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Lookup NU author(s): Professor Nicola PaveseORCiD, Professor David BrooksORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
Objective: Noradrenergic denervation is thought to aggravate motor dysfunction in Parkinson’s disease (PD). Our previous PET study with the norepinephrine transporter (NART) ligand 11C-MeNER detected reduced noradrenaline transporter binding in primary sensorimotor cortex (M1S1) of PD patients. Idiopathic rapid-eye-movement sleep behaviour disorder (iRBD) is a phenotype of prodromal PD. Using 11C-MeNER PET, we investigated whether iRBD patients showed similar NART binding reductions in M1S1 cortex as PD patients. Additionally, we investigated whether 11C-MeNER binding and loss of nigrostriatal dopamine storage capacity measured with 18F-DOPA PET were correlated. Methods: Methods: 17 iRBD patients, 16 PD patients with (PDRBD+) and 14 without RBD (PDRBD -), and 25 control subjects underwent 11C-MeNER PET. iRBD patients also had 18F-DOPA PET. Volume-of-interest analyses and voxel-level statistical parametric mapping were performed. Results: Partial-volume corrected 11C-MeNER binding potential (BPND) values in M1S1 differed across the groups (P=0.022) with the iRBD and PDRBD+ groups showing significant reductions (controls vs. iRBD P=0.007; control vs. PDRBD+ P=0.008). Voxel-wise comparisons confirmed reductions of M1S1 11C-MeNER binding in PD and iRBD patients. Significant correlation was seen between putaminal 18F-DOPA uptake and thalamic 11C-MeNER binding in iRBD patients (r2=0.343, P=0.013). Conclusions: This study found altered noradrenergic neurotransmission in the M1S1 cortex of iRBD patients. The observed reduction of M1S1 11C-MeNER binding in iRBD may represent noradrenergic terminal degeneration or physiological down-regulation of NARTs in this prodromal phenotype of PD. The correlation between thalamic 11C-MeNER binding and putaminal 18F-DOPA binding suggests that these neurotransmitter systems degenerate in parallel in the iRBD phenotype of prodromal PD.
Author(s): Andersen K, Hansen AK, Sommerauer M, Fedorova TD, Knudsen K, Vang K, VanDenBerge N, Kinnerup M, Nahimi A, Pavese N, Brooks DJ, Borghammer P
Publication type: Article
Publication status: Published
Journal: Parkinsonism & Related Disorders
Year: 2020
Volume: 75
Pages: 63-69
Print publication date: 01/06/2020
Online publication date: 19/05/2020
Acceptance date: 02/04/2018
Date deposited: 11/07/2019
ISSN (print): 1353-8020
ISSN (electronic): 1873-5126
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.parkreldis.2020.05.013
DOI: 10.1016/j.parkreldis.2020.05.013
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