{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T07:16:32Z","timestamp":1783322192523,"version":"3.54.6"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014392","name":"Avid Radiopharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015595","name":"GHR Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000009","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"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U24AG057437"],"award-info":[{"award-number":["U24AG057437"]}],"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":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Biomarkers identify Alzheimer's disease pathology in cognitively unimpaired adults, but the timing and rate of cognitive decline vary widely. This study aimed to identify subgroups of cognitive decline and baseline predictors of heterogeneity in preclinical progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Data were drawn from the Anti\u2010Amyloid Treatment in Asymptomatic Alzheimer's Disease Study, which enrolled amyloid beta\u2010positive (A\u03b2+) participants, and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study, which enrolled amyloid beta\u2010negative (A\u03b2\u2212) individuals. Latent class mixed\u2010effects models identified cognitive trajectory classes. Associations between class membership and demographic, clinical, and biomarker variables were evaluated. The primary outcome was change in the Preclinical Alzheimer Cognitive Composite.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Three trajectory classes were identified: stable, slow decliners, and fast decliners. Higher phosphorylated tau at 217 (p\u2010tau217), smaller hippocampal volume, and elevated tau positron emission tomography were associated with declining classes. About 70% of A\u03b2+ individuals were stable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Latent class modeling reveals substantial heterogeneity in preclinical trajectories with important implications for prevention trial design.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71366","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:11:21Z","timestamp":1776831081000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Divergent patterns of cognitive decline in preclinical Alzheimer's disease: Implications for secondary prevention trials"],"prefix":"10.1002","volume":"22","author":[{"given":"Runpeng","family":"Li","sequence":"first","affiliation":[{"name":"USC Epstein Family Alzheimer's Therapeutic Research Institute University of Southern California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Langford","sequence":"additional","affiliation":[{"name":"USC Epstein Family Alzheimer's Therapeutic Research Institute University of Southern California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip S.","family":"Insel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reisa A.","family":"Sperling","sequence":"additional","affiliation":[{"name":"Center for Alzheimer Research and Treatment Brigham and Women's Hospital Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rema","family":"Raman","sequence":"additional","affiliation":[{"name":"USC Epstein Family Alzheimer's Therapeutic Research Institute University of Southern California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Aisen","sequence":"additional","affiliation":[{"name":"USC Epstein Family Alzheimer's Therapeutic Research Institute University of Southern California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6026-2238","authenticated-orcid":false,"given":"Michael C.","family":"Donohue","sequence":"additional","affiliation":[{"name":"USC Epstein Family Alzheimer's Therapeutic Research Institute University of Southern California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.3098"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2305032"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.6669"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbas.2023.100074"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2024.122"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v078.i02"},{"issue":"1","key":"e_1_2_9_8_1","first-page":"459","article-title":"Distinct cognitive trajectories in late life and associated predictors and outcomes: a systematic review","volume":"4","author":"Wu Z","year":"2020","journal-title":"J Alzheimers Dis"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.04.004"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2019.08.009"},{"key":"e_1_2_9_11_1","unstructured":"A4 Study Team.A4 study data portal. 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