Chronic neuropathologies of single and repetitive TBI: substrates of dementia?
Open accessAbstract
Traumatic brain injury (TBI) has long been recognized to be a risk factor for dementia. This association has, however, only recently gained widespread attention through the increased awareness of 'chronic traumatic encephalopathy' (CTE) in athletes exposed to repetitive head injury. Originally termed 'dementia pugilistica' and linked to a career in boxing, descriptions of the neuropathological features of CTE include brain atrophy, cavum septum pellucidum, and amyloid-β, tau and TDP-43 pathologies, many of which might contribute to clinical syndromes of cognitive impairment. Similar chronic pathologies are also commonly found years after just a single moderate to severe TBI. However, little consensus currently exists on specific features of these post-TBI syndromes that might permit their confident clinical and/or pathological diagnosis. Moreover, the mechanisms contributing to neurodegeneration following TBI largely remain unknown. Here, we review the current literature and controversies in the study of chronic neuropathological changes after TBI.
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Individuals with a history of TBI are at higher risk for dementia, neurodegenerative diseases, psychiatric illness, and mortality, indicating long-term progression of sub-clinical pathology that manifests in late adulthood.
“Furthermore, individuals with a history of TBI are at higher risk for dementia, neurodegenerative diseases, psychiatric illness, and even mortality, indicating long-term progression of sub-clinical pathology that manifests only in late adulthood (Smith et al., 2013;Wilson et al., 2017).”
From NODDI in clinical research (2020) · cites this paper as Smith et al., 2013
The Introduction and “Single TBI” section support increased risk of later dementia and neurodegenerative disease, particularly after moderate to severe TBI. “Repetitive mild TBI” reports neuropsychiatric symptoms in selected cases and higher neurodegenerative mortality in former NFL players, but does not establish a general increased risk of psychiatric illness or mortality for everyone with a TBI history. The “Histological features” section also describes pathology appearing within hours of injury, so the claim that it manifests only in late adulthood is not supported. (LLM, conf=0.87)
Experimental — accuracy not yet measuredLife events associated with psychological stress and injury can lead to accelerated aging-associated impairments and dementia.
“Conversely, life events associated with psychological stress and injury can also lead to accelerated aging-associated impairments and dementia (Epel et al, 2004;Smith et al, 2013).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Smith et al, 2013
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“TBI are at higher risk for dementia, neurodegenerative diseases, psychiatric illness, and even mortality, indicating long-term progression of sub-clinical pathology that manifests only in late adulthood (Smith et al., 2013; Wilson et al., 2017).”
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- Authors
- Smith, D. H., Johnson, V. E., & Stewart, W.
- Affiliations
- University of Pennsylvania (US)
- Venue
- Nature Reviews Neurology
- Published
- 2013-03-05
- Volume
- 9
- Issue
- 4
- Pages
- 211-221
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- PMC
- PMC4513655
- OpenAlex
- W2161569931
- Cited by
- 699
- References
- 129
- Citations by year
- 2026: 23 · 2025: 39 · 2024: 53 · 2023: 53 · 2022: 46 · 2021: 58 · 2020: 73 · 2019: 62 · 2018: 46 · 2017: 58 · 2016: 59 · 2015: 71 · 2014: 43 · 2013: 12
- FWCI
- 7.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG038911, R03AG038911)
- National Institute of Neurological Disorders and Stroke (NS-038104, R01NS038104, P01NS056202, NS 056202)
- Topics
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
- Keywords
- chronic traumatic encephalopathy, traumatic brain injury, dementia, repetitive head injury, athletes, neuropathology, amyloid-beta, tau pathology, TDP-43, brain atrophy, cavum septum pellucidum, cognitive impairment, neurodegeneration, boxing
- MeSH terms
- Aged, Athletic Injuries, Brain, Brain Injuries, Chronic Disease, Dementia, Humans, Male, Risk Factors, Neurofibrillary Tangles, Disease Progression, Young Adult
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