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

Abstract

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 ¹¹C-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 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: 17 iRBD patients, 16 PD patients with (PD^RBD+) and 14 without RBD (PD^RBD-), 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 (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 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.

Keywords: (11)C-MeNER positron emission tomography (PET); Idiopathic rapid-eye-movement (REM) sleep behaviour disorder (RBD); Motor cortex; Noradrenaline; Parkinson's disease; Primary motor-sensory cortex.