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

M. Gersel Stokholm, A. Iranzo, K. Østergaard, M. Serradell, M. Otto, K. Bacher Svendsen, A. Garrido, D. Vilas, T. D. Fedorova, J. Santamaria, A. Møller, C. Gaig, K. Hiraoka, D. J. Brooks, N. Okamura, P. Borghammer, E. Tolosa, N. Pavese

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)644-652
Number of pages9
JournalEuropean Journal of Neurology
Volume27
Issue number4
DOIs
Publication statusPublished - 2020 Apr 1

Keywords

  • Lewy body disease
  • Parkinson’s disease
  • acetylcholine
  • positron emission tomography
  • rapid eye movement sleep behaviour disorder

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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