{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:41:20Z","timestamp":1792269680193,"version":"4.4.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T00:00:00Z","timestamp":1558396800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Canadian Institutes for Health Research, the Healthy Brains for Healthy Lives (HBHL) initiative"},{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fonds de la Recherche Sante Quebec"},{"DOI":"10.13039\/501100000243","name":"W. Garfield Weston Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Parkinson\u2019s disease has a long prodromal stage with various subclinical motor and non-motor manifestations; however, their evolution in the years before Parkinson\u2019s disease is diagnosed is unclear. We traced the evolution of early motor and non-motor manifestations of synucleinopathy from the stage of idiopathic rapid eye movement (REM) sleep behaviour disorder until defined neurodegenerative disease. During 2004\u201316, we recruited and then annually followed 154 polysomnography-proven patients with idiopathic REM sleep behaviour disorder, of whom 55 phenoconverted to defined parkinsonism or dementia. Longitudinal data on multiple prodromal features, including the Unified Parkinson\u2019s Disease Rating Scale parts I\u2013III, quantitative motor tests, olfaction, colour vision, cognition, and autonomic functions were gathered annually (average = five follow-up visits, range: 2\u201312 years). The same measures were also assessed in 102 age- and sex-matched healthy control subjects. By looking backward from the time of dementia or parkinsonism diagnosis, we examined trajectories of each prodromal feature using mixed effect models. Based on analysis, olfactory loss was first to develop, with predicted onset &gt;20 years before phenoconversion. This was followed by impaired colour vision, constipation, and erectile dysfunction, starting 10\u201316 years prior to phenoconversion. At 7\u20139 years before phenoconversion, slight urinary dysfunction and subtle cognitive decline could be detected. Among motor symptoms altered handwriting, turning in bed, walking, salivation, speech, and facial expression began to be disrupted starting 7\u201311 years prior to parkinsonism diagnosis, but remained mild until soon before phenoconversion. Motor examination abnormalities began 5\u20137 years before phenoconversion, with the alternate tap test having the longest interval (8 years before phenoconversion). Among cardinal motor phenotypes, bradykinesia appeared first, \u223c5\u20136 years prior to phenoconversion, followed by rigidity (Year \u22123) and tremor (Year \u22122). With direct prospective evaluation of an idiopathic REM sleep behaviour disorder cohort during phenoconversion, we documented an evolution of prodromal manifestations similar to that predicted by pathological staging models, with predicted prodromal intervals as long as 20 years.<\/jats:p>","DOI":"10.1093\/brain\/awz111","type":"journal-article","created":{"date-parts":[[2019,4,6]],"date-time":"2019-04-06T15:13:19Z","timestamp":1554563599000},"page":"2051-2067","source":"Crossref","is-referenced-by-count":389,"title":["Evolution of prodromal Parkinson\u2019s disease and dementia with Lewy bodies: a prospective study"],"prefix":"10.1093","volume":"142","author":[{"given":"Seyed-Mohammad","family":"Fereshtehnejad","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada"},{"name":"Division of Neurology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada"},{"name":"Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Yao","sequence":"additional","affiliation":[{"name":"Integrated Program in Neuroscience, McGill University, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Pelletier","sequence":"additional","affiliation":[{"name":"Research Institute of the McGill University Health Centre, Montreal General Hospital, Department of Neurology, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques Y","family":"Montplaisir","sequence":"additional","affiliation":[{"name":"Centre for Advanced Research in Sleep Medicine, H\u00f4pital du Sacr\u00e9-C\u0153ur de Montr\u00e9al, Montr\u00e9al, QC, Canada"},{"name":"Department of Psychiatry, Universit\u00e9 de Montr\u00e9al, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Gagnon","sequence":"additional","affiliation":[{"name":"Centre for Advanced Research in Sleep Medicine, H\u00f4pital du Sacr\u00e9-C\u0153ur de Montr\u00e9al, Montr\u00e9al, QC, Canada"},{"name":"Department of Psychology, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald B","family":"Postuma","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada"},{"name":"Centre for Advanced Research in Sleep Medicine, H\u00f4pital du Sacr\u00e9-C\u0153ur de Montr\u00e9al, Montr\u00e9al, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,20]]},"reference":[{"key":"2019062810125949300_awz111-B1","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1002\/mds.26605","article-title":"Neuropathological basis of nonmotor manifestations of Parkinson\u2019s disease","volume":"31","author":"Adler","year":"2016","journal-title":"Mov Disord"},{"key":"2019062810125949300_awz111-B2","volume-title":"The international classification of sleep disorders: diagnostic and coding manual","year":"2007","edition":"2nd edn"},{"key":"2019062810125949300_awz111-B3","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1212\/WNL.0000000000000842","article-title":"Predictors of dementia in Parkinson disease: a prospective cohort 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