Universität zu Köln

Sommerauer, Michael, Fedorova, Tatyana D., Hansen, Allan K., Knudsen, Karoline, Otto, Marit, Jeppesen, Jesper ORCID: 0000-0002-3095-2040, Frederiksen, Yoon, Blicher, Jakob U., Geday, Jacob, Nahimi, Adjmal, Damholdt, Malene F., Brooks, David J. and Borghammer, Per ORCID: 0000-0001-6391-8052 (2018). Evaluation of the noradrenergic system in Parkinson's disease: an C-11-MeNER PET and neuromelanin MRI study. Brain, 141. S. 496 - 505. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2156

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Abstract

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 behaviour disorder (RBD) accompanies Parkinson's disease and its presence predicts an unfavourable disease course with a higher propensity to cognitive impairment and orthostatic hypotension. MRI can detect neuromelanin in the locus coeruleus while C-11-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 and Yahr, 2.3 +/- 0.5)], had imaging of the locus coeruleus with neuromelanin sensitive MRI and brain noradrenaline transporter availability with C-11-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 C-11-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 EEG activity, and orthostatic hypotension. Reduced C-11-MeNER binding correlated with EEG 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sommerauer, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Fedorova, Tatyana D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansen, Allan K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Knudsen, Karoline UNSPECIFIED UNSPECIFIED UNSPECIFIED Otto, Marit UNSPECIFIED UNSPECIFIED UNSPECIFIED Jeppesen, Jesper UNSPECIFIED orcid.org/0000-0002-3095-2040 UNSPECIFIED Frederiksen, Yoon UNSPECIFIED UNSPECIFIED UNSPECIFIED Blicher, Jakob U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Geday, Jacob UNSPECIFIED UNSPECIFIED UNSPECIFIED Nahimi, Adjmal UNSPECIFIED UNSPECIFIED UNSPECIFIED Damholdt, Malene F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brooks, David J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Borghammer, Per UNSPECIFIED orcid.org/0000-0001-6391-8052 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-196360
DOI:	10.1093/brain/awx348
Journal or Publication Title:	Brain
Volume:	141
Page Range:	S. 496 - 505
Date:	2018
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2156
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SLEEP BEHAVIOR DISORDER; NOREPINEPHRINE; NUCLEUS; ATOMOXETINE; PROGRESSION; VALIDATION; DEMENTIA; NEURONS Multiple languages Clinical Neurology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19636