and motor symptoms. DTI-ALPS index, EPVS number, and CPV were compared among the three groups, and a composite model integrating these multimodal metrics was developed.Additionally,a partial correlation analysis was conducted to investigate the relationship between the above three imaging indicators and clinical characteristics in PD-A. Results: (P =0.046) increased in PD-A group. DTI-ALPS index was negatively correlated with CPV in PD patients.Based on receiver operating curve (ROC) analysis, the Top Single-Markers model demonstrated superior efficacy in discriminating PD from HC (AUC =0.847). Furthermore, a composite model showed predictive value for anxiety in PD (AUC =0.748). After controlling for age, gender, and education, CPV was correlated positively with Hamilton Anxiety Rating Scale (HAM-A) (r =0.657, P =0.031) and Non-Motor Symptom Scale(NMSS) (r =0.617, P =0.041).Standardized CPV was correlated negatively with Montreal Cognitive Assessment (MoCA) (r =-0.640, P =0.034) and Unified Parkinson's Disease Rating Scale III (UPDRS III) (r =0.659, P =0.03). Conclusion: PD patients exhibit cerebral glymphatic dysfunction, which is more severe in those with anxiety. Increased CPV is associated with anxiety, depression, and cognitive decline in PD-A patients. Combining multimodal MRI metrics shows potential clinical utility for evaluating glymphatic function. Trial registration number: NCT06858176.