{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:33:13Z","timestamp":1790674393632,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2010,7,9]],"date-time":"2010-07-09T00:00:00Z","timestamp":1278633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes for Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["NS40068"],"award-info":[{"award-number":["NS40068"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005725","name":"CHDI Foundation, Inc","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"PREDICT-HD"},{"name":"National Research Roster for Huntington Disease Patients and Families"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2010,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The basic aim of this study was to evaluate the current accepted standard clinical endpoint for the earliest\u2010studied HD participants likely to be recruited into clinical trials. As the advent of genetic testing for HD, it is possible to identify gene carriers before the diagnosis of disease, which opens up the possibility of clinical trials of disease\u2010modifying treatments in clinically asymptomatic persons. Current accepted standard clinical endpoints were examined as part of a multinational, 32\u2010site, longitudinal, observational study of 786 research participants currently in the HD prodrome (gene\u2010positive but not clinically diagnosed). Clinical signs and symptoms were used to prospectively predict functional loss as assessed by current accepted standard endpoints over 8 years of follow\u2010up. Functional capacity measures were not sensitive for HD in the prodrome; over 88% scored at ceiling. Prospective evaluation revealed that the first functional loss was in their accustomed work. In a survival analysis, motor, cognitive, and psychiatric measures were all predictors of job change. To our knowledge, this is the first prospective study ever conducted on the emergence of functional loss secondary to brain disease. We conclude that future clinical trials designed for very early disease will require the development of new and more sensitive measures of real\u2010life function. \u00a9 2010 Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.23337","type":"journal-article","created":{"date-parts":[[2010,7,12]],"date-time":"2010-07-12T01:43:42Z","timestamp":1278899022000},"page":"2595-2603","source":"Crossref","is-referenced-by-count":67,"title":["Challenges assessing clinical endpoints in early Huntington disease"],"prefix":"10.1002","volume":"25","author":[{"given":"Jane S.","family":"Paulsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiachi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Duff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Nance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh","family":"Beglinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Moser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet K.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Langbehn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"van Kammen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the PREDICT\u2010HD Investigators of the Huntington Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,11,10]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2008.01.008"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2007.128728"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000261918.90053.96"},{"key":"e_1_2_8_5_2","first-page":"1715","article-title":"fMRI biomarker of early neuronal dysfunction in presymptomatic Huntington's disease","volume":"25","author":"Paulsen JS","year":"2004","journal-title":"AJNR"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.6.883"},{"key":"e_1_2_8_7_2","volume-title":"The importance of patient\u2010reported outcomes\u2014it's all about the patients","author":"Bren L","year":"2006"},{"key":"e_1_2_8_8_2","volume-title":"Biomarkers and surrogate endpoints: clinical research and applications","author":"Downing GJ","year":"2000"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000275235.43506.d2"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001504-200411000-00003"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.67.9_suppl_3.S12"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1602\/neurorx.1.2.273"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.66.10_suppl_4.S50"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10566"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.29.1.1"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70170-X"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.7.991"},{"issue":"2","key":"e_1_2_8_18_2","first-page":"136","article-title":"Unified Huntington's Disease Rating Scale: reliability and consistency","volume":"11","year":"1996","journal-title":"Huntington Study Group. Mov Disord"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870110204"},{"key":"e_1_2_8_20_2","volume-title":"Beck depression inventory\u2010II: Manual","author":"Beck AT","year":"1996"},{"key":"e_1_2_8_21_2","volume-title":"Symbol digit modalities test manual","author":"Smith A","year":"1973"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2004.00241.x"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30992"},{"key":"e_1_2_8_24_2","volume-title":"Applied mixed models in medicine","author":"Brown H","year":"1999"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1972.tb00899.x"},{"key":"e_1_2_8_26_2","volume-title":"Analysis of survival data","author":"Cox DR","year":"1984"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471722146"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.74.1.120"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.2.452"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2010.04.030"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.13.3.342"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.nmd.0000106004.67587.57"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.71.3.310"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.17.4.496"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.162.4.725"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmds.23337","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmds.23337","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.23337","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T12:16:43Z","timestamp":1760962603000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.23337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11,10]]},"references-count":34,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2010,11,15]]}},"alternative-id":["10.1002\/mds.23337"],"URL":"https:\/\/doi.org\/10.1002\/mds.23337","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11,10]]}}}