{{Short description|Neurodegenerative disease caused by head injury}} {{redirect|Punch drunk}} {{cs1 config|name-list-style=vanc|display-authors=3}} {{Use dmy dates|date=July 2020}} {{Infobox medical condition | name = Chronic traumatic encephalopathy | synonyms = Traumatic encephalopathy syndrome, dementia pugilistica,<ref name=JAMA2017/> punch drunk syndrome | image = Chronic Traumatic Encephalopathy.png | caption = A normal brain (left) and one with advanced CTE (right) | field = Neurology, psychiatry, sports medicine | symptoms = Behavioral problems, mood problems, problems with thinking<ref name=JAMA2017/> | complications = Brain damage, dementia,<ref name=Ste2014/> aggression,<!--<ref name=Alz2017/> --> depression,<!--<ref name=Alz2017/> --> suicide<ref name=Alz2017/> | onset = Years after initial injuries<ref name=Ste2014/> | duration = | causes = Repeated head injuries<ref name=JAMA2017/> | risks = Contact sports, military service, repeated banging of the head<ref name=JAMA2017/> | diagnosis = Autopsy<ref name=JAMA2017/> | differential = Alzheimer's disease, Parkinson's disease<ref name=Alz2017/> | prevention = | treatment = Supportive care<ref name=Alz2017/> | medication = | prognosis = Worsens over time<ref name=Ste2014/> | frequency = Uncertain<ref name=Ste2014/> | deaths = }} <!-- Definition and symptoms -->
'''Chronic traumatic encephalopathy''' ('''CTE''') is a neurodegenerative disease linked to repeated trauma to the head. The encephalopathy symptoms can include behavioral problems, mood problems, and problems with thinking.<ref name="JAMA2017">{{cite journal |last1=Asken |first1=Breton M. |last2=Sullan |first2=Molly J. |last3=DeKosky |first3=Steven T. |last4=Jaffee |first4=Michael S. |last5=Bauer |first5=Russell M. |title=Research Gaps and Controversies in Chronic Traumatic Encephalopathy: A Review |journal=JAMA Neurology |date=October 2017 |volume=74 |issue=10 |pages=1255–1262 |doi=10.1001/jamaneurol.2017.2396 |pmid=28975240 }}</ref><ref name="mckee23">{{cite journal |last1=McKee |first1=Ann C. |last2=Stein |first2=Thor D. |last3=Huber |first3=Bertrand R. |last4=Crary |first4=John F. |last5=Bieniek |first5=Kevin |last6=Dickson |first6=Dennis |last7=Alvarez |first7=Victor E. |last8=Cherry |first8=Jonathan D. |last9=Farrell |first9=Kurt |last10=Butler |first10=Morgane |last11=Uretsky |first11=Madeline |last12=Abdolmohammadi |first12=Bobak |last13=Alosco |first13=Michael L. |last14=Tripodis |first14=Yorghos |last15=Mez |first15=Jesse |last16=Daneshvar |first16=Daniel H. |title=Chronic traumatic encephalopathy (CTE): criteria for neuropathological diagnosis and relationship to repetitive head impacts |journal=Acta Neuropathologica |date=April 2023 |volume=145 |issue=4 |pages=371–394 |doi=10.1007/s00401-023-02540-w |pmid=36759368 |pmc=10020327 }}</ref> The disease often gets worse over time and can result in dementia.<ref name=Ste2014>{{cite journal |last1=Stein |first1=Thor D |last2=Alvarez |first2=Victor E |last3=McKee |first3=Ann C |title=Chronic traumatic encephalopathy: a spectrum of neuropathological changes following repetitive brain trauma in athletes and military personnel |journal=Alzheimer's Research & Therapy |date=2014 |volume=6 |issue=1 |pages=4 |doi=10.1186/alzrt234 |pmid=24423082 |pmc=3979082 |doi-access=free }}</ref>
<!-- Cause and diagnosis --> Most documented cases have occurred in athletes involved in striking-based combat sports, such as boxing, kickboxing, and mixed martial arts, and contact sports, such as rugby union, rugby league, gridiron football, Australian rules football, professional wrestling, and ice hockey. It is also an issue in association football, but largely as a result of heading the ball rather than player contact.<ref name=JAMA2017/><ref name=Mar2015>{{cite journal|last1=Maroon|first1=Joseph C|last2=Winkelman|first2=Robert|last3=Bost|first3=Jeffrey|last4=Amos|first4=Austin C|last5=Mathyssek|first5=Christina|last6=Miele|first6=Vincent|title=Chronic Traumatic Encephalopathy in Contact Sports: A Systematic Review of All Reported Pathological Cases|journal=PLOS One|date=2015|volume=10|issue=2|doi=10.1371/journal.pone.0117338|pmc=4324991|pmid=25671598|article-number=e0117338|bibcode=2015PLoSO..1017338M|doi-access=free}}{{Erratum|doi=10.1371/journal.pone.0130507|pmid=26039052|http://retractionwatch.com/2015/07/24/authors-ties-to-nfl-lead-to-correction-for-review-that-cast-doubt-on-brain-risk-from-sports/ ''Retraction Watch''|doi-access=free}}</ref> Other risk factors include being in the military (combat arms) or law enforcement,<ref>{{Cite web | title=Researchers investigating link between head injuries and CTE in law enforcement officers | url=https://www.police1.com/research/researchers-investigating-link-between-head-injuries-and-cte-in-law-enforcement-officers | access-date=2026-05-11 | website=www.police1.com}}</ref> prior domestic violence, and repeated injuries to the head.<ref name=JAMA2017/> The exact amount of trauma required for the condition to occur is unknown, and as of 2026 definitive diagnosis can only occur at autopsy, thus, it can only be diagnosed postmortem.<ref name=JAMA2017/> The disease is classified as a tauopathy.<ref name=JAMA2017/>
<!-- Epidemiology and history --> CTE is considered uncommon but significant in the general population, with an estimated rate of ~0.6%–6%,<ref>{{Cite web | title=Largest study of CTE finds it in 6% of subjects {{!}} ScienceDaily | url=https://www.sciencedaily.com/releases/2019/06/190620153548.htm | access-date=2026-05-11 | website=www.sciencedaily.com}}</ref><ref>https://academic.oup.com/jnen/advance-article/doi/10.1093/jnen/nlaf150/8454899?login=false</ref> but is highly common among individuals with histories of repetitive head impacts, such as contact sports athletes. A study of donated post-mortem brains of American football players identified CTE in 99% of brains from donated NFL players and 87% of all former players.<ref name=":6">{{Cite journal |last=Mez |first=Jesse |last2=Daneshvar |first2=Daniel H. |last3=Kiernan |first3=Patrick T. |last4=Abdolmohammadi |first4=Bobak |last5=Alvarez |first5=Victor E. |last6=Huber |first6=Bertrand R. |last7=Alosco |first7=Michael L. |last8=Solomon |first8=Todd M. |last9=Nowinski |first9=Christopher J. |last10=McHale |first10=Lisa |last11=Cormier |first11=Kerry A. |last12=Kubilus |first12=Caroline A. |last13=Martin |first13=Brett M. |last14=Murphy |first14=Lauren |last15=Baugh |first15=Christine M. |date=2017-07-25 |title=Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football |url=http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2017.8334 |journal=JAMA |language=en |volume=318 |issue=4 |pages=360 |doi=10.1001/jama.2017.8334 |issn=0098-7484 |pmc=5807097 |pmid=28742910}}</ref> The risk of CTE is regardless of diagnosed concussions, as it is driven by the cumulative, total number of repetitive head impacts (RHI), also known as subconcussive impacts, rather than diagnosed concussions.<ref>https://www.bumc.bu.edu/camed/2018/01/18/study-hits-not-concussions-cause-cte/#:~:text=%E2%80%9COur%20experimental%20results%20showed%20no,co%2Dauthor%20on%20this%20study.</ref> Exact population rates are unclear.<ref name=Ste2014/> The largest study has found CTE in 6% of the general population.<ref>https://news.uthscsa.edu/largest-study-of-cte-finds-it-in-6-of-subjects/</ref><ref>https://www.science.org/content/article/even-if-you-don-t-play-contact-sports-you-could-develop-signs-traumatic-brain-injury</ref><ref>{{Cite web | title=Largest study of CTE finds it in 6% of subjects {{!}} ScienceDaily | url=https://www.sciencedaily.com/releases/2019/06/190620153548.htm | access-date=2026-05-11 | website=www.sciencedaily.com}}</ref> Research in brain damage as a result of repeated head injuries began in the 1920s, at which time the condition was known as ''dementia pugilistica'' or "boxer's dementia", "boxer's madness", or "punch drunk syndrome".<ref name=JAMA2017/><ref name=Alz2017 /> It has been proposed that the rules of some sports be changed as a means of prevention.<ref name=JAMA2017/> There is currently no specific treatment for the disease,<ref name=Alz2017>{{cite web|title=Alzheimer's & Dementia|url=https://www.alz.org/dementia/chronic-traumatic-encephalopathy-cte-symptoms.asp |publisher=Alzheimer's Association |access-date=21 September 2017}}</ref> with research advancing in this area.<ref>https://pmc.ncbi.nlm.nih.gov/articles/PMC7381336/</ref> {{TOC limit}}
==Signs and symptoms== Symptoms of CTE, which typically occur in four stages, are wide-ranging, can fluctuate, and vary significantly between individuals. The variability is due to factors such as genetics, injury history and location of damage which mean two people with similar impacts can have vastly different clinical presentations and outcomes.<ref>{{cite web|vauthors= Kunz SP| title=Understanding CTE: The hidden cost of repeated head trauma in sports | date=10 September 2025 | url=https://www.ohio.edu/news/2025/09/understanding-cte-hidden-cost-repeated-head-trauma-sports|publisher=Ohio University }}</ref> There is a delayed onset, and it is common for behavioral changes to begin years or decades after the impacts have stopped. For athletes, symptoms typically appear about 8–14.5 years after retiring from their sport. Patients who present with psychiatric and behavioral issues tend to have a younger age of onset, with a mean age of 35.<ref>{{cite journal |last1=Bailes |first1=Julian E. |last2=Origenes |first2=Andrea Kristin |last3=Alleva |first3=Joseph T. |title=Chronic traumatic encephalopathy |journal=Disease-a-Month |date=October 2019 |volume=65 |issue=10 |pages=100855 |doi=10.1016/j.disamonth.2019.02.008 |pmid=30878141 }}</ref>
Contrary to widespread belief, many people with CTE never go on to commit violent acts, and CTE does not always present with speech issues (dysarthria). Motor features such as this, including parkinsonism, ataxia, and dysarthria, typically appear in a subset of cases, predominantly boxers,<ref>{{Cite web| title=Current Understanding of Chronic Traumatic Encephalopathy | url=https://accurateclinic.com/wp-content/uploads/2018/11/Current-Understanding-of-Chronic-Traumatic-Encephalopathy-2014-1.pdf | archive-url=https://web.archive.org/web/20211204105740/https://accurateclinic.com/wp-content/uploads/2018/11/Current-Understanding-of-Chronic-Traumatic-Encephalopathy-2014-1.pdf | archive-date=2021-12-04}}</ref> due to specific rotational and shearing impacts. Boxing involves frequent, powerful punches to the head that cause rapid rotational acceleration. These "shearing" forces are particularly effective at damaging the brainstem and cerebellum, the areas responsible for speech production, coordination, balance, and motor control.<ref>{{Cite web | title=Dementia Pugilistica - an overview {{!}} ScienceDirect Topics | url=https://www.sciencedirect.com/topics/medicine-and-dentistry/dementia-pugilistica | archive-url=https://web.archive.org/web/20210109201822/https://www.sciencedirect.com/topics/medicine-and-dentistry/dementia-pugilistica | access-date=2026-05-11 | archive-date=2021-01-09}}</ref>
Experts{{who|date=April 2026}} believe CTE often presents in two distinct forms. One form, typically appearing in a person's 20s or 30s, focuses on behavioral and mood changes (such as anxiety, irritability, impulsivity or mood swings) rather than physical symptoms like dizziness or headaches, although physical symptoms can still occur with this variant. The other form is the cognitive variant, which typically appears later in life, often in a person's late 50s or 60s. While the younger-onset form focuses on mood and behavior, this second form is characterized by significant trouble with memory and executive function, such as difficulty planning, organizing, and multitasking.<ref name=fesh/> This variant is much more likely to progress into full-blown dementia. Physical and motor symptoms, such as tremors, balance issues, or Parkinsonism, are more frequently observed in this later-life variant or in the advanced stages of the disease.
Symptoms of both variants can "wax and wane," often resulting in periods where the person's "old self" or some form of clarity appears to return before symptoms worsen again. While CTE is a progressive degenerative disease, its symptoms do not always progress in a straight line and can fluctuate in intensity. A person may have "good days" where their original personality is more present. Fluctuations in symptoms can be influenced by external factors like stress, activity levels, and adequate rest. Symptoms can also fluctuate significantly based on the situation, often appearing differently in structured environments like work compared to more personal settings like home. As the disease reaches advanced stages (Stages 3 and 4), the "old self" typically becomes less visible as the pathology spreads and symptoms like profound memory loss, paranoia, and dementia become more constant.<ref name=fesh/>
General symptoms include anger and irritability, memory loss, loss of empathy, confusion, apathy, impaired judgment, impulse control problems, aggression, withdrawal or isolation, depression, and anxiety.<ref name=statpearls/> Symptoms generally start to appear eight to ten years after an individual experiences repetitive mild traumatic brain injuries.<ref name="pmid19535999">{{cite journal |vauthors=McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA |title=Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury |journal=J Neuropathol Exp Neurol |volume=68 |issue=7 |pages=709–35 |year=2009 |pmid=19535999 |pmc=2945234 |doi= 10.1097/NEN.0b013e3181a9d503}}</ref><ref>{{cite journal | title=Chronic Traumatic Encephalopathy in Athletes Involved with High-impact Sports | journal=Journal of Vascular and Interventional Neurology | date=2016 | volume=9 | issue=2 | pages=34–48 | pmid=27829969 | pmc=5094259 | vauthors = Safinia C, Bershad EM, Clark HB, Santacruz K, Alakbarova N, Suarez JI, Divani AA }}</ref> They typically follow a pattern of early behavioral issues followed by later cognitive decline.<ref name=fesh/>
''Stage 1'': In the earliest stage, many individuals are asymptomatic or experience mild, intermittent symptoms that are often dismissed. Symptoms can include, but are not limited to: moodiness, emotional lability, difficulty with attention and concentration, hyper vigilance or mild paranoia, depression or irritability, headaches and occasional dizziness, loss of interest in previously enjoyed activities (anhedonia), and short-term memory deficits. Personality change begins in this stage, often noticeable only to those closest to the patient.<ref name=fesh/>
Dizziness and headaches, while recognized symptoms of CTE and sometimes reported in early stages, are not required for the diagnoses of traumatic encephalopathy syndrome. Especially in the behavioral variant, physical symptoms like dizziness or balance issues are not required for diagnosis and may never appear. As well, a small group of patients with predominantly behavioral or mood symptoms can remain stable for years, sometimes 11 to 14 years, before any other cognitive or physical symptoms progress.<ref name="fesh">{{cite journal | title=Chronic Traumatic Encephalopathy: A Brief Overview | journal=Frontiers in Neurology | date=2019 | volume=10 | article-number=713 | doi=10.3389/fneur.2019.00713 | doi-access=free | pmid=31333567 | pmc=6616127 | vauthors = Fesharaki-Zadeh A }}</ref>
These subtle changes can be easily missed or attributed to other causes or conditions, such as personality disorders, mood disorders, or attachment styles before progressing.<ref name=fesh/> In particular among those is an Obsessive–compulsive personality disorder (OCPD) pattern of personality traits, as OCPD displays high correlation with both traumatic brain injury<ref>https://pubmed.ncbi.nlm.nih.gov/28043199/</ref> and parkinsonism and the "parkinsonism personality" profile.<ref>https://pmc.ncbi.nlm.nih.gov/articles/PMC6340987/</ref> Parkinsonism and thus its characteristics are highly linked to CTE, with approximately 25% of patients with CTE having traits of parkinsonism.<ref>{{Cite web | title=Study Reveals Link Between Playing Contact Sports, Parkinsonism in Individuals with Chronic Traumatic Encephalopathy {{!}} Chobanian & Avedisian School of Medicine | url=https://www.bumc.bu.edu/camed/medicine/articles/2025/study-reveals-link-between-playing-contact-sports-parkinsonism-in-individuals-with-chronic-traumatic-encephalopathy/ | access-date=2026-05-11 | website=www.bumc.bu.edu}}</ref>
''Stage 2'': Symptoms become more frequent and impact social or professional life. This stage is often defined by explosive emotional shifts. Symptoms can include loss of empathy, executive dysfunction, increased aggression or irritability including outbursts or withdrawal, poor impulse control, and worsening emotional instability. In the context of relationships by this stage, CTE can contribute to a cycle of abuse where the individual has poor impulse control and struggles to regulate anger.<ref>{{Cite web | title=Domestic Violence and Traumatic Brain Injury: The Chilling Truth of This Hits Home {{!}} American Brain Foundation | url=https://www.americanbrainfoundation.org/domestic-violence-and-traumatic-brain-injury-the-chilling-truth-of-this-hits-home/#:~:text=%E2%80%9CSymptoms%20of%20CTE%20can%20include,only%20be%20diagnosed%20after%20death.%E2%80%9D | archive-url=https://web.archive.org/web/20230630164244/https://www.americanbrainfoundation.org/domestic-violence-and-traumatic-brain-injury-the-chilling-truth-of-this-hits-home/ | access-date=2026-05-11 | archive-date=2023-06-30}}</ref> The disease can manifest in various ways within relationships, such as jealousy, high-conflict personality when attempting to communicate, stonewalling, grudge-holding (perseveration), sometimes with obsessiveness and paranoia. Short-term memory loss can become more pronounced.<ref name=fesh/>
''Stage 3'': Stage three is characterized by significant cognitive decline. Symptoms can include worsening executive dysfunction and visuospatial difficulties such as getting lost in familiar places, significant memory loss, and a loss of insight into their own condition (anosognosia). Profound apathy may be present, as well as difficulty maintaining focus.<ref name=fesh/>
''Stage 4'': The final stage (usually reached around age 50–60 for those with the behavioral variant) is characterized by advanced dementia. Symptoms can include severe memory loss, psychotic symptoms including paranoia, severe personality changes, parkinsonism, slurred speech, and unsteady gait.<ref name="fesh"/>
Autonomic symptoms may or may not be present. They are similar to those of other TBIs, and can include abnormal sweating (excess or reduced), temperature sensitivities, abnormally low heart rate (bradycardia) or high heart rate (tachycardia), seizures (aural seizures or Post-Traumatic Epilepsy) and neurogenic or psychogenic fevers.
Additional symptoms include dysarthria, dysphagia, cognitive disorders such as amnesia, and ocular abnormalities, such as ptosis. Patients with CTE may be prone to inappropriate or explosive behavior and may display pathological jealousy or paranoia.<ref name="Mendez">{{cite journal |last1=Mendez |first1=Mario F. |title=The Neuropsychiatric Aspects of Boxing |journal=The International Journal of Psychiatry in Medicine |date=September 1995 |volume=25 |issue=3 |pages=249–262 |doi=10.2190/CUMK-THT1-X98M-WB4C |pmid=8567192 }}</ref>
==Cause== {{See also|Chronic traumatic encephalopathy in sports}} CTE is not caused by a single concussion, but by repetitive, long-term hits to the head, often occurring over many years. Most documented cases have occurred in athletes with mild repetitive head impacts (RHI) over an extended period. Evidence indicates that repetitive concussive and subconcussive blows to the head cause CTE.<ref name="statpearls">{{cite book |last1=Munakomi |first1=Sunil |last2=Puckett |first2=Yana |title=StatPearls |date=2025 |publisher=StatPearls Publishing |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK541013/ |chapter=Chronic Traumatic Encephalopathy |pmid=31082057 }}</ref> In particular, it is associated with contact sports such as boxing, American football, Australian rules football, wrestling, mixed martial arts, ice hockey, rugby, and association football.<ref name=JAMA2017/><ref name=Mar2015/> "In association football, research has since confirmed that heading the ball is the primary mechanism of risk, leading countries such as England and Scotland to ban heading in youth training as of 2020.".<ref>{{cite journal |last1=Nitrini |first1=Ricardo |title=Soccer (Football Association) and chronic traumatic encephalopathy: A short review and recommendation |journal=Dementia & Neuropsychologia |date=September 2017 |volume=11 |issue=3 |pages=218–220 |doi=10.1590/1980-57642016dn11-030002 |pmid=29213517 |pmc=5674664 }}</ref> Other potential risk factors include military personnel (repeated exposure to explosive charges or large caliber ordnance), domestic violence, and repeated impact to the head.<ref name=JAMA2017/> Although many military personnel are around blasts and explosions very often, it is very rare for these personnel to be diagnosed with CTE. Studies have shown that 4.4% of deceased military veterans have been diagnosed with CTE.<ref>{{cite web |last1=Ruprecht |first1=Michał |title=Evidence of CTE Rare in Military Personnel |url=https://www.medpagetoday.com/neurology/headtrauma/99138#:~:text=Evidence%20of%20chronic%20traumatic%20encephalopathy%20(CTE)%20was,Services%20University%20in%20Bethesda%2C%20Maryland%2C%20and%20colleagues |publisher=MedPage Today |access-date=15 December 2024 |language=en |date=8 June 2022}}</ref> Exposure to blasts from explosives can produce symptoms of CTE.<ref>{{Cite web |title=Study Shows First Case Series of Chronic Traumatic Encephalopathy in Blast-Exposed Military Service Personnel and Mechanism of Injury in Blast Neurotrauma {{!}} Chobanian & Avedisian School of Medicine |url=https://www.bumc.bu.edu/camed/2012/05/17/study-shows-first-case-series-of-chronic-traumatic-encephalopathy-in-blast-exposed-military-service-personnel-and-mechanism-of-injury-in-blast-neurotrauma/#:~:text=The%20blast%20wind%20from%20an,and/or%20a%20concussive%20injury |access-date=2024-11-19 |website=www.bumc.bu.edu}}</ref>
The exact amount of trauma required for the condition to occur is unknown.<ref name=JAMA2017/> Scientists are finding that there isn't a safe specific number of hits, but rather a threshold. Once someone's brain receives a certain amount of "force" over their lifetime, the tau protein starts to misfold and spread, even if the hits stop.<ref>{{Cite web | title=Young Amateur Athletes at Risk of CTE, BU Study Finds {{!}} The Brink {{!}} Boston University | url=https://www.bu.edu/articles/2023/young-amateur-athletes-at-risk-of-cte-study-finds/ | access-date=2026-05-11 | website=www.bu.edu}}</ref>
==Pathology== The neuropathological appearance of CTE is distinguished from other tauopathies, such as Alzheimer's disease. The four clinical stages of observable CTE disability have been correlated with tau pathology in brain tissue, ranging in severity from focal perivascular epicenters of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions.<ref name="McKee2013">{{cite journal |vauthors=McKee AC, Stern RA, Nowinski CJ, Stein TD, Alvarez VE, Daneshvar DH, Lee HS, Wojtowicz SM, Hall G, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC |title=The spectrum of disease in chronic traumatic encephalopathy |journal= Brain |volume=136 |issue=Pt 1 |pages=43–64 |year=2013 |pmid=23208308 |pmc=3624697 |doi=10.1093/brain/aws307}}</ref>
The primary physical manifestations of CTE include a reduction in brain weight, associated with atrophy of the frontal and temporal cortices and medial temporal lobe. The lateral ventricles and the third ventricle are often enlarged, with rare instances of dilation of the fourth ventricle.<ref name="Baugh C et al 2012 244–254">{{cite journal |last1=Baugh |first1=Christine M. |last2=Stamm |first2=Julie M. |last3=Riley |first3=David O. |last4=Gavett |first4=Brandon E. |last5=Shenton |first5=Martha E. |last6=Lin |first6=Alexander |last7=Nowinski |first7=Christopher J. |last8=Cantu |first8=Robert C. |last9=McKee |first9=Ann C. |last10=Stern |first10=Robert A. |title=Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma |journal=Brain Imaging and Behavior |date=June 2012 |volume=6 |issue=2 |pages=244–254 |doi=10.1007/s11682-012-9164-5 |pmid=22552850 }}</ref> Other physical manifestations of CTE include anterior cavum septi pellucidi and posterior fenestrations, pallor of the substantia nigra and locus ceruleus, and atrophy of the olfactory bulbs, thalamus, mammillary bodies, brainstem and cerebellum.<ref>{{cite journal |last1=Jancin |first1=Bruce |title=Chronic traumatic encephalopathy test sought |journal=Internal Medicine News |date=June 2011 |volume=44 |issue=10 |pages=16–17 |doi=10.1016/S1097-8690(11)70490-5 |id={{Gale|A291245393}} }}</ref> As CTE progresses, there may be marked atrophy of the hippocampus, entorhinal cortex, and amygdala.<ref name="pmid19535999" />
On a microscopic scale, a pathognomonic CTE lesion involves p-tau aggregates in neurons, with or without thorn-shaped astrocytes, at the depths of the cortical sulcus around a small blood vessel, deep in the parenchyma, and not restricted to the subpial and superficial region of the sulcus; the pathognomonic lesion must include p-tau in neurons to distinguish CTE from aging-related tau astrogliopathy (ARTAG).<ref name="auto">{{cite journal |last1=Bieniek |first1=Kevin F |last2=Cairns |first2=Nigel J |last3=Crary |first3=John F |last4=Dickson |first4=Dennis W |last5=Folkerth |first5=Rebecca D |last6=Keene |first6=C Dirk |last7=Litvan |first7=Irene |last8=Perl |first8=Daniel P |last9=Stein |first9=Thor D |last10=Vonsattel |first10=Jean-Paul |last11=Stewart |first11=William |last12=Dams-O’Connor |first12=Kristen |last13=Gordon |first13=Wayne A |last14=Tripodis |first14=Yorghos |last15=Alvarez |first15=Victor E |last16=Mez |first16=Jesse |last17=Alosco |first17=Michael L |last18=McKee |first18=Ann C |last19=Babcock |first19=Debra |last20=Bellgowan |first20=Patrick |last21=Crane |first21=Paul |last22=Edlow |first22=Brian |last23=Huber |first23=Bertrand Russ |last24=Kiernan |first24=Patrick |last25=Koroshetz |first25=Walter |title=The Second NINDS/NIBIB Consensus Meeting to Define Neuropathological Criteria for the Diagnosis of Chronic Traumatic Encephalopathy |journal=Journal of Neuropathology & Experimental Neurology |date=22 February 2021 |volume=80 |issue=3 |pages=210–219 |doi=10.1093/jnen/nlab001 |pmid=33611507 |pmc=7899277 }}</ref> Supporting features of CTE are: superficial neurofibrillary tangles (NFTs); p–tau in CA2 and CA4 hippocampus; p-tau in: mammillary bodies, hypothalamic nuclei, amygdala, nucleus accumbens, thalamus, midbrain tegmentum, nucleus basalis of Meynert, raphe nuclei, substantia nigra and locus coeruleus; p-tau thorn-shaped astrocytes (TSA) in the subpial region; p-tau dot-like neurites.<ref>{{cite journal |last1=McKee |first1=Ann C. |last2=Cairns |first2=Nigel J. |last3=Dickson |first3=Dennis W. |last4=Folkerth |first4=Rebecca D. |last5=Dirk Keene |first5=C. |last6=Litvan |first6=Irene |last7=Perl |first7=Daniel P. |last8=Stein |first8=Thor D. |last9=Vonsattel |first9=Jean-Paul |last10=Stewart |first10=William |last11=Tripodis |first11=Yorghos |last12=Crary |first12=John F. |last13=Bieniek |first13=Kevin F. |last14=Dams-O’Connor |first14=Kristen |last15=Alvarez |first15=Victor E. |last16=Gordon |first16=Wayne A. |title=The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy |journal=Acta Neuropathologica |date=January 2016 |volume=131 |issue=1 |pages=75–86 |doi=10.1007/s00401-015-1515-z |pmid=26667418 |pmc=4698281 }}</ref> Purely astrocytic perivascular p-tau pathology represents ARTAG and does not meet the criteria for CTE.<ref name="auto"/>
A small group of individuals with CTE have chronic traumatic encephalomyopathy (CTEM), which is characterized by symptoms of motor-neuron disease and which mimics amyotrophic lateral sclerosis (ALS). Progressive muscle weakness and balance and gait problems (problems with walking) seem to be early signs of CTEM.<ref name="Baugh C et al 2012 244–254"/>
Exosome vesicles created by the brain are potential biomarkers of TBI, including CTE.<ref name=Taylor2014>{{cite journal |vauthors=Taylor DD, Gercel-Taylor C |title=Exosome platform for diagnosis and monitoring of traumatic brain injury |journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences |volume=369 |issue=1652 |article-number=20130503 |year=2014 |pmid=25135964 |pmc=4142024 |doi=10.1098/rstb.2013.0503}}</ref>
Loss of neurons, scarring of brain tissue, collection of proteinaceous senile plaques, hydrocephalus, attenuation of the corpus callosum, diffuse axonal injury, neurofibrillary tangles, and damage to the cerebellum are implicated in the syndrome. Neurofibrillary tangles have been found in the brains of dementia pugilistica patients, but not in the same distribution as is usually found in people with Alzheimer's.<ref name="Hof">{{cite journal |last1=Hof |first1=P. R. |last2=Bouras |first2=C. |last3=Buée |first3=L. |last4=Delacourte |first4=A. |last5=Perl |first5=D. P. |last6=Morrison |first6=J. H. |title=Differential distribution of neurofibrillary tangles in the cerebral cortex of dementia pugilistica and Alzheimer's disease cases |journal=Acta Neuropathologica |date=December 1992 |volume=85 |issue=1 |pages=23–30 |doi=10.1007/BF00304630 |pmid=1285493 }}</ref> One group examined slices of brain from patients having had multiple mild traumatic brain injuries and found changes in the cells' cytoskeletons, which they suggested might be due to damage to cerebral blood vessels.<ref>{{cite journal |last1=Geddes |first1=J. F. |last2=Vowles |first2=G. H. |last3=Nicoll |first3=J. A. R. |last4=Révész |first4=T. |title=Neuronal cytoskeletal changes are an early consequence of repetitive head injury |journal=Acta Neuropathologica |date=6 August 1999 |volume=98 |issue=2 |pages=171–178 |doi=10.1007/s004010051066 |pmid=10442557 }}</ref>
==Diagnosis== There is currently no definitive test to prove the presence of CTE in a living person. In the living, possible CTE is instead diagnosed as traumatic encephalopathy syndrome using the 2021 NINDS Consensus Criteria.<ref>{{Cite web| title=New Criteria Published for Diagnosing the Clinical Syndrome of CTE During Life | url=https://www.usuhs.edu/sites/default/files/media/documents/release_no._21-03-16_new_criteria_published_for_diagnosing_the_clinical_syndrome_of_cte_during_life_1_1.pdf | archive-url=https://web.archive.org/web/20210917232545/https://www.usuhs.edu/sites/default/files/media/documents/release_no._21-03-16_new_criteria_published_for_diagnosing_the_clinical_syndrome_of_cte_during_life_1_1.pdf | archive-date=2021-09-17}}</ref> Traumatic Encephalopathy Syndrome (TES) is the clinical diagnosis used to describe the symptoms of a living person suspected of having CTE. While CTE can only be definitively diagnosed after death via brain autopsy, TES allows doctors to identify and manage the condition's progressive cognitive and behavioral impacts in living patients<ref>{{Cite web | title=Chronic Traumatic Encephalopathy (CTE) - Biggs Institute | url=https://biggsinstitute.org/patient-care/cte/#:~:text=Chronic%20Traumatic%20Encephalopathy%20(CTE)%20is,any%20concerns%2C%20contact%20your%20doctor. | archive-url=https://web.archive.org/web/20250729224003/https://biggsinstitute.org/patient-care/cte/ | access-date=2026-05-11 | archive-date=2025-07-29}}</ref><ref>{{cite journal |last1=Beversdorf |first1=David Q. |last2=Paretsky |first2=Melissa |title=Traumatic Encephalopathy Syndrome: Can It Stand the Test of Time? |journal=Neurology |date=12 September 2023 |volume=101 |issue=11 |pages=461–462 |doi=10.1212/WNL.0000000000207711 |pmid=37380430 }}</ref><ref name=":1">{{Cite journal|last=Concannon|first=Leah|date=2014|title=Counseling Athletes on the Risk on Chronic Traumatic Encephalopathy|journal=Sports Health|volume=6|issue=5|pages=396–401|doi=10.1177/1941738114530958|pmid=25177414|pmc=4137675}}</ref> Significant progress has been made in research, with some experts predicting diagnosis via blood test and/or PET scan could be available for clinical use within a few years.<ref>{{cite news |id={{ProQuest|2736970602}} |last1=Belson |first1=Ken |title=A Test for C.T.E. in the Living May Be Closer Than Ever |url=https://www.nytimes.com/2022/11/17/sports/football/cte-test-concussions-alzheimers.html |work=The New York Times |date=17 November 2022 }}</ref>
The lack of distinct biomarkers is the reason CTE cannot typically be diagnosed while a person is alive. Concussions are non-structural injuries and do not result in brain bleeding, which is why most concussions cannot be spotted on routine neuroimaging tests such as CT or MRI.<ref>{{cite journal |author=Poirier MP |title=Concussions: Assessment, management, and recommendations for return to activity |journal=Clinical Pediatric Emergency Medicine |volume=4|issue=3|pages=179–85|year=2003 |doi=10.1016/S1522-8401(03)00061-2}}</ref> Acute concussion symptoms (those that occur shortly after an injury) should not be confused with CTE. Differentiating between prolonged post-concussion syndrome (PCS, where symptoms begin shortly after a concussion and last for weeks, months, and sometimes even years) and CTE symptoms can be difficult. Research studies are examining whether neuroimaging can detect subtle changes in axonal integrity and structural lesions that can occur in CTE.<ref name="pmid19535999"/> By the early 2010s, more progress in in-vivo diagnostic techniques for CTE had been made, using DTI, fMRI, MRI, and MRS imaging; however, more research needs to be done before any such techniques can be validated.<ref name="Baugh C et al 2012 244–254"/>
PET tracers that bind specifically to tau protein are desired to aid the diagnosis of CTE in living individuals. One candidate is the tracer {{Not a typo|[<u></u><sup>18</sup>F]FDDNP}}, which is retained in the brain in individuals with several dementing disorders such as Alzheimer's disease, Down syndrome, progressive supranuclear palsy, corticobasal degeneration, familial frontotemporal dementia, and Creutzfeldt–Jakob disease.<ref name=Villemagne2015>{{cite journal |last1=Villemagne |first1=Victor L |last2=Fodero-Tavoletti |first2=Michelle T |last3=Masters |first3=Colin L |last4=Rowe |first4=Christopher C |title=Tau imaging: early progress and future directions |journal=The Lancet Neurology |date=January 2015 |volume=14 |issue=1 |pages=114–124 |doi=10.1016/S1474-4422(14)70252-2 |pmid=25496902 }}</ref> In a small study of 5 retired NFL players with cognitive and mood symptoms, the PET scans revealed accumulation of the tracer in their brains.<ref>{{cite journal |last1=Small |first1=Gary W. |last2=Kepe |first2=Vladimir |last3=Siddarth |first3=Prabha |last4=Ercoli |first4=Linda M. |last5=Merrill |first5=David A. |last6=Donoghue |first6=Natacha |last7=Bookheimer |first7=Susan Y. |last8=Martinez |first8=Jacqueline |last9=Omalu |first9=Bennet |last10=Bailes |first10=Julian |last11=Barrio |first11=Jorge R. |title=PET Scanning of Brain Tau in Retired National Football League Players: Preliminary Findings |journal=The American Journal of Geriatric Psychiatry |date=February 2013 |volume=21 |issue=2 |pages=138–144 |doi=10.1016/j.jagp.2012.11.019 |pmid=23343487 }}</ref> However, {{Not a typo|[<sup>18</sup>F]FDDNP}} binds to beta-amyloid and other proteins as well. Moreover, the sites in the brain where the tracer was retained were inconsistent with the known neuropathology of CTE.<ref name=Montenigro2015>{{cite journal |last1=Montenigro |first1=Philip H. |last2=Corp |first2=Daniel T. |last3=Stein |first3=Thor D. |last4=Cantu |first4=Robert C. |last5=Stern |first5=Robert A. |title=Chronic Traumatic Encephalopathy: Historical Origins and Current Perspective |journal=Annual Review of Clinical Psychology |date=28 March 2015 |volume=11 |issue=1 |pages=309–330 |doi=10.1146/annurev-clinpsy-032814-112814 |pmid=25581233 |doi-access=free }}</ref> A more promising candidate is the tracer [<sup>18</sup>F]-T807, which binds only to tau. It is being tested in several clinical trials.<ref name=Montenigro2015/>{{Update inline|date=July 2024|reason=The main text says the T807 tracer is "being" tested in several clinical trials, but the cited medical reference is 9 years out of date, having been written in March 2015.}}
A putative biomarker for CTE is the presence in serum of autoantibodies against the brain. The autoantibodies were detected in football players who experienced a large number of head hits but no concussions, suggesting that even sub-concussive episodes may be damaging to the brain. The autoantibodies may enter the brain using a disrupted blood-brain barrier, and attack neuronal cells, which are normally protected from an immune onslaught.<ref>John Mangels, [https://www.cleveland.com/science/index.ssf/2013/03/non-concussion_football_head_h.html Cleveland ''Plain Dealer''], 2013/03.</ref> Given the large numbers of neurons present in the brain (86 billion), and considering the poor penetration of antibodies across a normal blood-brain barrier, there is an extended period between the initial events (head hits) and the development of any signs or symptoms. Nevertheless, autoimmune changes in blood of players may constitute the earliest measurable event predicting CTE.<ref name="ReferenceA">{{cite journal |vauthors=Marchi N, Bazarian JJ, Puvenna V, Janigro M, Ghosh C, Zhong J, Zhu T, Blackman E, Stewart D, Ellis J, Butler R, Janigro D |title=Consequences of repeated blood-brain barrier disruption in football players |journal=PLOS ONE |volume=8 |issue=3 |article-number=e56805 |year=2013 |pmid=23483891 |pmc=3590196 |doi=10.1371/journal.pone.0056805 |bibcode=2013PLoSO...856805M |doi-access=free }}</ref>
=== Imaging === Although the diagnosis of CTE cannot be determined by imaging, the effects of head trauma may be seen with the use of structural imaging.<ref name=":0">{{Cite journal|last=Concannon|first=Leah|date=October 2014|title=Counseling Athletes on the Risk of Chronic Traumatic Encephalopathy|journal=Sports Health|volume=6|issue=5|pages=396–401|doi=10.1177/1941738114530958|pmid=25177414|pmc=4137675}}</ref> Imaging techniques include the use of magnetic resonance imaging, nuclear magnetic resonance spectroscopy, CT scan, single-photon emission computed tomography, Diffusion MRI, and Positron emission tomography (PET).<ref name=":0" /> One specific use of imaging is the use of a PET scan to evaluate for tau deposition, which has been conducted on retired NFL players.<ref name="SternAdler2019">{{cite journal |last1=Stern |first1=Robert A. |last2=Adler |first2=Charles H. |last3=Chen |first3=Kewei |last4=Navitsky |first4=Michael |last5=Luo |first5=Ji |last6=Dodick |first6=David W. |last7=Alosco |first7=Michael L. |last8=Tripodis |first8=Yorghos |last9=Goradia |first9=Dhruman D. |last10=Martin |first10=Brett |last11=Mastroeni |first11=Diego |last12=Fritts |first12=Nathan G. |last13=Jarnagin |first13=Johnny |last14=Devous |first14=Michael D. |last15=Mintun |first15=Mark A. |last16=Pontecorvo |first16=Michael J. |last17=Shenton |first17=Martha E. |last18=Reiman |first18=Eric M. |title=Tau Positron-Emission Tomography in Former National Football League Players |journal=New England Journal of Medicine |date=2 May 2019 |volume=380 |issue=18 |pages=1716–1725 |doi=10.1056/NEJMoa1900757 |pmid=30969506 |pmc=6636818 }}</ref>
Research published in 2026 found that using MRI on living patients to detect a leaky blood-brain barrier can be used as an early warning sign for CTE development in patients with a history of repetitive head impact exposure. These scans focused on the blood-brain barrier could serve as an early warning system, identifying athletes at the highest risk for future brain disease while they are still living and possibly while still playing.<ref>[https://neurosciencenews.com/blood-brain-barrier-sports-injury-cte-30361/ "How Blood-Brain Barrier Failure Drives CTE in Athletes"], Neuroscience News, March 21, 2026. Accessed March 29, 2026. "New research has identified a leaky blood-brain barrier (BBB) as the primary mechanism linking repetitive head injuries to long-term cognitive decline in retired athletes. By comparing MRI scans of living rugby players and boxers with post-mortem tissue from athletes diagnosed with Chronic Traumatic Encephalopathy (CTE), the team discovered that this barrier remains compromised years after retirement."</ref>
== Prevention ==
The use of helmets and mouth guards has been put forward as a possible preventative measure; though neither has significant research to support its use,<ref>{{cite journal |last1=Sone |first1=Je Yeong |last2=Kondziolka |first2=Douglas |last3=Huang |first3=Jason H. |last4=Samadani |first4=Uzma |title=Helmet efficacy against concussion and traumatic brain injury: a review |journal=Journal of Neurosurgery |date=March 2017 |volume=126 |issue=3 |pages=768–781 |doi=10.3171/2016.2.JNS151972 |pmid=27231972 }}</ref> both have been shown to reduce direct head trauma.<ref name=":2">{{cite journal |last1=Saffary |first1=Roya |last2=Chin |first2=Lawrence S. |last3=Cantu |first3=Robert C. |title=From Concussion to Chronic Traumatic Encephalopathy: A Review |journal=Journal of Clinical Sport Psychology |date=December 2012 |volume=6 |issue=4 |pages=351–362 |doi=10.1123/jcsp.6.4.351 }}</ref> Although there is no significant research to support the use of helmets to reduce the risk of concussions, there is evidence to support that helmet use reduces impact forces. The sports in which a helmet was effective in preventing TBI and concussions were skiing and snowboarding.<ref>{{cite journal |last1=Emery |first1=Carolyn A |last2=Black |first2=Amanda M |last3=Kolstad |first3=Ash |last4=Martinez |first4=German |last5=Nettel-Aguirre |first5=Alberto |last6=Engebretsen |first6=Lars |last7=Johnston |first7=Karen |last8=Kissick |first8=James |last9=Maddocks |first9=David |last10=Tator |first10=Charles |last11=Aubry |first11=Mark |last12=Dvořák |first12=Jiří |last13=Nagahiro |first13=Shinji |last14=Schneider |first14=Kathryn |title=What strategies can be used to effectively reduce the risk of concussion in sport? A systematic review |journal=British Journal of Sports Medicine |date=June 2017 |volume=51 |issue=12 |pages=978–984 |doi=10.1136/bjsports-2016-097452 |pmid=28254746 }}</ref> Mouth guards have been shown to decrease dental injuries, but again have not shown significant evidence to reduce concussions.<ref name=":0" /> Because repeated impacts are thought to increase the likelihood of CTE development, a growing area of practice is improved recognition and treatment for concussions and other head trauma; removal from sport participation during recovery from these traumatic injuries is essential.<ref name=":0" /> Proper return-to-play protocol after possible brain injuries is also important in decreasing the significance of future impacts.<ref name=":0" />
Medications to prevent tau misfolding and aggregation are currently under investigation, with several in clinical trials, but none having been approved. Key therapeutic approaches include tau aggregation inhibitors, kinase inhibitors to reduce phosphorylation, and tau immunotherapies designed to block the spread of toxic tau.<ref>Robbins, Miranda. [https://pmc.ncbi.nlm.nih.gov/articles/PMC10358644/ "Therapies for Tau-associated neurodegenerative disorders: targeting molecules, synapses, and cells"], ''Neural Regeneration Research'', April 20, 2023. Accessed March 29, 2026.</ref>
Efforts are being made to change the rules of contact sports to reduce the frequency and severity of blows to the head.<ref name=":0" /> Examples of these rule changes are the evolution of tackling technique rules in American football, such as the banning of helmet-first tackles, and the addition of rules to protect defenseless players. Likewise, another growing area of debate is better implementation of rules already in place to protect athletes.<ref name=":0" />
Because of the concern that boxing may cause CTE, there is a movement among medical professionals to ban the sport.<ref name="Mendez" /> Medical professionals have called for such a ban as early as the 1950s.<ref name="Mendez"/><ref name="donn">{{cite journal |vauthors=Donnelly RR, Ugbolue UC, Gao Y, Gu Y, Dutheil F, Baker JS |title=A Systematic Review and Meta-Analysis Investigating Head Trauma in Boxing |journal=Clinical Journal of Sport Medicine |volume=33 |issue=6 |pages=658–674 |date=November 2023 |pmid=37862081 |doi=10.1097/JSM.0000000000001195 |pmc=10597432}}</ref>
==Management== No disease-modifying therapy exists for CTE, and it cannot be diagnosed until a post-mortem autopsy is performed.<ref name="Alz20172">{{cite web|url=https://www.alz.org/dementia/chronic-traumatic-encephalopathy-cte-symptoms.asp|title=Alzheimer's & Dementia|website=Alzheimer's Association|publisher=alz.org|access-date=21 September 2017}}</ref> Treatment is supportive as with other forms of dementia.<ref name="NHS">{{cite web |url=https://www.nhs.uk/conditions/chronic-traumatic-encephalopathy/#treating-cte |title=Treating CTE |author=<!--Not stated--> |date= 1 October 2017|website=NHS Choices |publisher=GOV.UK |access-date=14 February 2018}}</ref> Those with CTE-related symptoms may receive medication and non-medication-related treatments.<ref>{{cite journal |last1=Cantu |first1=Robert |last2=Budson |first2=Andrew |title=Management of chronic traumatic encephalopathy |journal=Expert Review of Neurotherapeutics |date=3 October 2019 |volume=19 |issue=10 |pages=1015–1023 |doi=10.1080/14737175.2019.1633916 |pmid=31215252 }}</ref> Currently, there is no way to stop or slow the development of CTE. However, medications like Aricept (donepezil) and Namenda (memantine) can mitigate memory loss and confusion, and Aricept can improve memory, motivation, and attention by increasing acetylcholine levels in the brain. Memantine is a cognitive enhancer that can help with memory loss and confusion. These medications are also treatments for Alzheimer's disease and dementia.<ref>{{Cite web |title=CTE Treatments |url=https://concussionfoundation.org/cte-resources/treatments/#:~:text=According%20to%20Dr.,mitigate%20memory%20loss%20and%20confusion. |access-date=2024-11-19 |website=Concussion Legacy Foundation |language=en-usa}}</ref> There are also antidepressants like selective serotonin reuptake inhibitors (SSRIs), which can potentially help manage some of the behavioral and emotional symptoms associated with chronic traumatic encephalopathy (CTE) and may have a small improvement in memory function, mood, and alertness. SSRIs are often the first choice of treatment for CTE due to their effectiveness.<ref>{{Cite web |last=Memory and aging center |first=Weill Institute for Neurosciences |title=A Healthcare Provider's Guide To Chronic Traumatic Encephalopathy (CTE) |url=https://memory.ucsf.edu/sites/memory.ucsf.edu/files/wysiwyg/UCSF_CTE_Providers_7-13-17.pdf}}</ref>
Low-level laser therapy (LLLT), also known as photobiomodulation, is being investigated as a promising, non-invasive potential treatment for CTE symptoms and the underlying brain damage caused by repetitive head impacts. Research into its application for brain injuries is primarily in the stage of case studies and small clinical trials, with strong evidence from animal models.<ref>{{cite journal | title=Transcranial low level laser (Light) therapy for traumatic brain injury | journal=Journal of Biophotonics | date=2012 | volume=5 | issue=11–12 | pages=827–837 | doi=10.1002/jbio.201200077 | pmid=22807422 | pmc=5379852 | vauthors = Huang YY, Gupta A, Vecchio D, Bil De Arce VJ, Huang SF, Xuan W, Hamblin MR }}</ref>
==Epidemiology== Rates of disease vary widely according to exposure group. CTE has been diagnosed post-mortem in 99% of NFL players studied,<ref>https://www.ninds.nih.gov/news-events/news/news/cte-found-99-percent-former-nfl-players-studied</ref><ref>https://www.bumc.bu.edu/camed/2023/02/06/researchers-find-cte-in-345-of-376-former-nfl-players-studied/</ref> 96% of studied NHL players,<ref>https://www.bumc.bu.edu/camed/news-events/articles/2024/largest-study-of-cte-in-male-ice-hockey-players-finds-odds-increased-34-with-each-year-played/</ref> and over 40% of youth, high school, and college athletes under the age of 30.<ref>https://www.espn.com/espn/story/_/id/38276973/study-finds-cte-40-percent-athletes-died-30</ref> Population rates, however, are unclear.<ref name=Ste2014/> Tracking the epidemiology of CTE is difficult due to the inability to diagnose this syndrome during life.<ref>{{Cite journal |last=Stein |first=Thor |date=16 October 2024 |title=Concussion in Chronic Traumatic Encephalopathy |journal= Current Pain and Headache Reports|volume=19 |issue=10 |article-number=47 |doi=10.1007/S11916-015-0522-Z |pmid=26260277 |pmc=4633042 }}</ref>
Professional level athletes are the largest group with CTE, due to frequent concussions and sub-concussive impacts from play in contact sport.<ref name="Saulle M and Greenwald B3">{{cite journal |last1=Saulle |first1=Michael |last2=Greenwald |first2=Brian D. |title=Chronic Traumatic Encephalopathy: A Review |journal=Rehabilitation Research and Practice |date=2012 |volume=2012 |pages=1–9 |doi=10.1155/2012/816069 |pmid=22567320 |pmc=3337491 |doi-access=free }}</ref> These contact-sports include American football, Australian rules football,<ref name="urlCTE discovered in Polly Farmers brain in AFL-first">{{cite web |url=https://www.theage.com.au/sport/afl/cte-discovered-in-polly-farmer-s-brain-in-landmark-afl-first-20200226-p544oq.html |title=CTE discovered in Polly Farmer's brain in AFL-first |date=26 February 2020 }}</ref> ice hockey, Rugby football (Rugby union and Rugby league),<ref name="Soccer and Rugby3">{{cite web|url=https://www.traumaticbraininjury.net/first-soccer-and-rugby-players-diagnosed-with-cte/|title=First Soccer and Rugby Players Diagnosed With CTE|author=Stone, Paul|date=18 March 2014|publisher=Neurologic Rehabilitation Institute at Brookhaven Hospital|access-date=21 March 2016}}</ref> boxing, kickboxing, mixed martial arts, association football,<ref name="NEUROPATH20172">{{cite journal|last1=Ling|first1=Helen|last2=Morris|first2=Huw R.|last3=Neal|first3=James W.|last4=Lees|first4=Andrew J.|last5=Hardy|first5=John|last6=Holton|first6=Janice L.|last7=Revesz|first7=Tamas|last8=Williams|first8=David D.R.|date=March 2017|title=Mixed pathologies including chronic traumatic encephalopathy account for dementia in retired association football (soccer) players|journal=Acta Neuropathologica|volume=133|issue=3|pages=337–52|doi=10.1007/s00401-017-1680-3|pmc=5325836|pmid=28205009}}</ref><ref name="Soccer and Rugby3" /> and wrestling.<ref name="Daneshvar DH 20113">{{cite journal|vauthors=Daneshvar DH, Nowinski CJ, McKee AC, Cantu RC|year=2011|title=The epidemiology of sport-related concussion|journal=Clin Sports Med|volume=30|issue=1|pages=1–17, vii|doi=10.1016/j.csm.2010.08.006|pmc=2987636|pmid=21074078}}</ref> In association football, only prolific headers are known to have developed CTE.<ref name="NEUROPATH20172" /> Cases of CTE have also been recorded in baseball.<ref name="urlBaseballs New Three-Letter Word: CTE - The Good Men Project">{{cite news |url=https://goodmenproject.com/featured-content/baseballs-new-three-letter-word-cte/ |title=Baseball's New Three-Letter Word: CTE |newspaper= The Good Men Project |date=2 November 2018 |last1=Cohen |first1=Neil }}</ref> While not a contact sport, dangers include collisions between fielders, being struck by a ball travelling at {{Convert|90|to|105|mph}} and collisions at bases with other players.<ref>{{cite magazine|last=Comeaux|first=Eddie|url=https://www.abca.org/magazine/magazine/2014-2-Spring/Quick_Pitch_Less_Violent_Sports_Arent_Exempt.aspx |title=Quick Pitch: Less Violent Sports Aren't Exempt – Evidence of Brain Trauma Disease CTE Found in Baseball|work=Inside Pitch|date=Spring 2014|access-date=March 29, 2026}}</ref>
According to a 2017 study on brains of deceased football players that were donated to a brain bank, 99% of tested brains of NFL players, 88% of CFL players, 64% of semi-professional players, 91% of college football players, and 21% of high school football players had various stages of CTE.<ref name=":6" /> A 2023 study found the presence of CTE in over 40% of all athletes exposed to repetitive head impacts and who had died before the age of 30.<ref>https://www.espn.com/espn/story/_/id/38276973/study-finds-cte-40-percent-athletes-died-30</ref>
In regards to ice hockey, as with other sports, the risk is highly linked to career duration. The odds of developing CTE increase by 34% for every additional year of hockey played.<ref>{{Cite web | title=Study reveals cumulative CTE risk in ice hockey players: years of play linked to increased odds — Concussion Alliance | url=https://www.concussionalliance.org/blog/study-reveals-cumulative-cte-risk-in-ice-hockey-players-years-of-play-linked-to-increased-odds#:~:text=A%20recent%20study%20published%20in,the%20severity%20of%20the%20condition. | access-date=2026-05-11 | website=www.concussionalliance.org}}</ref> The following percentages having been determined from study: < 13 years of play has a ~19% prevalence of CTE. 13–23 years of play has a ~52% prevalence. 23 years of play has a ~96% prevalence.<ref>{{Cite web | title=CTE Evident in Brains of Deceased Ice Hockey Players {{!}} MedPage Today | url=https://www.medpagetoday.com/neurology/headtrauma/113223#:~:text=Key%20Takeaways,a%20new%20tab%20or%20window. | archive-url=https://web.archive.org/web/20241219113925/https://www.medpagetoday.com/neurology/headtrauma/113223 | access-date=2026-05-11 | archive-date=2024-12-19}}</ref> In 69% of cases studied, other neuropathologies were present, 54% of which coexisted alongside CTE, highlighting that CTE frequently co-occurs with other brain pathologies rather than developing in isolation.<ref>https://pubmed.ncbi.nlm.nih.gov/33627496/</ref>
As reported in a study published by Roberts, about 11% of the retired boxers he examined had a mild case of CTE, and about 6% of the boxers had major neurological problems. Through these clinical examinations, Roberts was able to establish associations between exposure to violence and the effects of CTE. He stated that among the boxers who are over the age of 50 and fought in over 150 fights, about 50% of them had CTE. This number was compared to the 7% of the boxers who had CTE and had less than 50 fights.<ref>{{cite journal |last1=Iverson |first1=Grant L. |title=Suicide and Chronic Traumatic Encephalopathy |journal=The Journal of Neuropsychiatry and Clinical Neurosciences |date=January 2016 |volume=28 |issue=1 |pages=9–16 |doi=10.1176/appi.neuropsych.15070172 |pmid=26449269 }}</ref>
Other individuals diagnosed with CTE were those involved in military or police service, had a previous history of chronic seizures, were domestically abused, or were involved in activities resulting in repetitive head collisions.<ref>{{cite journal|vauthors=Daneshvar DH, Riley DO, Nowinski CJ, McKee AC, Stern RA, Cantu RC|year=2011|title=Long-term consequences: effects on normal development profile after concussion|journal=Phys Med Rehabil Clin N Am|volume=22|issue=4|pages=683–700, ix|doi=10.1016/j.pmr.2011.08.009|pmc=3208826|pmid=22050943}}</ref><ref name=":0"/><ref name=":22">{{Cite journal|last=Shetty|first=Teena|title=Imaging in Chronic Traumatic Encephalopathy and Traumatic Brain Injury|journal=Sports Health|volume=8|issue=1|pages=26–36|pmid=26733590|year=2016|doi=10.1177/1941738115588745|pmc=4702153}}</ref>
===Comorbidity===
====Parkinsonism====
In individuals with diagnosed CTE, roughly 24.7% exhibited parkinsonism during their lives.<ref>{{Cite web | title=Archived copy | url=https://jamanetwork.com/journals/jamaneurology/fullarticle/2820667#:~:text=Results%20Of%20481%20male%20brain,02)%20were%20associated%20with%20parkinsonism. | archive-url=https://web.archive.org/web/20240715164552/https://jamanetwork.com/journals/jamaneurology/fullarticle/2820667 | archive-date=2024-07-15}}</ref> It's been found that the risk of developing Lewy Body Disease or advanced parkinsonism increases by roughly 50% for every 8 years of participation in contact sports.<ref>{{Cite web | title=Study Reveals Link Between Playing Contact Sports, Parkinsonism in Individuals with Chronic Traumatic Encephalopathy {{!}} Chobanian & Avedisian School of Medicine | url=https://www.bumc.bu.edu/camed/medicine/articles/2025/study-reveals-link-between-playing-contact-sports-parkinsonism-in-individuals-with-chronic-traumatic-encephalopathy/#:~:text=Research-,Study%20Reveals%20Link%20Between%20Playing%20Contact%20Sports%2C%20Parkinsonism%20in%20Individuals,not%20have%20Lewy%20body%20pathology. | access-date=2026-05-11 | website=www.bumc.bu.edu}}</ref> While typical Parkinson’s disease is defined by Lewy bodies, most (75.9%) of CTE donors with parkinsonism did not have Lewy bodies. Instead, their symptoms were primarily driven by CTE-related tau pathology and neuronal loss in the areas associated with classic parkinsonism (the substantia nigra).<ref>{{Cite web | title=Archived copy | url=https://jamanetwork.com/journals/jamaneurology/fullarticle/2820667#:~:text=Results%20Of%20481%20male%20brain,02)%20were%20associated%20with%20parkinsonism. | archive-url=https://web.archive.org/web/20240715164552/https://jamanetwork.com/journals/jamaneurology/fullarticle/2820667 | archive-date=2024-07-15}}</ref> CTE patients with parkinsonism were typically older at death (average age 71.5 vs. 54.1) and had more advanced CTE (such as Stage IV) than those without motor symptoms.<ref>https://neurologytoday.aan.com/doi/10.1097/01.NT.0001052396.65577.2e</ref>
====Lou Gehrig's disease====
There is an association between head trauma and amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, in which the risk of ALS has been reported to be higher among contact sport athletes and veterans.<ref>{{Cite web | title=Researchers Discover Brain Trauma in Sports May Cause a New Disease That Mimics ALS {{!}} Chobanian & Avedisian School of Medicine | url=https://www.bumc.bu.edu/camed/2010/08/17/researchers-discover-brain-trauma-in-sports-may-cause-a-new-disease-that-mimics-als/#:~:text=CTE%2C%20originally%20referred%20to%20as,Head%2C%20Neck%20and%20Spine%20Committee. | access-date=2026-05-11 | website=www.bumc.bu.edu}}</ref> Lou Gehrig was famous as a baseball player, a sport with minimal contact, but he had suffered numerous concussions as a football player in his early career. There is a possible link between intense or repetitive head trauma and an ALS-like motor neuron disease in some individuals, sometimes referred to as CTE-M or CTE-ALS. 4-6% of those with CTE ended up demonstrating either clinical or pathological characteristics of ALS (referred to as CTE-ALS), and the exact mechanism for the correlation between the two disorders remains unclear.<ref>{{Cite web | title=Researchers Uncover a Common Link Between ALS and CTE {{!}} The ALS Association | url=https://www.als.org/blog/researchers-uncover-common-link-between-als-and-cte#:~:text=Recent%20studies%20point%20to%20a,that%20lead%20to%20cell%20death. | archive-url=https://web.archive.org/web/20210702133048/https://www.als.org/blog/researchers-uncover-common-link-between-als-and-cte | access-date=2026-05-11 | archive-date=2021-07-02}}</ref> It is known that both diseases involve abnormal protein accumulations. While CTE is primarily a tauopathy, ALS is often linked to a protein called TDP-43, which is also frequently found in advanced CTE cases.<ref>{{Cite web | title=Checking your browser - reCAPTCHA | url=https://pmc.ncbi.nlm.nih.gov/articles/PMC6927868/#:~:text=Abstract,changes%20(p%20%3C%200.001). | access-date=2026-05-11 | website=pmc.ncbi.nlm.nih.gov}}</ref><ref>{{Cite web | title=Checking your browser - reCAPTCHA | url=https://pmc.ncbi.nlm.nih.gov/articles/PMC5451091/#:~:text=More%20recently%2C%20a%20large%20population,head%20injuries%20on%20ALS%20risk. | access-date=2026-05-11 | website=pmc.ncbi.nlm.nih.gov}}</ref>
Patients with both conditions (comorbid ALS and CTE) often experience a more severe clinical course, including earlier behavioral changes, with speech and swallowing being affected earlier than in typical ALS.<ref>{{Cite web | title=CTE link to ALS strengthened with findings of Kevin Turner's autopsy | url=https://www.statnews.com/2016/11/03/cte-als-kevin-turner-autopsy/#:~:text=Head%20trauma%20link%20to%20ALS,ALS%2C%20and%20may%20be%20misdiagnosed. | access-date=2026-05-11 | website=www.statnews.com}}</ref>
====Substance misuse====
High rates of alcohol and drug abuse are documented in patients with suspected CTE, often as a way to self-medicate for chronic pain, mood swings, or sleep issues.<ref>{{Cite web | title=Behavioral Health Symptoms Associated With Chronic Traumatic Encephalopathy: A Critical Review of the Literature and Recommendations for Treatment and Research {{!}} The Journal of Neuropsychiatry and Clinical Neurosciences | url=https://psychiatryonline.org/doi/full/10.1176/appi.neuropsych.13090201 | archive-url=https://web.archive.org/web/20241127021036/https://psychiatryonline.org/doi/full/10.1176/appi.neuropsych.13090201 | access-date=2026-05-11 | archive-date=2024-11-27}}</ref>
==History== CTE was originally studied in boxers in the 1920s as "punch-drunk syndrome." The punch-drunk syndrome was first described in 1928 by a forensic pathologist, Harrison Stanford Martland, who was the chief medical examiner of Essex County in Newark, New Jersey, in a ''Journal of the American Medical Association'' article, in which he noted the tremors, slowed movement, confusion and speech problems typical of the condition.<ref>{{cite journal |author= Martland HS|title=Punch Drunk |journal=Journal of the American Medical Association |volume=91 |issue=15 |pages=1103–07|year=1928 |doi=10.1001/jama.1928.02700150029009 }}</ref> The term "punch-drunk" was replaced with "dementia pugilistica" in 1937 by J.A. Millsbaugh, as he felt the term was condescending to former boxers.<ref>{{cite journal |last1=Castellani |first1=Rudy J. |last2=Perry |first2=George |title=Dementia Pugilistica Revisited |journal=Journal of Alzheimer's Disease |date=7 November 2017 |volume=60 |issue=4 |pages=1209–21|doi=10.3233/JAD-170669 |pmid=29036831 |pmc=5676846 }}</ref> The initial diagnosis of ''dementia pugilistica'' was derived from the Latin word for boxer, ''pugil'' (akin to ''pugnus'' 'fist', ''pugnāre'' 'to fight').<ref>[http://dictionary.reference.com/browse/pugilism Pugilism (origin)], retrieved on 2 February 2013.</ref><ref>NCERx. 2005. [http://www.about-dementia.com/dementia/brain-trauma.php Brain Trauma, Subdural Hematoma and Dementia Pugilistica] {{Webarchive|url=https://web.archive.org/web/20070527104633/http://www.about-dementia.com/dementia/brain-trauma.php |date=27 May 2007 }}. About – dementia.com. Retrieved on 19 December 2007.</ref>
Other terms for the condition have included chronic boxer's encephalopathy, traumatic boxer's encephalopathy, boxer's dementia, pugilistic dementia, chronic traumatic brain injury associated with boxing (CTBI-B), and punch-drunk syndrome.<ref name="Alz2017" />
Neurologist Macdonald Critchley wrote a 1949 paper titled "Punch-drunk syndromes: the chronic traumatic encephalopathy of boxers".<ref>[https://newyork.cbslocal.com/2015/12/17/concussion-bennet-omalu-nfl/ "'Concussion' Subject Bennet Omalu Exaggerated His Role, Researchers Say"]. CBS New York. 17 December 2015.</ref> CTE was first recognized as affecting individuals who took considerable blows to the head, but was believed to be confined to boxers and not other athletes. As evidence pertaining to the clinical and neuropathological consequences of repeated mild head trauma grew, it became clear that this pattern of neurodegeneration was not restricted to boxers, and the term chronic traumatic encephalopathy became most widely used.<ref>{{cite journal |author=Martland H | title=Punch Drunk|journal=The Journal of the American Medical Association |volume=91|issue=15 |pages=1103–07 |year=1928 |doi=10.1001/jama.1928.02700150029009}}</ref><ref>{{cite journal | pmc = 2995699 |pmid=21074091 |doi=10.1016/j.csm.2010.09.007 |volume=30 |issue=1 |title=Chronic traumatic encephalopathy: a potential late effect of sport-related concussive and subconcussive head trauma |year=2011 |journal=Clin Sports Med |pages=179–88, xi |vauthors=Gavett BE, Stern RA, McKee AC}}</ref>
In 2002, Bennet Omalu<ref>{{Cite web |date=2016-11-12 |title=Physician who discovered CTE in NFL players gets AMA's highest honor |url=https://www.ama-assn.org/delivering-care/public-health/physician-who-discovered-cte-nfl-players-gets-ama-s-highest-honor |access-date=2024-11-19 |website=American Medical Association |language=en}}</ref> performed an autopsy on American football player Mike Webster. Omalu concluded that Webster was the first person to be officially diagnosed with CTE. Omalu expected the autopsy to reveal a brain affected by Alzheimer's.<ref>{{Cite web |title=tag page |url=https://www.pbs.org/wgbh/pages/frontline/oral-history/league-of-denial/cte-discovery-of-a-new-disease/#:~:text=Mike%20Webster's%20Legacy-,Dr.,chronic%20traumatic%20encephalopathy,%20or%20CTE. |access-date=2024-11-19 |website=FRONTLINE |language=en}}</ref> Instead, after fixing and dissecting the brain, Omalu observed abnormal proteins tangles that distinguish CTE from Alzheimer's disease.{{fact|date=August 2025}}
A famous case of CTE is that of former NFL player Aaron Hernandez.<ref>{{Cite web |last=Levenson |first=Eric |date=2024-10-21 |title=A timeline of Aaron Hernandez's football career, criminal cases and death |url=https://www.cnn.com/2024/10/21/us/aaron-hernandez-life-death-timeline/index.html |access-date=2024-11-19 |website=CNN |language=en}}</ref> Two years into a jail sentence for murder, Hernandez was found dead after he hanged himself in his cell. An autopsy found stage 3 CTE, a severity rarely seen at his age of 27 at death.<ref>{{Cite web |last=Bracken |first=Tara |date=2020-01-20 |title=Aaron Hernandez's CTE Worst Seen in a Young Person |url=https://www.bu.edu/articles/2017/aaron-hernandez-cte-worst-seen-in-young-person/ |access-date=2024-11-19 |website=Boston University |language=en}}</ref>
In October 2022, the United States National Institutes of Health formally acknowledged there was a causal link between repeated blows to the head and CTE.<ref>{{Cite web |date=2022-10-24 |title=US health body rules collision sports cause CTE in landmark change |url=https://www.theguardian.com/sport/2022/oct/24/us-health-body-rules-collision-sports-cause-cte-in-landmark-change |access-date=2022-10-25 |website=The Guardian |language=en}}</ref>
==Research== In 2005, forensic pathologist Bennet Omalu, along with colleagues in the Department of Pathology at the University of Pittsburgh, published a paper, "Chronic Traumatic Encephalopathy in a National Football League Player", in the journal ''Neurosurgery'', based on analysis of the brain of deceased former NFL center Mike Webster. This was then followed by a paper on a second case in 2006 describing similar pathology, based on findings in the brain of former NFL player Terry Long.<ref>{{cite journal |last1=Omalu |first1=Bennet I. |last2=DeKosky |first2=Steven T. |last3=Hamilton |first3=Ronald L. |last4=Minster |first4=Ryan L. |last5=Kamboh |first5=M. Ilyas |last6=Shakir |first6=Abdulrezak M. |last7=Wecht |first7=Cyril H. |title=Chronic traumatic encephalopathy in a national football league player: part II |journal=Neurosurgery |date=November 2006 |volume=59 |issue=5 |pages=1086–1093 |doi=10.1227/01.NEU.0000245601.69451.27 |pmid=17143242 }}</ref>
In 2008, the Center for the Study of Traumatic Encephalopathy at the BU School of Medicine (now the BU CTE Center) started the VA-BU-CLF Brain Bank at the Bedford Veterans Administration Hospital to analyze the effects of CTE and other neurodegenerative diseases on the brain and spinal cord of athletes, military veterans, and civilians.<ref name="McKee2013"/><ref>{{Cite web|title=VA-BU-CLF Brain Bank {{!}} CTE Center|url=https://www.bu.edu/cte/our-research/brain-bank/|access-date=2021-08-12|website=www.bu.edu|language=en}}</ref> To date, the VA-BU-CLF Brain Bank is the largest CTE tissue repository in the world, with over 1000 brain donors.<ref name="Baugh C et al 2012 244–254"/><ref>{{Cite web|title=1000 Reasons {{!}} Concussion Legacy Foundation|url=https://concussionfoundation.org/1000reasons|access-date=2021-08-12|website=concussionfoundation.org}}</ref>
On 21 December 2009, the National Football League Players Association announced that it would collaborate with the BU CTE Center to support the center's study of repetitive brain trauma in athletes.<ref>Staff. [https://www.bu.edu/cste/news/press-releases/december-21-2009/ "NFL Players Association to Support Brain Trauma Research at Boston University"], Center for the Study of Traumatic Encephalopathy press release dated 21 December 2009. Accessed 17 August 2010.</ref> Additionally, in 2010 the National Football League gave the BU CTE Center a $1 million gift with no strings attached.<ref>[http://www.bu.edu/cste/about/support-and-funding/ Support and Funding] {{webarchive |url=https://web.archive.org/web/20100715102220/http://www.bu.edu/cste/about/support-and-funding/ |date=15 July 2010 }}, Center for the Study of Traumatic Encephalopathy. Accessed 17 August 2010.</ref><ref>{{cite news |id={{ProQuest|2218823712}} |last1=Schwarz |first1=Alan |title=N.F.L. Donates $1 Million for Brain Studies |url=https://archive.nytimes.com/fifthdown.blogs.nytimes.com/2010/04/20/n-f-l-donates-1-million-for-brain-studies/ |work=The Fifth Down |publisher=The New York Times |date=20 April 2010 }}</ref> In 2008, twelve living athletes (active and retired), including hockey players Pat LaFontaine and Noah Welch as well as former NFL star Ted Johnson, committed to donate their brains to VA-BU-CLF Brain Bank after their deaths.<ref>{{cite news |url=http://www.canada.com/edmontonjournal/news/sports/story.html?id=4d141696-f5f9-411c-92a2-57d3aa5802b1 |title=Welch to donate brain for concussion study |access-date=18 December 2008 |newspaper=Edmonton Journal |archive-url=https://web.archive.org/web/20101006035427/http://www.canada.com/edmontonjournal/news/sports/story.html?id=4d141696-f5f9-411c-92a2-57d3aa5802b1 |archive-date=6 October 2010 }}</ref> In 2009, NFL Pro Bowlers Matt Birk, Lofa Tatupu, and Sean Morey pledged to donate their brains to the VA-BU-CLF Brain Bank.<ref>Staff. [https://www.bu.edu/cste/news/press-releases/september-14-2009/ "Three active NFL Pro Bowl players to donate brains to research"], Center for the Study of Traumatic Encephalopathy press release dated 14 September 2009. Accessed 17 August 2010.</ref>
In 2010, 20 more NFL players and former players pledged to join the VA-BU-CLF Brain Donation Registry, including Chicago Bears linebacker Hunter Hillenmeyer, Hall of Famer Mike Haynes, Pro Bowlers Zach Thomas, Kyle Turley, and Conrad Dobler, Super Bowl Champion Don Hasselbeck and former pro players Lew Carpenter, and Todd Hendricks. In 2010, professional wrestlers Mick Foley, Booker T and Matt Morgan also agreed to donate their brains upon their deaths. Also in 2010, MLS player Taylor Twellman, who had to retire from the New England Revolution because of post-concussion symptoms, agreed to donate his brain upon his death. As of 2010, the VA-BU-CLF Brain Donation Registry consists of over 250 current and former athletes.<ref>Staff. [https://www.bu.edu/cste/news/press-releases/february-1-2010/ "20 more NFL stars to donate brains to research"], Center for the Study of Traumatic Encephalopathy press release dated 1 February 2010. Accessed 17 August 2010.</ref>
In 2011, former North Queensland Cowboys player Shaun Valentine became the first Australian National Rugby League player to agree to donate his brain upon his death, in response to recent concerns about the effects of concussions on Rugby League players, who do not use helmets. Also in 2011, boxer Micky Ward, whose career inspired the film ''The Fighter'', agreed to donate his brain upon his death. In 2018, NASCAR driver Dale Earnhardt Jr., who retired in 2017 citing multiple concussions, became the first auto racing competitor to agree to donate his brain upon his death.<ref>Boren, Cindy. [https://www.washingtonpost.com/news/early-lead/wp/2016/03/28/dale-earnhardt-jr-plans-to-donate-his-brain-for-concussion-research/ "Dale Earnhardt Jr. plans to donate his brain for concussion research"], ''The Washington Post'', 28 March 2016. Accessed 28 December 2021. "He announced the most Dale Earnhardt Jr. way possible, with a nonchalant tweet on a Saturday night. That's how NASCAR's most popular driver disclosed that he would donate his brain posthumously to science. His announcement came in response to a ''Sports Illustrated'' tweet and responses about three members of the Oakland Raiders decided to donate their brains to the Concussion Legacy Foundation after learning that Hall of Famer Ken Stabler's brain showed evidence of chronic traumatic encephalopathy at autopsy."</ref>
In related research, the Center for the Study of Retired Athletes, which is part of the Department of Exercise and Sport Science at the University of North Carolina at Chapel Hill, is conducting research funded by National Football League Charities to "study former football players, a population with a high prevalence of exposure to prior Mild Traumatic Brain Injury (MTBI) and sub-concussive impacts, in order to investigate the association between increased football exposure and recurrent MTBI and neurodegenerative disorders such as cognitive impairment and Alzheimer's disease (AD)".<ref>{{cite web |url=http://exss.unc.edu/research-and-laboratories/center-for-the-study-of-retired-athletes/current-research/ |title=A Study on the Association Between Football Exposure and Dementia in Retired Football Players |publisher=UNC College of Arts and Sciences |access-date=1 August 2012 |archive-url=https://web.archive.org/web/20120811082425/http://exss.unc.edu/research-and-laboratories/center-for-the-study-of-retired-athletes/current-research/ |archive-date=11 August 2012 }}</ref>
In February 2011, former NFL player Dave Duerson committed suicide via a gunshot to his chest, thus leaving his brain intact.<ref name=NBC01>Smith, Michael David, [http://profootballtalk.nbcsports.com/2012/05/03/boston-researchers-request-junior-seaus-brain/ "Boston researchers request Junior Seau's brain"]. NBC Sports Pro Football Talk, 3 May 2012. Retrieved 3 May 2012.</ref> Duerson left text messages to loved ones asking that his brain be donated to research for CTE.<ref>{{cite web |url=http://www.nbcchicago.com/blogs/grizzly-detail/Dave-Duerson-Committed-Suicide-Medical-Examiner-116539023.html |title=Dave Duerson Committed Suicide: Medical Examiner |access-date=20 February 2011 |last=Kusinski |first=Peggy |date=1 February 2011|work=NBC Chicago}}</ref> The family got in touch with representatives of the Boston University center studying the condition, said Robert Stern, the co-director of the research group. Stern said Duerson's gift was the first time of which he was aware that such a request had been made by someone who had committed suicide that was potentially linked to CTE.<ref name=NYT220>{{cite news |url=https://www.nytimes.com/2011/02/20/sports/football/20duerson.html |title=Before Suicide, Duerson Asked for Brain Study |work=The New York Times |first=Alan |last=Schwarz |author-link=Alan Schwarz |date=20 February 2011}}</ref> Stern and his colleagues found high levels of the protein tau in Duerson's brain. These elevated levels, which were abnormally clumped and pooled along the brain sulci,<ref name="McKee2013"/> are indicative of CTE.<ref name="Deardorff">{{cite news |last1=Deardorff |first1=Julie |date=2 May 2011 |title=Duerson's brain was damaged, study shows |newspaper=Chicago Tribune |url=http://articles.chicagotribune.com/2011-05-02/sports/ct-spt-0503-duerson-brain--20110502_1_study-of-traumatic-encephalopathy-duerson-family-brain-bank |archive-url=https://web.archive.org/web/20111008104702/http://articles.chicagotribune.com/2011-05-02/sports/ct-spt-0503-duerson-brain--20110502_1_study-of-traumatic-encephalopathy-duerson-family-brain-bank |archive-date=8 October 2011 }}</ref>
In July 2010, NHL enforcer Bob Probert died of heart failure. Before his death, he asked his wife to donate his brain to CTE research because it was noticed that Probert experienced a mental decline in his 40s. In March 2011, researchers at Boston University concluded that Probert had CTE upon analysis of the brain tissue he donated. He was the second NHL player from the program at the BU CTE Center to be diagnosed with CTE postmortem.<ref>{{cite news |url=https://www.nytimes.com/2011/03/03/sports/hockey/03fighter.html |author= Schwarz, Alan |title=Hockey Brawler Paid Price, With Brain Trauma |newspaper=The New York Times |date=2 March 2011 |access-date=14 March 2011}}</ref>
The BU CTE Center has also found indications of links between amyotrophic lateral sclerosis (ALS) and CTE in athletes who have participated in contact sports. Tissue for the study was donated by twelve athletes and their families to the VA-BU-CLF Brain Bank at the Bedford, Massachusetts VA Medical Center.<ref>[https://www.bumc.bu.edu/busm-news/2010/08/17/researchers-discover-brain-trauma-in-sports-may-cause-a-new-disease-that-mimics-als/ "Researchers Discover Brain Trauma in Sports May Cause a New Disease That Mimics ALS"], BUSM press release, 17 August 2010 3:41 pm. Retrieved 11 September 2011.</ref>
In 2013, President Barack Obama announced the creation of the Chronic Effects of Neurotrauma Consortium or CENC, a federally funded research project devised to address the long-term effects of mild traumatic brain injury in military service personnel (SMs) and veterans.<ref>{{cite web |title=Obama Introduces New PTSD and Education Programs | website=military.com |last=Jordan |first=Bryant |date=12 August 2013 |url=https://www.military.com/daily-news/2013/08/12/obama-introduces-new-ptsd-and-education-programs.html |access-date=2 May 2014}}</ref><ref>{{cite web|title=Obama administration to research TBI, PTSD in new efforts Read more: Chronic Effects of Neurotrauma Consortium |website=fiercegovernment.com |url=http://www.fiercegovernment.com/story/obama-administration-research-tbi-ptsd-new-efforts/2013-08-14 |access-date=2 May 2014 |archive-url=https://web.archive.org/web/20140502230312/http://www.fiercegovernment.com/story/obama-administration-research-tbi-ptsd-new-efforts/2013-08-14 |archive-date=2 May 2014 }}</ref><ref>{{cite web |title=DoD, VA Establish Two Multi-Institutional Consortia to Research PTSD and TBI |website=va.gov |url=https://www.va.gov/opa/pressrel/pressrelease.cfm?id=2473 |access-date=2 May 2014}}</ref> The CENC is a multi-center collaboration linking premiere basic science, translational, and clinical neuroscience researchers from the DoD, VA, academic universities, and private research institutes to effectively address the scientific, diagnostic, and therapeutic ramifications of mild TBI and its long-term effects.<ref name="http://www.spectrum.vcu.edu"/><ref name="http://www.grpva.com"/><ref name="http://www.army-technology.com"/><ref name="http://www.army.mil"/><ref name="army-technology.com">{{cite web |title=RTI to research mild traumatic brain injury effects in US soldiers |website=army-technology.com |url=http://www.army-technology.com/news/newsrti-brain-injury-effects-soldiers |access-date=2 May 2014|date=2 August 2013}}</ref>
Nearly 20% of the more than 2.5 million U.S. service members (SMs) deployed since 2003 to Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) have sustained at least one traumatic brain injury (TBI), predominantly concussions (mTBI),<ref>Warden D. Military TBI during the Iraq and Afghanistan wars. J Head Trauma Rehabil. 2006; 21 (5): 398–402.</ref><ref>{{cite web |title=DoD Worldwide Numbers for TBI |website=dvbic.dcoe.mil |url=http://dvbic.dcoe.mil/dod-worldwide-numbers-tbi |access-date=4 February 2013 |archive-date=17 January 2014 |archive-url=https://web.archive.org/web/20140117020937/http://dvbic.dcoe.mil/dod-worldwide-numbers-tbi }}</ref> and almost 8% of all OEF/OIF Veterans demonstrate persistent post-TBI symptoms more than six months post-injury.<ref name="pmid22646489">{{cite journal |last1=Scholten |first1=Joel D. |last2=Sayer |first2=Nina A. |last3=Vanderploeg |first3=Rodney D. |last4=Bidelspach |first4=Douglas E. |last5=Cifu |first5=David X. |title=Analysis of US Veterans Health Administration comprehensive evaluations for traumatic brain injury in Operation Enduring Freedom and Operation Iraqi Freedom Veterans |journal=Brain Injury |date=September 2012 |volume=26 |issue=10 |pages=1177–1184 |doi=10.3109/02699052.2012.661914 |pmid=22646489 }}</ref><ref name="pmid22228249">{{cite journal |last1=Taylor |first1=Brent C. |last2=Hagel |first2=Emily M. |last3=Carlson |first3=Kathleen F. |last4=Cifu |first4=David X. |last5=Cutting |first5=Andrea |last6=Bidelspach |first6=Douglas E. |last7=Sayer |first7=Nina A. |title=Prevalence and Costs of Co-occurring Traumatic Brain Injury With and Without Psychiatric Disturbance and Pain Among Afghanistan and Iraq War Veteran VA Users |journal=Medical Care |date=April 2012 |volume=50 |issue=4 |pages=342–346 |doi=10.1097/MLR.0b013e318245a558 |pmid=22228249 }}</ref> Unlike those head injuries incurred in most sporting events, recent military head injuries are most often the result of blast wave exposure.<ref>{{cite journal |last1=Weppner |first1=Justin |last2=Linsenmeyer |first2=Mark |last3=Ide |first3=William |title=Military Blast-Related Traumatic Brain Injury |journal=Current Physical Medicine and Rehabilitation Reports |date=December 2019 |volume=7 |issue=4 |pages=323–332 |doi=10.1007/s40141-019-00241-8 }}</ref>
After a competitive application process, a consortium led by Virginia Commonwealth University was awarded funding to study brain injuries in military veterans.<ref name="http://www.spectrum.vcu.edu">{{cite web |title=Fact Sheet: Largest federal grant in VCU's history |website=spectrum.vcu.edu| url=http://www.spectrum.vcu.edu/inside-research/vcu-will-lead-62-million-study-of-traumatic-brain-injuries-in-military-personnel/ |access-date=2 May 2014}}</ref><ref name="http://www.grpva.com">{{cite web |title=VCU to lead major study of concussions |website=grpva.com |url=http://www.grpva.com/news-and-media/details/vcu-to-lead-major-study-of-concussions |access-date=2 May 2014 |archive-url=https://web.archive.org/web/20140503003008/http://www.grpva.com/news-and-media/details/vcu-to-lead-major-study-of-concussions |archive-date=3 May 2014 }}</ref><ref name="http://www.army-technology.com">{{cite web |title=Brain trust – the US consortia tacking military PTSD and brain injury | website=army-technology.com |url=http://www.army-technology.com/features/featurebrain-trust-us-consortia-tacking-military-ptsd-brain-injury/ |access-date=2 May 2014| date=9 March 2014 }}</ref>{{Unreliable source? |reason=domain on WP:BLACKLIST|date=June 2016}}<ref name="http://www.army.mil">{{cite web |title=DOD partners to combat brain injury |website=army.mil|date=19 August 2013 | url=https://www.army.mil/article/109492/DOD_partners_to_combat_brain_injury/|access-date=2 May 2014}}</ref><ref name="http://www.whitehouse.gov">{{cite web |title=Fact Sheet: The Obama Administration's Work to Honor Our Military Families and Veterans | url=https://obamawhitehouse.archives.gov/the-press-office/2013/08/10/fact-sheet-obama-administration-s-work-honor-our-military-families-and-v |access-date=2 May 2014|via=National Archives |work=whitehouse.gov |date=1 August 2013}}</ref><ref name="http://www.news.vcu.edu">{{cite web |title=Fact Sheet: VCU will lead $62 million study of traumatic brain injuries in military personnel |website=news.vcu.edu| url=https://www.news.vcu.edu/article/VCU_Will_Lead_62_Million_Study_of_Traumatic_Brain_Injuries_in |access-date=2 May 2014}}</ref> The project principal investigator for the CENC is David Cifu, chairman and Herman J. Flax professor<ref>[http://www.pmr.vcu.edu/Department/Default.aspx About Us] {{webarchive |url=https://web.archive.org/web/20151222213718/http://www.pmr.vcu.edu/Department/Default.aspx |date=22 December 2015 }}, Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University. Retrieved 21 December 2015.</ref> of the Department of Physical Medicine and Rehabilitation (PM&R) at Virginia Commonwealth University (VCU) in Richmond, Virginia, with co-principal investigators Ramon Diaz-Arrastia, Professor of Neurology, Uniformed Services University of the Health Sciences,<ref name="http://www.army.mil"/> and Rick L. Williams, statistician at RTI International.{{fact|date=August 2025}}
In 2017, Aaron Hernandez, a former professional football player and convicted murderer, committed suicide at the age of 27 while in prison. His family donated his brain to the BU CTE Center. Ann McKee, the head of Center, concluded that "Hernandez had Stage 3 CTE, which researchers had never seen in a brain younger than 46 years old."<ref>{{cite news |last=Kilgore |first=Adam |title=Aaron Hernandez suffered from most severe CTE ever found in a person his age |url=https://www.washingtonpost.com/sports/aaron-hernandez-suffered-from-most-severe-cte-ever-found-in-a-person-his-age/2017/11/09/fa7cd204-c57b-11e7-afe9-4f60b5a6c4a0_story.html|access-date=12 July 2020 |newspaper=Washington Post |date=9 November 2017}}</ref>
In 2022, former NRL player and coach Paul Green died by suicide at the age of 49. Green's brain was donated to the Australian Sports Brain Bank, with his family posting on the website "In memory of our beloved Paul, we ask that you support the pioneering work of the Australian Sports Brain Bank" to raise money for further understanding of CTE.<ref>{{cite news |last1=Proszenko |first1=Adrian |title=Paul Green's brain donated to Australian Sports Brain Bank |url=https://www.brisbanetimes.com.au/sport/nrl/paul-green-s-brain-donated-to-australian-sports-brain-bank-20220818-p5bavo.html |access-date=18 August 2022 |work=Brisbane Times |publisher=Nine Media}}</ref> A post-mortem examination revealed that Green was suffering from one of the most "severe forms" of CTE. Professor Michael Buckland said Green had "an organic brain disease which robbed him of his decision-making and impulse control." He added Green would likely have been "symptomatic for some time."<ref>{{cite web |last1=Waterworth |first1=Ben |title='Daddy's brain was sick': Paul Green's wife Amanda reveals truth behind death that rocked NRL |url=https://www.foxsports.com.au/nrl/nrl-news-2022-paul-green-cause-of-death-was-cte-brain-disease-wife-amanda-green-interview/news-story/509fec274b55b3d1879875b276f6b5f9 |website=foxsports.com.au |publisher=News Corporation Australia |access-date=26 October 2022 |date=22 October 2022}}</ref>
Research into the genetic component of CTE is evolving and well summarized in a recent review.<ref name=":3">{{cite journal |last1=Abdolmohammadi |first1=Bobak |last2=Dupre |first2=Alicia |last3=Evers |first3=Laney |last4=Mez |first4=Jesse |title=Genetics of Chronic Traumatic Encephalopathy |journal=Seminars in Neurology |date=August 2020 |volume=40 |issue=4 |pages=420–429 |doi=10.1055/s-0040-1713631 |pmid=32712945 }}</ref> The minor allele of TMEM106B is associated with a protective phenotype.<ref name=":3" />
In 2023, Australian rules football player Heather Anderson became the first female athlete diagnosed with CTE after her death by suicide on 13 November 2022, at the age of 28. Her brain, which was donated to the Australian Sports Brain Bank, was found to contain multiple CTE lesions, and abnormalities were found "nearly everywhere" in the cortex.<ref>{{cite web |title=Heather Anderson diagnosed with CTE in 1st case for female athlete |url=https://www.espn.com/afl/story/_/id/37956773/aflw-player-heather-anderson-first-woman-diagnosed-cte |website=ESPN |date=4 July 2023 }}</ref> Also in 2023, a study was published on 28 August in ''JAMA Neurology'' regarding brain autopsies of athletes, one of whom was the first American female athlete diagnosed with CTE; her name is unknown, but she died at age 28 and was a collegiate soccer player.<ref>{{Cite web|url=https://simhcottumwa.org/autopsy-study-of-athletes-who-died-young-shows-many-had-signs-of-cte/|title=Autopsy Study of Athletes Who Died Young Shows Many Had Signs of CTE|first=Alan|last=Mozes|date=29 August 2023}}</ref>
In March 2024, former rugby union player Billy Guyton became the first New Zealand-based athlete diagnosed with CTE following his forced retirement in 2018, due to the complications of multiple concussions, and his death by suspected suicide in 2023.<ref name=":4">{{Cite web |last=RNZ |author-link=Radio New Zealand |date=14 March 2024 |title=Brain injury from head knocks discovered in late Blues halfback |url=https://www.nzherald.co.nz/sport/rugby/brain-injury-from-head-knocks-discovered-in-late-blues-halfback-billy-guyton/5W7WY5CREFHK3HPZMDJTDMFNHY/ |access-date=16 March 2024 |website= |publisher=The New Zealand Herald |language=en-NZ}}</ref><ref name=":5">{{Cite news |last=Aylwin |first=Michael |date=14 March 2024 |title=First professional rugby union player confirmed to have died with CTE |url=https://www.theguardian.com/sport/2024/mar/14/first-professional-rugby-union-player-cte-billy-guyton |access-date=16 March 2024 |work=The Guardian |language=en-GB |issn=0261-3077}}</ref> His brain had been donated by his family to the Neurological Foundation Human Brain Bank at the University of Auckland,<ref name=":4" /> with post-mortem analyses conducted in New Zealand and Australia eventually finding "background changes consistent with global hypoxic ischaemic encephalopathy",<ref name=":4" /> as well as trauma-induced cavum septi pellucidi and age-related tau deposits.<ref name=":5" />
==See also== {{sister project|project=Wikiversity|text= Wikiversity is calling for essays on '''Concussions in Sports'''}} * Acquired brain injury * Brain damage * Chronic traumatic encephalopathy in sports * Concussions in American football * Concussions in rugby union * Health issues in American football **List of NFL players with chronic traumatic encephalopathy **Chuck Bednarik **The Hit (Chuck Bednarik) * Traumatic brain injury
== References == {{reflist}}
==External links== *{{commons category-inline}} {{Medical condition classification and resources | DiseasesDB = | ICD10 = {{ICD10|G93.8}} | ICD9 = | ICDO = | OMIM = | MedlinePlus = | eMedicineSubj = sports | eMedicineTopic = | MeshID = }} {{Neurotrauma}} {{Trauma|state=autocollapse}} {{Authority control}}
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