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Progression of brain cholinergic dysfunction in patients with isolated REM sleep behaviour disorder

Lookup NU author(s): Professor David BrooksORCiD, Professor Nicola PaveseORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

Background Reduced cortical acetylcholinesterase activity, as measured by ¹¹C-donepezil PET, has been reported in patients with isolated REM sleep behaviour disorder (iRBD). However, its progression and clinical implications have not been fully investigated. Here, we explored the relationship between longitudinal changes in brain acetylcholinesterase activity and cognitive function in iRBD. Methods Twelve iRBD patients underwent ¹¹C-donepezil PET at baseline and after 3 years. PET images were interrogated with Statistical Parametric Mapping (SPM) and a regions of interest (ROI) approach. Clinical progression was assessed with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS III). Cognitive function was rated using the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Results From baseline to follow-up, the mean ¹¹C-donepezil distribution volume ratio (DVR) decreased in the cortex (p = 0.006), thalamus (p = 0.013) and caudate (p = 0.013) ROI. Despite no significant changes in the group mean MMSE or MoCA scores being observed, individually, seven patients showed a decline in their scores on these cognitive tests. Subgroup analysis showed that only the subgroup of patients with a decline in cognitive scores had a significant reduction in mean cortical ¹¹C-donepezil DVR. Conclusion Our results show that severity of brain cholinergic dysfunction in iRBD patients increases significantly over 3 years, and those changes are more severe in those with a decline in cognitive test scores.

Publication metadata

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

Publication type: Article

Publication status: Published

Journal: European Journal of Neurology

Year: 2024

Volume: 31

Issue: 1

Print publication date: 01/01/2024

Online publication date: 17/10/2023

Acceptance date: 27/09/2023

Date deposited: 29/09/2023

ISSN (print): 1351-5101

ISSN (electronic): 1468-1331

Publisher: Wiley

URL: https://doi.org/10.1111/ene.16101

DOI: 10.1111/ene.16101

ePrints DOI: 10.57711/dhhj-wg83

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