Journal
GEROSCIENCE
Volume 43, Issue 4, Pages 2015-2039Publisher
SPRINGER
DOI: 10.1007/s11357-021-00355-9
Keywords
Traumatic brain injury; Alzheimer’ s disease; Mild cognitive impairment; Neuroimaging
Categories
Funding
- NIH [R01 NS 100973]
- DoD [W81-XWH-1810413]
- Hanson-Thorell Research Scholarship
- Undergraduate Research Associate Program (URAP) at the University of Southern California
- Alzheimer's Disease Neuroimaging Initiative (ADNI, NIH) [U01 AG024904]
- DoD ADNI [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Cogstate
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- Lumosity
- Neurotrack Technologies
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This study systematically explores how TBI affects white matter and gray matter properties in AD-like patterns, finding substantial similarities in neurodegeneration patterns between mTBI and AD. Using machine learning, it is possible to accurately predict the severity of AD-like brain changes observed during the chronic stage of mTBI based on acute assessments of post-traumatic mild cognitive impairment.
Traumatic brain injuries (TBIs) are often followed by persistent structural brain alterations and by cognitive sequalae, including memory deficits, reduced neural processing speed, impaired social function, and decision-making difficulties. Although mild TBI (mTBI) is a risk factor for Alzheimer's disease (AD), the extent to which these conditions share patterns of macroscale neurodegeneration has not been quantified. Comparing such patterns can not only reveal how the neurodegenerative trajectories of TBI and AD are similar, but may also identify brain atrophy features which can be leveraged to prognosticate AD risk after TBI. The primary aim of this study is to systematically map how TBI affects white matter (WM) and gray matter (GM) properties in AD-analogous patterns. Our findings identify substantial similarities in the regional macroscale neurodegeneration patterns associated with mTBI and AD. In cerebral GM, such similarities are most extensive in brain areas involved in memory and executive function, such as the temporal poles and orbitofrontal cortices, respectively. Our results indicate that the spatial pattern of cerebral WM degradation observed in AD is broadly similar to the pattern of diffuse axonal injury observed in TBI, which frequently affects WM structures like the fornix, corpus callosum, and corona radiata. Using machine learning, we find that the severity of AD-like brain changes observed during the chronic stage of mTBI can be accurately prognosticated based on acute assessments of post-traumatic mild cognitive impairment. These findings suggest that acute post-traumatic cognitive impairment predicts the magnitude of AD-like brain atrophy, which is itself associated with AD risk.
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