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-).