Objective: To use [¹¹C]DTBZ PET imaging to explore vesicular monoamine transporter 2 (VMAT2) availability in Parkinson’s disease (PD) with and without rapid eye movement sleep behaviour disorder (RBD).

Background: RBD is a condition marked by the lack of normal skeletal muscle atonia during REM sleep, resulting in dream enacting behaviours. RBD is one of the strong prodromal clinical predictors of PD. Molecular imaging evidence shows that PD with RBD (PD-RBD+) show lower dopamine transporter activity within the caudate and putamen compared to PD without RBD (PD-RBD–). However, the characterization of the VMAT2, an index of nigrostriatal dopamine innervation, has been rarely explored in PD patients with RBD.

Method: We enrolled 15 PD-RBD+, 15 PD-RBD– and 15 age matched healthy controls (HC) for the [¹¹C]DTBZ PET imaging study. This technique measures VMAT2 availability within striatal regions of interest (ROI). Mixed effect model was used to compare the radioligand binding of VMAT2 between the three groups for each striatal ROI, while co-varying for sex, cognitive and depression scores. The fixed factors in this model were group and ROI hemisphere (i.e., left vs. right ROI), while participants were kept as a random factor. Significant level was set at p<0.05 (Bonferroni corrected).

Results: Significant main effect was observed within the caudate, putamen, ventral striatum, globus pallidus, substantia nigra and subthalamus. Specifically for substantia nigra and subthalamus—we observed that PD-RBD+ group was statistically higher in VMAT2 availability compared to PD-RBD– group. For these two ROIs, statistical difference between HC and PD-RBD– was observed, however, this was not the case for PD-RBD+. The main effects for caudate, putamen, ventral striatum and globus pallidus were driven by the reduced VMAT2 availability in both PD patient subgroups relative to HC, and not the differences between PD-RBD– and PD-RBD+ groups.

Conclusion: Our results show that both patient subgroups have lower VMAT2 availability relative to HC—which reflects denervation within the nigrostriatal pathway. The VMAT2 levels in subthalamus and substantia nigra, regions involved in sleep, was elevated in PD-RBD+ patients compared to PD-RBD– patients. Results imply that there may be a contributing role of VMAT2 within the nigrostriatal system associated with RBD in PD patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/vmat2-availability-in-parkinsons-disease-with-rapid-eye-movement-sleep-behaviour-disorder/