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

AbstractREM 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.

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VMAT2 Availability in Parkinson’s Disease with REM Sleep Behaviour Disorder

10.21203/rs.3.rs-915716/v1 ◽

2021 ◽

Author(s):

Mikaeel Valli ◽

Sang Soo Cho ◽

Carme Uribe ◽

Mario Masellis ◽

Robert Chen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rem Sleep ◽

Radioligand Binding ◽

Negative Relationship ◽

Behaviour Disorder ◽

Mixed Effect ◽

Group Condition ◽

Sleep Behaviour ◽

Rem Sleep Behaviour Disorder

Abstract REM sleep behaviour disorder (RBD) is an early sleep disturbance symptom of Parkinson’s disease (PD) thought to be caused by the disruption of normal basal ganglia function due to neurodegeneration. To further elucidate the neuropathological contribution of RBD in PD, we aimed to characterize the role of vesicular monoamine transporter 2 (VMAT2), an index of nigrostriatal dopamine innervation, in PD patients with RBD (PD-RBD+). We identified 15 PD-RBD+, 15 PD patients without RBD (PD-RBD–) and 15 age matched healthy controls (HC) who underwent [11C]DTBZ PET imaging. 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 function and depression scores. Multiple regressions were also computed to predict clinical measures from group condition and VMAT2 binding within all ROIs explored. Significant level was set at p < 0.05 (Bonferroni corrected). We observed significant main effect of group condition on VMAT2 availability within the caudate, putamen, ventral striatum, globus pallidus, substantia nigra, and subthalamus. Specifically, we observed that both PD-RBD + and PD-RBD– group had lower VMAT2 availability compared to HC. PD-RBD– showed a negative relationship between motor severity and VMAT2 availability within the left caudate. This relationship was not found in the PD-RBD + group. Our findings reveal that both PD patient subgroups had reduced VMAT2 levels relative to HC—which reflects denervation within the nigrostriatal pathway. No significant interactions were detected between radioligand binding and clinical scores in PD-RBD+. Taken together, we found limited evidence that VMAT2 may contribute differently in PD-RBD + relative to PD-RBD–. Future studies are encouraged to explore other underlying neural chemistry mechanisms contributing to RBD in PD patients.

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Parkinson’s Disease with and without REM Sleep Behaviour Disorder: Are There Any Clinical Differences?

European Neurology ◽

10.1159/000189269 ◽

2009 ◽

Vol 61 (3) ◽

pp. 164-170 ◽

Cited By ~ 70

Author(s):

Asako Yoritaka ◽

Hideki Ohizumi ◽

Shigeki Tanaka ◽

Nobutaka Hattori

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rem Sleep ◽

Behaviour Disorder ◽

Sleep Behaviour ◽

Rem Sleep Behaviour Disorder

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REM sleep behaviour disorder in Parkinson’s disease

Non-Motor Symptoms of Parkinson's Disease ◽

10.1093/med/9780199237234.003.0014 ◽

2009 ◽

pp. 177-194 ◽

Cited By ~ 5

Author(s):

Alex Iranzo ◽

Eduardo Tolosa

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rem Sleep ◽

Behaviour Disorder ◽

Sleep Behaviour ◽

Rem Sleep Behaviour Disorder

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REM sleep behaviour disorder and cognitive functions in Parkinson's disease

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2015.10.061 ◽

2016 ◽

Vol 22 ◽

pp. e39-e40

Author(s):

Elena Lyashenko ◽

Oleg Levin ◽

Mihail Poluektov

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rem Sleep ◽

Cognitive Functions ◽

Behaviour Disorder ◽

Sleep Behaviour ◽

Rem Sleep Behaviour Disorder

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Evolution of prodromal Parkinson’s disease and dementia with Lewy bodies: a prospective study

Brain ◽

10.1093/brain/awz111 ◽

2019 ◽

Vol 142 (7) ◽

pp. 2051-2067 ◽

Cited By ~ 35

Author(s):

Seyed-Mohammad Fereshtehnejad ◽

Chun Yao ◽

Amelie Pelletier ◽

Jacques Y Montplaisir ◽

Jean-François Gagnon ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rem Sleep ◽

Colour Vision ◽

Rating Scale ◽

Lewy Bodies ◽

Behaviour Disorder ◽

Mixed Effect ◽

Sleep Behaviour ◽

Rem Sleep Behaviour Disorder

Abstract Parkinson’s disease has a long prodromal stage with various subclinical motor and non-motor manifestations; however, their evolution in the years before Parkinson’s disease is diagnosed is unclear. We traced the evolution of early motor and non-motor manifestations of synucleinopathy from the stage of idiopathic rapid eye movement (REM) sleep behaviour disorder until defined neurodegenerative disease. During 2004–16, we recruited and then annually followed 154 polysomnography-proven patients with idiopathic REM sleep behaviour disorder, of whom 55 phenoconverted to defined parkinsonism or dementia. Longitudinal data on multiple prodromal features, including the Unified Parkinson’s Disease Rating Scale parts I–III, quantitative motor tests, olfaction, colour vision, cognition, and autonomic functions were gathered annually (average = five follow-up visits, range: 2–12 years). The same measures were also assessed in 102 age- and sex-matched healthy control subjects. By looking backward from the time of dementia or parkinsonism diagnosis, we examined trajectories of each prodromal feature using mixed effect models. Based on analysis, olfactory loss was first to develop, with predicted onset >20 years before phenoconversion. This was followed by impaired colour vision, constipation, and erectile dysfunction, starting 10–16 years prior to phenoconversion. At 7–9 years before phenoconversion, slight urinary dysfunction and subtle cognitive decline could be detected. Among motor symptoms altered handwriting, turning in bed, walking, salivation, speech, and facial expression began to be disrupted starting 7–11 years prior to parkinsonism diagnosis, but remained mild until soon before phenoconversion. Motor examination abnormalities began 5–7 years before phenoconversion, with the alternate tap test having the longest interval (8 years before phenoconversion). Among cardinal motor phenotypes, bradykinesia appeared first, ∼5–6 years prior to phenoconversion, followed by rigidity (Year −3) and tremor (Year −2). With direct prospective evaluation of an idiopathic REM sleep behaviour disorder cohort during phenoconversion, we documented an evolution of prodromal manifestations similar to that predicted by pathological staging models, with predicted prodromal intervals as long as 20 years.

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