VMAT2 availability in Parkinson’s disease with probable REM sleep behaviour disorder

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.

Imaging the Limbic System in Parkinson’s Disease—A Review of Limbic Pathology and Clinical Symptoms

“…Other studies examined general neuroimaging changes of the accumbens in PD during the course of disease such as reduction in VMAT2 density [ 257 ], lower gray matter volume [ 57 , 258 ] and a lower orientation dispersion of the amygdala accumbens pathway [ 62 ]. In an MRI-study, the volume of the ventral striatum was reduced in later-disease stages of PD as compared to earlier disease-stages.…”

Molecular Imaging in Parkinsonian Disorders—What’s New and Hot?

“…Furthermore, the authors subsequently showed that de novo PD patients with RBD and patients with idiopathic RBD had significantly more symmetric nigrostriatal dopaminergic degeneration, possibly reflecting more symmetric α-synuclein spreading in the brainstem related to overlapping vagal innervation [ 79 ]. Interestingly, no difference in presynaptic VMAT2 and postsynaptic D2R dopaminergic function, using 11C-DTBZ and 11C-FLB-457, respectively, was found in PD patients with or without probable RBD, with the extrastriatal decline of 11C-FLB-457 binding in the temporal cortex, involving the uncus parahippocampus, superior, lateral, and inferior temporal cortex, although group size was limited [ 80 , 81 ].…”

Sleep Disorders in Older People with Special Focus on Parkinson’s Disease

“…There is a strong association between RBD and neurodegenerative disease, especially PD, in which the first manifestations of PD may be the RBD, necessitating careful follow-up of any patients presenting with RBD [41]. While routine neuroimaging, with magnetic resonance and computer tomography, is unlikely to contribute to the evaluation of RBD [41], more sophisticated evaluation, using [ 11 C]DTBZ PET imaging has shown that there is pathology, mainly involving the pontine nuclei [43] but it is unclear if those with RBD and PD have greater affected denervation of striatal dopamine when compared with PD patients who do not exhibit RBD [43]. Valli et al [43] examined availability of vesicular monoamine transporter 2 (VMAT2) which is an index of nigrostriatal dopamine innervation and reported that those with PD and RBD had lower availability of VMAT2, than did healthy controls, within the putamen, ventral striatum and globus pallidus but not within the substantia nigra or subthalamus.…”

“…While routine neuroimaging, with magnetic resonance and computer tomography, is unlikely to contribute to the evaluation of RBD [41], more sophisticated evaluation, using [ 11 C]DTBZ PET imaging has shown that there is pathology, mainly involving the pontine nuclei [43] but it is unclear if those with RBD and PD have greater affected denervation of striatal dopamine when compared with PD patients who do not exhibit RBD [43]. Valli et al [43] examined availability of vesicular monoamine transporter 2 (VMAT2) which is an index of nigrostriatal dopamine innervation and reported that those with PD and RBD had lower availability of VMAT2, than did healthy controls, within the putamen, ventral striatum and globus pallidus but not within the substantia nigra or subthalamus. When compared with those who had PD but not RBD, they concluded that VMAT2 and striatal dopamine denervation, in general, may not be a significant contributor to the pathophysiology of RBD in PD patients [43].…”

“…Valli et al [43] examined availability of vesicular monoamine transporter 2 (VMAT2) which is an index of nigrostriatal dopamine innervation and reported that those with PD and RBD had lower availability of VMAT2, than did healthy controls, within the putamen, ventral striatum and globus pallidus but not within the substantia nigra or subthalamus. When compared with those who had PD but not RBD, they concluded that VMAT2 and striatal dopamine denervation, in general, may not be a significant contributor to the pathophysiology of RBD in PD patients [43].…”