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":"孤立性快速眼动睡眠行为障碍中的胆碱能功能障碍与即将出现的表型转换有关。","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":"<div>\n \n \n <section>\n \n <h3> Background and purpose</h3>\n \n <p>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>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Follow-up was accomplished in 17 patients. Eight patients progressed to either Parkinson's disease (<i>n</i> = 4) or dementia with Lewy bodies (<i>n</i> = 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 (<i>p</i> = 0.032) and frontal cortex (<i>p</i> = 0.042), whereas mean <sup>11</sup>C-donepezil uptake in 3-year phenoconverters was lower in the parietal cortex (<i>p</i> = 0.005), frontal cortex (<i>p</i> = 0.025), thalamus (<i>p</i> = 0.043) and putamen (<i>p</i> = 0.049). Phenoconverters within 3 years and 8 years had lower <sup>18</sup>F-DOPA uptake in the putamen (<i>p</i> < 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 <i>(p</i> = 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 (<i>p</i> = 0.0002).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>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>\n </section>\n </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"31 12","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554850/pdf/","citationCount":"0","resultStr":"{\"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\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background and purpose</h3>\\n \\n <p>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>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Follow-up was accomplished in 17 patients. Eight patients progressed to either Parkinson's disease (<i>n</i> = 4) or dementia with Lewy bodies (<i>n</i> = 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 (<i>p</i> = 0.032) and frontal cortex (<i>p</i> = 0.042), whereas mean <sup>11</sup>C-donepezil uptake in 3-year phenoconverters was lower in the parietal cortex (<i>p</i> = 0.005), frontal cortex (<i>p</i> = 0.025), thalamus (<i>p</i> = 0.043) and putamen (<i>p</i> = 0.049). Phenoconverters within 3 years and 8 years had lower <sup>18</sup>F-DOPA uptake in the putamen (<i>p</i> < 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 <i>(p</i> = 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 (<i>p</i> = 0.0002).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>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>\\n </section>\\n </div>\",\"PeriodicalId\":11954,\"journal\":{\"name\":\"European Journal of Neurology\",\"volume\":\"31 12\",\"pages\":\"\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-10-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554850/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/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}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Neurology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/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}
Cholinergic dysfunction in isolated rapid eye movement sleep behaviour disorder links to impending phenoconversion
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).
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