{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:26:52Z","timestamp":1791502012631,"version":"4.3.4"},"reference-count":66,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T00:00:00Z","timestamp":1457913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013322","name":"European Federation of Pharmaceutical Industries and Associations","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Alzheimer's disease (AD) is among the most significant health care burdens. Disappointing results from clinical trials in late\u2010stage AD persons combined with hopeful results from trials in persons with early\u2010stage suggest that research in the preclinical stage of AD is necessary to define an optimal therapeutic success window. We review the justification for conducting trials in the preclinical stage and highlight novel ethical challenges that arise and are related to determining appropriate risk\u2010benefit ratios and disclosing individuals' biomarker status. We propose that to conduct clinical trials with these participants, we need to improve public understanding of AD using unified vocabulary, resolve the acceptable risk\u2010benefit ratio in asymptomatic participants, and disclose or not biomarker status with attention to study type (observational studies vs clinical trials). Overcoming these challenges will justify clinical trials in preclinical AD at the societal level and aid to the development of societal and legal support for trial participants.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jalz.2016.01.009","type":"journal-article","created":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T01:54:54Z","timestamp":1458006894000},"page":"614-622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Ethical challenges in preclinical Alzheimer's disease observational studies and trials: Results of the Barcelona summit"],"prefix":"10.1002","volume":"12","author":[{"given":"Jos\u00e9 L.","family":"Molinuevo","sequence":"first","affiliation":[{"name":"Barcelona\u03b2eta Brain Research Center Pasqual Maragall Foundation  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Cami","sequence":"additional","affiliation":[{"name":"Pompeu Fabra University and Pasqual Maragall Foundation  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Carn\u00e9","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Clinic and IDIBAPS  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Carrillo","sequence":"additional","affiliation":[{"name":"Medical &amp; Scientific Relations Alzheimer's Association  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Georges","sequence":"additional","affiliation":[{"name":"Alzheimer Europe  Luxembourg Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria B.","family":"Isaac","sequence":"additional","affiliation":[{"name":"European Medicines Agency (EMA)  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaven","family":"Khachaturian","sequence":"additional","affiliation":[{"name":"The Campaign to Prevent Alzheimer by 2020 (PAD2020)  Potomac MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott Y.H.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Bioethics, Clinical Center National Institutes of Health  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Morris","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine  St Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Pasquier","sequence":"additional","affiliation":[{"name":"Inserm 1171 Universit\u00e9 Lille2, CHU, Memory Centre Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Centre for Clinical Brain Sciences University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reisa","family":"Sperling","sequence":"additional","affiliation":[{"name":"Center for Alzheimer Research and Treatment Brigham and Women's Hospital, Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Karlawish","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,14]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"Policy Brief for Heads of Government: The Global Impact of Dementia 2013\u20132050","author":"Alzheimer's Disease International","year":"2013"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.223"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70178-3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70223-4"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1202753"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182563bbe"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000431"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70228-4"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70044-9"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70194-7"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt269"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.20.2701"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt59"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/15672050113109990156"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03550160069041"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70291-0"},{"key":"e_1_2_7_22_1","first-page":"CD004816","article-title":"Statins for the primary prevention of cardiovascular disease","volume":"1","author":"Taylor F","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110184"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt213"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2011-0059"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007941"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2013.12.002"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.03.007"},{"key":"e_1_2_7_29_1","unstructured":"OECD(2014) \u201cUnleashing the Power of Big Data for Alzheimer's Disease and Dementia Research: Main Points of the OECD Expert Consultation on Unlocking Global Collaboration to accelerate Innovation for Alzheimer's Disease and Dementia\u201d OECD Digital Economy Papers No. 233 OECD Publishing.https:\/\/doi.org\/10.1787\/5jz73kvmvbwb\u2010en."},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.65.11.1509"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.04.002"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23650"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.803"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182918ca6"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24040"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001451"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2012.09.014"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.2217\/nmt.13.25"},{"key":"e_1_2_7_39_1","volume-title":"Impure Science: AIDS, Activism and the Politics of Knowledge","author":"Epstein S","year":"1998"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.598"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-720X.2000.tb00685.x"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.49.1.38"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610213000252"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2012.0350"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.GIM.0000132679.92238.58"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-092010-110722"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0809578"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1086\/302388"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2013.12121590"},{"key":"e_1_2_7_50_1","unstructured":"Alzheimer Europe \u2010 Research \u2010 Value of Knowing n.d. Available from:http:\/\/www.alzheimer\u2010europe.org\/Research\/Value\u2010of\u2010Knowing. Accessed February 1 \u00a02015."},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e31815a9dcc"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2009.28981"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1037\/0021-843X.94.2.140"},{"key":"e_1_2_7_54_1","unstructured":"KolataGHow Do You Live Knowing You Might Have an Alzheimer's Gene?The New York Times2012June 7 \u00a02012."},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000596"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.58.11.1828"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-015-0112-7"},{"key":"e_1_2_7_58_1","volume-title":"Disclosing Amyloid Status in the Anti\u2010Amyloid Treatment of Asymptomatic Alzheimer's Disease (A4) Study","author":"Sperling R","year":"2015"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afg097"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-138-11-200306030-00015"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.160.19.2964"},{"key":"e_1_2_7_62_1","unstructured":"Alzheimer Europe \u2010 Alzheimer Europe \u2010 Our work \u2010 Completed projects \u2010 2006: Dementia Carers' Survey n.d. Available from:http:\/\/www.alzheimer\u2010europe.org\/Alzheimer\u2010Europe\/Our\u2010work\/Completed\u2010projects\/2006\u2010Dementia\u2010Carers\u2010Survey. Accessed November 27 \u00a02014."},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1368-504X.2005.00480.x"},{"key":"e_1_2_7_64_1","first-page":"903645","article-title":"The Impact of Experience with a Family Member with Alzheimer's Disease on Views about the Disease across Five Countries","volume":"2012","author":"Blendon RJ","year":"2012","journal-title":"Int J Alzheimers Dis"},{"key":"e_1_2_7_65_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1212\/WNL.0000000000000153","article-title":"Confidentiality in preclinical Alzheimer disease studies When research and medical records meet","volume":"82","author":"Arias JJ","year":"2014","journal-title":"Neurology"},{"key":"e_1_2_7_66_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/0778-7367-71-15","article-title":"Ethics, privacy and the legal framework governing medical data: opportunities or threats for biomedical and public health research?","volume":"71","author":"Coppieters Y","year":"2013","journal-title":"Arch Public Health"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(15)00454-X"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1552526016000765?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1552526016000765?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.jalz.2016.01.009","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.jalz.2016.01.009","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1016\/j.jalz.2016.01.009","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.jalz.2016.01.009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T21:49:36Z","timestamp":1759873776000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1016\/j.jalz.2016.01.009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,14]]},"references-count":66,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1016\/j.jalz.2016.01.009"],"URL":"https:\/\/doi.org\/10.1016\/j.jalz.2016.01.009","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,14]]},"assertion":[{"value":"2016-03-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}