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

Area of Science:

• Neuroscience
• Radiology
• Neurology

Background:

• Noradrenergic denervation is implicated in Parkinson's disease (PD) motor dysfunction.
• Previous PET studies detected reduced norepinephrine transporter (NART) binding in the primary sensorimotor cortex (M1S1) of PD patients.
• Idiopathic rapid-eye-movement sleep behaviour disorder (iRBD) is a prodromal phenotype of PD.

Purpose of the Study:

• To investigate NART binding reductions in the M1S1 cortex of iRBD patients using ¹¹C-MeNER PET.
• To compare NART binding in iRBD patients with PD patients (with and without RBD) and controls.
• To explore correlations between ¹¹C-MeNER binding and nigrostriatal dopamine storage capacity (measured with ¹⁸F-DOPA PET) in iRBD patients.

Main Methods:

• ¹¹C-MeNER PET scans were performed on 17 iRBD patients, 16 PD patients with RBD (PD^RBD+), 14 PD patients without RBD (PD^RBD-), and 25 controls.
• iRBD patients also underwent ¹⁸F-DOPA PET scans.
• Volume-of-interest analyses and voxel-level statistical parametric mapping were used to analyze PET data.

Main Results:

• Partial-volume corrected ¹¹C-MeNER binding potential (BP^ND) in M1S1 differed significantly across groups (P = 0.022).
• iRBD and PD^RBD+ groups showed significant reductions in M1S1 ¹¹C-MeNER binding compared to controls (P = 0.007 and P = 0.008, respectively).
• A significant correlation was observed between putaminal ¹⁸F-DOPA uptake and thalamic ¹¹C-MeNER binding in iRBD patients (r² = 0.343, P = 0.013).

Conclusions:

• Altered noradrenergic neurotransmission, indicated by reduced M1S1 ¹¹C-MeNER binding, was found in iRBD patients.
• This reduction may reflect noradrenergic terminal degeneration or NART down-regulation in this prodromal PD phenotype.
• Parallel degeneration of noradrenergic and dopaminergic systems is suggested in prodromal PD.