{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T19:51:33Z","timestamp":1772135493066,"version":"3.50.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","award":["G-1606"],"award-info":[{"award-number":["G-1606"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","award":["G-1606"],"award-info":[{"award-number":["G-1606"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","award":["J-1101"],"award-info":[{"award-number":["J-1101"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","award":["J-1101"],"award-info":[{"award-number":["J-1101"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","award":["G-1606"],"award-info":[{"award-number":["G-1606"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","award":["G-1606"],"award-info":[{"award-number":["G-1606"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","award":["G-1606"],"award-info":[{"award-number":["G-1606"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Parkinson\u2019s UK"},{"name":"Parkinson\u2019s UK"},{"name":"Parkinson\u2019s UK"},{"name":"Parkinson\u2019s UK"},{"name":"Parkinson\u2019s UK"},{"name":"Parkinson\u2019s UK"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Parkinsons Dis."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Olfactory loss, motor impairment, anxiety\/depression, and REM-sleep behaviour disorder (RBD) are prodromal Parkinson\u2019s disease (PD) features. PD risk prediction models typically dichotomize test results and apply likelihood ratios (LRs) to scores above and below cut-offs. We investigate whether LRs for specific test values could enhance classification between PD and controls. PD patient data on smell (UPSIT), possible RBD (RBD Screening Questionnaire), and anxiety\/depression (LADS) were taken from the Tracking Parkinson\u2019s study (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091046). For motor impairment (BRAIN test) in PD cases, published data were supplemented (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200987). Control data (HADS for anxiety\/depression) were taken from the PREDICT-PD pilot study (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091314). UPSIT, RBDSQ, and anxiety\/depression data were analysed using logistic regression to determine which items were associated with PD. Gaussian distributions were fitted to BRAIN test scores. LRs were calculated from logistic regression models or score distributions. False-positive rates (FPRs) for specified detection rates (DRs) were calculated. Sixteen odours were associated with PD; LRs for this set ranged from 0.005 to 5511. Six RBDSQ and seven anxiety\/depression questions were associated with PD; LRs ranged from 0.35 to 69 and from 0.002 to 402, respectively. BRAIN test LRs ranged from 0.16 to 1311. For a 70% DR, the FPR was 2.4% for the 16 odours, 4.6% for anxiety\/depression, 16.0% for the BRAIN test, and 20.0% for the RBDSQ. Specific selections of (prodromal) PD marker features rather than dichotomized marker test results optimize PD classification. Such optimized classification models could improve the ability of algorithms to detect prodromal PD; however, prospective studies are needed to investigate their value for PD-prediction models.\n                  <\/jats:p>","DOI":"10.1038\/s41531-021-00226-2","type":"journal-article","created":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T08:05:45Z","timestamp":1634025945000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Optimising classification of Parkinson\u2019s disease based on motor, olfactory, neuropsychiatric and sleep features"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3088-8616","authenticated-orcid":false,"given":"Jonathan P.","family":"Bestwick","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen D.","family":"Auger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9872-6680","authenticated-orcid":false,"given":"Anette E.","family":"Schrag","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald G.","family":"Grosset","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Kanavou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin","family":"Giovannoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-4385","authenticated-orcid":false,"given":"Andrew J.","family":"Lees","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7420-7512","authenticated-orcid":false,"given":"Jack","family":"Cuzick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3027-5497","authenticated-orcid":false,"given":"Alastair J.","family":"Noyce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,9,24]]},"reference":[{"key":"226_CR1","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1212\/01.wnl.0000341769.50075.bb","volume":"72","author":"JA Driver","year":"2009","unstructured":"Driver, J. A. et al. Incidence and remaining lifetime risk of Parkinson disease in advanced age. Neurology 72, 432\u2013438 (2009).","journal-title":"Neurology"},{"key":"226_CR2","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.1093\/brain\/114.5.2283","volume":"114","author":"JM Fearnley","year":"1991","unstructured":"Fearnley, J. M. & Lees, A. J. Ageing and Parkinson\u2019s disease: substantia nigra regional selectivity. Brain 114, 2283\u20132301 (1991).","journal-title":"Brain"},{"key":"226_CR3","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1002\/mds.25017","volume":"27","author":"JR Streffer","year":"2012","unstructured":"Streffer, J. R. et al. Prerequisites to launch neuroprotective trials in Parkinson\u2019s disease: an industry perspective. Mov. Disord. 27, 651\u2013655 (2012).","journal-title":"Mov. Disord."},{"key":"226_CR4","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1136\/jnnp-2013-305420","volume":"85","author":"AJ Noyce","year":"2014","unstructured":"Noyce, A. J. et al. PREDICT-PD: identifying risk of Parkinson\u2019s disease in the community: methods and baseline results. J. Neruol. Neurosurg. Psychiatry 85, 31\u201337 (2014).","journal-title":"J. Neruol. Neurosurg. Psychiatry"},{"key":"226_CR5","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":"226_CR6","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":"226_CR7","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1002\/mds.27802","volume":"34","author":"S Heinzel","year":"2019","unstructured":"Heinzel, S. et al. MDS task force on the definition of Parkinson\u2019s disease. Update of the MDS research criteria for prodromal Parkinson\u2019s disease. Mov. Disord. 34, 1464\u20131470 (2019).","journal-title":"Mov. Disord."},{"key":"226_CR8","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1002\/mds.27616","volume":"34","author":"A Schrag","year":"2019","unstructured":"Schrag, A., Anastasiou, Z., Ambler, G., Noyce, A. & Walters, K. Predicting diagnosis of Parkinson\u2019s disease: a risk algorithm based on primary care presentations. Mov. Disord. 34, 480\u2013486 (2019).","journal-title":"Mov. Disord."},{"key":"226_CR9","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1016\/S1474-4422(15)00178-7","volume":"14","author":"MA Nalls","year":"2015","unstructured":"Nalls, M. A. et al. Diagnosis of Parkinson\u2019s disease on the basis of clinical and genetic classification: a population-based modelling study. Lancet Neurol. 14, 1002\u20131009 (2015).","journal-title":"Lancet Neurol."},{"key":"226_CR10","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-323646","author":"BM Jacobs","year":"2020","unstructured":"Jacobs, B. M. et al. Parkinson\u2019s disease determinants, prediction and gene-environment interactions in the UK Biobank. J. Neurol. Neurosurg. Psychiatry https:\/\/doi.org\/10.1136\/jnnp-2020-323646 (2020).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"226_CR11","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1136\/bmj.332.7549.1080","volume":"332","author":"DG Altman","year":"2006","unstructured":"Altman, D. G. & Royston, P. The cost of dichotomising continuous variables. BMJ 332, 1080 (2006).","journal-title":"BMJ"},{"key":"226_CR12","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1002\/mds.26898","volume":"32","author":"AJ Noyce","year":"2017","unstructured":"Noyce, A. J. et al. PREDICT-PD: an online approach to prospectively identify risk indicators of Parkinson\u2019s disease. Mov. Disord. 32, 219\u2013226 (2017).","journal-title":"Mov. Disord."},{"key":"226_CR13","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 behaviour disorder screening questionnaire \u2013 a new diagnostic instrument. Mov. Disord. 22, 2386\u20132393 (2007).","journal-title":"Mov. Disord."},{"key":"226_CR14","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/0031-9384(84)90269-5","volume":"32","author":"RL Doty","year":"1984","unstructured":"Doty, R. L., Shaman, P. & Dann, M. Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol. Behav. 32, 489\u2013502 (1984).","journal-title":"Physiol. Behav."},{"key":"226_CR15","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1007\/s00415-019-09340-x","volume":"226","author":"T Joseph","year":"2019","unstructured":"Joseph, T. et al. Screening performance of abbreviated versions of the UPSIT smell test. J. Neurol. 226, 1897\u20131906 (2019).","journal-title":"J. Neurol."},{"key":"226_CR16","doi-asserted-by":"publisher","first-page":"e96260","DOI":"10.1371\/journal.pone.0096260","volume":"9","author":"AJ Noyce","year":"2014","unstructured":"Noyce, A. J. et al. Bradykinesia-Akinesia Incoordination Test: validating an online keyboard test of upper limb function. PLoS ONE 9, e96260 (2014).","journal-title":"PLoS ONE"},{"key":"226_CR17","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1111\/j.1600-0447.1983.tb09716.x","volume":"67","author":"A Zigmond","year":"1983","unstructured":"Zigmond, A. & Snaith, R. P. The hospital anxiety and depression scale. Acta Psychiatr. Scand. 67, 361\u2013370 (1983).","journal-title":"Acta Psychiatr. Scand."},{"key":"226_CR18","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1002\/mdc3.12928","volume":"21","author":"SD Auger","year":"2020","unstructured":"Auger, S. D. et al. Testing shortened versions of smell tests to screen for hyposmia in Parkinson\u2019s disease. Mov. Disord. Clin. Pract. 21, 394\u2013398 (2020).","journal-title":"Mov. Disord. Clin. Pract."},{"key":"226_CR19","first-page":"56","volume":"10","author":"NJ Wald","year":"2003","unstructured":"Wald, N. J. et al. First and second trimester antenatal screening for Down\u2019s syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). J. Med. Screen. 10, 56\u2013104 (2003).","journal-title":"J. Med. Screen."},{"key":"226_CR20","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.parkreldis.2016.09.023","volume":"33","author":"M Lawton","year":"2016","unstructured":"Lawton, M. et al. Equating score of the University of Pennsylvania Smell Identification Test and Sniffin\u2019 Sticks test in patients with Parkinson\u2019s disease. Parkinsonism Relat. Disord. 33, 96\u2013101 (2016).","journal-title":"Parkinsonism Relat. Disord."},{"key":"226_CR21","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1001\/archneur.60.4.545","volume":"60","author":"KL Double","year":"2003","unstructured":"Double, K. L. et al. Identifying the pattern of olfactory deficits in Parkinson disease using the Brief Smell Identification Test. Arch. Neurol. 60, 545\u2013549 (2003).","journal-title":"Arch. Neurol."},{"key":"226_CR22","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/0140-6736(93)93027-X","volume":"341","author":"CH Hawkes","year":"1993","unstructured":"Hawkes, C. H. & Shephard, B. C. Selective anosmia in Parkinson\u2019s disease? Lancet 341, 435\u2013436 (1993).","journal-title":"Lancet"},{"key":"226_CR23","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1007\/s00415-006-0284-y","volume":"254","author":"NI Bohnen","year":"2007","unstructured":"Bohnen, N. I. et al. Selective hyposmia and nigrostriatal dopaminergic denervation in Parkinson\u2019s disease. J. Neurol. 254, 84\u201390 (2007).","journal-title":"J. Neurol."},{"key":"226_CR24","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/s41531-017-0039-8","volume":"4","author":"JF Morely","year":"2018","unstructured":"Morely, J. F. et al. Optimizing olfactory testing for the diagnosis of Parkinson\u2019s disease:item analysis of the university of Pennsylvania smell identification test. npj Parkinsons Dis. 4, 2, https:\/\/doi.org\/10.1038\/s41531-017-0039-8 (2018).","journal-title":"npj Parkinsons Dis."},{"key":"226_CR25","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s10994-009-5119-5","volume":"77","author":"DJ Hand","year":"2009","unstructured":"Hand, D. J. Measuring classifier performance: a coherent alternative to the area under the ROC curve. Mach. Learn 77, 103\u2013123 (2009).","journal-title":"Mach. Learn"},{"key":"226_CR26","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1177\/0969141313517497","volume":"21","author":"NJ Wald","year":"2014","unstructured":"Wald, N. J. & Bestwick, J. P. Is the area under an ROC curve a valid measure of the performance of a screening or diagnostic test? J. Med. Screen. 21, 51\u201356 (2014).","journal-title":"J. Med. Screen."},{"key":"226_CR27","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1177\/0969141313484904","volume":"20","author":"JP Bestwick","year":"2013","unstructured":"Bestwick, J. P., Huttly, W. J. & Wald, N. J. Detection of trisomy 18 and trisomy 13 using first and second trimester Down\u2019s syndrome screening markers. J. Med. Screen. 20, 57\u201365 (2013). Corrigendum in J. Med. Screen, 22, 52\u20134 (2015).","journal-title":"J. Med. Screen."},{"key":"226_CR28","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1212\/WNL.38.8.1237","volume":"38","author":"RL Doty","year":"1988","unstructured":"Doty, R. L., Deems, D. A. & Stellar, S. Olfactory function in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration. Neurology 38, 1237\u20131244 (1988).","journal-title":"Neurology"},{"key":"226_CR29","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13195-019-0494-z","volume":"11","author":"M Yahiaoui-Doktor","year":"2019","unstructured":"Yahiaoui-Doktor, M. et al. Olfactory function is associated with cognitive performance: results from the population-based LIFE-Adult-Study. Alzheimers Res. Ther. 11, 43 (2019).","journal-title":"Alzheimers Res. Ther."},{"key":"226_CR30","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41531-021-00176-9","volume":"7","author":"JP Bestwick","year":"2021","unstructured":"Bestwick, J. P. et al. Improving estimation of Parkinson\u2019s disease risk \u2013 the enhanced PREDICT-PD algorithm. npj Parkinsons Dis. 7, 33 (2021).","journal-title":"npj Parkinsons Dis."},{"key":"226_CR31","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/S0895-4356(01)00341-9","volume":"54","author":"EW Steyerberg","year":"2001","unstructured":"Steyerberg, E. W. et al. Internal validation of predictive models: efficiency of some procedures for logistic regression analysis. J. Clin. Epidemiol. 54, 774\u2013781 (2001).","journal-title":"J. Clin. Epidemiol."},{"key":"226_CR32","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.jclinepi.2015.04.005","volume":"69","author":"EW Steyerberg","year":"2016","unstructured":"Steyerberg, E. W. & Harrell, F. E. Jr Prediction models need appropriate internal, internal-external, and external validation. J. Clin. Epidemiol. 69, 245\u2013247 (2016).","journal-title":"J. Clin. Epidemiol."},{"key":"226_CR33","doi-asserted-by":"publisher","first-page":"947","DOI":"10.3233\/JPD-150662","volume":"5","author":"N Malek","year":"2015","unstructured":"Malek, N. et al. Tracking Parkinson\u2019s: study design and baseline patient. Data. J. Parkinsons Dis. 5, 947\u2013959 (2015).","journal-title":"Data. J. Parkinsons Dis."},{"key":"226_CR34","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1002\/mdc3.12798","volume":"6","author":"H Hasan","year":"2019","unstructured":"Hasan, H. et al. The Bradykinesia Akinesia INcorodination (BRAIN) Tap Test: capturing the sequence effect. Mov. Disord. 6, 462\u2013469 (2019).","journal-title":"Mov. Disord."},{"key":"226_CR35","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1258\/0969141054855283","volume":"12","author":"JK Morris","year":"2005","unstructured":"Morris, J. K. & Wald, N. J. Graphical presentation of distributions of risk in screening. J. Med. Screen. 12, 155\u2013160 (2005).","journal-title":"J. Med. Screen."},{"key":"226_CR36","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1192\/bjp.128.2.156","volume":"128","author":"RP Snaith","year":"1976","unstructured":"Snaith, R. P., Bridge, G. W. K. & Hamilton, M. The Leeds scales for the self-assessment of anxiety and depression. Brit. J. Psychiatr. 128, 156\u2013165 (1976).","journal-title":"Brit. J. Psychiatr."}],"container-title":["npj Parkinson's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00226-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00226-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00226-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T16:57:12Z","timestamp":1670000232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00226-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,24]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["226"],"URL":"https:\/\/doi.org\/10.1038\/s41531-021-00226-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.03.03.20023994","asserted-by":"object"}]},"ISSN":["2373-8057"],"issn-type":[{"value":"2373-8057","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,24]]},"assertion":[{"value":"10 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A.J.N. is funded by the Barts Charity. A.N. reports additional grants from Parkinson\u2019s UK, Virginia Keiley benefaction, UCL-Movement Disorders Centre, grants and non-financial support from GE Healthcare, and personal fees from LEK, Guidepoint, Profile, Roche, Biogen Bial, and Britannia, outside the submitted work. A.E.S. is employed by University College London and NHS National Institute for Health Research UCL Biomedical Research Centre. She has received grants from the European Commission, Parkinson\u2019s UK, GE Healthcare, Economic and Social Research Council (ESRC), International Parkinson\u2019s and Movement Disorders Society, University College London, National Institute of Health (NIHR), National Institute for Health Research ULCH Biomedical Research Centre; honoraria from Health Advances; advisory board fees from GE Healthcare, Roche, Biogen, Bial; and royalties from Oxford University Press for Rating Scales in PD, University College London Business. A.J.L. is funded by the Reta Lila Weston Institute of Neurological Studies, University College London, Institute of Neurology, and reports consultancies from Britannia Pharmaceuticals and BIAL Portela. He also reports grants and\/or research support from the Frances and Renee Hock Fund, and honoraria from Britannia, Profle Pharma, UCB, Roche, BIAL, STADA Nordic, Nordiclnfu Care, and NeuroDerm. S.D.A. is employed by Health Education England. D.G.G. is employed by NHS Greater Glasgow and Clyde. He has current grant funding from Parkinson\u2019s UK. He has personal fees from Merz Pharma, Vectura plc, and the Glasgow Memory Clinic. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"87"}}