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Although sensitive to Alzheimer\u2019s disease (AD) pathology, its longitudinal patterns across the clinical AD continuum and prognostic relevance remain unclear.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    577 participants from the DELCODE cohort (&gt;2,100 MRI scans) were analysed: healthy controls individuals (HC, N=202), and patients with subjective cognitive decline (SCD, N=248), mild cognitive impairment (N=93), and AD dementia (N=34). All underwent structural MRI, amyloid (A\u03b2\n                    <jats:sub>42\/40<\/jats:sub>\n                    ) and phosphorylated tau181 assessment, and lifestyle-related dementia risk profiling (LIBRA). BAG was derived using brainageR. Associations with baseline cognition, cognitive decline, and clinical progression (up to eight years) were examined using mixed-effects and Cox models. Mediation analyses tested whether BAG accounted for LIBRA-cognition associations. Biomarker-related and clinical findings were replicated in ADNI (N=461).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Findings<\/jats:title>\n                  <jats:p>BAG showed excellent short-term reliability, increased stepwise across the clinical spectrum and was elevated in amyloid-positive SCD, but not in asymptomatic amyloid-positive HC. Longitudinal BAG increases were strongest in amyloid- and tau-positive participants (A\u03b2+T+). Higher BAG was associated with poorer baseline cognition and predicted cognitive decline, with strongest effects in A\u03b2+T+. All main findings replicated in ADNI. BAG was associated with LIBRA only in biomarker-negative participants and partly mediated associations with cognitive outcomes in DELCODE.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>BAG is a reliable non-invasive marker of structural brain health sensitive to AD pathology and to modifiable AD risk. Detectable divergence prior to objective cognitive impairment supports its relevance for early risk stratification and prevention-oriented research.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>Helmholtz AI Cooperation Unit (ZT-I-PF-5-163).<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.19.26360525","type":"posted-content","created":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T02:40:11Z","timestamp":1787452811000},"source":"Crossref","is-referenced-by-count":0,"title":["MRI-derived brain aging trajectories across the Alzheimer\u2019s continuum: links to cognition, pathology and lifestyle risk factors"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3744-1155","authenticated-orcid":false,"given":"Elizabeth","family":"Kuhn","sequence":"first","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Bonn, Venusberg-Campus 1\/99, 53127, Bonn, Germany"},{"name":"Department of Cognitive Disorders and Old Age Psychiatry, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1274-5160","authenticated-orcid":false,"given":"Georgios","family":"Antonopoulos","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre J\u00fclich, 52428 J\u00fclich, Germany"},{"name":"Institute of Systems Neuroscience, Heinrich Heine University D\u00fcsseldorf, 40204 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3309-6856","authenticated-orcid":false,"given":"Luca","family":"Kleineidam","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Bonn, Venusberg-Campus 1\/99, 53127, Bonn, Germany"},{"name":"Department of Cognitive Disorders and Old Age Psychiatry, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3812-023X","authenticated-orcid":false,"given":"Melina","family":"Stark","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Bonn, Venusberg-Campus 1\/99, 53127, Bonn, Germany"},{"name":"Department of Cognitive Disorders and Old Age Psychiatry, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8262-4356","authenticated-orcid":false,"given":"Sandra","family":"Roeske","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Bonn, Venusberg-Campus 1\/99, 53127, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7163-3110","authenticated-orcid":false,"given":"Felix","family":"Hoffstaedter","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre J\u00fclich, 52428 J\u00fclich, Germany"},{"name":"Institute of Systems Neuroscience, Heinrich Heine University D\u00fcsseldorf, 40204 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Waite","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre J\u00fclich, 52428 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0568-2998","authenticated-orcid":false,"given":"Oliver","family":"Peters","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany"},{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, Department of Psychiatry and Neurosciences, Hindenburgdamm 30, 12203 Berlin, Germany"},{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, ECRC Experimental and Clinical Research Center, Lindenberger Weg 80, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0411-9204","authenticated-orcid":false,"given":"Julian","family":"Hellmann-Regen","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany"},{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, Department of Psychiatry and Neurosciences, Hindenburgdamm 30, 12203 Berlin, Germany"},{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, ECRC Experimental and Clinical Research Center, Lindenberger Weg 80, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7601-6410","authenticated-orcid":false,"given":"Lukas","family":"Preis","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, Department of Psychiatry and Neurosciences, Hindenburgdamm 30, 12203 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2497-9324","authenticated-orcid":false,"given":"Daria","family":"Gref","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany"},{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, ECRC Experimental and Clinical Research Center, Lindenberger Weg 80, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7596-0979","authenticated-orcid":false,"given":"Josef","family":"Priller","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Charit\u00e9, Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Department of Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich, and German Center for Mental Health (DZPG), Munich, Germany"},{"name":"University of Edinburgh and UK DRI, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8976-7309","authenticated-orcid":false,"given":"Eike Jakob","family":"Spruth","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Charit\u00e9, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gemenetzi","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Charit\u00e9, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9540-8700","authenticated-orcid":false,"given":"Anja","family":"Schneider","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Bonn, Venusberg-Campus 1\/99, 53127, Bonn, Germany"},{"name":"Department of Cognitive Disorders and Old Age Psychiatry, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0183-7510","authenticated-orcid":false,"given":"Klaus","family":"Fliessbach","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Bonn, Venusberg-Campus 1\/99, 53127, Bonn, Germany"},{"name":"Department of Cognitive Disorders and Old Age Psychiatry, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1492-5330","authenticated-orcid":false,"given":"Jens","family":"Wiltfang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Von-Siebold-Str. 5, 37075 Goettingen, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Goettingen, Goettingen, Germany"},{"name":"Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8237-4481","authenticated-orcid":false,"given":"Bj\u00f6rn H.","family":"Schott","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Von-Siebold-Str. 5, 37075 Goettingen, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Goettingen, Goettingen, Germany"},{"name":"Leibniz Institute for Neurobiology, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9335-9594","authenticated-orcid":false,"given":"Franziska","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Cologne, Medical Faculty, Kerpener Strasse 62, 50924, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-5388","authenticated-orcid":false,"given":"Emrah","family":"D\u00fczel","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Magdeburg, Magdeburg, Germany"},{"name":"Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5865-4176","authenticated-orcid":false,"given":"Wenzel","family":"Glanz","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Magdeburg, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2014-4098","authenticated-orcid":false,"given":"Enise","family":"Incesoy","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Magdeburg, Magdeburg, Germany"},{"name":"Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany"},{"name":"Department for Psychiatry and Psychotherapy, University Clinic Magdeburg, 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) Magdeburg, Magdeburg, Germany"},{"name":"Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5770-0727","authenticated-orcid":false,"given":"Falk","family":"L\u00fcsebrink","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Magdeburg, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5898-9953","authenticated-orcid":false,"given":"Katharina","family":"Buerger","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich, Feodor-Lynen-Strasse 17, 81377 Munich, Germany"},{"name":"Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Feodor-Lynen-Strasse 17, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4090-547X","authenticated-orcid":false,"given":"Daniel","family":"Janowitz","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich, Feodor-Lynen-Strasse 17, 81377 Munich, Germany"},{"name":"Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Feodor-Lynen-Strasse 17, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0325-4674","authenticated-orcid":false,"given":"Sophia","family":"St\u00f6cklein","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich, Feodor-Lynen-Strasse 17, 81377 Munich, Germany"},{"name":"Department of Radiology, Ludwig Maximilian University Hospital, Munich 81377, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1981-7435","authenticated-orcid":false,"given":"Robert","family":"Perneczky","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Munich, Feodor-Lynen-Strasse 17, 81377 Munich, Germany"},{"name":"Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy) Munich, Munich, Germany"},{"name":"Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4547-6240","authenticated-orcid":false,"given":"Boris-Stephan","family":"Rauchmann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany"},{"name":"Department of Neuroradiology, University Hospital, LMU Munich, Munich, Germany"},{"name":"Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3586-3194","authenticated-orcid":false,"given":"Stefan J.","family":"Teipel","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Rostock, Rostock, Germany"},{"name":"Department of Psychosomatic Medicine, Rostock University Medical Center, Gehlsheimer Str. 20, 18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3269-4452","authenticated-orcid":false,"given":"Ingo","family":"Kilimann","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Rostock, Rostock, Germany"},{"name":"Department of Psychosomatic Medicine, Rostock University Medical Center, Gehlsheimer Str. 20, 18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3434-936X","authenticated-orcid":false,"given":"Christoph","family":"Laske","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Tuebingen, Tuebingen, Germany"},{"name":"Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9118-0621","authenticated-orcid":false,"given":"Sebastian","family":"Sodenkamp","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Tuebingen, Tuebingen, Germany"},{"name":"Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9854-2972","authenticated-orcid":false,"given":"Annika","family":"Spottke","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Bonn, Venusberg-Campus 1\/99, 53127, Bonn, Germany"},{"name":"Clinic for Parkinson\u2019s, Sleep and Movement Disorders, Centre for Neurology, University Hospital Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3137-7516","authenticated-orcid":false,"given":"Frederic","family":"Brosseron","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Bonn, Venusberg-Campus 1\/99, 53127, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4991-763X","authenticated-orcid":false,"given":"Aflredo","family":"Ramirez","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Bonn, Venusberg-Campus 1\/99, 53127, Bonn, Germany"},{"name":"Department of Cognitive Disorders and Old Age Psychiatry, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany"},{"name":"Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931, K\u00f6ln, Germany"},{"name":"Division of 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