ArticleNature medicine2024
Brain aging patterns in a large and diverse cohort of 49,482 individuals.
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Article in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55citing papers in PubMed
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Who cites it
55 citing papers in PubMed.
- Trial
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- Elevated BrainAGE precedes cognitive impairment and improves prediction of future cognitive decline.medRxiv : the preprint server for health sciences · 2026Article
- Association of sleep duration with Alzheimer's disease and cognition.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Plasma GDF15 affects long-term dementia risk and alters neuroimmune signaling.Science advances · 2026Article
- Charting Cervical Spinal Cord Morphometry Across the Lifespan.bioRxiv : the preprint server for biology · 2026Article
- Accelerated brain aging in prolonged grief disorder of later life: Influence of comorbid depression.Journal of affective disorders · 2026Article
- Alzheimer's disease biological domain sub-stratification enhances the precision of functional analyses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Brain-heart-eye axis revealed by multi-organ imaging genetics and proteomics.Nature biomedical engineering · 2026Article
- Mechanisms by Which Exercise Delays Brain Aging Through Regulation of the Mitochondrial Quality Control System.Biology · 2026Review
- Diffusion-relaxation MRI as virtual histology: separable microstructural signatures of AD pathology in ex vivo human brain.Research square · 2026Article
- The influence of vascular risk factors and aging on choroid plexus enlargement.European radiology · 2026Article
- Coupled cross-sectional and longitudinal non-negative matrix factorization reveals dominant brain aging trajectories in 48,949 individuals.Nature communications · 2026Article
- Alzheimer's Disease Brain Phenotypes are Age-dependent.bioRxiv : the preprint server for biology · 2026Article
- CMV titer associations with cognition and the plasma proteome implicate FLT1 and neurovascular mechanisms as potential moderators.Journal of neuroinflammation · 2026Article
- Exposome-wide patterns predict brain health in aging.Nature communications · 2026Article
- Separable multidimensional MRI signatures of cellular and structural pathology in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- NeuroFM: Toward Precision Neuroimaging with Foundation Models for Individualized Brain Health Estimation.medRxiv : the preprint server for health sciences · 2026Article
Corrections and comments
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Authors and funding
53 authors.
Zhijian YangArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-7863-827X
Junhao WenLaboratory of AI and Biomedical Science (LABS), Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-2077-3070
Guray ErusArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-6633-4861
Sindhuja T GovindarajanArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Randa MelhemArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Elizabeth MamourianArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8581-4887
Yuhan CuiArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Dhivya SrinivasanArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ahmed AbdulkadirLaboratory for Research in Neuroimaging, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
Paraskevi ParmpiArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Katharina WittfeldDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0003-4383-5043
Hans J GrabeDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Robin BülowInstitute of Diagnostic Radiology and Neuroradiology, University of Greifswald, Greifswald, Germany.
Stefan FrenzelDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Duygu TosunDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8644-7724
Murat BilgelLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-5042-7422
Yang AnLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Dahyun YiInstitute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0002-0860-0946
Daniel S MarcusMallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
Pamela LaMontagneMallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-6752-8518
Tammie L S BenzingerMallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-8114-0552
Susan R HeckbertCardiovascular Health Research Unit and Department of Epidemiology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7100-512X
Thomas R AustinCardiovascular Health Research Unit and Department of Epidemiology, University of Washington, Seattle, WA, USA.
Shari R WaldsteinDepartment of Psychology, University of Maryland, Baltimore County, Baltimore, MD, USA.
Michele K EvansHealth Disparities Research Section, Laboratory of Epidemiology and Population Sciences, NIA/NIH/IRP, Baltimore, MD, USA.
Alan B ZondermanHealth Disparities Research Section, Laboratory of Epidemiology and Population Sciences, NIA/NIH/IRP, Baltimore, MD, USA.
Lenore J LaunerNeuroepidemiology Section, Intramural Research Program, National Institute on Aging, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-3238-7612
Aristeidis SotirasDepartment of Radiology and Institute for Informatics, Data Science & Biostatistics, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-0795-8820
Mark A EspelandDepartment of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Colin L MastersFlorey Institute, The University of Melbourne, Parkville, Victoria, Australia.
Paul MaruffFlorey Institute, The University of Melbourne, Parkville, Victoria, Australia.ORCID http://orcid.org/0000-0002-6947-9537
Jurgen FrippCSIRO Health and Biosecurity, Australian e-Health Research Centre CSIRO, Brisbane, Queensland, Australia.
Arthur W TogaLaboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Sid O'BryantInstitute for Translational Research University of North Texas Health Science Center, Fort Worth, TX, USA.
Mallar M ChakravartyComputational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, McGill University, Verdun, Quebec, Canada.ORCID http://orcid.org/0000-0002-0759-5508
Sylvia VilleneuveMcConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0003-2338-0467
Sterling C JohnsonWisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.ORCID http://orcid.org/0000-0002-8501-545X
John C MorrisKnight Alzheimer Disease Research Center, Dept of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Marilyn S AlbertDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kristine YaffeDepartments of Neurology, Psychiatry and Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
Henry VölzkeInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Luigi FerrucciTranslational Gerontology Branch, Longitudinal Studies Section, National Institute on Aging, National Institutes of Health, MedStar Harbor Hospital, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-6273-1613
R Nick BryanDepartment of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
Russell T ShinoharaArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yong FanArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-9869-4685
Mohamad HabesNeuroimage Analytics Laboratory and Biggs Institute Neuroimaging Core, Glenn Biggs Institute for Neurodegenerative Disorders, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0001-9447-5805
Paris Alexandros LalousisDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Nikolaos KoutsoulerisDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.ORCID http://orcid.org/0000-0001-6825-6262
David A WolkDepartment of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Susan M ResnickLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-1115-7145
Haochang ShouArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-3043-047X
Ilya M NasrallahArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2346-7562
Christos DavatzikosArtificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Christos.Davatzikos@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0002-1025-8561
Funding
Healthy Aging In Neighborhoods of Diversity Across the Life Span (HANDLS)ZIAAG000513 · NIA · NATIONAL INSTITUTE ON AGING · PI EVANS, MICHELE K · 2009 to 2025
$70.9MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5MProject 2 MeasurementU19AG033655 · NIA · JOHNS HOPKINS UNIVERSITY · PI Abhay Moghekar · 2014 to 2026
$51.5MThe natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5MHealth and Aging Brain among Latino Elders (HABLE-AT(N)) StudyR01AG058533 · NIA · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI JOHNSON, LEIGH A, O'BRYANT, SID E · 2020 to 2025
$45.4MMVP Data Integration into the ADSP Phenotype Harmonization ConsortiumU24AG074855 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CUCCARO, MICHAEL L, HOHMAN, TIMOTHY J · 2021 to 2025
$37.5MUniversity of Maryland Claude D. Pepper Older Americans Independence Center (UM-OAIC)P30AG028747 · NIA · UNIVERSITY OF MARYLAND BALTIMORE · PI ALICE S. RYAN · 2006 to 2026
$28.9MUSCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI · 2020 to 2026
$27.8MNeuroimaging Predictors of Cognitive Decline, Impairment, and ResilienceZIAAG000191 · NIA · NATIONAL INSTITUTE ON AGING · PI FERRUCCI, LUIGI · 2009 to 2025
$26.4MResearch Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DAVID A WOLK · 2021 to 2026
$24.8MSouth Texas Alzheimer's Disease Research CenterP30AG066546 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Sudha Seshadri · 2021 to 2026
$24.0MUltrascale Machine Learning to Empower Discovery in Alzheimers Disease BiobanksU01AG068057 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Christos Davatzikos, Heng Huang · 2020 to 2026
$20.7MIntramural NIH HHS ZIA AG000513NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG028747NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072979NIA NIH HHS R01 AG034161NIA NIH HHS R01 AG054073NIA NIH HHS R01 AG058533NIA NIH HHS R01 AG066650NIA NIH HHS R01 AG067103NIA NIH HHS R01 AG080821NIA NIH HHS R01 AG083865NIA NIH HHS R01 AG085571NIA NIH HHS R56 AG064088NIA NIH HHS RF1 AG054409NIA NIH HHS U01 AG068057NIA NIH HHS U19 AG033655NIA NIH HHS U24 AG074855NIDA NIH HHS HHSN271201300284PNIDA NIH HHS HHSN271201600059CNIH HHS S10 OD032285NIMH NIH HHS R01 MH112847NIMH NIH HHS R01 MH123550NINDS NIH HHS U24 NS130411
Abstract
Brain aging process is influenced by various lifestyle, environmental and genetic factors, as well as by age-related and often coexisting pathologies. Magnetic resonance imaging and artificial intelligence methods have been instrumental in understanding neuroanatomical changes that occur during aging. Large, diverse population studies enable identifying comprehensive and representative brain change patterns resulting from distinct but overlapping pathological and biological factors, revealing intersections and heterogeneity in affected brain regions and clinical phenotypes. Herein, we leverage a state-of-the-art deep-representation learning method, Surreal-GAN, and present methodological advances and extensive experimental results elucidating brain aging heterogeneity in a cohort of 49,482 individuals from 11 studies. Five dominant patterns of brain atrophy were identified and quantified for each individual by respective measures, R-indices. Their associations with biomedical, lifestyle and genetic factors provide insights into the etiology of observed variances, suggesting their potential as brain endophenotypes for genetic and lifestyle risks. Furthermore, baseline R-indices predict disease progression and mortality, capturing early changes as supplementary prognostic markers. These R-indices establish a dimensional approach to measuring aging trajectories and related brain changes. They hold promise for precise diagnostics, especially at preclinical stages, facilitating personalized patient management and targeted clinical trial recruitment based on specific brain endophenotypic expression and prognosis.
Indexed as
AgingBrainMagnetic Resonance ImagingAdultAgedAged, 80 and overAtrophyCohort StudiesFemaleHumansLife StyleMaleMiddle Aged
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