{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:40:00Z","timestamp":1793824800488,"version":"4.6.1"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["U01AG042791"],"award-info":[{"award-number":["U01AG042791"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["U01AG042791-S1"],"award-info":[{"award-number":["U01AG042791-S1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG046179, R01AG053267-S1"],"award-info":[{"award-number":["R01AG046179, R01AG053267-S1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["U19AG032438"],"award-info":[{"award-number":["U19AG032438"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging"},{"name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging"},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2021,7]]},"DOI":"10.1038\/s41591-021-01369-8","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T16:04:08Z","timestamp":1624291448000},"page":"1187-1196","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":328,"title":["A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2631-0942","authenticated-orcid":false,"given":"Stephen","family":"Salloway","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Farlow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6764-3866","authenticated-orcid":false,"given":"Eric","family":"McDade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Clifford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-7750","authenticated-orcid":false,"given":"Jorge J.","family":"Llibre-Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice M.","family":"Hitchcock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Mills","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4110-6472","authenticated-orcid":false,"given":"Anna M.","family":"Santacruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Aschenbrenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Hassenstab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8114-0552","authenticated-orcid":false,"given":"Tammie L. S.","family":"Benzinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2109-2955","authenticated-orcid":false,"given":"Brian A.","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Fagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelley A.","family":"Coalier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Cruchaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0576-2472","authenticated-orcid":false,"given":"Alison A.","family":"Goate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3443-7716","authenticated-orcid":false,"given":"Richard J.","family":"Perrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjie","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Joy","family":"Snider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6739-0803","authenticated-orcid":false,"given":"Catherine","family":"Mummery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Mustafa","family":"Surti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Hannequin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wallon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah B.","family":"Berman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Lah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne Z.","family":"Jimenez-Velazquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1810-9763","authenticated-orcid":false,"given":"Erik D.","family":"Roberson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H.","family":"van Dyck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9703-2265","authenticated-orcid":false,"given":"Lawrence S.","family":"Honig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7750-896X","authenticated-orcid":false,"given":"Raquel","family":"S\u00e1nchez-Valle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8603-4233","authenticated-orcid":false,"given":"William S.","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Gauthier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas R.","family":"Galasko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin L.","family":"Masters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared R.","family":"Brosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ging-Yuek Robin","family":"Hsiung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Jayadev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mait\u00e9","family":"Formaglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Masellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Clarnette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9mie","family":"Pariente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Dubois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9880-9788","authenticated-orcid":false,"given":"Florence","family":"Pasquier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7916-622X","authenticated-orcid":false,"suffix":"Jr","given":"Clifford R.","family":"Jack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Koeppe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0555-4654","authenticated-orcid":false,"given":"Peter J.","family":"Snyder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Aisen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1686-4965","authenticated-orcid":false,"given":"Ronald G.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4426-9602","authenticated-orcid":false,"given":"Barbara A.","family":"Wendelberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott W.","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen C.","family":"Holdridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Mintun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Yaari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Sims","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Baudler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Delmar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachelle S.","family":"Doody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo","family":"Fontoura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Giacobino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey A.","family":"Kerchner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7729-1702","authenticated-orcid":false,"given":"Randall J.","family":"Bateman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Dominantly Inherited Alzheimer Network\u2013Trials Unit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mait\u00e9","family":"Formaglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Mills","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9mie","family":"Pariente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H.","family":"van Dyck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"1369_CR1","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jr Jack","year":"2018","unstructured":"Jack, C. R. Jr. et al. NIA-AA Research Framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement. 14, 535\u2013562 (2018).","journal-title":"Alzheimers Dement."},{"key":"1369_CR2","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1097\/NEN.0b013e318232a379","volume":"70","author":"H Braak","year":"2011","unstructured":"Braak, H., Thal, D. R., Ghebremedhin, E. & Del Tredici, K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J. Neuropathol. Exp. Neurol. 70, 960\u2013969 (2011).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"1369_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/alzrt59","volume":"3","author":"RJ Bateman","year":"2011","unstructured":"Bateman, R. J. et al. Autosomal-dominant Alzheimer\u2019s disease: a review and proposal for the prevention of Alzheimer\u2019s disease. Alzheimers Res. Ther. 3, 1 (2011).","journal-title":"Alzheimers Res. Ther."},{"key":"1369_CR4","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1212\/WNL.0000000000000596","volume":"83","author":"DC Ryman","year":"2014","unstructured":"Ryman, D. C. et al. Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology 83, 253\u2013260 (2014).","journal-title":"Neurology"},{"key":"1369_CR5","doi-asserted-by":"publisher","first-page":"975","DOI":"10.4155\/cli.12.93","volume":"2","author":"JC Morris","year":"2012","unstructured":"Morris, J. C. et al. Developing an international network for Alzheimer\u2019s research: the Dominantly Inherited Alzheimer Network. Clin. Investig. (Lond.) 2, 975\u2013984 (2012).","journal-title":"Clin. Investig. (Lond.)"},{"key":"1369_CR6","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1056\/NEJMoa1202753","volume":"367","author":"RJ Bateman","year":"2012","unstructured":"Bateman, R. J. et al. Clinical and biomarker changes in dominantly inherited Alzheimer\u2019s disease. N. Engl. J. Med. 367, 795\u2013804 (2012).","journal-title":"N. Engl. J. Med."},{"key":"1369_CR7","doi-asserted-by":"publisher","first-page":"e1295","DOI":"10.1212\/WNL.0000000000006277","volume":"91","author":"E McDade","year":"2018","unstructured":"McDade, E. et al. Longitudinal cognitive and biomarker changes in dominantly inherited Alzheimer disease. Neurology 91, e1295\u2013e1306 (2018).","journal-title":"Neurology"},{"key":"1369_CR8","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S1474-4422(18)30028-0","volume":"17","author":"BA Gordon","year":"2018","unstructured":"Gordon, B. A. et al. Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer\u2019s disease: a longitudinal study. Lancet Neurol. 17, 241\u2013250 (2018).","journal-title":"Lancet Neurol."},{"key":"1369_CR9","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/nature19323","volume":"537","author":"J Sevigny","year":"2016","unstructured":"Sevigny, J. et al. The antibody aducanumab reduces A\u03b2 plaques in Alzheimer\u2019s disease. Nature 537, 50\u201356 (2016).","journal-title":"Nature"},{"key":"1369_CR10","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/S1474-4422(19)30202-9","volume":"18","author":"D Selkoe","year":"2019","unstructured":"Selkoe, D. \u03b2-secretase inhibitors for Alzheimer\u2019s disease: heading in the wrong direction? Lancet Neurol. 18, 624\u2013626 (2019).","journal-title":"Lancet Neurol."},{"key":"1369_CR11","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1056\/NEJMc1813435","volume":"380","author":"D Henley","year":"2019","unstructured":"Henley, D. et al. Preliminary results of a trial of atabecestat in preclinical Alzheimer\u2019s disease. N. Engl. J. Med. 380, 1483\u20131485 (2019).","journal-title":"N. Engl. J. Med."},{"key":"1369_CR12","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1056\/NEJMoa1812840","volume":"380","author":"MF Egan","year":"2019","unstructured":"Egan, M. F. et al. Randomized trial of verubecestat for prodromal Alzheimer\u2019s disease. N. Engl. J. Med. 380, 1408\u20131420 (2019).","journal-title":"N. Engl. J. Med."},{"key":"1369_CR13","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/jnc.13632","volume":"139","author":"E Karran","year":"2016","unstructured":"Karran, E. & De Strooper, B. The amyloid cascade hypothesis: are we poised for success or failure? J. Neurochem. 139, 237\u2013252 (2016).","journal-title":"J. Neurochem."},{"key":"1369_CR14","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/alzrt269","volume":"6","author":"JL Cummings","year":"2014","unstructured":"Cummings, J. L., Morstorf, T. & Zhong, K. Alzheimer\u2019s disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res. Ther. 6, 37 (2014).","journal-title":"Alzheimers Res. Ther."},{"key":"1369_CR15","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/alzrt213","volume":"5","author":"KL Moulder","year":"2013","unstructured":"Moulder, K. L. et al. Dominantly Inherited Alzheimer Network: facilitating research and clinical trials. Alzheimers Res. Ther. 5, 48 (2013).","journal-title":"Alzheimers Res. Ther."},{"key":"1369_CR16","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.neurol.2013.07.017","volume":"169","author":"SM Mills","year":"2013","unstructured":"Mills, S. M. et al. Preclinical trials in autosomal dominant AD: Implementation of the DIAN-TU trial. Rev. Neurol. (Paris) 169, 737\u2013743 (2013).","journal-title":"Rev. Neurol. (Paris)"},{"key":"1369_CR17","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.jalz.2016.07.005","volume":"13","author":"RJ Bateman","year":"2017","unstructured":"Bateman, R. J. et al. The DIAN-TU Next Generation Alzheimer\u2019s prevention trial: adaptive design and disease progression model. Alzheimers Dement. 13, 8\u201319 (2017).","journal-title":"Alzheimers Dement."},{"key":"1369_CR18","doi-asserted-by":"publisher","first-page":"2412","DOI":"10.1212\/WNL.43.11.2412-a","volume":"43","author":"JC Morris","year":"1993","unstructured":"Morris, J. C. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 43, 2412\u20132414 (1993).","journal-title":"Neurology"},{"key":"1369_CR19","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1007\/s43441-019-00014-4","volume":"54","author":"J Lim","year":"2020","unstructured":"Lim, J. et al. Reducing patient burden in clinical trials through the use of historical controls: appropriate selection of historical data to minimize risk of bias. Ther. Innov. Regul. Sci. 54, 850\u2013860 (2020).","journal-title":"Ther. Innov. Regul. Sci."},{"key":"1369_CR20","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.1002\/sim.7811","volume":"37","author":"G Wang","year":"2018","unstructured":"Wang, G. et al. A novel cognitive disease progression model for clinical trials in autosomal-dominant Alzheimer\u2019s disease. Stat. Med. 37, 3047\u20133055 (2018).","journal-title":"Stat. Med."},{"key":"1369_CR21","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1002\/pst.1589","volume":"13","author":"K Viele","year":"2014","unstructured":"Viele, K. et al. Use of historical control data for assessing treatment effects in clinical trials. Pharm. Stat. 13, 41\u201354 (2014).","journal-title":"Pharm. Stat."},{"key":"1369_CR22","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1002\/ana.410230509","volume":"23","author":"L Berg","year":"1988","unstructured":"Berg, L. et al. Mild senile dementia of the Alzheimer type: 2. longitudinal assessment. Ann. Neurol. 23, 477\u2013484 (1988).","journal-title":"Ann. Neurol."},{"key":"1369_CR23","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1177\/000841748805500306","volume":"55","author":"E Breines","year":"1988","unstructured":"Breines, E. The functional assessment scale as an instrument for measuring changes in levels of function of nursing home residents following occupational therapy. Can. J. Occup. Ther. 55, 135\u2013140 (1988).","journal-title":"Can. J. Occup. Ther."},{"key":"1369_CR24","doi-asserted-by":"crossref","unstructured":"Fitzmaurice, G. M., Laird, N. M. & Ware, J. H. Applied Longitudinal Analysis (John Wiley & Sons, 2012).","DOI":"10.1002\/9781119513469"},{"key":"1369_CR25","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.jalz.2015.06.1893","volume":"12","author":"ER Siemers","year":"2016","unstructured":"Siemers, E. R. et al. Phase 3 solanezumab trials: secondary outcomes in mild Alzheimer\u2019s disease patients. Alzheimers Dement. 12, 110\u2013120 (2016).","journal-title":"Alzheimers Dement."},{"key":"1369_CR26","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1056\/NEJMoa1705971","volume":"378","author":"LS Honig","year":"2018","unstructured":"Honig, L. S. et al. Trial of solanezumab for mild dementia due to Alzheimer\u2019s disease. N. Engl. J. Med. 378, 321\u2013330 (2018).","journal-title":"N. Engl. J. Med."},{"key":"1369_CR27","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13195-016-0207-9","volume":"8","author":"J Cummings","year":"2016","unstructured":"Cummings, J. et al. Drug development in Alzheimer\u2019s disease: the path to 2025. Alzheimers Res. Ther. 8, 39 (2016).","journal-title":"Alzheimers Res. Ther."},{"key":"1369_CR28","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1111\/cts.12491","volume":"11","author":"J Cummings","year":"2018","unstructured":"Cummings, J. Lessons learned from Alzheimer disease: clinical trials with negative outcomes. Clin. Transl. Sci. 11, 147\u2013152 (2018).","journal-title":"Clin. Transl. Sci."},{"key":"1369_CR29","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/547153a","volume":"547","author":"E McDade","year":"2017","unstructured":"McDade, E. & Bateman, R. J. Stop Alzheimer\u2019s before it starts. Nature 547, 153\u2013155 (2017).","journal-title":"Nature"},{"key":"1369_CR30","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.nicl.2018.04.022","volume":"19","author":"Y Su","year":"2018","unstructured":"Su, Y. et al. Utilizing the Centiloid scale in cross-sectional and longitudinal PiB PET studies. Neuroimage Clin. 19, 406\u2013416 (2018).","journal-title":"Neuroimage Clin."},{"key":"1369_CR31","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1002\/ana.24719","volume":"80","author":"AG Vlassenko","year":"2016","unstructured":"Vlassenko, A. G. et al. Imaging and cerebrospinal fluid biomarkers in early preclinical Alzheimer disease. Ann. Neurol. 80, 379\u2013387 (2016).","journal-title":"Ann. Neurol."},{"key":"1369_CR32","first-page":"3","volume":"8","author":"G Klein","year":"2021","unstructured":"Klein, G. et al. Thirty-six-month amyloid positron emission tomography results show continued reduction in amyloid burden with subcutaneous gantenerumab. J. Prev. Alzheimers Dis. 8, 3\u20136 (2021).","journal-title":"J. Prev. Alzheimers Dis."},{"key":"1369_CR33","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s00401-009-0521-4","volume":"118","author":"C Shepherd","year":"2009","unstructured":"Shepherd, C., McCann, H. & Halliday, G. M. Variations in the neuropathology of familial Alzheimer\u2019s disease. Acta Neuropathol. 118, 37\u201352 (2009).","journal-title":"Acta Neuropathol."},{"key":"1369_CR34","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1093\/jnen\/nlv028","volume":"75","author":"JM Ringman","year":"2016","unstructured":"Ringman, J. M. et al. Neuropathology of autosomal dominant Alzheimer disease in the national Alzheimer coordinating center database. J. Neuropathol. Exp. Neurol. 75, 284\u2013290 (2016).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"1369_CR35","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1093\/brain\/awz019","volume":"142","author":"BA Gordon","year":"2019","unstructured":"Gordon, B. A. et al. Tau PET in autosomal dominant Alzheimer\u2019s disease: relationship with cognition, dementia and other biomarkers. Brain 142, 1063\u20131076 (2019).","journal-title":"Brain"},{"key":"1369_CR36","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1056\/NEJMoa2100708","volume":"384","author":"MA Mintun","year":"2021","unstructured":"Mintun, M. A. et al. Donanemab in early Alzheimer\u2019s disease. N. Engl. J. Med. 384, 1691\u20131704 (2021).","journal-title":"N. Engl. J. Med."},{"key":"1369_CR37","doi-asserted-by":"publisher","first-page":"e047259","DOI":"10.1002\/alz.047259","volume":"16","author":"SB Haeberlein","year":"2020","unstructured":"Haeberlein, S. B. et al. Emerge and Engage topline results: phase 3 studies of aducanumab in early Alzheimer\u2019s disease. Alzheimers Dement. 16, e047259 (2020).","journal-title":"Alzheimers Dement."},{"key":"1369_CR38","doi-asserted-by":"publisher","first-page":"P1582","DOI":"10.1016\/j.jalz.2019.09.023","volume":"15","author":"EL Schuck","year":"2019","unstructured":"Schuck, E. L. et al. Population pharmacokinetic\/pharmacodynamic analyses of BAN2401 in patients with early Alzheimer\u2019s disease: correlation of BAN2401 exposure, pet standard uptake value ratio, and cognitive outcomes. Alzheimers Dement. 15, P1582\u2013P1583 (2019).","journal-title":"Alzheimers Dement."},{"key":"1369_CR39","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1056\/NEJMra1510062","volume":"377","author":"J Woodcock","year":"2017","unstructured":"Woodcock, J. & LaVange, L. M. Master protocols to study multiple therapies, multiple diseases, or both. N. Engl. J. Med. 377, 62\u201370 (2017).","journal-title":"N. Engl. J. Med."},{"key":"1369_CR40","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1002\/cpt1974155443","volume":"15","author":"DR Taves","year":"1974","unstructured":"Taves, D. R. Minimization: a new method of assigning patients to treatment and control groups. Clin. Pharmacol. Ther. 15, 443\u2013453 (1974).","journal-title":"Clin. Pharmacol. Ther."},{"key":"1369_CR41","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s13195-017-0318-y","volume":"9","author":"S Ostrowitzki","year":"2017","unstructured":"Ostrowitzki, S. et al. A phase III randomized trial of gantenerumab in prodromal Alzheimer\u2019s disease. Alzheimers Res. Ther. 9, 95 (2017).","journal-title":"Alzheimers Res. Ther."},{"key":"1369_CR42","unstructured":"Wechsler, D. WMS-R: Wechsler Memory Scale\u2013Revised: manual (Psychological Corporation, 1987)."},{"key":"1369_CR43","unstructured":"Wechsler, D. Wechsler Adult Intelligence Scale\u2013Revised (Psychological Corporation, 1981)."},{"key":"1369_CR44","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.3758\/BRM.41.4.1190","volume":"41","author":"YY Lim","year":"2009","unstructured":"Lim, Y. Y. et al. A method for cross-cultural adaptation of a verbal memory assessment. Behav. Res. Methods 41, 1190\u20131200 (2009).","journal-title":"Behav. Res. Methods"},{"key":"1369_CR45","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1093\/arclin\/acr039","volume":"26","author":"TAC Thompson","year":"2011","unstructured":"Thompson, T. A. C. et al. Sensitivity and test\u2013retest reliability of the International Shopping List Test in assessing verbal learning and memory in mild Alzheimer\u2019s disease. Arch. Clin. Neuropsychol. 26, 412\u2013424 (2011).","journal-title":"Arch. Clin. Neuropsychol."},{"key":"1369_CR46","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","volume":"12","author":"MF Folstein","year":"1975","unstructured":"Folstein, M. F., Folstein, S. E. & McHugh, P. R. \u201cMini-mental state\u201d: a practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189\u2013198 (1975).","journal-title":"J. Psychiatr. Res."},{"key":"1369_CR47","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S1474-4422(12)70015-7","volume":"11","author":"R Sperling","year":"2012","unstructured":"Sperling, R. et al. Amyloid-related imaging abnormalities in patients with Alzheimer\u2019s disease treated with bapineuzumab: a retrospective analysis. Lancet Neurol. 11, 241\u2013249 (2012).","journal-title":"Lancet Neurol."},{"key":"1369_CR48","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/j.neuroimage.2012.01.021","volume":"62","author":"B Fischl","year":"2012","unstructured":"Fischl, B. FreeSurfer. Neuroimage 62, 774\u2013781 (2012).","journal-title":"Neuroimage"},{"key":"1369_CR49","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1093\/cercor\/bhg087","volume":"14","author":"B Fischl","year":"2004","unstructured":"Fischl, B. et al. Automatically parcellating the human cerebral cortex. Cereb. Cortex 14, 11\u201322 (2004).","journal-title":"Cereb. Cortex"},{"key":"1369_CR50","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.neuroimage.2004.06.018","volume":"23","author":"RL Buckner","year":"2004","unstructured":"Buckner, R. L. et al. A unified approach for morphometric and functional data analysis in young, old, and demented adults using automated atlas-based head size normalization: reliability and validation against manual measurement of total intracranial volume. Neuroimage 23, 724\u2013738 (2004).","journal-title":"Neuroimage"},{"key":"1369_CR51","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.neuroimage.2014.11.058","volume":"107","author":"Y Su","year":"2015","unstructured":"Su, Y. et al. Partial volume correction in quantitative amyloid imaging. Neuroimage 107, 55\u201364 (2015).","journal-title":"Neuroimage"},{"key":"1369_CR52","unstructured":"Rousset, O. G., Ma, Y. & A. C. Correction for partial volume effects in PET: principle and validation. J. Nucl. Med. 39, 904\u2013911 (1998)."},{"key":"1369_CR53","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.jalz.2011.09.224","volume":"8","author":"M Farlow","year":"2012","unstructured":"Farlow, M. et al. Safety and biomarker effects of solanezumab in patients with Alzheimer\u2019s disease. Alzheimers Dement. 8, 261\u2013271 (2012).","journal-title":"Alzheimers Dement."},{"key":"1369_CR54","doi-asserted-by":"crossref","unstructured":"Robert, C. P. & Casella, G. Monte Carlo Statistical Methods (Springer, 2004).","DOI":"10.1007\/978-1-4757-4145-2"},{"key":"1369_CR55","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.jalz.2016.04.001","volume":"12","author":"S Weninger","year":"2016","unstructured":"Weninger, S. et al. Collaboration for Alzheimer\u2019s prevention: principles to guide data and sample sharing in preclinical Alzheimer\u2019s disease trials. Alzheimers Dement. 12, 631\u2013632 (2016).","journal-title":"Alzheimers Dement."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-021-01369-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-021-01369-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-021-01369-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,4]],"date-time":"2023-02-04T06:15:50Z","timestamp":1675491350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-021-01369-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,21]]},"references-count":55,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["1369"],"URL":"https:\/\/doi.org\/10.1038\/s41591-021-01369-8","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,21]]},"assertion":[{"value":"1 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"S.S. was the Project Arm Leader for the gantenerumab arm. He also receives research support and is a consultant to Eisai, Novartis, Genentech, F. Hoffmann-La Roche Ltd, GemVax, Avid Radiopharmaceuticals and Eli Lilly and Company. M. Farlow was the Project Arm Leader for the solanezumab arm. He receives research support and is consultant to Eli Lilly and Company, Eisai, Novartis, Green Valley, AbbVie, Biogen, Eisai, F. Hoffmann-La Roche Ltd, Suvan, vTv Therapeutics, Vaccinex, QR Pharma, Avanir Pharmaceuticals, AZTherapies, Cerecin, Cognition Therapeutics, Cortexyme, Longeveron, Otsuka Pharmaceutical, Samumed and Takeda. A.M.F. is the Biomarker Core Leader of DIAN\u2013TU. She is a member of the scientific advisory boards (SABs) for Roche Diagnostics, Genentech and AbbVie and also consults for Araclon\/Grifols, DiademRes, DiamiR and Otsuka Pharmaceuticals. T.L.S.B. has investigator-initiated research funding from the NIH, the Alzheimer\u2019s Association, the Barnes-Jewish Hospital Foundation and Avid Radiopharmaceuticals. She participates as a site investigator in clinical trials sponsored by Avid Radiopharmaceuticals, Eli Lilly and Company, Biogen, Eisai, Janssen and F. Hoffmann-La Roche Ltd. She serves as an unpaid consultant to Eisai and Siemens. She is on the Speaker\u2019s Bureau for Biogen. J.C.M. is the Friedman Distinguished Professor of Neurology, Director of the Charles F. and Joanne Knight Alzheimer\u2019s Disease Research Center, Associate Director of DIAN and Founding Principal Investigator of DIAN. He is funded by NIH grant nos. P30 AG066444, P01AG003991, P01AG026276, U19 AG032438 and U19 AG024904. Neither J.C.M. nor his family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. J.H. is an employee of Hitchcock Regulatory Consulting and has consulted for Acumen Pharmaceuticals, Axon Advisors, Critical Path Institute, Gerson Lehrman Group, H. Lundbeck, High Lantern Group, Regenera Pharma Ltd, UCB Biopharma SPRL, United Neuroscience, Vaccinex and Washington University. She is retired from Eli Lilly and Company and is an Eli Lilly and Company shareholder. E.M. is the Associate Director of the DIAN\u2013TU. He reports serving on a Data Safety Committee for Eli Lilly and Company and Alector. He is scientific consultant for Eisai and Eli Lilly and Company and has received institutional grant support from Eli Lilly and Company, F. Hoffmann-La Roche Ltd. and Janssen. D.B.C. is Medical Director of DIAN\u2013TU and serves as scientific consultant to Biogen, Takeda, Millennium, Genzyme, Amgen, F. Hoffmann-La Roche Ltd\/Genentech, GlaxoSmithKline, Serono, Inhibikase Therapeutics, Dr Reddy\u2019s Laboratories, Bristol Myers Squibb, Atara, Mitsubishi Tanabe Pharma, Excision BioTherapeutics, UpToDate and Wolters Kluwer. He serves on the Data and Safety Monitoring Board (DSMB)\/Data Monitoring Committees for F. Hoffmann-La Roche Ltd\/Genentech, Wave, EMD Serono, Shire, Pfizer and Sanofi. He has carried out legal consulting for Cook County, State Farm, Wilke & Wilke PC, Shevlin Smith and Sal Indomenico & Associates PC. He receives research support from the NIH National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences and NIA. A.J.A. has served as a consultant for Biogen and H. Lundbeck. J.H. is a paid consultant for F. Hoffmann-La Roche Ltd, Takeda and H. Lundbeck and is on the Data Safety and Monitoring Board for Eisai. C.R.J. Jr serves on an independent data monitoring board for F. Hoffmann-La Roche Ltd, has consulted for and served as a speaker for Eisai and consulted for Biogen, but he receives no personal compensation from any commercial entity. He receives research support from the NIH and the Alexander Family Alzheimer\u2019s Disease Research Professorship of the Mayo Clinic. C.C. receives research support from Biogen, Eisai, Alector and Parabon. C.C. is a member of the advisory board of Vivid Genetics, Halia Therapeutics and ADx Healthcare. C.M. is a consultant for Biogen. L.S.H. is a consultant for Cortexyme, Eisai, Eli Lilly and Company, Medscape and Prevail. He receives research grant support from Abbvie, Alector, Biogen, Genentech, Eli Lilly and Company and F. Hoffmann-La Roche Ltd. J.P. is on the Speakers\u2019 Bureau for Biogen. E.D.R. is a consultant for Biogen, Applied Genetic Technologies Corporation and AVROBIO, receives funding from Alector and is the owner of intellectual property related to tau. S.G. is a member of the SAB for Alzheon, Biogen, Eli Lilly and Company and TauRx and a member of the Data Safety Monitoring Board for Alzheimer\u2019s Disease Cooperative Study, ATRI and Banner Health. C.H.V.D. has served as a consultant for F. Hoffmann-La Roche Ltd and Eisai and received grant support for clinical trials from F. Hoffmann-La Roche Ltd, Eli Lilly and Company, Biogen, Genetech, Merck, Janssen, Eisai, Novartis and Biohaven Pharmaceuticals. R.S.V. served on a SAB for Ionis Pharmaceuticals. B.D. receives research support from F. Hoffmann-La Roche Ltd. M.M. is a consultant to Arkuda Therapeutics, Ionis and Alector and receives research funding from F. Hoffmann-La Roche Ltd, Novartis and Alector. D.R.G. is a consultant to Biogen, Esai, Fujirebio and Amprion and is on the DSMB for Cognition Therapeutics. G.R.H. has received research support as a clinical trial site investigator for Anavax, Biogen and F. Hoffmann-La Roche Ltd. He has received research funding from the Canadian Institutes of Health Research, Alzheimer Society of Canada and the NIH. P.S.A. collaborates with Eli Lilly and Company and F. Hoffmann-La Roche Ltd on drug development in AD and has a research grant from Eli Lilly and Company. M.B., P.D., R.S.D., P.F., C.G. and G.A.K. are employees and shareholders of F. Hoffmann-La Roche Ltd. S.W.A., K.C.H., M.A.M., J.R.S. and R.Y. are employees and shareholders of Eli Lilly and Company. R.J.B. is Director of DIAN\u2013TU and Principal Investigator of DIAN\u2013TU-001. He receives research support from the NIA of the NIH, DIAN\u2013TU trial pharmaceutical partners (Eli Lilly and Company, F. Hoffman-La Roche Ltd and Avid Radiopharmaceuticals), Alzheimer\u2019s Association, GHR Foundation, Anonymous Organization, DIAN\u2013TU Pharma Consortium (active: Biogen, Eisai, Eli Lilly and Company, Janssen, F. Hoffmann-La Roche Ltd\/Genentech; previous: AbbVie, Amgen, AstraZeneca, Forum, Mithridion, Novartis, Pfizer, Sanofi, United Neuroscience). He has been an invited speaker and consultant for AC Immune, F. Hoffman-La Roche Ltd and Janssen and a consultant for Amgen and Eisai. D.H., the Department Head of Neurology where the research is being conducted, is an inventor on patents for solanezumab, currently being tested in the DIAN\u2013TU clinical trials. If solanezumab is approved as a treatment for AD or dominantly inherited AD, Washington University and D.H. will receive part of the net sales of solanezumab from Eli Lilly and Company, which has licensed patents related to solanezumab from Washington University. The funders of the study had no role in the collection, analysis or interpretation of the data, the writing of the report or in the decision to submit the paper for publication. S.B.B., S.M.B., W.S.B., K.A.C., D.H., B.A.G., J.J.L., J.J.L.G., M. Formaglio, S.J., R.C., Y.L., R.K., I.Z.J.V., S.L.M., G.M.S., C.X., D.W. and J.R.B. do not declare any competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}