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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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010one polysomnography\u2010confirmed iRBD patients underwent baseline <jats:sup>11<\/jats:sup>C\u2010donepezil and 6\u2010Fluoro\u2010(<jats:sup>18<\/jats:sup>F)\u2010l\u20103,4\u2010dihydroxyphenylalanine (<jats:sup>18<\/jats:sup>F\u2010DOPA) positron emission tomography (PET). Potential phenoconversion was monitored for up to 8\u2009years. PET images were analysed according to patients' diagnoses after 3 and 8\u2009years using linear regression. Time\u2010to\u2010event analysis was made with Cox regression, dividing patients into low and high tracer uptake groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Follow\u2010up was accomplished in 17 patients. Eight patients progressed to either Parkinson's disease (<jats:italic>n<\/jats:italic>\u2009=\u20094) or dementia with Lewy bodies (<jats:italic>n<\/jats:italic>\u2009=\u20094), while nine remained non\u2010phenoconverters. Compared with non\u2010phenoconverters, 8\u2010year phenoconverters had lower mean <jats:sup>11<\/jats:sup>C\u2010donepezil uptake in the parietal (<jats:italic>p<\/jats:italic>\u2009=\u20090.032) and frontal cortex (<jats:italic>p<\/jats:italic>\u2009=\u20090.042), whereas mean <jats:sup>11<\/jats:sup>C\u2010donepezil uptake in 3\u2010year phenoconverters was lower in the parietal cortex (<jats:italic>p<\/jats:italic>\u2009=\u20090.005), frontal cortex (<jats:italic>p<\/jats:italic>\u2009=\u20090.025), thalamus (<jats:italic>p<\/jats:italic>\u2009=\u20090.043) and putamen (<jats:italic>p<\/jats:italic>\u2009=\u20090.049). Phenoconverters within 3\u2009years and 8\u2009years had lower <jats:sup>18<\/jats:sup>F\u2010DOPA uptake in the putamen (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). iRBD patients with low parietal <jats:sup>11<\/jats:sup>C\u2010donepezil uptake had a 13.46 (95% confidence interval 1.42;127.21) times higher rate of phenoconversion compared with those with higher uptake <jats:italic>(p<\/jats:italic>\u2009=\u20090.023). iRBD patients with low <jats:sup>18<\/jats:sup>F\u2010DOPA uptake in the most affected putamen were all phenoconverters with higher rate of phenoconversion (<jats:italic>p<\/jats:italic>\u2009=\u20090.0002).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that cortical cholinergic dysfunction, particularly within the parietal cortex, could be a biomarker candidate for predicting short\u2010term phenoconversion in iRBD patients. This study aligns with previous reports suggesting dopaminergic dysfunction is associated with forthcoming phenoconversion.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.16503","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T06:39:55Z","timestamp":1727937595000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cholinergic dysfunction in isolated rapid eye movement sleep behaviour disorder links to impending phenoconversion"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0971-3747","authenticated-orcid":false,"given":"Miriam H.","family":"Terkelsen","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine and PET Institute of Clinical Medicine, Aarhus University  Aarhus Denmark"},{"name":"Department of Neurology Aarhus University Hospital  Aarhus 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