The Brain Chart of Aging: Machine‐learning analytics reveals links between brain aging, white matter disease, amyloid burden, and cognition in the iSTAGING consortium of 10,216 harmonized MR scans
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Introduction: Relationships between brain atrophy patterns of typical aging and Alzheimer's disease (AD), white matter disease, cognition, and AD neuropathology were investigated via machine learning in a large harmonized magnetic resonance imaging database (11 studies; 10,216 subjects). Methods: Three brain signatures were calculated: Brain‐age, AD‐like neurodegeneration, and white matter hyperintensities (WMHs). Brain Charts measured and displayed the relationships of these signatures to cognition and molecular biomarkers of AD. Results: WMHs were associated with advanced brain aging, AD‐like atrophy, poorer cognition, and AD neuropathology in mild cognitive impairment (MCI)/AD and cognitively normal (CN) subjects. High WMH volume was associated with brain aging and cognitive decline occurring in an ≈10‐year period in CN subjects. WMHs were associated with doubling the likelihood of amyloid beta (Aβ) positivity after age 65. Brain aging, AD‐like atrophy, and WMHs were better predictors of cognition than chronological age in MCI/AD. Discussion: A Brain Chart quantifying brain‐aging trajectories was established, enabling the systematic evaluation of individuals’ brain‐aging patterns relative to this large consortium.
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Ageing is associated with a decrease in grey matter volume, and the reduction is more pronounced in regions such as the hippocampus.
“Ageing is associated with a decrease in grey matter volume, which consists of neuronal cell bodies, dendrites, and synapses. The reduction in the grey matter volume is more pronounced in regions such as the hippocampus, which plays a critical role in memory and learning.162”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [162]
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- Authors
- Habes, M., Pomponio, R., Shou, H., Doshi, J., Mamourian, E., Erus, G., Nasrallah, I., Launer, L. J., Rashid, T., Bilgel, M., Fan, Y., Toledo, J. B., Yaffe, K., Sotiras, A., Srinivasan, D., Espeland, M., Masters, C., Maruff, P., Fripp, J., Völzk, H., Johnson, S. C., Morris, J. C., Albert, M. S., Miller, M. I., Bryan, R. N., Grabe, H. J., Resnick, S. M., Wolk, D. A., Davatzikos, C., & for the iSTAGING consortium, T. P. A. C.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- University of Pennsylvania (US)
- Center for Biomedical Image Computing and Analytics University of Pennsylvania Philadelphia Pennsylvania USA
- National Institutes of Health (US)
- National Institute on Aging (US)
- Houston Methodist (US)
- University of California, San Francisco (US)
- Washington University in St. Louis (US)
- Wake Forest University Health Sciences (US)
- The University of Melbourne (AU)
- CSIRO Health and Biosecurity Australian e‐Health Research Centre CSIRO Australia
- Universitätsmedizin Greifswald (DE)
- University of Wisconsin–Madison (US)
- Johns Hopkins University (US)
- The University of Texas at Austin (US)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Habes, Mohamad
- ORCID
- Habes, Mohamad
- Pomponio, Raymond
- Shou, Haochang
- Doshi, Jimit
- Mamourian, Elizabeth
- Nasrallah, Ilya
- Launer, Lenore J.
- Rashid, Tanweer
- Bilgel, Murat
- Toledo, Jon B.
- Yaffe, Kristine
- Sotiras, Aristeidis
- Srinivasan, Dhivya
- Espeland, Mark
- Masters, Colin
- Maruff, Paul
- Johnson, Sterling C.
- Morris, John C.
- Albert, Marilyn S.
- Miller, Michael I.
- Bryan, R. Nick
- Grabe, Hans J.
- Resnick, Susan M.
- Wolk, David A.
- Davatzikos, Christos
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2020-09-13
- Volume
- 17
- Issue
- 1
- Pages
- 89-102
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC7923395
- OpenAlex
- W3084546953
- Cited by
- 173
- References
- 43
- Citations by year
- 2026: 23 · 2025: 28 · 2024: 35 · 2023: 27 · 2022: 39 · 2021: 19 · 2020: 2
- FWCI
- 15.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- National Institutes of Health (1s10od023495-01)
- National Institute on Aging (R01AG063887, P30AG049638, U19AG033655, RF1AG059869, RF1AG054409, P30AG066507, P30AG062715, U01AG068057)
- National Heart, Lung, and Blood Institute (HHSN271201600059C)
- National Institute on Drug Abuse (HHSN271201600059C)
- National Institute of Biomedical Imaging and Bioengineering (R01EB022573)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- brain aging, white matter hyperintensities
- MeSH terms
- Machine Learning, Adult, Aged, Aged, 80 and over, Aging, Atrophy, Brain, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Biomarkers, Amyloid beta-Peptides, Disease Progression, Young Adult, Cerebral Small Vessel Diseases, Cognitive Dysfunction, White Matter
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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