{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:41:04Z","timestamp":1791384064854,"version":"4.3.3"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Early-onset Alzheimer\u2019s disease (EOAD) is less investigated than the more common late-onset Alzheimer\u2019s disease (LOAD) despite its more aggressive course. A cortical signature of EOAD was recently proposed and may facilitate EOAD investigation. Here, we aimed to validate this proposed MRI biomarker of EOAD neurodegeneration in an Appalachian clinical cohort. We also compared differences in EOAD signature atrophy in participants with biomarker-positive EOAD, LOAD, early-onset non-AD pathologies, and cognitively normal individuals. Cortical thinning was reliably detected in eight of nine signature areas of persons with EOAD relative to cognitively normal individuals despite very early disease stage. Additionally, individuals with EOAD showed thinner cortex in most signature regions relative to those with early-onset non-AD pathologies. EOAD and LOAD showed similar cortical atrophy within most EOAD signature regions. Whole-brain vertex-wise cortical analyses supported these findings. Furthermore, signature cortical atrophy showed expected relationships with measures of global and specific cognitive and functional status. This investigation further validates and expands upon the recently defined EOAD signature and suggests its robustness within a rural population, even at early disease stage. Larger scale and longitudinal studies employing this marker of EOAD neurodegeneration are needed to further understand clinical effects and appropriate management of persons with EOAD.<\/jats:p>","DOI":"10.1093\/cercor\/bhae475","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T15:26:34Z","timestamp":1732634794000},"source":"Crossref","is-referenced-by-count":15,"title":["The early-onset Alzheimer\u2019s disease MRI signature: a replication and extension analysis in early-stage AD"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2532-7435","authenticated-orcid":false,"given":"Rashi I","family":"Mehta","sequence":"first","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]},{"name":"The Departments of Neuroradiology , 1 Medical Center Dr. PO Box 8063 Morgantown, WV 26506 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cierra M","family":"Keith","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]},{"name":"Behavioral Medicine and Psychiatry , 33 Medical Center Dr. Morgantown, WV 26505 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Vieira Ligo","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick D","family":"Worhunsky","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly E","family":"Phelps","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]},{"name":"Behavioral Medicine and Psychiatry , 33 Medical Center Dr. Morgantown, WV 26505 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Ward","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]},{"name":"Neurology , 33 Medical Center Dr. Morgantown, WV 26505 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Miller","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]},{"name":"Behavioral Medicine and Psychiatry , 33 Medical Center Dr. Morgantown, WV 26505 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Osvaldo","family":"Navia","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]},{"name":"Medicine , 33 Medical Center Dr. Morgantown, WV 26505 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Pockl","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]},{"name":"Medicine , 33 Medical Center Dr. Morgantown, WV 26505 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nafiisah","family":"Rajabalee","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]},{"name":"Medicine , 33 Medical Center Dr. Morgantown, WV 26505 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M","family":"Coleman","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Fran\u00e7ois","family":"D\u2019Haese","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]},{"name":"The Departments of Neuroradiology , 1 Medical Center Dr. PO Box 8063 Morgantown, WV 26506 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali R","family":"Rezai","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]},{"name":"Neurosurgery West Virginia University , 33 Medical Center Dr. Morgantown, WV 26505 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk C","family":"Wilhelmsen","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]},{"name":"Neurology , 33 Medical Center Dr. Morgantown, WV 26505 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc W","family":"Haut","sequence":"additional","affiliation":[{"name":"Rockefeller Neuroscience Institute 33 Medical Center Dr. Morgantown , WV 26505 ,","place":["United States"]},{"name":"Behavioral Medicine and Psychiatry , 33 Medical Center Dr. Morgantown, WV 26505 ,","place":["United States"]},{"name":"Neurology , 33 Medical Center Dr. Morgantown, WV 26505 ,","place":["United 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