Altered sensorimotor cortex noradrenergic function in idiopathic REM sleep behaviour disorder - A PET study.

Introduction: Noradrenergic denervation is thought to aggravate motor dysfunction in Parkinson's disease (PD). In a previous PET study with the norepinephrine transporter (NART) ligand ¹¹ C-MeNER, we detected reduced NART binding in primary sensorimotor cortex (M1S1) of PD patients. Idiopathic rapid-eye-movement sleep behaviour disorder (iRBD) is a phenotype of prodromal PD. Using ¹¹ C-MeNER PET, we investigated whether iRBD patients showed similar NART binding reductions in M1S1 cortex as PD patients. Additionally, we investigated whether ¹¹ C-MeNER binding and loss of nigrostriatal dopamine storage capacity measured with ¹⁸ F-DOPA PET were correlated.
Methods: 17 iRBD patients, 16 PD patients with (PD ^RBD+ ) and 14 without RBD (PD ^RBD- ), and 25 control subjects underwent ¹¹ C-MeNER PET. iRBD patients also had ¹⁸ F-DOPA PET. Volume-of-interest analyses and voxel-level statistical parametric mapping were performed.
Results: Partial-volume corrected ¹¹ C-MeNER binding potential (BP ^ND ) values in M1S1 differed across the groups (P = 0.022) with the iRBD and PD ^RBD+ groups showing significant reductions (controls vs. iRBD P = 0.007; control vs. PD ^RBD+ P = 0.008). Voxel-wise comparisons confirmed reductions of M1S1 ¹¹ C-MeNER binding in PD and iRBD patients. Significant correlation was seen between putaminal ¹⁸ F-DOPA uptake and thalamic ¹¹ C-MeNER binding in iRBD patients (r ²  = 0.343, P = 0.013).
Conclusions: This study found altered noradrenergic neurotransmission in the M1S1 cortex of iRBD patients. The observed reduction of M1S1 ¹¹ C-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 ¹¹ C-MeNER binding and putaminal ¹⁸ F-DOPA binding suggests that these neurotransmitter systems degenerate in parallel in the iRBD phenotype of prodromal PD.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)