{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:53:37Z","timestamp":1793120017161,"version":"4.5.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Early studies have reported that APOE is strongly associated with brain atrophy and cognitive decline among healthy elders and Alzheimer\u2019s disease (AD). However, previous research has not directly outlined the modulation of APOE on the trajectory of cerebral atrophy with aging during the conversion from cognitive normal (CN) to dementia (CN2D).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study tried to elucidate this issue from a voxel-wise whole-brain perspective based on 416 qualified participants from a longitudinal OASIS-3 neuroimaging cohort. A voxel-wise linear mixed-effects model was applied for detecting cerebrum regions whose nonlinear atrophic trajectories were driven by AD conversion and to elucidate the effect of APOE variants on the cerebral atrophic trajectories during the process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that CN2D participants had faster quadratically accelerated atrophy in bilateral hippocampi than persistent CN. Moreover, APOE \u03b54 carriers had faster-accelerated atrophy in the left hippocampus than \u03b54 noncarriers in both CN2D and persistent CN, and CN2D \u03b54 carriers an noncarriers presented a faster atrophic speed than CN \u03b54 carriers. These findings could be replicated in a sub-sample with a tough match in demographic information.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings filled the gap that APOE \u03b54 accelerates hippocampal atrophy and the conversion from normal cognition to dementia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2023.1158579","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T06:07:47Z","timestamp":1685513267000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Apolipoprotein E \u03b54 accelerates the longitudinal cerebral atrophy in open access series of imaging studies-3 elders without dementia at enrollment"],"prefix":"10.3389","volume":"15","author":[{"given":"Yuda","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhi","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoguang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e12117","DOI":"10.1002\/trc2.12117","article-title":"APOE epsilon4\/epsilon4 homozygotes with early Alzheimer\u2019s disease show accelerated hippocampal atrophy and cortical thinning that correlates with cognitive decline","volume":"6","author":"Abushakra","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/S1474-4422(19)30435-1","article-title":"Interpretation of risk loci from genome-wide association studies of Alzheimer\u2019s disease","volume":"19","author":"Andrews","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.neuroimage.2016.02.079","article-title":"Single subject prediction of brain disorders in neuroimaging: promises and pitfalls","volume":"145","author":"Arbabshirani","year":"2017","journal-title":"NeuroImage"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.neuroimage.2007.07.007","article-title":"A fast diffeomorphic image registration algorithm","volume":"38","author":"Ashburner","year":"2007","journal-title":"NeuroImage"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1016\/j.neuron.2019.01.056","article-title":"A quarter century of APOE and Alzheimer\u2019s disease: Progress to date and the path forward","volume":"101","author":"Belloy","year":"2019","journal-title":"Neuron"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.neuroimage.2012.10.065","article-title":"Statistical analysis of longitudinal neuroimage data with linear mixed effects models","volume":"66","author":"Bernal-Rusiel","year":"2013","journal-title":"NeuroImage"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.dadm.2019.01.005","article-title":"Predicting time to dementia using a quantitative template of disease progression","volume":"11","author":"Bilgel","year":"2019","journal-title":"Alzheimers Dement. 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