Both brain network topology and striatal dopamine depletion mediate the effects of autonomic dysfunction on disease burden of Parkinson’s disease

Abstract

Background: Autonomic dysfunction is one of the most common non-motor symptoms in Parkinson's disease (PD). Whether autonomic dysfunction contributes to disease progression and brain network abnormalities in PD remain largely unknown. The objective of this study is to evaluate how autonomic dysfunction affects clinical features and brain networks of PD patients. Methods: PD patients from Parkinson's Progression Markers Initiative (PPMI) database were included if they received magnetic resonance imaging. According to the scores of Scale for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), PD patients were classified into lower quartile group (SCOPA-AUT score rank: 0%~25%), interquartile group (SCOPA-AUT score rank: 26%~75%), and upper quartile group (SCOPA-AUT score rank: 76%~100%) based on their SCOPA-AUT score quartiles to examine how autonomic dysfunction shapes clinical manifestations and brain networks. Results: PD patients in the upper quartile group showed more severe motor and non-motor symptoms, as well as more deficits in dopamine transporter binding compared to lower quartile group. Additionally, they also showed statistically different topological properties in structural and functional network compared to lower quartile group. Both structural and functional network metrics mediated the effects of autonomic dysfunction on clinical symptoms of PD patients. Reduced dopamine transporter binding also contributed to the effects of autonomic dysfunction on disease burden of PD patients. Conclusions: PD patients with more severe autonomic dysfunction exhibit worse disease and impairment of brain network topology. Both network topology and striatal dopamine depletion mediate the effects of autonomic dysfunction on clinical symptoms of PD patients.