Extra‐striatal dopamine in Parkinson's disease with rapid eye movement sleep behavior disorder

Rapid eye movement sleep behavior disorder (RBD) is a common condition found in more than 50% of the patients with Parkinson's disease (PD). Molecular imaging shows that PD with RBD (PD‐RBD+) have lower striatal dopamine transporter activity within the caudate and putamen relative to PD without RBD (PD‐RBD−). However, the characterization of the extra‐striatal dopamine within the mesocortical and mesolimbic pathways remains unknown. We aim to elucidate this with PET imaging in 15 PD‐RBD+ and 15 PD‐RBD− patients, while having 15 age‐matched healthy controls (HC). Each participant underwent a single PET scan with [11C]FLB‐457 to detect the D2 receptor availability within the extra‐striatal regions of interest (ROI), including the prefrontal, temporal, and limbic areas. [11C]FLB‐457 retention was expressed as the nondisplaceable binding potential. Our results reveal that relative to HC, PD‐RBD+ and PD‐RBD− patients have lower levels of D2 receptor availability within the uncus parahippocampus, superior, lateral, and inferior temporal cortex. PD‐RBD+ showed steep decline in D2 receptors within the left uncus parahippocampus with increasing disease severity, but this was not observed for PD‐RBD− patients. Findings imply that extra‐striatal dopaminergic system may play a role in contributing to symptomatic progress in PD patients with RBD. However, validation with more advanced PD patients are needed. This PET study characterized D2 receptor (D2R) availability within extra‐striatal regions in Parkinson's disease (PD) patients with (+) and without (−) REM sleep behavior disorder (RBD). With disease progression, only PD‐RBD+ patients showed steep decline in D2R availability within the left uncus parahippocampus. Beyond the striatum, extra‐striatal dopaminergic system may also contribute to PD‐RBD in advanced stages.