Chronic traumatic encephalopathy: Where are we and where are we going?

Mez, Jesse; Stern, Robert A.; McKee, Ann C.

doi:10.1007/s11910-013-0407-7

Cited by 120Traumatic Brain Injury ResearchTraumatic Brain Injury and Neurovascular DisturbancesAlzheimer's disease research and treatments

Chronic traumatic encephalopathy: Where are we and where are we going?

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Mez, Jesse, Stern, Robert A., McKee, Ann C.·2013·Current Neurology and Neuroscience Reports

DOI 10.1007/s11910-013-0407-7PMC PMC4550089

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Abstract

Chronic traumatic encephalopathy (CTE, previously called punch drunk and dementia pugilistica) has a rich history in the medical literature in association with boxing, but has only recently been recognized with other contact sports, such as football and ice hockey, as well as with military blast injuries. CTE is thought to be a neurodegenerative disease associated with repeated concussive and subconcussive blows to the head. There is characteristic gross and microscopic pathology found in the brain, including frontal and temporal atrophy, axonal degeneration, and hyperphosphorylated tau and TAR DNA-binding protein 43 pathology. Clinically, there are characteristic progressive deficits in cognition (memory, executive dysfunction), behavior (explosivity, aggression), mood (depression, suicidality), and motor function (parkinsonism), which correlate with the anatomic distribution of brain pathology. While CTE shares clinical and neuropathological traits with other neurodegenerative diseases, the clinical syndrome and the neuropathology as a whole are distinct from other neurodegenerative diseases. Here we review the CTE literature to date. We also draw on the literature from mild traumatic brain injury and other neurodegenerative dementias, particularly when these studies provide guidance for future CTE research. We conclude by suggesting seven essential areas for future CTE research.

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The prevailing theory of CTE, often expressed in articles as fact, is that it is a distinct and unique neurodegenerative disease.
“In conclusion, the prevailing theory of CTE, often expressed in articles as fact, is that it is a distinct (1, 3, 9-11) and unique (10) neurodegenerative disease (9-13).”
From Mild Chronic Traumatic Encephalopathy Neuropathology in People With No Known Participation in Contact Sports or History of Repetitive Neurotrauma (2019) · cites this paper as [11]

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Untitled work
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The Epidemiology of Outpatient Visits for Minor Head Injury
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Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy
Puvenna, V., Engeler, M., Banjara, M., Brennan, C., Schreiber, P., Dadas, A., Bahrami, A., Solanki, J., Bandyopadhyay, A., Morris, J. K., et al. (2016) · Brain Research · doi:10.1016/j.brainres.2015.11.007 · Cited by 144 · see citing works
Assessing clinicopathological correlation in chronic traumatic encephalopathy: rationale and methods for the UNITE study
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Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers
Ojo, J. O., Mouzon, B., Algamal, M., Leary, P., Lynch, C., Abdullah, L. I., Evans, J., MULLAN, M. J., Bachmeier, C. J., Stewart, W. B., Jr., et al. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlw035 · Cited by 132 · see citing works
Chronic Traumatic Encephalopathy: Historical Origins and Current Perspective
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Subconcussive Blows to the Head
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Supplements, nutrition, and alternative therapies for the treatment of traumatic brain injury
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Characterization of Early Pathological Tau Conformations and Phosphorylation in Chronic Traumatic Encephalopathy
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A critical review of chronic traumatic encephalopathy
Iverson, G. L., Gardner, A. J., McCrory, P., Zafonte, R., & Castellani, R. J. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.008 · Cited by 103 · see citing works
Chronic traumatic encephalopathy neuropathology might not be inexorably progressive or unique to repetitive neurotrauma
Iverson, G. L., Gardner, A. J., Shultz, S. R., Solomon, G. S., McCrory, P. R., ZAFONTE, R. D., Perry, G. L., Hazrati, L., Keene, C. D., & Castellani, R. J. (2019) · Brain · doi:10.1093/brain/awz286 · Cited by 99 · see citing works
Age at First Exposure to Repetitive Head Impacts Is Associated with Smaller Thalamic Volumes in Former Professional American Football Players
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Propagation of Tau Pathology: Integrating Insights From Postmortem and In Vivo Studies
Vogels, T., Leuzy, A., Cicognola, C., Ashton, N. J., Smolek, T., Novák, M., Blennow, K., Zetterberg, H., Hromádka, T., Žilka, N., et al. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.09.019 · Cited by 94 · see citing works
A Clinical Approach to the Diagnosis of Traumatic Encephalopathy Syndrome
Reams, N., Eckner, J. T., Almeida, A. A., Aagesen, A. L., Giordani, B., Paulson, H. L., Lorincz, M. T., & Kutcher, J. S. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2015.5015 · Cited by 87 · see citing works
Molecular imaging in dementia: Past, present, and future
Laforce, R. J., Soucy, J., Sellami, L., Dallaire‐Théroux, C., Brunet, F., Bergeron, D., Miller, B. L., & Ossenkoppele, R. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.06.2855 · Cited by 87 · see citing works
Clinical Features of Repetitive Traumatic Brain Injury and Chronic Traumatic Encephalopathy
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Potential Long-Term Consequences of Concussive and Subconcussive Injury
Huber, B. R., Alosco, M. L., Stein, T. D., & McKee, A. C. (2016) · Physical Medicine and Rehabilitation Clinics of North America · doi:10.1016/j.pmr.2015.12.007 · Cited by 72 · see citing works
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Association of <i>APOE</i> Genotypes and Chronic Traumatic Encephalopathy
Atherton, K., Han, X., Chung, J., Cherry, J. D., Baucom, Z., Saltiel, N., Nair, E., Abdolmohammadi, B., Uretsky, M., Khan, M. M., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2022.1634 · Cited by 70 · see citing works
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Clinical relevance of midline fluid percussion brain injury: acute deficits, chronic morbidities, and the utility of biomarkers
Lifshitz, J., Rowe, R. K., Griffiths, D. R., Evilsizor, M. N., Thomas, T. C., Adelson, P., & McIntosh, T. (2016) · Brain Injury · doi:10.1080/02699052.2016.1193628 · Cited by 66 · see citing works
Alzheimer’s disease and chronic traumatic encephalopathy: Distinct but possibly overlapping disease entities
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Exposure to mild blast forces induces neuropathological effects, neurophysiological deficits and biochemical changes
Hernández, A., Tan, C., Plattner, F., Logsdon, A. F., Pozo, K., Yousuf, M. A., Singh, T., Turner, R. C., Lucke-Wold, B. P., Huber, J. D., et al. (2018) · Molecular Brain · doi:10.1186/s13041-018-0408-1 · Cited by 64 · see citing works
Repetitive mild traumatic brain injury induces ventriculomegaly and cortical thinning in juvenile rats
Goddeyne, C., Nichols, J., Wu, C. H., & Anderson, T. R. (2015) · Journal of Neurophysiology · doi:10.1152/jn.00970.2014 · Cited by 64 · see citing works
Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy
Lucke-Wold, B. P., Turner, R. C., Logsdon, A. F., Nguyen, L., Bailes, J. E., Lee, J. M., Robson, M. J., Omalu, B. I., Huber, J. D., & Rosen, C. L. (2015) · Journal of neurosurgery · doi:10.3171/2015.3.jns141802 · Cited by 64 · see citing works
Mild Chronic Traumatic Encephalopathy Neuropathology in People With No Known Participation in Contact Sports or History of Repetitive Neurotrauma
Iverson, G. L., Luoto, T. M., Karhunen, P. J., & Castellani, R. J. (2019) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlz045 · Cited by 63 · see citing works
Animal models of sports‐related head injury: bridging the gap between pre‐clinical research and clinical reality
Angoa‐Pérez, M., Kane, M. J., Briggs, D. I., Herrera‐Mundo, N., Viano, D. C., & Kuhn, D. M. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12690 · Cited by 59 · see citing works
Blast-induced temporal alterations in blood–brain barrier properties in a rodent model
Kawoos, U., Abutarboush, R., Gu, M., Chen, Y., Statz, J. K., Goodrich, S. Y., & Ahlers, S. T. (2021) · Scientific Reports · doi:10.1038/s41598-021-84730-8 · Cited by 58 · see citing works
Using transcranial magnetic stimulation to quantify electrophysiological changes following concussive brain injury: A systematic review
Major, B., Rogers, M., & Pearce, A. (2015) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12363 · Cited by 58 · see citing works
Imaging of Traumatic Brain Injury
Bodanapally, U. K., Sours, C., Zhuo, J., & Shanmuganathan, K. (2015) · Radiologic Clinics of North America · doi:10.1016/j.rcl.2015.02.011 · Cited by 50 · see citing works
Sensory coding and cognitive processing of sound in Veterans with blast exposure
Bressler, S., Goldberg, H., & Shinn‐Cunningham, B. G. (2016) · Hearing Research · doi:10.1016/j.heares.2016.10.018 · Cited by 48 · see citing works
Cognitive Neuroscience of Memory
Slotnick, S. D. (2017) · Cambridge University Press eBooks · doi:10.1017/9781316026687 · Cited by 48 · see citing works
The Biological Basis of Chronic Traumatic Encephalopathy following Blast Injury: A Literature Review
Aldag, M., Armstrong, R. C., Bandak, F. A., Bellgowan, P. S. F., Bentley, T. B., Biggerstaff, S., Caravelli, K., Cmarik, J. L., Crowder, A. T., DeGraba, T. J., et al. (2017) · Journal of Neurotrauma · doi:10.1089/neu.2017.5218 · Cited by 37 · see citing works
Head trauma in sport and neurodegenerative disease: an issue whose time has come?
Pearce, N. E., Gallo, V., & McElvenny, D. M. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.12.024 · Cited by 36 · see citing works
Traumatic brain injuries in mixed martial arts: A systematic review
Lockwood, J., Frape, L., Lin, S., & Ackery, A. (2017) · Trauma · doi:10.1177/1460408617740902 · Cited by 35 · see citing works
A Systematic Review and Meta-Analysis Investigating Head Trauma in Boxing
Donnelly, R. R., Ugbolue, U. C., Gao, Y., Gu, Y., Dutheil, F., & Baker, J. S. (2023) · Clinical Journal of Sport Medicine · doi:10.1097/jsm.0000000000001195 · Cited by 31 · see citing works
Risk of Misdiagnosing Chronic Traumatic Encephalopathy in Men With Depression
Iverson, G. L., & Gardner, A. J. (2019) · Journal of Neuropsychiatry · doi:10.1176/appi.neuropsych.19010021 · Cited by 30 · see citing works
Chronic Traumatic Encephalopathy in Athletes Involved with High-impact Sports.
Safinia, C., Bershad, E. M., Clark, H. B., SantaCruz, K. S., Alakbarova, N., Suárez, J. I., & Divani, A. A. (2016) · PubMed Central · Cited by 28 · see citing works
A quantitative risk assessment for chronic traumatic encephalopathy (CTE) in football: How public health science evaluates evidence
Finkel, A. M., & Bieniek, K. F. (2018) · Human and Ecological Risk Assessment An International Journal · doi:10.1080/10807039.2018.1456899 · Cited by 27 · see citing works
Retired National Football League Players are Not at Greater Risk for Suicide
Iverson, G. L. (2019) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/acz023 · Cited by 29 · see citing works
Chronic Cognitive and Cerebrovascular Function after Mild Traumatic Brain Injury in Rats
Griffiths, D. R., Law, L., Young, C., Fuentes, A., Truran, S., Karamanova, N., Bell, L., Turner, G., Emerson, H. M., Mastroeni, D., et al. (2022) · bioRxiv · doi:10.1089/neu.2022.0015 · Cited by 21 · see citing works
Modelling idiopathic Parkinson disease as a complex illness can inform incidence rate in healthy adults: the PREDIGT score
Schlossmacher, M. G., Tomlinson, J. J., dos Santos, G. M., Shutinoski, B., Brown, E. G., Manuel, D. G., & Mestre, T. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13476 · Cited by 26 · see citing works
The Impact of a Concussion-U Educational Program on Knowledge of and Attitudes about Concussion
Eagles, M. E., Bradbury-Squires, D. J., Powell, M. F., Murphy, J. R., Campbell, G. D., & Maroun, F. (2016) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2016.263 · Cited by 25 · see citing works
Longitudinal changes in brain volumetry and cognitive functions after moderate and severe diffuse axonal injury
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Chronische traumatische encefalopathie
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Authors: Mez, J., Stern, R. A., & McKee, A. C.
Affiliations: Boston University (US)
Corresponding author: Mez, Jesse
ORCID: Mez, Jesse
Stern, Robert A.
McKee, Ann C.
Venue: Current Neurology and Neuroscience Reports
Publisher: Springer Science and Business Media LLC
Published: 2013-10-18
Volume: 13
Issue: 12
Pages: 407-407
ISSN: 1528-4042 (ISSN-L)
1534-6293
DOI: 10.1007/s11910-013-0407-7
PMC: PMC4550089
OpenAlex: W2043633971
Cited by: 120
References: 124
Citations by year: 2026: 1 · 2025: 2 · 2024: 2 · 2023: 6 · 2022: 9 · 2021: 5 · 2020: 2 · 2019: 15 · 2018: 10 · 2017: 26 · 2016: 19 · 2015: 18 · 2014: 5
FWCI: 1.66
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Current Neurology and Neuroscience Reports (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (P30AG013846, P30-AG13846))
National Institute of Neurological Disorders and Stroke (T32NS007153, R01NS078337)
Topics: Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords: chronic traumatic encephalopathy, repetitive head impacts, concussion, subconcussive impacts, tau hyperphosphorylation, TDP-43, axonal degeneration, cognitive impairment, executive dysfunction, parkinsonism, mild traumatic brain injury, neurodegenerative dementia, contact sports, future research directions
MeSH terms: Animals, Boxing, Humans, Magnetic Resonance Imaging, Neuropsychological Tests, Tomography, X-Ray Computed, Biomarkers, Tomography, Emission-Computed, Single-Photon, Brain Injury, Chronic, Positron-Emission Tomography, Neuroimaging

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