Objective: Our aim was to characterize the extra-striatal dopamine in Parkinson’s disease (PD) with and without rapid eye movement sleep behaviour disorder (RBD) using in vivo PET imaging.

Background: RBD is one of the strongest prodromal clinical predictors of PD. Molecular imaging evidence revealed that PD with RBD (PD-RBD+) has a distinct striatal dopamine phenotype where they specifically showed lower dopamine transporter activity within the caudate and putamen compared to PD without RBD (PD-RBD–). However, the characterization of the extra-striatal dopamine within the mesocortical and mesolimbic pathways remains unclear.

Method: To address this knowledge gap, we recruited 15 PD-RBD+, 15 PD-RBD– and 15 age matched healthy controls (HC) in which they underwent PET imaging with [¹¹C]FLB-457 radioligand. This technique measures the radioligand binding of D2 receptors within extra-striatal regions of interest (ROI), including the prefrontal and temporal areas. ANOVA was used to compare the binding between the three groups for each ROI; significant level was set at p<0.05 (FDR corrected).

Results: Significant main effect was observed within the superior temporal region bilaterally; and left uncus parahippocampus. Specifically, we found that PD-RBD+ binding was lower relative to HC on the right side of the superior temporal region, and slightly higher than PD-RBD–, but this did not reach significance. However, PD-RBD– binding was lower than HC in this region bilaterally. Regarding the left uncus parahippocampus, both PD-RBD+ and PD-RBD– binding was lower than HC, but PD-RBD+ was slightly higher than PD-RBD–, which also did not reach significance. Significant correlation was observed between the binding of PD-RBD+ for the left uncus parahippocampus and the Hoehn and Yahr score, but not for PD-RBD–.

Conclusion: Our results show that relative to HC, PD-RBD+ has lower levels of D2 receptor availability within the left uncus para-hippocampus and the right superior temporal region. These are areas involved in the limbic system, which influences sleep. Results imply that extra-striatal dopaminergic system may play a role in contributing to symptomatic progress in PD patients with RBD, but validations with more advanced patients are needed.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuroimaging-extra-striatal-d2-receptors-in-parkinsons-disease-with-rapid-eye-movement-sleep-behaviour-disorder/