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Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder

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

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by Wiley-Blackwell, 2020.

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Abstract

© 2019 European Academy of Neurology. Background and purpose: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson’s disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson’s disease and dementia with Lewy bodies. Methods: A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11C-donepezil PET) and nigrostriatal dopaminergic function (18F-DOPA PET). Clinical examination included the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. Results: The 11C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11C-donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. Conclusion: Reduced neocortical 11C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.


Publication metadata

Author(s): Gersel Stokholm M, Iranzo A, Ostergaard K, Serradell M, Otto M, Bacher Svendsen K, Garrido A, Vilas D, Fedorova TD, Santamaria J, Moller A, Gaig C, Hiraoka K, Brooks DJ, Okamura N, Borghammer P, Tolosa E, Pavese N

Publication type: Article

Publication status: Published

Journal: European Journal of Neurology

Year: 2020

Volume: 27

Issue: 4

Pages: 644-652

Print publication date: 01/04/2020

Online publication date: 14/11/2019

Acceptance date: 11/11/2019

Date deposited: 17/03/2020

ISSN (print): 1351-5101

ISSN (electronic): 1468-1331

Publisher: Wiley-Blackwell

URL: https://doi.org/10.1111/ene.14127

DOI: 10.1111/ene.14127

PubMed id: 31725927


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