{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T03:36:57Z","timestamp":1773977817293,"version":"3.50.1"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"EC | Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["634821"],"award-info":[{"award-number":["634821"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Parkinsons Dis."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A prodromal phase of Parkinson\u2019s disease (PD) may precede motor manifestations by decades. PD patients\u2019 siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel\/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (<jats:italic>p<\/jats:italic>\u2009=\u20090.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3\/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173\/300 siblings had &lt;1% probability of having prodromal PD; 100 between 1 and 10%, 26 siblings between 10 and 80%, one fulfilled the criteria for prodromal PD. According to the current analysis, we cannot confirm the increased risk of PD siblings for prodromal PD. Siblings showed a heterogeneous distribution of prodromal PD markers and probability. Additional parameters, including strong disease markers, should be investigated to verify if these results depend on validity and sensitivity of prodromal PD criteria, or if siblings\u2019 risk is not elevated.<\/jats:p>","DOI":"10.1038\/s41531-021-00219-1","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T10:03:12Z","timestamp":1631008992000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Heterogeneity of prodromal Parkinson symptoms in siblings of Parkinson disease patients"],"prefix":"10.1038","volume":"7","author":[{"given":"Luca","family":"Baldelli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6316-6804","authenticated-orcid":false,"given":"Sebastian","family":"Schade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Jes\u00fas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian R.","family":"Schreglmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Sambati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0437-6182","authenticated-orcid":false,"given":"Pilar","family":"G\u00f3mez-Garre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Halsband","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Calandra-Buonaura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid Daniela","family":"Adarmes-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friederike","family":"Sixel-D\u00f6ring","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corrado","family":"Zenesini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Pirazzini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Garagnani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Giulia","family":"Bacalini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kailash P.","family":"Bhatia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Cortelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brit","family":"Mollenhauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Franceschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"PROPAG-AGEING consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Li\u00f2","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Luchinat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Delledonne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Mills","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy L.","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiago","family":"Azevedo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Bartoletti-Stella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Bonilla-Toribio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Buiza-Rueda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabina","family":"Capellari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Carri\u00f2n-Claro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Clayton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Dal Molin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna Maria","family":"Dimitri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Doykov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Giuliani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"H\u00e4gg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"H\u00e4llqvist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Heywood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ismael","family":"Huertas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juulia","family":"Jylh\u00e4v\u00e4","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel A.","family":"Labrador-Espinosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Licari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Macias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Magrinelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Francisco Mart\u00edn","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Giovanna","family":"Maturo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo","family":"Mengozzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaia","family":"Meoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maddalena","family":"Milazzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Nardini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy L.","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Teresa","family":"Peri\u00f1\u00e1n-Tocino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Ravaioli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Sala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simeon","family":"Spasov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Tejera-Parrado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Tenori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Turano","family":"Paola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dylan","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciano","family":"Xumerle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Zago","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcella","family":"Broli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Buiza-Rueda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"De Massis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocio","family":"Escuela-Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Fabbri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Gabellini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Guaraldi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Macr\u00ec","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania Alessandra","family":"Nassetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cesa Lorella Maria","family":"Scaglione","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Valzania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cilea","family":"Rosaria","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Mignani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosario Vigo","family":"Ortega","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Boninsegna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"De Luca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1656-302X","authenticated-orcid":false,"given":"Pablo","family":"Mir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Trenkwalder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9063-2658","authenticated-orcid":false,"given":"Federica","family":"Provini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"219_CR1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1002\/mdc3.12568","volume":"5","author":"MM Abbas","year":"2018","unstructured":"Abbas, M. M., Xu, Z. & Tan, L. C. S. Epidemiology of Parkinson\u2019s Disease-East versus West. Mov. Disord. Clin. Pract. 5, 14\u201328 (2018).","journal-title":"Mov. Disord. Clin. Pract."},{"key":"219_CR2","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41531-018-0058-0","volume":"4","author":"C Marras","year":"2018","unstructured":"Marras, C. et al. Prevalence of Parkinson\u2019s disease across North America. NPJ Parkinsons Dis. 4, 21 (2018).","journal-title":"NPJ Parkinsons Dis."},{"key":"219_CR3","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1097\/NHH.0000000000000398","volume":"34","author":"T Capriotti","year":"2016","unstructured":"Capriotti, T. & Terzakis, K. Parkinson disease. Home Healthc. Now 34, 300\u2013307 (2016).","journal-title":"Home Healthc. Now"},{"key":"219_CR4","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1212\/WNL.0000000000009107","volume":"94","author":"AJ Espay","year":"2020","unstructured":"Espay, A. J. et al. Disease modification and biomarker development in Parkinson disease: revision or reconstruction? Neurology 94, 481\u2013494 (2020).","journal-title":"Neurology"},{"key":"219_CR5","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.cell.2015.01.019","volume":"160","author":"J Br\u00e1s","year":"2015","unstructured":"Br\u00e1s, J., Guerreiro, R. & Hardy, J. SnapShot: genetics of Parkinson\u2019s disease. Cell 160, 570\u2013570.e571 (2015).","journal-title":"Cell"},{"key":"219_CR6","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1016\/S1474-4422(19)30320-5","volume":"18","author":"MA Nalls","year":"2019","unstructured":"Nalls, M. A. et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson\u2019s disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 18, 1091\u20131102 (2019).","journal-title":"Lancet Neurol."},{"key":"219_CR7","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1111\/acel.12312","volume":"14","author":"M Rodriguez","year":"2015","unstructured":"Rodriguez, M., Rodriguez-Sabate, C., Morales, I., Sanchez, A. & Sabate, M. Parkinson\u2019s disease as a result of aging. Aging Cell 14, 293\u2013308 (2015).","journal-title":"Aging Cell"},{"key":"219_CR8","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.parkreldis.2019.07.008","volume":"66","author":"I Stankovic","year":"2019","unstructured":"Stankovic, I. et al. Longitudinal assessment of autonomic dysfunction in early Parkinson\u2019s disease. Parkinson. Relat. Disord. 66, 74\u201379 (2019).","journal-title":"Parkinson. Relat. Disord."},{"key":"219_CR9","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1002\/mds.26281","volume":"30","author":"F Baig","year":"2015","unstructured":"Baig, F. et al. Delineating nonmotor symptoms in early Parkinson\u2019s disease and first-degree relatives. Mov. Disord. 30, 1759\u20131766 (2015).","journal-title":"Mov. Disord."},{"key":"219_CR10","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1002\/mds.26058","volume":"29","author":"K Dujardin","year":"2014","unstructured":"Dujardin, K. et al. Apathy in untreated early-stage Parkinson disease: relationship with other non-motor symptoms. Mov. Disord. 29, 1796\u20131801 (2014).","journal-title":"Mov. Disord."},{"key":"219_CR11","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/nrn.2017.62","volume":"18","author":"AHV Schapira","year":"2017","unstructured":"Schapira, A. H. V., Chaudhuri, K. R. & Jenner, P. Non-motor features of Parkinson disease. Nat. Rev. Neurosci. 18, 435\u2013450 (2017).","journal-title":"Nat. Rev. Neurosci."},{"key":"219_CR12","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1111\/ene.13919","volume":"26","author":"R Durcan","year":"2019","unstructured":"Durcan, R. et al. Prevalence and duration of non-motor symptoms in prodromal Parkinson\u2019s disease. Eur J Neurol 26, 979\u2013985 (2019).","journal-title":"Eur J Neurol"},{"key":"219_CR13","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.parkreldis.2019.05.013","volume":"64","author":"A Schrag","year":"2019","unstructured":"Schrag, A. et al. Heterogeneity in progression of prodromal features in Parkinson\u2019s disease. Parkinson. Relat. Disord. 64, 275\u2013279 (2019).","journal-title":"Parkinson. Relat. Disord."},{"key":"219_CR14","doi-asserted-by":"publisher","unstructured":"Postuma, R. B. & Berg, D. Prodromal Parkinson\u2019s disease: the decade past, the decade to come. Mov. Disord. https:\/\/doi.org\/10.1002\/mds.27670 (2019).","DOI":"10.1002\/mds.27670"},{"key":"219_CR15","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1002\/mds.26431","volume":"30","author":"D Berg","year":"2015","unstructured":"Berg, D. et al. MDS research criteria for prodromal Parkinson\u2019s disease. Mov. Disord. 30, 1600\u20131611 (2015).","journal-title":"Mov. Disord."},{"key":"219_CR16","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1111\/j.1468-1331.2012.03798.x","volume":"20","author":"D Berg","year":"2013","unstructured":"Berg, D. et al. The PRIPS study: screening battery for subjects at risk for Parkinson\u2019s disease. Eur. J. Neurol. 20, 102\u2013108 (2013).","journal-title":"Eur. J. Neurol."},{"key":"219_CR17","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1002\/mds.27281","volume":"33","author":"P Mahlknecht","year":"2018","unstructured":"Mahlknecht, P. et al. Performance of the Movement Disorders Society criteria for prodromal Parkinson\u2019s disease: a population-based 10-year study. Mov. Disord. 33, 405\u2013413 (2018).","journal-title":"Mov. Disord."},{"issue":"Suppl 1","key":"219_CR18","doi-asserted-by":"publisher","first-page":"S199","DOI":"10.1016\/S1353-8020(11)70062-1","volume":"18","author":"GW Ross","year":"2012","unstructured":"Ross, G. W., Abbott, R. D., Petrovitch, H., Tanner, C. M. & White, L. R. Pre-motor features of Parkinson\u2019s disease: the Honolulu-Asia Aging Study experience. Parkinson. Relat. Disord. 18(Suppl 1), S199\u2013202 (2012).","journal-title":"Parkinson. Relat. Disord."},{"key":"219_CR19","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1002\/ana.23687","volume":"72","author":"AJ Noyce","year":"2012","unstructured":"Noyce, A. J. et al. Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Ann. Neurol. 72, 893\u2013901 (2012).","journal-title":"Ann. Neurol."},{"key":"219_CR20","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27802","author":"S Heinzel","year":"2019","unstructured":"Heinzel, S. et al. Update of the MDS research criteria for prodromal Parkinson\u2019s disease. Mov. Disord. https:\/\/doi.org\/10.1002\/mds.27802 (2019).","journal-title":"Mov. Disord."},{"key":"219_CR21","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.1212\/WNL.0000000000001684","volume":"84","author":"H Gustafsson","year":"2015","unstructured":"Gustafsson, H., Nordstr\u00f6m, A. & Nordstr\u00f6m, P. Depression and subsequent risk of Parkinson disease: a nationwide cohort study. Neurology 84, 2422\u20132429 (2015).","journal-title":"Neurology"},{"key":"219_CR22","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/ana.21291","volume":"63","author":"GW Ross","year":"2008","unstructured":"Ross, G. W. et al. Association of olfactory dysfunction with risk for future Parkinson\u2019s disease. Ann. Neurol. 63, 167\u2013173 (2008).","journal-title":"Ann. Neurol."},{"key":"219_CR23","doi-asserted-by":"publisher","first-page":"3673","DOI":"10.1007\/s00415-020-10048-6","volume":"267","author":"P Marrero-Gonz\u00e1lez","year":"2020","unstructured":"Marrero-Gonz\u00e1lez, P. et al. Prodromal Parkinson disease in patients with idiopathic hyposmia. J. Neurol. 267, 3673\u20133682 (2020).","journal-title":"J. Neurol."},{"key":"219_CR24","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1111\/ene.13082","volume":"23","author":"P Stirpe","year":"2016","unstructured":"Stirpe, P., Hoffman, M., Badiali, D. & Colosimo, C. Constipation: an emerging risk factor for Parkinson\u2019s disease? Eur. J. Neurol. 23, 1606\u20131613 (2016).","journal-title":"Eur. J. Neurol."},{"key":"219_CR25","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.parkreldis.2020.10.003","volume":"81","author":"M Moscovich","year":"2020","unstructured":"Moscovich, M. et al. How specific are non-motor symptoms in the prodrome of Parkinson\u2019s disease compared to other movement disorders? Parkinson. Relat. Disord. 81, 213\u2013218 (2020).","journal-title":"Parkinson. Relat. Disord."},{"key":"219_CR26","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.1093\/brain\/aws093","volume":"135","author":"RB Postuma","year":"2012","unstructured":"Postuma, R. B., Lang, A. E., Gagnon, J. F., Pelletier, A. & Montplaisir, J. Y. How does parkinsonism start? Prodromal parkinsonism motor changes in idiopathic REM sleep behaviour disorder. Brain 135, 1860\u20131870 (2012).","journal-title":"Brain"},{"key":"219_CR27","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1002\/mds.26674","volume":"31","author":"P Mahlknecht","year":"2016","unstructured":"Mahlknecht, P. et al. Prodromal Parkinson\u2019s disease as defined per MDS research criteria in the general elderly community. Mov. Disord. 31, 1405\u20131408 (2016).","journal-title":"Mov. Disord."},{"key":"219_CR28","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1002\/ana.20228","volume":"56","author":"WA Rocca","year":"2004","unstructured":"Rocca, W. A. et al. Familial aggregation of Parkinson\u2019s disease: The Mayo Clinic family study. Ann. Neurol. 56, 495\u2013502 (2004).","journal-title":"Ann. Neurol."},{"key":"219_CR29","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1002\/mds.22067","volume":"23","author":"EL Thacker","year":"2008","unstructured":"Thacker, E. L. & Ascherio, A. Familial aggregation of Parkinson\u2019s disease: a meta-analysis. Mov. Disord. 23, 1174\u20131183 (2008).","journal-title":"Mov. Disord."},{"key":"219_CR30","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1002\/mds.26132","volume":"30","author":"MS Petersen","year":"2015","unstructured":"Petersen, M. S., Bech, S., Nosova, E., Aasly, J. & Farrer, M. J. Familial aggregation of Parkinson\u2019s disease in the Faroe Islands. Mov. Disord. 30, 538\u2013544 (2015).","journal-title":"Mov. Disord."},{"key":"219_CR31","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1002\/mds.26166","volume":"30","author":"MJ Barrett","year":"2015","unstructured":"Barrett, M. J., Hac, N. E., Yan, G., Harrison, M. B. & Wooten, G. F. Relationship of age of onset and family history in Parkinson disease. Mov. Disord. 30, 733\u2013735 (2015).","journal-title":"Mov. Disord."},{"key":"219_CR32","doi-asserted-by":"publisher","first-page":"e0152841","DOI":"10.1371\/journal.pone.0152841","volume":"11","author":"B Liu","year":"2016","unstructured":"Liu, B., Chen, H., Fang, F., Tillander, A. & Wirdefeldt, K. Early-life factors and risk of Parkinson\u2019s disease: A Register-Based Cohort Study. PLoS ONE 11, e0152841 (2016).","journal-title":"PLoS ONE"},{"key":"219_CR33","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.parkreldis.2018.03.021","volume":"52","author":"JB Liu","year":"2018","unstructured":"Liu, J. B. et al. Investigation of non-motor symptoms in first-degree relatives of patients with Parkinson\u2019s disease. Parkinson. Relat. Disord. 52, 62\u201368 (2018).","journal-title":"Parkinson. Relat. Disord."},{"key":"219_CR34","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1001\/archpsyc.64.12.1385","volume":"64","author":"G Arabia","year":"2007","unstructured":"Arabia, G. et al. Increased risk of depressive and anxiety disorders in relatives of patients with Parkinson disease. Arch. Gen. Psychiatry 64, 1385\u20131392 (2007).","journal-title":"Arch. Gen. Psychiatry"},{"key":"219_CR35","doi-asserted-by":"publisher","unstructured":"Pirazzini, C. et al. A Geroscience approach for Parkinson\u2019s Disease: conceptual framework and design of PROPAG-AGEING project. Mech. Ageing Dev. 111426, https:\/\/doi.org\/10.1016\/j.mad.2020.111426 (2020).","DOI":"10.1016\/j.mad.2020.111426"},{"key":"219_CR36","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1212\/WNL.0b013e3182a6cbd5","volume":"81","author":"B Mollenhauer","year":"2013","unstructured":"Mollenhauer, B. et al. Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort. Neurology 81, 1226\u20131234 (2013).","journal-title":"Neurology"},{"key":"219_CR37","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1016\/j.parkreldis.2015.10.006","volume":"21","author":"K Horvath","year":"2015","unstructured":"Horvath, K. et al. Minimal clinically important difference on the Motor Examination part of MDS-UPDRS. Parkinson. Relat. Disord. 21, 1421\u20131426 (2015).","journal-title":"Parkinson. Relat. Disord."},{"key":"219_CR38","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1002\/mds.26960","volume":"32","author":"K Horvath","year":"2017","unstructured":"Horvath, K. et al. Minimal clinically important differences for the experiences of daily living parts of movement disorder society-sponsored unified Parkinson\u2019s disease rating scale. Mov. Disord. 32, 789\u2013793 (2017).","journal-title":"Mov. Disord."},{"key":"219_CR39","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1159\/000444021","volume":"46","author":"MR Keezer","year":"2016","unstructured":"Keezer, M. R., Wolfson, C. & Postuma, R. B. Age, gender, comorbidity, and the MDS-UPDRS: Results from a Population-Based Study. Neuroepidemiology 46, 222\u2013227 (2016).","journal-title":"Neuroepidemiology"},{"key":"219_CR40","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1136\/jnnp-2016-314524","volume":"88","author":"AJ Noyce","year":"2017","unstructured":"Noyce, A. J. et al. Subtle motor disturbances in PREDICT-PD participants. J. Neurol. Neurosurg. Psychiatry 88, 212\u2013217 (2017).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"219_CR41","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1002\/mds.27135","volume":"32","author":"S Fengler","year":"2017","unstructured":"Fengler, S. et al. Cognitive changes in prodromal Parkinson\u2019s disease: a review. Mov. Disord. 32, 1655\u20131666 (2017).","journal-title":"Mov. Disord."},{"key":"219_CR42","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.jns.2016.10.007","volume":"371","author":"C Pausch","year":"2016","unstructured":"Pausch, C. et al. Neuropsychological impairment in prodromal Parkinson\u2019s disease. J. Neurol. Sci. 371, 117\u2013120 (2016).","journal-title":"J. Neurol. Sci."},{"key":"219_CR43","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1001\/jamaneurol.2017.2248","volume":"74","author":"SKL Darweesh","year":"2017","unstructured":"Darweesh, S. K. L. et al. Association between poor cognitive functioning and risk of incident Parkinsonism: The Rotterdam Study. JAMA Neurol. 74, 1431\u20131438 (2017).","journal-title":"JAMA Neurol."},{"key":"219_CR44","doi-asserted-by":"publisher","first-page":"e2261","DOI":"10.1212\/WNL.0000000000007453","volume":"92","author":"A Bougea","year":"2019","unstructured":"Bougea, A. et al. Higher probability of prodromal Parkinson disease is related to lower cognitive performance. Neurology 92, e2261\u2013e2272 (2019).","journal-title":"Neurology"},{"key":"219_CR45","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1002\/mdc3.12591","volume":"5","author":"C Halsband","year":"2018","unstructured":"Halsband, C., Zapf, A., Sixel-Doring, F., Trenkwalder, C. & Mollenhauer, B. The REM sleep behavior disorder screening questionnaire is not valid in de novo Parkinson\u2019s disease. Mov. Disord. Clin. Pract. 5, 171\u2013176 (2018).","journal-title":"Mov. Disord. Clin. Pract."},{"key":"219_CR46","doi-asserted-by":"publisher","first-page":"2386","DOI":"10.1002\/mds.21740","volume":"22","author":"K Stiasny-Kolster","year":"2007","unstructured":"Stiasny-Kolster, K. et al. The REM sleep behavior disorder screening questionnaire-a new diagnostic instrument. Mov. Disord. 22, 2386\u20132393 (2007).","journal-title":"Mov. Disord."},{"key":"219_CR47","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/mdc3.12448","volume":"4","author":"A Stefani","year":"2017","unstructured":"Stefani, A. et al. Consistency of \u201cProbable RBD\u201d diagnosis with the RBD screening questionnaire: A Follow-up Study. Mov. Disord. Clin. Pract. 4, 403\u2013405 (2017).","journal-title":"Mov. Disord. Clin. Pract."},{"key":"219_CR48","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1111\/ene.12382","volume":"21","author":"A Gaenslen","year":"2014","unstructured":"Gaenslen, A. et al. Prodromal features for Parkinson\u2019s disease-baseline data from the TREND study. Eur. J. Neurol. 21, 766\u2013772 (2014).","journal-title":"Eur. J. Neurol."},{"key":"219_CR49","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1002\/mds.28145","volume":"35","author":"N Giagkou","year":"2020","unstructured":"Giagkou, N. et al. A prospective validation of the updated movement disorders society research criteria for prodromal Parkinson\u2019s disease. Mov. Disord. 35, 1802\u20131809 (2020).","journal-title":"Mov. Disord."},{"key":"219_CR50","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1002\/mds.27035","volume":"32","author":"A Pilotto","year":"2017","unstructured":"Pilotto, A. et al. Application of the movement disorder society prodromal Parkinson\u2019s disease research criteria in 2 independent prospective cohorts. Mov. Disord. 32, 1025\u20131034 (2017).","journal-title":"Mov. Disord."},{"key":"219_CR51","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1001\/archneur.1993.00540020018011","volume":"50","author":"AJ Hughes","year":"1993","unstructured":"Hughes, A. J., Daniel, S. E., Blankson, S. & Lees, A. J. A clinicopathologic study of 100 cases of Parkinson\u2019s disease. Arch. Neurol. 50, 140\u2013148 (1993).","journal-title":"Arch. Neurol."},{"key":"219_CR52","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1002\/mds.22340","volume":"23","author":"CG Goetz","year":"2008","unstructured":"Goetz, C. G. et al. Movement disorder Society-sponsored revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov. Disord. 23, 2129\u20132170 (2008).","journal-title":"Mov. Disord."},{"key":"219_CR53","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1002\/mds.20844","volume":"21","author":"KR Chaudhuri","year":"2006","unstructured":"Chaudhuri, K. R. et al. International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson\u2019s disease: the NMSQuest study. Mov. Disord. 21, 916\u2013923 (2006).","journal-title":"Mov. Disord."},{"key":"219_CR54","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1002\/mds.22260","volume":"24","author":"ML Evatt","year":"2009","unstructured":"Evatt, M. L. et al. Dysautonomia rating scales in Parkinson\u2019s disease: sialorrhea, dysphagia, and constipation-critique and recommendations by movement disorders task force on rating scales for Parkinson\u2019s disease. Mov. Disord. 24, 635\u2013646 (2009).","journal-title":"Mov. Disord."},{"key":"219_CR55","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1053\/j.gastro.2005.11.061","volume":"130","author":"GF Longstreth","year":"2006","unstructured":"Longstreth, G. F. et al. Functional bowel disorders. Gastroenterology 130, 1480\u20131491 (2006).","journal-title":"Gastroenterology"},{"key":"219_CR56","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","volume":"53","author":"ZS Nasreddine","year":"2005","unstructured":"Nasreddine, Z. S. et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J. Am. Geriatr. Soc. 53, 695\u2013699 (2005).","journal-title":"J. Am. Geriatr. Soc."},{"key":"219_CR57","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1055\/s-0033-1364034","volume":"93","author":"BA Stuck","year":"2014","unstructured":"Stuck, B. A. et al. Position paper \u201cChemosensory testing for expert opinion in smell disorders\u201d. Laryngorhinootologie 93, 327\u2013329 (2014).","journal-title":"Laryngorhinootologie"},{"key":"219_CR58","unstructured":"Berry, R. et al. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications, Version 2.6 (American Academy of Sleep Medicine, Darien, IL, 2020)."},{"key":"219_CR59","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1212\/WNL.0b013e31822e560e","volume":"77","author":"F Sixel-D\u00f6ring","year":"2011","unstructured":"Sixel-D\u00f6ring, F., Trautmann, E., Mollenhauer, B. & Trenkwalder, C. Associated factors for REM sleep behavior disorder in Parkinson disease. Neurology 77, 1048\u20131054 (2011).","journal-title":"Neurology"}],"container-title":["npj Parkinson's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00219-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00219-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00219-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T21:56:23Z","timestamp":1670018183000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00219-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,7]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["219"],"URL":"https:\/\/doi.org\/10.1038\/s41531-021-00219-1","relation":{},"ISSN":["2373-8057"],"issn-type":[{"value":"2373-8057","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,7]]},"assertion":[{"value":"6 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"L.B., S.S., S.J., S.R.S., C.H., and A.A.-G. have received salaries from the EU Horizon 2020 research and innovation program under Grant Agreement No. 634821. K.P.B., P.M., and F.P. have received research funds from the EU Horizon 2020 research and innovation program under Grant Agreement No. 634821. B.M. has received research funds from the European Union. C.T. has received research funds from the Michael J. Fox Foundation and the EU Horizon 2020 research and innovation program under Grant Agreement No. 634821. L.S., P.G.-G., G.C.-B., F.S.-D., C.Z., C.P., P.G., M.G.B., P.C., and C.F. declares no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"78"}}