Relationship of Glymphatic Function with Cognitive Impairment, Sleep Disorders, Anxiety and Depression in Patients with Parkinson’s Disease

Qian Gui,1,* Jingcai Meng,2,* Mingqiang Shen,1 Hongxuan Feng,1 Xiaofeng Dong,1 Daqiang Xu,3 Wenxin Zhu,2 Qingzhang Cheng,1 Linhui Wang,2 Guanhui Wu,1 Yanli Lu3 1Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, 215002, People’s Republic of China; 2Department of Physiology and Neurobiology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 3Department of Radiology, the Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, 215002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanli Lu, Department of Radiology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), 26 Daoqian Street, Suzhou City, Jiangsu Province, People’s Republic of China, Tel +8618251135654, Email luyanli.2009@163.com Guanhui Wu, Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), 26 Daoqian Street, Suzhou City, Jiangsu Province, People’s Republic of China, Email ghwusz26@njmu.edu.cnIntroduction: Previous studies have predominantly explored the relationship of the glymphatic system with motor symptoms in Parkinson’s disease (PD); however, research on non-motor symptoms remains limited. Therefore, this study investigated the association between glymphatic function and non-motor symptoms, including cognitive impairment and sleep disorders, in PD patients.Methods: This study recruited 49 PD patients and 38 healthy controls (HC). Glymphatic function was evaluated using enlarged perivascular spaces (EPVS) in the basal ganglia (BG) region and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Cognition, sleep, anxiety, and depression scales were assessed in all participants. According to the scale scores, PD patients were further divided into several groups to identify the presence of non-motor symptoms. Differences in EPVS numbers and ALPS index between PD subgroups and HC group were compared. Spearman correlation analysis was performed to investigate the association between the PD non-motor symptoms and ALPS index. Additionally, receiver operating characteristic (ROC) curves analysis was conducted for ALPS index to predict cognitive impairment and insomnia in PD patients.Results: PD patients with and without non-motor symptoms all showed more EPVS numbers than the controls, and the EPVS numbers in PD patients with cognitive impairment were also greater than those without. Notably, except for the depression subgroup, PD patients with non-motor symptoms showed significantly lower ALPS index than the controls. The Montreal Cognitive Assessment (MoCA) scores were positively correlated, whereas the Parkinson’s Disease Sleep Scale (PDSS)-2 and REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores were negatively correlated with the ALPS index in PD patients (r=0.3618, P=0.0053; r=− 0.4146, P=0.0015; r=− 0.2655, P=0.0326, respectively). The ALPS index proved to be predictive of cognitive impairment and insomnia in PD patients (AUC=0.7733, P=0.001; AUC=0.7993, P=0.0004, respectively).Conclusion: Glymphatic function is closely associated with cognition and sleep of PD patients.Keywords: glymphatic system, parkinson’s disease, non-motor symptoms, cognition, sleep