{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:06:33Z","timestamp":1760403993934,"version":"build-2065373602"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT2009550","GNT2019129"],"award-info":[{"award-number":["GNT2009550","GNT2019129"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp;amp; Dem Diag Ass &amp;amp; Dis Mo"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Emergent Alzheimer's disease (AD) represents a transitional stage where cognitively unimpaired (CU) individuals exhibit subthreshold but increasing amyloid\u2010\u03b2 (A\u03b2) levels. The impact of A\u03b2 accumulation on brain volume loss and cognition during this early stage remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>This retrospective cohort study analyzed data from 408 CU participants who were initially A\u03b2\u2212 (&lt;\u00a015 Centiloids) and followed for up to 15 years. Changes in basal forebrain and hippocampal volume, along with domain\u2010specific cognitive performance, were compared between those who progressed to A\u03b2+ (\u226520 Centiloids) and those who remained A\u03b2\u2212.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Sixty\u2010five CU participants progressed to A\u03b2+, indicating emergent AD, and showed faster A\u03b2 accumulation and subtle memory decline. However, no significant differences in rate of BF and hippocampal atrophy were observed between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>The results suggest that during this emergent phase of AD, A\u03b2 accumulation is associated with episodic memory loss, in the absence of detectable accelerated brain atrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Identified cognitively unimpaired individuals in the emergent stage of Alzheimer's disease (AD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Emergent AD exhibits a greater rate of amyloid\u2010\u03b2 (A\u03b2) accumulation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>No accelerated volume loss detected in the basal forebrain or hippocampus.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Emergent AD is also associated with a subtle decline in memory.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Early A\u03b2 accumulation may impair cognitive function before structural atrophy.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/dad2.70155","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T09:09:06Z","timestamp":1753780146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Amyloid accumulation, brain atrophy, and cognitive decline in emergent Alzheimer's disease"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3107-7759","authenticated-orcid":false,"given":"Ying","family":"Xia","sequence":"first","affiliation":[{"name":"The Australian e\u2010Health Research Centre CSIRO Health and Biosecurity  Herston Queensland Australia"},{"name":"School of Biomedical Sciences The University of Queensland  St Lucia Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierrick","family":"Bourgeat","sequence":"additional","affiliation":[{"name":"The Australian e\u2010Health Research Centre CSIRO Health and Biosecurity  Herston Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Dor\u00e9","sequence":"additional","affiliation":[{"name":"Austin Health  Heidelberg Victoria Australia"},{"name":"The Australian e\u2010Health Research Centre CSIRO Health and Biosecurity  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurgen","family":"Fripp","sequence":"additional","affiliation":[{"name":"The Australian e\u2010Health Research Centre CSIRO Health and Biosecurity  Herston Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen Ying","family":"Lim","sequence":"additional","affiliation":[{"name":"Turner Institute of Brain and Mental Health School of Psychological Sciences Monash University  Clayton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon M.","family":"Laws","sequence":"additional","affiliation":[{"name":"Centre for Precision Health Edith Cowan University  Joondalup Western Australia Australia"},{"name":"Collaborative Genomics and Translation Group School of Medical and Health Sciences Edith Cowan University  Joondalup Western Australia Australia"},{"name":"Curtin Medical School Curtin University  Bentley Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Fowler","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher C.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Austin Health  Heidelberg Victoria Australia"},{"name":"The Florey Institute of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin L.","family":"Masters","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth J.","family":"Coulson","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The University of Queensland  St Lucia Queensland Australia"},{"name":"Queensland Brain Institute The University of Queensland  St Lucia Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Maruff","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"},{"name":"Cogstate Ltd.  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