Glymphatic Dysfunction Is Related to Comorbidity of Parkinson's Disease and Anxiety: A Multimodal MRI Study

Abstract

Aims: This study aimed to explore the relationship between glymphatic dysfunction and anxiety in patients with Parkinson's disease (PD). Methods: A total of 21 patients with PD with anxiety (PD-A), 47 patients with PD without anxiety (PD-NA), and 38 healthy subjects were prospectively enrolled. Participants underwent neuropsychiatric assessment, motor examinations, and magnetic resonance imaging. Brain glymphatic function was evaluated using diffusion tensor image analysis along the perivascular spaces (DTI-ALPS) and global blood oxygen level-dependent signal and cerebrospinal fluid dynamics coupling (gBOLD-CSF coupling). Correlations between glymphatic function and anxiety (quantified using Hamilton Anxiety Rating Scale [HAMA] scores) were analyzed. Receiver operating characteristic analysis was used to assess the diagnostic performance of clinical features, ALPS index, and gBOLD-CSF coupling strength, and multivariate models were used to distinguish patients with PD-A from those with PD-NA. Results: The PD-A group exhibited longer PD duration, higher Hoehn and Yahr (H&Y) stage, and higher HAMA scores compared to the PD-NA group. Both DTI-ALPS and gBOLD-CSF coupling analyses revealed significant glymphatic dysfunction in patients with PD-A. The ALPS index and gBOLD-CSF coupling strength were inversely correlated with HAMA scores and positively correlated with each other. The multivariate diagnostic model combining clinical variables and glymphatic indices outperformed univariate models. Conclusions: The DTI-ALPS index and gBOLD-CSF coupling strength may serve as novel neuroimaging markers for PD-A, with diagnostic performance enhanced by combining these markers with clinical features.