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Consecutive participants with video\u2010polysomnography\u2010confirmed iRBD, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and controls underwent neurological, clinical and <jats:sup>123<\/jats:sup>I\u2010FP\u2010CIT SPECT imaging assessments. Individuals with iRBD were longitudinally monitored to collect clinical phenoconversion to PD or DLB. The main outcome was to identify whole brain <jats:sup>123<\/jats:sup> I\u2010FP\u2010CIT SPECT measures reflecting monoaminergic deficits in each clinical group as compared to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cohort (<jats:italic>n<\/jats:italic>\u2009=\u2009184) included 45 patients with iRBD, 47 PD, 42 DLB and 50 age\u2010matched controls. Individuals with iRBD were categorized as RBD\u2010DAT\u2212 (<jats:italic>n<\/jats:italic>\u2009=\u200932) and RBD\u2010DAT+ (<jats:italic>n<\/jats:italic>\u2009=\u200913), according to nigrostriatal assessment used in clinical practice. Compared to controls, RBD\u2010DAT\u2212 showed an early involvement of the left insula, which increased in RBD\u2010DAT+, and was present in patients with Parkinson's disease and dementia with Lewy bodies. Longitudinal cox regression analyses revealed a higher risk of phenoconversion in individuals with iRBD and insular monoaminergic deficits [HR\u2009=\u20093.387; CI 95%: 1.18\u201310.27].<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>In this study, altered insular monoaminergic binding in iRBD was associated with phenoconversion to DLB or PD. These findings may provide a helpful stratification approach for future pharmacological or non\u2010pharmacological interventions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52151","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T05:40:44Z","timestamp":1729748444000},"page":"2836-2845","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Insular monoaminergic deficits in prodromal \u03b1\u2010synucleinopathies"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2029-6606","authenticated-orcid":false,"given":"Andrea","family":"Pilotto","sequence":"first","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Sciences University of Brescia  Brescia 25123 Italy"},{"name":"Department of Continuity of Care and Frailty, Neurology Unit ASST Spedali Civili of Brescia  Brescia 25123 Italy"},{"name":"Laboratory of Digital Neurology and Biosensors University of Brescia  Brescia 25123 Italy"},{"name":"Neurobiorepository and Laboratory of Advanced Biological Markers University of Brescia and ASST Spedali Civili Hospital  25123 Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7804-5106","authenticated-orcid":false,"given":"Alice","family":"Galli","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Sciences University of Brescia  Brescia 25123 Italy"},{"name":"Laboratory of Digital Neurology and Biosensors University of Brescia  Brescia 25123 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5648-0408","authenticated-orcid":false,"given":"Cinzia","family":"Zatti","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Sciences University of Brescia  Brescia 25123 Italy"},{"name":"Department of Continuity of Care and Frailty, Neurology Unit ASST Spedali Civili of Brescia  Brescia 25123 Italy"},{"name":"Laboratory of Digital Neurology and Biosensors University of Brescia  Brescia 25123 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Placidi","sequence":"additional","affiliation":[{"name":"Sleep Medicine Centre, Neurology Unit University Hospital of Rome Tor Vergata  00133 Italy"},{"name":"Department of Systems Medicine University of Rome Tor Vergata  Rome 00133 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Izzi","sequence":"additional","affiliation":[{"name":"Sleep Medicine Centre, Neurology Unit University Hospital of Rome Tor Vergata  00133 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Premi","sequence":"additional","affiliation":[{"name":"Vascular Neurology ASST Spedali Civili of Brescia  Brescia 25123 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4568-1738","authenticated-orcid":false,"given":"Silvia P.","family":"Caminiti","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences Univeristy of Pavia  Pavia 27100 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Presotto","sequence":"additional","affiliation":[{"name":"Department of Physics \u201cG. 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