Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/221142
Title: Cholinergic dysfunction in isolated rapid eye movement sleep behaviour disorder links to impending phenoconversion
Author: Terkelsen, Miriam H.
Iranzo, Alex
Serradell, Mónica
Baun, Andreas M.
Stokholm, Morten G.
Danielsen, Erik Hvid
Østergaard, Karen
Otto, Maritt
Svendsen, Kristina B.
Møller, Mette
Johnsen, Erik L.
Garrido, Alicia
Vilas Rolán, Dolores
Santamaria Cano, Joan
Møller, Arne
Gaig Ventura, Carles
Brooks, David J.
Borghammer, Per
Tolosa, Eduardo
Pavese, Nicola
Keywords: Dopamina
Tomografia per emissió de positrons
Receptors colinèrgics
Trastorns del son
Malaltia de Parkinson
Dopamine
Positron emission tomography
Acetylcholine receptors
Sleep disorders
Parkinson's disease
Issue Date: 3-Oct-2024
Publisher: Wiley
Abstract: Background and purpose: Most patients with isolated rapid eye movement sleep behaviour disorder (iRBD) progress to a parkinsonian alpha-synucleinopathy. However, time to phenoconversion shows great variation. The aim of this study was to investigate whether cholinergic and dopaminergic dysfunction in iRBD patients was associated with impending phenoconversion. Methods: Twenty-one polysomnography-confirmed iRBD patients underwent baseline 11C-donepezil and 6-Fluoro-(18F)-l-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET). Potential phenoconversion was monitored for up to 8 years. PET images were analysed according to patients' diagnoses after 3 and 8 years using linear regression. Time-to-event analysis was made with Cox regression, dividing patients into low and high tracer uptake groups. Results: Follow-up was accomplished in 17 patients. Eight patients progressed to either Parkinson's disease (n = 4) or dementia with Lewy bodies (n = 4), while nine remained non-phenoconverters. Compared with non-phenoconverters, 8-year phenoconverters had lower mean 11C-donepezil uptake in the parietal (p = 0.032) and frontal cortex (p = 0.042), whereas mean 11C-donepezil uptake in 3-year phenoconverters was lower in the parietal cortex (p = 0.005), frontal cortex (p = 0.025), thalamus (p = 0.043) and putamen (p = 0.049). Phenoconverters within 3 years and 8 years had lower 18F-DOPA uptake in the putamen (p < 0.001). iRBD patients with low parietal 11C-donepezil uptake had a 13.46 (95% confidence interval 1.42;127.21) times higher rate of phenoconversion compared with those with higher uptake (p = 0.023). iRBD patients with low 18F-DOPA uptake in the most affected putamen were all phenoconverters with higher rate of phenoconversion (p = 0.0002). Conclusions: These findings suggest that cortical cholinergic dysfunction, particularly within the parietal cortex, could be a biomarker candidate for predicting short-term phenoconversion in iRBD patients. This study aligns with previous reports suggesting dopaminergic dysfunction is associated with forthcoming phenoconversion.
Note: Reproducció del document publicat a: https://doi.org/10.1111/ene.16503
It is part of: European Journal of Neurology, 2024, vol. 31, num.12
URI: https://hdl.handle.net/2445/221142
Related resource: https://doi.org/10.1111/ene.16503
ISSN: 1351-5101
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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