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      <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Early\u2010onset and late\u2010onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head\u2010to\u2010head comparison of cortical atrophy in EOAD and LOAD, using two large and well\u2010characterized cohorts (LEADS and ADNI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic EOAD patients and 317 sporadicLOAD patients who were amyloid positive and had mild cognitive impairment (MCI) or mild dementia (i.e., early\u2010stage AD), along with cognitively unimpaired participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>After controlling for the level of cognitive impairment, we found a double dissociation between AD clinical phenotype and localization\/magnitude of atrophy, characterized by predominant neocortical involvement in EOAD and more focal anterior medial temporal involvement in LOAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our findings point to the clinical utility of MRI\u2010based biomarkers of atrophy in differentiating between EOAD and LOAD, which may be useful for diagnosis, prognostication, and treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Early\u2010onset Alzheimer's disease (EOAD) and late\u2010onset AD (LOAD) patients showed distinct and overlapping cortical atrophy patterns.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>EOAD patients showed prominent atrophy in widespread neocortical regions.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>LOAD patients showed prominent atrophy in the anterior medial temporal lobe.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Regional atrophy was correlated with the severity of global cognitive impairment.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Results were comparable when the sample was stratified for mild cognitive impairment (MCI) and dementia.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14489","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T05:14:37Z","timestamp":1739942077000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Dissociable spatial topography of cortical atrophy in early\u2010onset and late\u2010onset Alzheimer's disease: A head\u2010to\u2010head comparison of the LEADS and ADNI cohorts"],"prefix":"10.1002","volume":"21","author":[{"given":"Yuta","family":"Katsumi","sequence":"first","affiliation":[{"name":"Frontotemporal Disorders Unit and Massachusetts Alzheimer's Disease Research Center Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Touroutoglou","sequence":"additional","affiliation":[{"name":"Frontotemporal Disorders Unit and Massachusetts Alzheimer's Disease 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