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

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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 C-11-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 C-11-MeNER PET, we investigated whether iRBD patients showed similar NART binding reductions in M1S1 cortex as PD patients. Additionally, we investigated whether C-11-MeNER binding and loss of nigrostriatal dopamine storage capacity measured with F-18-DOPA PET were correlated.

Methods: 17 iRBD patients, 16 PD patients with (PDRBD+) and 14 without RBD (PDRBD-), and 25 control subjects underwent C-11-MeNER PET. iRBD patients also had F-18-DOPA PET. Volume-of-interest analyses and voxel-level statistical parametric mapping were performed.

Results: Partial-volume corrected C-11-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 C-11-MeNER binding in PD and iRBD patients. Significant correlation was seen between putaminal F-18-DOPA uptake and thalamic C-11-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 C-11-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 C-11-MeNER binding and putaminal F-18-DOPA binding suggests that these neurotransmitter systems degenerate in parallel in the iRBD phenotype of prodromal PD.

Original languageEnglish
JournalParkinsonism & Related Disorders
Pages (from-to)63-69
Number of pages7
Publication statusPublished - Jun 2020


  • 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


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