Extra‐striatal dopamine in Parkinson's disease with rapid eye movement sleep behavior disorder

Valli, Mikaeel; Cho, Sang Soo; Masellis, Mario; Chen, Robert; Koshimori, Yuko; Díez‐Cirarda, María; Mihaescu, Alexander; Christopher, Leigh; Strafella, Antonio P.

doi:10.1002/jnr.24779

Cited by 12 publications

(13 citation statements)

References 64 publications

(110 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As there were main effects of MoCA [F (2, 42) = 7.29, p = 0.002] and BDI [F (2, 42) = 3.89, p = 0.028], we followed up with Bonferroni post hoc t-tests to detect where the group differences occurred. These particular results were reported previously by Valli et al (23). In summary for BDI, patients with RBD had the highest depression score, then PD patients without RBD, then healthy controls.…”

Section: Resultssupporting

confidence: 89%

“…Previous literature shows other molecular structures and neurotransmitters may play a larger role contributing to RBD in PD apart from DAT (14,16,44). Outside the striatum, our group showed a negative relationship where D2 receptor availability within the uncus parahippocampus decreased with increasing disease severity in PD patients with RBD relative to PD patients without RBD (23). Other studies showed altered cholinergic (45) and noradrenaline levels (49), along with changes in glucose metabolic activity (15) in PD patients with RBD relative to patients without RBD, suggesting RBD pathophysiology in PD is multi-systemic that impacts regions beyond the striatum.…”

Section: Discussionsupporting

confidence: 53%

“…A total of 45 participants were enrolled in this study: 15 PD patients without RBD, 15 PD patients with RBD, and 15 age-matched healthy controls (Table 1). Some of the imaging, demographic, cognitive and psychological data from these participants have been reported previously (22,23). Both PD patient groups met the criteria for the UK Parkinson Disease Society Brain Bank.…”

Section: Participantsmentioning

confidence: 99%

“…a Pearson Chi-Square PD patients were screened for RBD as part of their routine neurology clinic visits. This screening was done prior to any imaging data collection, including patients reported previously by our group (22,23).…”

Section: Participantsmentioning

confidence: 99%

See 3 more Smart Citations

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

Valli¹,

Cho²,

Uribe³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 89%

Section: Discussionsupporting

confidence: 53%

Section: Participantsmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

See 2 more Smart Citations

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

Valli¹,

Cho²,

Uribe³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…A total of 45 participants were enrolled in this study: 15 PD patients without probable RBD, 15 PD patients with probable RBD, and 15 age-matched healthy controls (Table 1 ). Some of the imaging, demographic, cognitive and psychological data from these participants have been reported previously [ 23 , 24 ]. Both PD patient groups were diagnosed based on the UK Parkinson Disease Society Brain Bank criteria.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

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.

show abstract