Disruption of locus coeruleus-related functional networks in Parkinson’s disease

Locus coeruleus (LC) is severely affected in Parkinson’s Disease (PD). However, alterations in LC-related resting-state networks (RSNs) in PD remain unclear. We used resting-state functional MRI to investigate the alterations in functional connectivity (FC) of LC-related RSNs and the associations between RSNs changes and clinical features in idiopathic rapid eye movement sleep behavior disorder (iRBD) and PD patients with (PD(RBD+)) and without RBD (PD(RBD−)). There was a similarly disrupted FC pattern of LC-related RSNs in iRBD and PD(RBD+) patients, whereas LC-related RSNs were less damaged in PD(RBD−) patients than that in patients with iRBD and PD(RBD+). The FC of LC-related RSNs correlated with cognition and duration in iRBD, depression in PD(RBD−), and cognition and severity of RBD in patients with PD(RBD+). Our findings demonstrate that LC-related RSNs are significantly disrupted in the prodromal stage of α-synucleinopathies and proposed body-first PD (PD(RBD+)), but are less affected in brain-first PD (PD(RBD−)).