Neuroimaging evidence of glymphatic system dysfunction in possible REM sleep behavior disorder and Parkinson's disease

Xiaoli Si; Tao Guo; Zhiyun Wang; Yi Fang; Luyan Gu; Lanxiao Cao; Wenyi Yang; Ting Gao; Zhe Song; Jun Tian; Xinzhen Yin; Xiaojun Guan; Cheng Zhou; Jingjing Wu; Xueqin Bai; Xiaocao Liu; Guohua Zhao; Minming Zhang; Jiali Pu; Baorong Zhang

doi:10.1038/s41531-022-00316-9

Neuroimaging evidence of glymphatic system dysfunction in possible REM sleep behavior disorder and Parkinson's disease

NPJ Parkinsons Dis. 2022 Apr 29;8(1):54. doi: 10.1038/s41531-022-00316-9.

Authors

Xiaoli Si^#^{1

2}, Tao Guo^#³, Zhiyun Wang¹, Yi Fang¹, Luyan Gu¹, Lanxiao Cao², Wenyi Yang¹, Ting Gao¹, Zhe Song¹, Jun Tian¹, Xinzhen Yin¹, Xiaojun Guan³, Cheng Zhou³, Jingjing Wu³, Xueqin Bai³, Xiaocao Liu³, Guohua Zhao^{4

5}, Minming Zhang⁶, Jiali Pu⁷, Baorong Zhang⁸

Affiliations

¹ Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, Zhejiang, China.
² Department of Neurology, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, N1 Avenue, 322000, Yiwu, Zhejiang, China.
³ Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, Zhejiang, China.
⁴ Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, Zhejiang, China. gzhao@zju.edu.cn.
⁵ Department of Neurology, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, N1 Avenue, 322000, Yiwu, Zhejiang, China. gzhao@zju.edu.cn.
⁶ Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, Zhejiang, China. zhangminming@zju.edu.cn.
⁷ Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, Zhejiang, China. jialipu@zju.edu.cn.
⁸ Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310009, Hangzhou, Zhejiang, China. brzhang@zju.edu.cn.

^# Contributed equally.

Abstract

Alpha-synucleinopathy is postulated to be central to both idiopathic rapid eye movement sleep behaviour disorder (iRBD) and Parkinson's disease (PD). Growing evidence suggests an association between the diminished clearance of α-synuclein and glymphatic system dysfunction. However, evidence accumulating primarily based on clinical data to support glymphatic system dysfunction in patients with iRBD and PD is currently insufficient. This study aimed to use diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate glymphatic system activity and its relationship to clinical scores of disease severity in patients with possible iRBD (piRBDs) and those with PD. Further, we validated the correlation between the ALPS index and the prognosis of PD longitudinally. Overall, 168 patients with PD, 119 piRBDs, and 129 healthy controls were enroled. Among them, 50 patients with PD had been longitudinally reexamined. Patients with PD exhibited a lower ALPS index than those with piRBDs (P = 0.036), and both patient groups showed a lower ALPS index than healthy controls (P < 0.001 and P = 0.001). The ALPS index and elevated disease severity were negatively correlated in the piRBD and PD subgroups. Moreover, the ALPS index was correlated with cognitive decline in patients with PD in the longitudinal analyses. In conclusion, DTI-ALPS provided neuroimaging evidence of glymphatic system dysfunction in piRBDs and patients with PD; however, the potential of assessing the pathological progress of α-synucleinopathies as an indicator is worth verifying. Further development of imaging methods for glymphatic system function is also warranted.