Miriam H Terkelsen, Alex Iranzo, Mónica Serradell, Andreas M Baun, Morten G Stokholm, Erik Hvid Danielsen, Karen Østergaard, Marit Otto, Kristina B Svendsen, Mette Møller, Erik L Johnsen, Alicia Garrido, Dolores Vilas, Joan Santamaria, Arne Møller, Carles Gaig, David J Brooks, Per Borghammer, Eduardo Tolosa, Nicola Pavese
{"title":"Cholinergic dysfunction in isolated rapid eye movement sleep behaviour disorder links to impending phenoconversion.","authors":"Miriam H Terkelsen, Alex Iranzo, Mónica Serradell, Andreas M Baun, Morten G Stokholm, Erik Hvid Danielsen, Karen Østergaard, Marit Otto, Kristina B Svendsen, Mette Møller, Erik L Johnsen, Alicia Garrido, Dolores Vilas, Joan Santamaria, Arne Møller, Carles Gaig, David J Brooks, Per Borghammer, Eduardo Tolosa, Nicola Pavese","doi":"10.1111/ene.16503","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and purpose: </strong>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.</p><p><strong>Methods: </strong>Twenty-one polysomnography-confirmed iRBD patients underwent baseline <sup>11</sup>C-donepezil and 6-Fluoro-(<sup>18</sup>F)-l-3,4-dihydroxyphenylalanine (<sup>18</sup>F-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.</p><p><strong>Results: </strong>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 <sup>11</sup>C-donepezil uptake in the parietal (p = 0.032) and frontal cortex (p = 0.042), whereas mean <sup>11</sup>C-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 <sup>18</sup>F-DOPA uptake in the putamen (p < 0.001). iRBD patients with low parietal <sup>11</sup>C-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 <sup>18</sup>F-DOPA uptake in the most affected putamen were all phenoconverters with higher rate of phenoconversion (p = 0.0002).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/ene.16503","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
The European Journal of Neurology is the official journal of the European Academy of Neurology and covers all areas of clinical and basic research in neurology, including pre-clinical research of immediate translational value for new potential treatments. Emphasis is placed on major diseases of large clinical and socio-economic importance (dementia, stroke, epilepsy, headache, multiple sclerosis, movement disorders, and infectious diseases).