Pinpointing the brain dysconnectivity in idiopathic rapid eye movement sleep behaviour disorder (iRBD) can facilitate preventing the conversion of Parkinson's disease (PD) from prodromal phase. Recent neuroimage investigations reported disruptive brain white matter connectivity in both iRBD and PD, respectively. However, the intrinsic process of the human brain structural network evolving from iRBD to PD still remains largely unknown. To address this issue, 151 participants including iRBD, PD and age-matched normal controls were recruited to receive diffusion MRI scans and neuropsychological examinations. The connectome-wide association analysis was performed to detect reorganization of brain structural network along with PD progression. Eight brain seed regions in both cortical and subcortical areas demonstrated significant structural pattern changes along with the progression of PD. Applying machine learning on the key connectivity related to these seed regions demonstrated better classification accuracy compared to conventional network-based statistic. Our study shows that connectome-wide association analysis reveals the underlying structural connectivity patterns related to the progression of PD, and provide a promising distinct capability to predict prodromal PD patients.Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.