Concussion in chronic traumatic encephalopathy
Open accessAbstract
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid β peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Leading CTE researchers have indicated that a single concussion does not lead to CTE.
“Leading CTE researchers have clearly indicated that a single concussion does not lead to CTE (33).”
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 [33]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Chronic traumatic encephalopathy in athletes: Progressive tauopathy after repetitive head injury
McKee, A. C., Cantu, R. C., Nowinski, C. J., Hedley-Whyte, E. T., Gavett, B. E., Budson, A. E., Santini, V. E., Lee, H.-S., Kubilus, C. A., & Stern, R. A. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181a9d503 · Cited by 2,295 · see citing works
Self-citationStages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years
Braak, H., Thal, D. R., Ghebremedhin, E., & Del Tredici, K. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318232a379 · Cited by 2,194 · see citing works
The spectrum of disease in chronic traumatic encephalopathy
McKee, A. C., Stein, T. D., Nowinski, C. J., Stern, R. A., Daneshvar, D. H., Alvarez, V. E., Lee, H.-S., Hall, G., Wojtowicz, S. M., Baugh, C. M., et al. (2013) · Brain · doi:10.1093/brain/aws307 · Cited by 2,098 · see citing works
Self-citationAdamson, D. M., Burnam, M. A., Burns, R. M., Caldarone, L. B., Cox, R. A., D’Amico, E. J., Díaz, C., Eibner, C., Fisher, G., Helmus, T. C., et al. (2008) · RAND Corporation eBooks · doi:10.7249/mg720 · Cited by 1,713 · see citing works
Primary age-related tauopathy (PART): a common pathology associated with human aging
Crary, J. F., Trojanowski, J. Q., Schneider, J. A., Abisambra, J. F., Abner, E. L., Alafuzoff, I., Arnold, S. E., Attems, J., Beach, T. G., Bigio, E. H., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1349-0 · Cited by 1,467 · see citing works
Self-citationGoldstein, L. E., Fisher, A. M., Tagge, C. A., Zhang, X.-L., Velisek, L., Sullivan, J. A., Upreti, C., Kracht, J. M., Ericsson, M., Wojnarowicz, M. W., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003716 · Cited by 958 · see citing works
Self-citationDocumented head injury in early adulthood and risk of Alzheimer’s disease and other dementias
Plassman, B. L., Havlik, R. J., Steffens, D. C., Helms, M. J., Newman, T. N., Drosdick, D., Phillips, C., Gau, B. A., Welsh–Bohmer, K. A., Burke, J. R., et al. (2000) · Neurology · doi:10.1212/wnl.55.8.1158 · Cited by 896 · see citing works
McCrory, P. R., Meeuwisse, W. H., Aubry, M., Cantu, R. C., Dvořák, J., Echemendía, R. J., Engebretsen, L., Johnston, K. M., Kutcher, J. S., Raftery, M., et al. (2013) · PM&R · doi:10.1016/j.pmrj.2013.02.012 · Cited by 896 · see citing works
MARTLAND, H. S. (1928) · Journal of the American Medical Association · doi:10.1001/jama.1928.02700150029009 · Cited by 774 · see citing works
McCrory, P. R., Meeuwisse, W. H., Johnston, K., Dvořák, J., Aubry, M., Molloy, M., & Cantu, R. C. (2009) · Journal of Athletic Training · doi:10.4085/1062-6050-44.4.434 · Cited by 696 · see citing works
Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing
Jordan, B. D. (1997) · JAMA · doi:10.1001/jama.278.2.136 · Cited by 659 · see citing works
Neurodegenerative causes of death among retired National Football League players
Lehman, E. J., Hein, M. J., Baron, S. L., & Gersic, C. M. (2012) · Neurology · doi:10.1212/wnl.0b013e31826daf50 · Cited by 638 · see citing works
Mayeux, R., Ottman, R., Maestre, G., Ngai, C., Tang, M., Ginsberg, H., Chun, M., Tycko, B., & Shelanski, M. (1995) · Neurology · doi:10.1212/wnl.45.3.555 · Cited by 597 · see citing works
Traumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease?
Johnson, V. E., Stewart, W., & Smith, D. H. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2808 · Cited by 587 · see citing works
Clinical presentation of chronic traumatic encephalopathy
Stern, R. A., Daneshvar, D. H., Baugh, C. M., Seichepine, D. R., Montenigro, P. H., Riley, D. O., Fritts, N. G., Stamm, J. M., Robbins, C. A., McHale, L., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e3182a55f7f · Cited by 564 · see citing works
Self-citationAlzheimer's disease: A study of epidemiological aspects
Heyman, A., Wilkinson, W. E., Stafford, J. A., Helms, M. J., Sigmon, A. H., & Weinberg, T. (1984) · Annals of Neurology · doi:10.1002/ana.410150406 · Cited by 525 · see citing works
The occult aftermath of boxing.
Roberts, G. W., Allsop, D., & Bruton, C. (1990) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.53.5.373 · Cited by 518 · see citing works
Microscopic lesions in the brain following head injury.
Oppenheimer, D. R. (1968) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.31.4.299 · Cited by 501 · see citing works
Stalning af amyloid percursor protein to study axonal damage in mild head Injury
Blumbergs, P. C., Scott, G., Manavis, J., Wainwright, H., Simpson, D. A., & McLean, A. J. (1994) · The Lancet · doi:10.1016/s0140-6736(94)91712-4 · Cited by 454 · see citing works
Frequency and Location of Head Impact Exposures in Individual Collegiate Football Players
Crisco, J. J., Fiore, R., Beckwith, J. G., Chu, J. J., Brolinson, P. G., Duma, S., McAllister, T. W., Duhaime, A.-C., & Greenwald, R. M. (2010) · Journal of Athletic Training · doi:10.4085/1062-6050-45.6.549 · Cited by 429 · see citing works
Military-related traumatic brain injury and neurodegeneration
McKee, A. C., & Robinson, M. E. (2014) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.04.003 · Cited by 423 · see citing works
Self-citationMcKee, A. C., Daneshvar, D. H., Alvarez, V. E., & Stein, T. D. (2014) · Acta Neuropathologica · doi:10.1007/s00401-013-1230-6 · Cited by 422 · see citing works
Self-citationAlzheimer's pathology in human temporal cortex surgically excised after severe brain injury
Ikonomovic, M. D., Uryu, K., Abrahamson, E. E., Ciallella, J. R., Trojanowski, J. Q., Lee, V. M.-Y., Clark, R. S., Marion, D. W., Wisniewski, S. R., & DeKosky, S. T. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.06.011 · Cited by 399 · see citing works
Apolipoprotein E in Alzheimer's Disease: An Update
Yu, J.-T., Tan, L., & Hardy, J. (2014) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014300 · Cited by 394 · see citing works
Montenigro, P. H., Baugh, C. M., Daneshvar, D. H., Mez, J., Budson, A. E., Au, R., Katz, D. I., Cantu, R. C., & Stern, R. A. (2014) · Alzheimer's Research & Therapy · doi:10.1186/s13195-014-0068-z · Cited by 375 · see citing works
The clinical spectrum of sport-related traumatic brain injury
Jordan, B. D. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.33 · Cited by 347 · see citing works
Beta-amyloid deposition in chronic traumatic encephalopathy
Stein, T. D., Montenigro, P. H., Alvarez, V. E., Xia, W., Crary, J. F., Tripodis, Y., Daneshvar, D. H., Mez, J., Solomon, T., Meng, G., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1435-y · Cited by 291 · see citing works
Self-citationStein, T. D., Alvarez, V. E., & McKee, A. C. (2014) · Alzheimer s Research & Therapy · doi:10.1186/alzrt234 · Cited by 274 · see citing works
Self-citationSmith, D. H., Chen, X. H., Xu, B. N., McIntosh, T., Gennarelli, T., & Meaney, D. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199756070-00009 · Cited by 231 · see citing works
Mayeux, R. P., Ottman, R., Tang, M., Noboa‐Bauza, L., Marder, K. S., Gurland, B. J., & Stern, Y. (1993) · Annals of Neurology · doi:10.1002/ana.410330513 · Cited by 220 · see citing works
Abbas, K., Shenk, T. E., Poole, V. N., Breedlove, E. L., Leverenz, L. J., Nauman, E. A., Talavage, T. M., & Robinson, M. E. (2014) · Brain Connectivity · doi:10.1089/brain.2014.0279 · Cited by 202 · see citing works
Tokuda, T., Ikeda, S., Yanagisawa, N., Ihara, Y., & Glenner, G. G. (1991) · Acta Neuropathologica · doi:10.1007/bf00308813 · Cited by 197 · see citing works
Amyloid β accumulation in axons after traumatic brain injury in humans
Smith, D. H., Chen, X.-H., Iwata, A., & Graham, D. (2003) · Journal of neurosurgery · doi:10.3171/jns.2003.98.5.1072 · Cited by 196 · see citing works
Matser, J. T., Kessels, A. G. H., Lezak, M. D., & Troost, J. (2001) · Journal of Clinical and Experimental Neuropsychology · doi:10.1076/jcen.23.6.770.1029 · Cited by 181 · see citing works
McCrory, P. R., Meeuwisse, W. H., Johnston, K., Dvořák, J., Aubry, M., Molloy, M. J., & Cantu, R. C. (2009) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2009.02.002 · Cited by 180 · see citing works
Traumatic brain injury in the US military: epidemiology and key clinical and research programs
Helmick, K. M., Spells, C. A., Malik, S. Z., Davies, C. A., Marion, D. W., & Hinds, S. R. (2015) · Brain Imaging and Behavior · doi:10.1007/s11682-015-9399-z · Cited by 175 · see citing works
Lower Cognitive Performance of Older Football Players Possessing Apolipoprotein E ε4
Kutner, K. C., Erlanger, D. M., Tsai, J., Jordan, B. D., & Relkin, N. R. (2000) · Neurosurgery · doi:10.1097/00006123-200009000-00026 · Cited by 170 · see citing works
Altered Neurochemistry in Former Professional Soccer Players without a History of Concussion
Koerte, I. K., Lin, A. P., Muehlmann, M., Merugumala, S. K., Liao, H. V., Starr, T. C., Kaufmann, D., Mayinger, M. C., Steffinger, D., Fisch, B., et al. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2014.3715 · Cited by 158 · see citing works
Frequency of Head-Impact–Related Outcomes by Position in NCAA Division I Collegiate Football Players
Baugh, C. M., Kiernan, P. T., Kroshus, E., Daneshvar, D., Montenigro, P., Mckee, A., & Stern, R. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2014.3582 · Cited by 153 · see citing works
Self-citationDeKosky, S. T., Abrahamson, E. E., Ciallella, J. R., Paljug, W. R., Wisniewski, S. R., Clark, R. S. B., & Ikonomovic, M. D. (2007) · Archives of Neurology · doi:10.1001/archneur.64.4.541 · Cited by 152 · see citing works
Six-month recovery from mild to moderate Traumatic Brain Injury: the role of APOE- 4 allele
Chamelian, L. (2004) · Brain · doi:10.1093/brain/awh296 · Cited by 140 · see citing works
APOE, APOE Promoter, and Tau Genotypes and Risk for Concussion in College Athletes
Terrell, T. R., Bostick, R. M., Abramson, R., Xie, D., Barfield, W. R., Cantu, R. C., Stanek, M. K., & Ewing, T. (2008) · Clinical Journal of Sport Medicine · doi:10.1097/jsm.0b013e31815c1d4c · Cited by 129 · see citing works
Chronic Traumatic Encephalopathy: Historical Origins and Current Perspective
Montenigro, P. H., Stein, T. D., Cantu, R. C., & Stern, R. A. (2015) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-032814-112814 · Cited by 126 · see citing works
Self-citationSingh, R. P., Meier, T. B., Kuplicki, R., Savitz, J. B., Mukai, I., Cavanagh, L. E., Allen, T. W., Teague, T. K., Nerio, C. J., Polanski, D. W., et al. (2014) · JAMA · doi:10.1001/jama.2014.3313 · Cited by 125 · see citing works
Soccer heading frequency predicts neuropsychological deficits
Witol, A. D., & Webbe, F. M. (2003) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/18.4.397 · Cited by 117 · see citing works
Subconcussive Blows to the Head
Belanger, H. G., Vanderploeg, R. D., & McAllister, T. W. (2015) · Journal of Head Trauma Rehabilitation · doi:10.1097/htr.0000000000000138 · Cited by 111 · see citing works
Self-reported concussion history: impact of providing a definition of concussion
Robbins, C. A., Daneshvar, D. H., Picano, J. D., Gavett, B. E., Baugh, C. M., Riley, D., Nowinski, C. J., Cantu, R. C., Stern, R. A., & McKee, A. C. (2014) · Open Access Journal of Sports Medicine · doi:10.2147/oajsm.s58005 · Cited by 97 · see citing works
Self-citationTraumatic encephalopathy: Review and provisional research diagnostic criteria
Victoroff, J. (2013) · Neurorehabilitation · doi:10.3233/nre-130839 · Cited by 91 · see citing works
Kristman, V. L., Tator, C. H., Kreiger, N., Richards, D. W., Mainwaring, L. M., Jaglal, S. B., TOMLINSON, G. A., & Comper, P. (2008) · Clinical Journal of Sport Medicine · doi:10.1097/jsm.0b013e31817e6f3e · Cited by 91 · see citing works
Kontos, A. P., Dolese, A., Elbin, R. J., Covassin, T., & Warren, B. L. (2011) · Brain Injury · doi:10.3109/02699052.2011.608209 · Cited by 90 · see citing works
Zhang, M. R., Red, S. D., Lin, A. H., Patel, S. S., & Sereno, A. B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057364 · Cited by 89 · see citing works
MR Spectroscopic Evidence of Brain Injury in the Non-Diagnosed Collision Sport Athlete
Poole, V. N., Abbas, K., Shenk, T. E., Breedlove, E. L., Breedlove, K. M., Robinson, M. E., Leverenz, L. J., Nauman, E. A., Talavage, T. M., & Dydak, U. (2014) · Developmental Neuropsychology · doi:10.1080/87565641.2014.940619 · Cited by 89 · see citing works
The problem of axonal injury in the brains of veterans with histories of blast exposure
Ryu, J., Horkayne‐Szakaly, I., Xu, L., Pletniková, O., Leri, F., Eberhart, C. G., Troncoso, J. C., & Koliatsos, V. E. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0153-3 · Cited by 86 · see citing works
The Neuropsychology of Heading and Head Trauma in Association Football (Soccer): A Review
Rutherford, A., Stephens, R. J., & Potter, D. D. (2003) · Neuropsychology Review · doi:10.1023/a:1025525613477 · Cited by 84 · see citing works
Apolipoprotein E Genotype and Concussion in College Athletes
Tierney, R., Mansell, J. L., Higgins, M., McDevitt, J. K., Toone, N., Gaughan, J., Mishra, A., & Krynetskiy, E. Y. (2010) · Clinical Journal of Sport Medicine · doi:10.1097/jsm.0b013e3181fc0a81 · Cited by 83 · see citing works
Apolipoprotein E4 as a Predictor of Outcomes in Pediatric Mild Traumatic Brain Injury
Moran, L. M., Taylor, H. G., Ganesalingam, K., Gastier, J. M., Frick, J., Bangert, B. A., Dietrich, A. M., Nuss, K. E., Rusin, J. A., Wright, M., et al. (2009) · Journal of Neurotrauma · doi:10.1089/neu.2008.0767 · Cited by 82 · see citing works
Shankar, S., Pruthi, N., Chandramouli, B., Kuttappa, T., Rao, S., Subbakrishna, D., Abraham, M., & Mahadevan, A. (2010) · Neurology India · doi:10.4103/0028-3886.63810 · Cited by 43 · see citing works
Nauman, E. A., Breedlove, K. M., Breedlove, E. L., Talavage, T. M., Robinson, M. E., & Leverenz, L. J. (2015) · Developmental Neuropsychology · doi:10.1080/87565641.2015.1016161 · Cited by 40 · see citing works
APOE ε4 Status and Traumatic Brain Injury on the Gridiron or the Battlefield
Gandy, S., & DeKosky, S. T. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004274 · Cited by 34 · see citing works
McCrory, P. R., Meeuwisse, W. H., Johnston, K., Dvořák, J., Aubry, M., & Molloy, M. J. (2009) · Cited by 20 · see citing works
Researchers seek definition of head-trauma disorder
Shen, H. H. (2015) · Nature · doi:10.1038/518466a · Cited by 7 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [5]Montenigro PH Baugh CM Daneshvar DH Mez J Budson AE Au R Clinical subtypes of chronic traumatic encephalopathy: literature review and proposed research diagnostic criteria for traumatic encephalopathy syndrome Alzheimer's Research & therapy in press PMC4288217 25580160
Cited by
Sorted by citations
Ling, H., Morris, H. R., Neal, J. W., Lees, A. J., Hardy, J., Holton, J. L., Revesz, T., & Williams, D. D. R. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1680-3 · Cited by 252 · see citing works
Acabchuk, R. L., Brisson, J. M., Park, C. L., Babbott‐Bryan, N., Parmelee, O. A., & Johnson, B. T. (2021) · Applied Psychology: Health and Well-Being · doi:10.1111/aphw.12244 · Cited by 77 · see citing works
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
Psychiatric phenotypes in chronic traumatic encephalopathy
Mahar, I., Alosco, M. L., & McKee, A. C. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.08.023 · Cited by 36 · see citing works
Self-citation
- Authors
- Stein, T. D., Alvarez, V. E., & McKee, A. C.
- Affiliations
- VA Boston Healthcare System (US)
- Boston University (US)
- Corresponding author
- Stein, Thor D.
- Venue
- Current Pain and Headache Reports
- Published
- 2015-08-11
- Volume
- 19
- Issue
- 10
- Pages
- 47-47
- ISSN
- 1531-3433 (ISSN-L)
- 1534-3081
- PMC
- PMC4633042
- OpenAlex
- W1157923211
- Cited by
- 177
- References
- 62
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 17 · 2023: 10 · 2022: 13 · 2021: 34 · 2020: 20 · 2019: 12 · 2018: 22 · 2017: 20 · 2016: 9
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Current Pain and Headache Reports (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 CX001038)
- Clinical Science Research and Development
- National Institute on Aging (P30AG013846, P30-AG13846))
- National Institute of Neurological Disorders and Stroke (U01NS086659)
- National Institute of Biomedical Imaging and Bioengineering
- 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, concussion, repetitive mild traumatic brain injury, tau pathology, amyloid-beta deposition, Alzheimer's disease, contact sports, neurodegeneration, disease latency
- MeSH terms
- War-Related Injuries, Athletic Injuries, Brain Injuries, Humans, Military Personnel, Amyloid beta-Peptides, Neurodegenerative Diseases, Brain Injury, Chronic, Athletes
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 ›
Are you an author, or do you see a problem with this page? Request a review
