Abstract
REM sleep behaviour disorder (RBD) can be an early non-motor symptom of Parkinson’s disease (PD) with pathology involving mainly the pontine nuclei. Beyond the brainstem, it is unclear if RBD patients comorbid with PD have more affected striatal dopamine denervation compared to PD patients unaffected by RBD (PD-RBD−). To elucidate this, we evaluated the availability of vesicular monoamine transporter 2 (VMAT2), an index of nigrostriatal dopamine innervation, in 15 PD patients with probable RBD (PD-RBD+), 15 PD-RBD−, and 15 age-matched healthy controls (HC) using [11C]DTBZ PET imaging. This technique measured VMAT2 availability within striatal regions of interest (ROI). A 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 function and depression scores. Multiple regressions were also computed to predict clinical measures from group condition and VMAT2 binding within all ROIs explored. We observed a significant main effect of group condition on VMAT2 availability within the caudate, putamen, ventral striatum, globus pallidus, substantia nigra, and subthalamus. Specifically, our results revealed that PD-RBD+ had lower VMAT2 availability compared to HC in all these regions except for the subthalamus and substantia nigra, while PD-RBD− was significantly lower than HC in all these regions. PD-RBD− showed a negative relationship between motor severity and VMAT2 availability within the left caudate. Our findings reflect that both PD patient subgroups had similar denervation within the nigrostriatal pathway. There were no significant interactions detected between radioligand binding and clinical scores in PD-RBD+. Taken together, VMAT2 and striatal dopamine denervation in general may not be a significant contributor to the pathophysiology of RBD in PD patients. Future studies are encouraged to explore other underlying neural chemistry mechanisms contributing to RBD in PD patients.
Highlights
Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of normal skeletal muscle atonia during REM sleep [1]
There were no differences between all participant groups for age, radiotracer injected dose, injected mass, and specific activity
We showed a relationship between nigrostriatal innervation and motor score in Parkinson’s disease (PD) patients without probable REM sleep behaviour disorder (RBD), investigating motor features while “ON” and “OFF” medication and changes with vesicular monoamine transporter 2 (VMAT2) levels may provide more insight about the true relationship observed between PD with and without probable RBD and motor severity in relation to the left caudate VMAT2 availability
Summary
Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of normal skeletal muscle atonia during REM sleep [1]. The decline of striatal DAT has been demonstrated from healthy controls to sub-clinical RBD (REM sleep without atonia on polysomnography, but without abnormal nocturnal behaviours) to manifest RBD to PD [14, 15]. This worsening pattern continues in a subset of PD patients with probable RBD where they show greater DAT depletion in the caudate and putamen compared to PD patients without probable RBD [16, 17].
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