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

Lu Sa,1 Shan Li,2 Linyu Chen,3 Jin Wang,4 Yijin Wang,1 Changxin Cheng,1 Changyuan Xin,1 Shuni Zhang,1 Fan Ding,1 Bo Wang1 1Department of MRI, the First People’s Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, People’s Republic of China; 2Department of Neurology, the First People’s Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, People’s Republic of China; 3Department of Medical Imaging, the Third People’s Hospital of Honghe State, Gejiu, Yunnan, 661000, People’s Republic of China; 4Department of Medical Imaging, Southern Central Hospital of Yunnan Province (The First People’s Hospital of Honghe State), Mengzi, Yunnan, 661100, People’s Republic of ChinaCorrespondence: Bo Wang, Department of MRI, the First People’s Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, People’s Republic of China, Email wb13888564672@163.comPurpose: 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: Compared to the PD-NA, DTI-ALPSr (P =0.047) and DTI-ALPSb (P =0.01)decreased, and CPVl (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: NCT06858176Keywords: glymphatic system, diffusion tensor image analysis along the perivascular space, choroid plexus volume, enlarged perivascular space, anxiety, parkinson’s disease