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Extrastriatal monoaminergic dysfunction and enhanced microglial activation in idiopathic rapid eye movement sleep behaviour disorder

Lookup NU author(s): Professor David Brooks, Professor Nicola Pavese

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Abstract

Background The majority of patients diagnosed with idiopathic rapid eye movement sleep behaviour disorder (iRBD) progress over time to a Lewy-type α-synucleinopathy such as Parkinson’s disease or dementia with Lewy bodies. This in vivomolecular imaging study aimed to investigate if extrastriatal monoaminergic systems are affected in iRBD patients and if this coincides with neuroinflammation. Methods We studied twenty-one polysomnography-confirmed iRBD patients with 18F-DOPA and 11C-PK11195 positron emission tomography (PET) to investigate extrastriatal monoaminergic function and microglial activation. Twenty-nine healthy controls (n=9 18F-DOPA and n=20 11C-PK11195) were also investigated. Analyses were performed within predefined regions of interest and at voxel-level with Statistical Parametric Mapping. Results Regions of interest analysis detected monoaminergic dysfunction in iRBD thalamus with a 15% mean reduction of 18F-DOPA Ki values compared to controls (mean difference = -0.00026, 95% confidence interval [-0.00050 to -0.00002], p-value = 0.03). No associated thalamic changes in 11C-PK11195 binding were observed. Other regions sampled showed no 18F-DOPA or 11C-PK11195 PET differences between groups. Voxel-level interrogation of 11C-PK11195 binding identified areas with significantly increased binding within the occipital lobe of iRBD patients. Conclusion Thalamic monoaminergic dysfunction in iRBD patients may reflect terminal dysfunction of projecting neurons from the locus coeruleus and dorsal raphe nucleus, two structures that regulate REM sleep and are known to be involved in the early phase of PD. The observation of significantly raised microglial activation in the occipital lobe of these patients might suggest early local Lewy-type α-synuclein pathology and possibly an increased risk for later cognitive dysfunction.


Publication metadata

Author(s): Stokholm MG, Iranzo A, Østergaard K, Serradell M, Otto M, Svendsen KB, Garrido A, Vilas D, Parbo P, Borghammer P, Santamaria J, Møller A, Gaig C, Brooks DJ, Tolosa E, Pavese N

Publication type: Article

Publication status: Published

Journal: Neurobiology of Disease

Year: 2018

Volume: 115

Pages: 9-16

Print publication date: 01/07/2018

Online publication date: 06/03/2018

Acceptance date: 22/02/2018

Date deposited: 22/02/2018

ISSN (print): 0969-9961

ISSN (electronic): 1095-953X

Publisher: Elsevier

URL: https://doi.org/10.1016/j.nbd.2018.02.017

DOI: 10.1016/j.nbd.2018.02.017


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