{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:15:15Z","timestamp":1792178115992,"version":"4.4.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T00:00:00Z","timestamp":1713916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005224","name":"German Center for Neurodegenerative Diseases","doi-asserted-by":"publisher","award":["BN01"],"award-info":[{"award-number":["BN01"]}],"id":[{"id":"10.13039\/501100005224","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Memory clinic patients are a heterogeneous population representing various aetiologies of pathological ageing. It is not known whether divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer\u2019s disease patients, are prevalent and clinically meaningful in this group of older adults.<\/jats:p>\n                  <jats:p>To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean \u00b1 standard deviation, age = 70.67 \u00b1 6.07 years, 52% females). Participants were cognitively unimpaired (n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (n = 342), mild cognitive impairment (n = 118) or dementia of the Alzheimer\u2019s type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid Alzheimer\u2019s disease biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5) as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test whether baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and mild cognitive impairment conversion rates of cognitively unimpaired participants and those with subjective cognitive decline.<\/jats:p>\n                  <jats:p>Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy initially affected the medial temporal lobes, followed by further temporal regions and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological Alzheimer\u2019s disease biomarker levels, APOE \u03b54 carriership and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe, with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive Alzheimer\u2019s disease biomarkers and was associated with more generalized cognitive impairment. Limbic-predominant atrophy, in all participants and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of mild cognitive impairment conversion.<\/jats:p>\n                  <jats:p>SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, at both the subject and the group level, was excellent, indicating reliable performance in previously unseen data.<\/jats:p>\n                  <jats:p>The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for Alzheimer\u2019s disease in applied settings. The implementation of atrophy subtype- and stage-specific end points might increase the statistical power of pharmacological trials targeting early Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awae118","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T19:30:30Z","timestamp":1713295830000},"page":"2400-2413","source":"Crossref","is-referenced-by-count":38,"title":["A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5503-6308","authenticated-orcid":false,"given":"Hannah","family":"Baumeister","sequence":"first","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 39120 Magdeburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6394-9940","authenticated-orcid":false,"given":"Jacob W","family":"Vogel","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences Malm\u00f6, Lund University , 222 42 Lund , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6270-5490","authenticated-orcid":false,"given":"Philip S","family":"Insel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, University of California, San Francisco , San Francisco, CA 94143 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Kleineidam","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 53127 Bonn , Germany"},{"name":"Department of Neurodegenerative Disease and Geriatric Psychiatry, University of Bonn Medical Center , 53127 Bonn , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Wolfsgruber","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 53127 Bonn , Germany"},{"name":"Department of Neurodegenerative Disease and Geriatric Psychiatry, University of Bonn Medical Center , 53127 Bonn , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Stark","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease and Geriatric Psychiatry, University of Bonn Medical Center , 53127 Bonn , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena M","family":"Gellersen","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 39120 Magdeburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3868-284X","authenticated-orcid":false,"given":"Renat","family":"Yakupov","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 39120 Magdeburg , Germany"},{"name":"Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University , 39120 Magdeburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias C","family":"Schmid","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 53127 Bonn , Germany"},{"name":"Institute for Medical Biometry, University Hospital Bonn , 53127 Bonn , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falk","family":"L\u00fcsebrink","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 39120 Magdeburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Brosseron","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 53127 Bonn , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University , 39120 Magdeburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silka D","family":"Freiesleben","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 10117 Berlin , Germany"},{"name":"Department of Psychiatry and Neurosciences, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , 10117 Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Preis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurosciences, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , 10117 Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa-Sophie","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurosciences, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , 10117 Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eike J","family":"Spruth","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 10117 Berlin , Germany"},{"name":"Department of Psychiatry and Neurosciences, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , 10117 Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slawek","family":"Altenstein","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 10117 Berlin , Germany"},{"name":"Department of Psychiatry and Neurosciences, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , 10117 Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lohse","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurosciences, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , 10117 Berlin , 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H","family":"Schott","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center G\u00f6ttingen , 37075 G\u00f6ttingen , Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) , 37075 G\u00f6ttingen , Germany"},{"name":"Leibniz Institute for Neurobiology , 39118 Magdeburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayda","family":"Rostamzadeh","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Medical Faculty, University of Cologne , 50937 Cologne , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzel","family":"Glanz","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 39120 Magdeburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enise I","family":"Incesoy","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) 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H","family":"Munk","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) , 72076 T\u00fcbingen , Germany"},{"name":"Department of Psychiatry and Psychotherapy, University of T\u00fcbingen , 72076 T\u00fcbingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hetzer","sequence":"additional","affiliation":[{"name":"Berlin Center for Advanced Neuroimaging, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin , 10117 Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Dechent","sequence":"additional","affiliation":[{"name":"MR-Research in Neurosciences, Department of Cognitive Neurology, Georg-August-University G\u00f6ttingen , 37075 G\u00f6ttingen , 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