{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:26:42Z","timestamp":1790803602880,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To explore the clinical progression of the brain\u2010\/body\u2010first categories within Lewy body disease (LBD): Parkinson's disease (PD), dementia with Lewy bodies (DLB), and PD dementia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used of the Rochester Epidemiology Project to establish a population\u2010based cohort of clinically diagnosed LBD. We used two definitions for differentiating between brain\u2010 and body\u2010first LBD: a previously hypothesized body\u2010first presentation in patients with rapid eye movement sleep behavior onset before motor symptoms onset; and an expanded definition of body\u2010first LBD when a patient had at least 2 premotor symptoms between constipation, erectile dysfunction, rapid eye movement sleep behavior, anosmia, or neurogenic bladder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Brain\u2010first patients were more likely to be diagnosed with PD (RR\u2009=\u20091.43, <jats:italic>p<\/jats:italic>\u2009=\u20090.003), whereas body\u2010first patients were more likely to be diagnosed with DLB (RR\u2009=\u20093.15, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Under the expanded definition, there was no difference in LBD diagnosis between brain\u2010first and body\u2010first patients (PD: RR\u2009=\u20091.03, <jats:italic>p<\/jats:italic>\u2009=\u20090.10; DLB: RR\u2009=\u20090.88, <jats:italic>p<\/jats:italic>\u2009=\u20090.58) There were no patterns between brain\u2010 or body\u2010first presentation, PD dementia under either definition (original: <jats:italic>p<\/jats:italic>\u2009=\u20090.09, expanded: <jats:italic>p<\/jats:italic>\u2009=\u20090.97), and no significant difference in motor symptoms between brain\u2010first and body\u2010first.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our findings do not support the dichotomous classification of body\u2010first and brain\u2010first LBD with the currently proposed definition. Biological exposures resulting in PD and DLB are unlikely to converge on a binary classification of top\u2010down or bottom\u2010up synuclein pathology. ANN NEUROL 2024;96:551\u2013559<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.27006","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T09:55:48Z","timestamp":1718099748000},"page":"551-559","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A Population\u2010Based Approach to the Argument on Brain\u2010First and Body\u2010First Pathogenesis of Lewy Body Disease"],"prefix":"10.1002","volume":"96","author":[{"given":"Emanuele","family":"Camerucci","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester MN USA"},{"name":"Department of Neurology Kansas University Medical Center (KUMC)  Kansas City KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidan F.","family":"Mullan","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierpaolo","family":"Turcano","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cole D.","family":"Stang","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Bower","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo E.","family":"Benarroch","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley F.","family":"Boeve","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester MN 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