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However, data on premotor non-motor burden and motor progression in these subtypes remain inconsistent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To analyze the natural history of body-first versus brain-first PD subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from 400 PD patients enrolled at a single Italian center were analyzed. All patients underwent a standardized retrospective baseline assessment of premotor and motor symptoms at onset and were prospectively followed. Premotor REM sleep behavior disorder (RBD), considered a prodromal phenotype of the body-first subtype, was used to divide patients into two groups: 81 patients with probable premotor RBD (PD\n                      <jats:sup>preRBD+<\/jats:sup>\n                      ) and 319 patients without (PD\n                      <jats:sup>preRBD\u2212<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At motor onset, PD\n                      <jats:sup>preRBD+<\/jats:sup>\n                      patients were older than PD\n                      <jats:sup>preRBD\u2212<\/jats:sup>\n                      patients, exhibited less tremor, and more frequently presented with bilateral motor symptoms. PD\n                      <jats:sup>preRBD+<\/jats:sup>\n                      patients also reported a greater burden of premotor symptoms, including hyposmia, cognitive impairment, pain, constipation, and other dysautonomic symptoms. Over the follow-up period, PD\n                      <jats:sup>preRBD+<\/jats:sup>\n                      patients progressed more rapidly to Hoehn and Yahr stage 3, even after adjusting for sex, years of schooling, age at motor onset, and initial motor phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results align with the hypothesis of brain-first and body-first PD subtypes, providing novel insights into their different premotor non-motor burden and motor progression trajectories.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-025-13050-y","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T14:26:37Z","timestamp":1744208797000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The natural history of body-first versus brain-first Parkinson\u2019s disease subtypes"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9040-4884","authenticated-orcid":false,"given":"Vittorio","family":"Velucci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1593-5867","authenticated-orcid":false,"given":"Angelo Fabio","family":"Gigante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Iliceto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Pellicciari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7041-230X","authenticated-orcid":false,"given":"Barbara","family":"Vitucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4617-8961","authenticated-orcid":false,"given":"Sarah","family":"Idrissi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9028-5972","authenticated-orcid":false,"given":"Marcello Mario","family":"Mascia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4216-0822","authenticated-orcid":false,"given":"Antonella","family":"Muroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3260-1754","authenticated-orcid":false,"given":"Tommaso","family":"Ercoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2982-0665","authenticated-orcid":false,"given":"Paolo","family":"Solla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Defazio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"issue":"8","key":"13050_CR1","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1001\/jamaneurol.2015.0703","volume":"72","author":"SM Fereshtehnejad","year":"2015","unstructured":"Fereshtehnejad SM, Romenets SR, Anang JB, Latreille V, Gagnon JF, Postuma RB (2015) New clinical subtypes of parkinson disease and their longitudinal progression: a prospective cohort comparison with other phenotypes. 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