{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:32:02Z","timestamp":1790011922399,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U19AG024904"],"award-info":[{"award-number":["U19AG024904"]}],"id":[{"id":"10.13039\/100000049","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":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Alzheimer's Disease Neuroimaging Initiative (ADNI) has been pivotal in identifying and refining Alzheimer's disease (AD) biomarkers for clinical trials. This study leverages longitudinal data from participants who have progressed to amyloid\u2010positivity during their study participation to track evolution of biomarkers and cognitive function.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We modeled AD biomarker (positron emission tomography [PET], structural, cerebrospinal fluid [CSF], cognition) trajectories before and after observed amyloid\u2010positivity onset time to detect time at which each biomarker had detectable trajectory changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Analysis of a sub\u2010cohort of the 20\u2010year ADNI study (<jats:italic>N<\/jats:italic>\u00a0=\u00a090) recapitulated Alzheimer's progression beginning with amyloid alterations \u20104.8 to \u20105.3 years relative to amyloid\u2010positivity, succeeded by neurodegeneration (t\u00a0=\u00a0\u20104.0 to \u20104.1 years), and CSF tau (t\u00a0=\u00a0\u20100.4 to \u20100.5 years). Cognitive decline was observed to significantly correspond with emergence of amyloid\u2010positivity (t\u00a0=\u00a00.2 to 2.4 years).<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Our results corroborate temporal progression curves of AD biomarkers, providing insights on earliest detectable changes in objective and subjective cognitive function assessments.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14306","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T03:29:03Z","timestamp":1729481343000},"page":"9060-9067","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Timing of Alzheimer's disease biomarker progressions: A two\u2010decade observational study from the Alzheimer's Disease Neuroimaging Initiative (ADNI)"],"prefix":"10.1002","volume":"20","author":[{"given":"Tamar","family":"Schaap","sequence":"first","affiliation":[{"name":"Department of Veterans Affairs Medical Center Northern California Institute for Research and Education (NCIRE)  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5371-8667","authenticated-orcid":false,"given":"Pamela","family":"Thropp","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Medical Center Northern California Institute for Research and Education (NCIRE)  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8644-7724","authenticated-orcid":false,"given":"Duygu","family":"Tosun","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Medical Center Northern California Institute for Research and Education (NCIRE)  San Francisco California USA"},{"name":"Department of Radiology and Biomedical Imaging University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(91)90609-V"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90052-2"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70299-6"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70291-0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170261"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210525"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.117676"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012775"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac213"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2310168"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.05.001"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.01.010"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.08.005"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.021"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.07.002"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.056474"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.02.007"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14166"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00264"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116450"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781315370279"},{"key":"e_1_2_8_25_1","volume-title":"When Does Alzheimer's Disease Start? 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