{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:39:22Z","timestamp":1790635162494,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T00:00:00Z","timestamp":1617408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We classified non\u2010demented European Prevention of Alzheimer's Dementia (EPAD) participants through the amyloid\/tau\/neurodegeneration (ATN) scheme and assessed their neuropsychological and imaging profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      From 1500 EPAD participants, 312 were excluded. Cerebrospinal fluid cut\u2010offs of 1000 pg\/mL for amyloid beta (A\u00df)1\u201042 and 27 pg\/mL for p\u2010tau181 were validated using Gaussian mixture models. Given strong correlation of p\u2010tau and t\u2010tau (R\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.98,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001), neurodegeneration was defined by age\u2010adjusted hippocampal volume. Multinomial regressions were used to test whether neuropsychological tests and regional brain volumes could distinguish ATN stages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Age was 65 \u00b1 7 years, with 58% females and 38% apolipoprotein E (APOE) \u03b54 carriers; 57.1% were A\u2013T\u2013N\u2013, 32.5% were in the Alzheimer's disease (AD) continuum, and 10.4% suspected non\u2010Alzheimer's pathology. Age and cerebrovascular burden progressed with biomarker positivity (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). Cognitive dysfunction appeared with T+. Paradoxically higher regional gray matter volumes were observed in A+T\u2013N\u2013 compared to A\u2013T\u2013N\u2013 (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>In non\u2010demented individuals along the AD continuum, p\u2010tau drives cognitive dysfunction. Memory and language domains are affected in the earliest stages.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.12292","type":"journal-article","created":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T11:50:51Z","timestamp":1617450651000},"page":"1189-1204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Application of the ATN classification scheme in a population without dementia: Findings from the EPAD cohort"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2199-385X","authenticated-orcid":false,"given":"Silvia","family":"Ingala","sequence":"first","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC Location VUmc Vrije Universiteit Amsterdam, Amsterdam Neuroscience  Amsterdam the Netherlands"},{"name":"Alzheimer Center Amsterdam Department of Neurology Amsterdam UMC Location VUmc Vrije Universiteit Amsterdam, Amsterdam Neuroscience  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casper","family":"De Boer","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam Department of Neurology Amsterdam UMC Location VUmc Vrije Universiteit Amsterdam, Amsterdam Neuroscience  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa A","family":"Masselink","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam Department of Neurology Amsterdam UMC Location VUmc Vrije Universiteit Amsterdam, Amsterdam Neuroscience  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Vergari","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC Location VUmc Vrije Universiteit Amsterdam, Amsterdam Neuroscience  Amsterdam the Netherlands"},{"name":"Alzheimer Center Amsterdam Department of Neurology Amsterdam UMC Location VUmc Vrije Universiteit Amsterdam, Amsterdam Neuroscience  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9756-881X","authenticated-orcid":false,"given":"Luigi","family":"Lorenzini","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC Location VUmc Vrije Universiteit Amsterdam, Amsterdam Neuroscience  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4889-7932","authenticated-orcid":false,"given":"Ga\u00ebl","family":"Ch\u00e9telat","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNICAEN, INSERM, U1237, PhIND \u201cPhysiopathology and Imaging of Neurological Disorders,\u201d Institut Blood and Brain @ Caen\u2010Normandie  Cyceron Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0284-770X","authenticated-orcid":false,"given":"Carol","family":"Di Perri","sequence":"additional","affiliation":[{"name":"Centre for Dementia Prevention Edinburgh Imaging, UK Dementia Research Institute at The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ewers","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research Klinikum der Universitat M\u00fcnchen Ludwig\u2010Maximilians\u2010Universitat LMU  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8766-6224","authenticated-orcid":false,"given":"Wiesje M","family":"van der Flier","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam Department of Neurology Amsterdam UMC Location VUmc Vrije Universiteit Amsterdam, Amsterdam Neuroscience  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6660-657X","authenticated-orcid":false,"given":"Nick C","family":"Fox","sequence":"additional","affiliation":[{"name":"Dementia Research Centre Department of Neurodegenerative Disease &amp; 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