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Lookup NU author(s): Professor David BrooksORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Pathological involvement of the noradrenergic locus coeruleus occurs early in Parkinson’s disease, and widespread noradrenaline reductions are found at post-mortem. Rapid eye movement sleep behavior disorder (RBD) accompanies Parkinson’s disease and its presence predicts an unfavorable disease course with a higher propensity to cognitive impairment and orthostatic hypotension. MRI can detect neuromelanin in the locus coeruleus while 11C-MeNER PET is a marker of noradrenaline transporter availability. Here, we use both imaging modalities to study the association of RBD, cognition and autonomic dysfunction in Parkinson’s disease with loss of noradrenergic function. Thirty non-demented Parkinson’s disease patients (16 patients with RBD and 14 without RBD, comparable across age (66.6 ± 6.7 years), sex (22 males), and disease stage (Hoehn & Yahr, 2.3 ± 0.5)), had imaging of the locus coeruleus with neuromelanin sensitive MRI and brain noradrenaline transporter availability with 11C-MeNER PET. RBD was confirmed with polysomnography; cognitive function was assessed with a neuropsychological test-battery, and blood pressure changes on tilting were documented; results were compared to 12 matched control subjects. We found that Parkinson’s disease patients with RBD showed decreased locus coeruleus neuromelanin signal on MRI (p < 0.001) and widespread reduced binding of 11C-MeNER (p < 0.001) which correlated with amount of REM sleep without atonia. Parkinson’s disease with RBD was also associated with a higher incidence of cognitive impairment, slowed electroencephalographic activity, and orthostatic hypotension. Reduced 11C-MeNER binding correlated with electroencephalographic slowing, cognitive performance, and orthostatic hypotension. In conclusion, reduced noradrenergic function in Parkinson’s disease was linked to the presence of RBD and associated with cognitive deterioration and orthostatic hypotension. Noradrenergic impairment may contribute to the high prevalence of these non-motor symptoms in Parkinson’s disease, and may be of relevance when treating these conditions in Parkinson’s disease.
Author(s): Sommerauer M, Fedorova TD, Hansen AK, Knudsen K, Otto M, Jeppesen J, Frederiksen Y, Blicher JU, Geday J, Nahimi A, Damholdt MF, Brooks DJ, Borghammer P
Publication type: Article
Publication status: Published
Journal: Brain
Year: 2018
Volume: 141
Issue: 2
Pages: 496-504
Print publication date: 01/02/2018
Online publication date: 18/12/2017
Acceptance date: 30/10/2017
Date deposited: 31/10/2017
ISSN (print): 0006-8950
ISSN (electronic): 1460-2156
Publisher: Oxford University Press
URL: https://doi.org/10.1093/brain/awx348
DOI: 10.1093/brain/awx348
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