Chronic traumatic encephalopathy (CTE) has been scaring parents and kids away from football in recent years. However, the media exaggerates myths in life after football, including CTE.

Although head injuries are associated with CTE, there is no evidence showing that participation in collision sports or having multiple concussions cause CTE.¹

Knowledge about CTE is still in its infancy, yet research has flourished over the last 15-20 years. Despite all the research, some is good while other studies have holes. For this reason, the field of neuropathology contains controversy in the diagnosis and causes of CTE.

This post provides a brief history of CTE, the current research, and evidence that it is not specific to football. For a more detailed account on the controversy behind CTE, I highly recommend reading the book, Brainwashed: The Bad Science Behind CTE and the Plot to Destroy Football, by Merrill Hoge.

Brief History of Chronic Traumatic Encephalopathy

The disease was first termed to describe multiple psychiatric symptoms in a 28-year-old boxer in 1940.² There were other terms—Postconcussion Neurosis-Traumatic Encephalitis, Traumatic Encephalitis, Punch Drunk Syndrome—coined to describe the combination of symptoms and brain pathology seen in boxers during the 1900s; therefore, the disease term never took hold in the scientific community.²

The term reappeared in 2005 when Dr. Bennett Omalu found and named a specific pathology in the brain of former NFL player, Mike Webster. After he wrote his second CTE case study, Chris Nowinski approached Dr. Omalu about another potential case. Nowinski wanted to team up with Dr. Omalu to find and identify CTE in former athletes. They founded the Sports Legacy Institute with this goal in mind.

Then, in 2008, Nowinski decided to team up with Dr. Ann McKee at the Boston University Alzheimer’s Disease Research Center. Nowinski changed the name to the Concussion Legacy Foundation that helped find brains for the newly created Boston University Chronic Traumatic Encephalopathy (BU CTE) center. They now have a monopoly on most CTE research.

Scientific research should not be monopolized for capital gain; rather, it should involve multiple distinguished groups in the scientific community. All groups try to prove or disprove hypotheses, which then become published to build literature. Other groups can then review and replicate these studies. That is not the case for CTE research.

What is Chronic Traumatic Encephalopathy?

Chronic traumatic encephalopathy is a neurodegenerative disease associated with mild traumatic brain injuries, including concussion and non-symptomatic subconcussive impacts. Because it can only be diagnosed by neuropathological examination of the brain, the diagnosis is always post-mortem.

Specifically, CTE is a tauopathy due to accumulation of tau protein.³ Tau protein is a normal structural element in healthy neurons; however, when there is damage to neurons, tau can leak out and combine with phosphate groups (hyperphosphorylated) that leads to clumping and larger lesions.

In CTE, the tau is around neurons deep in the ridges of the brain in an irregular pattern.³ Therefore, CTE is a tauopathy that is specific to neurons located globally throughout and deep within the brain.

Discrepancies in Diagnosing Chronic Traumatic Encephalopathy

Just like any new discovery or theory in science, there has been much controversy over the definition of CTE. People often separate CTE into “classic” and “modern” forms because of the different pathologies seen in the 1900s verses the last couple of decades.^1,4

The “classic” CTE was first published in 1973 from 15 former boxers.⁵ The criteria were purely gross pathology seen with a naked eye. These criteria included atrophy or wasting of the cerebral cortex, enlarged ventricles (fluid-filled spaces within the brain), thinning of the corpus collosum that connects the two hemispheres, scarring of the cerebellum, and destruction of the septum pellucidum that separates the two hemisphere ventricles.⁵

On the other hand, “modern” CTE was first identified by Dr. Bennet Omalu in case reports from 2005-2010, but then, Dr. Ann McKee and Dr. Omalu had separate grading systems for CTE, which were published in 2009 and 2011, respectively.¹

Based on autopsies of 85 individuals with history of repetitive head trauma, McKee determined four stages of CTE that represented worsening pathology seen both globally and under the microscope. Worsening symptoms were also influential in grading stages.⁶

On the contrary, Omalu described four types of CTE based on autopsies from 17 individuals, but these types did not imply worsening pathology and did not include corresponding symptoms.⁷

Due to all these discrepancies, in 2015, the National Institute of Health (NIH) and NFL funded a consensus group to present a clear definition for CTE.⁸ While this sounds great, the group of seven neuropathologists handpicked 10 stage III and stage IV cases from BU’s files. None of Dr. Omalu’s cases nor experts from other nations were included in this consensus.

The group stated that CTE is a “pathognomonic lesion consist of [hyperphosphorylated] tau aggregates in neurons, astrocytes, and cell processes around small vessels in an irregular pattern at the depths of the cortical sulci.”⁸ While this is the current definition, the consensus group was poorly constructed, which leads to differing views across the scientific community.

Media Misconstrues CTE Prevalence Among Athletes

In recent years, the media portrays high rates of CTE among former NFL, NCAA, and high school football players; however, these results are often misconstrued. The main story that hit every major news source comes from a study showing that 99% of former NFL players had CTE.

This study is a case series of 202 former football players whose brains were donated to the BU CTE brain bank that began in 2008.⁹ The results showed that CTE were diagnosed in 177 of the 202 brains with “0 of 2 pre–high school, 3 of 14 high school, 48 of 53 college, 9 of 14 semiprofessional, 7 of 8 Canadian Football League, and 110 of 111 National Football League players.”⁹

This data show that playing football is a significant risk factor for CTE with more playing years increasing this risk. This study shows an association between football and CTE; however, there is no cause and effect relationship. Twenty-five brains that were not diagnosed with CTE; therefore, playing football for any number of years does not cause CTE.

Furthermore, the association looks so evident because the case series is from a convenience sample: players or their families donated their brains because they had mood and cognitive symptoms prior to death. They suspected something was wrong with their brains, so they were looking for a CTE diagnosis. Other former players do not have these symptoms and hence do not donate their brains.

Lastly, this study did not examine confounding variables like obesity, alcoholism, opioid abuse, and other chronic diseases, which can contribute to overall CTE pathology. For these reasons, this study does not properly identify the prevalence of CTE among former football players.

Another study from Canada examined 35 brains from 24 and 11 former football and hockey players, respectively.¹⁰ These researchers found that 17 of the 35 (49%) brains had evidence of CTE, and football players were slightly lower in percentage (46%) with 11 of 24 brains having CTE verses 6 of 11 in hockey players.¹⁰

Again, players or their families donated these brains, so they are not the best sample. At the same time, the rates of CTE are much different than the previous study by the BU CTE center. This adds to the controversy.

Better research uses randomized subjects that include players and non-players, with and without symptoms, and determining confounding variables.

Pathological Similarities Between CTE and Other Neurodegenerative Diseases

Making diagnosis more challenging, there are similarities among CTE and other neurodegenerative diseases.

Clinically, cognitive impairments and depression are present in Alzheimer’s disease, slowness in movements occur in Parkinson disease, personality changes and mood disorders are evident in Frontotemporal Dementia.¹ Pathologically, all neurodegenerative diseases share similar processes that lead to its overall presentation.

As mentioned previously, CTE is primarily a tauopathy that occurs in neurons located deep in the brain cerebral cortex.³ Alzheimer’s disease is also a tauopathy, but the pattern is more in the temporal lobe and hippocampus before spreading to the frontal lobe and rest of the brain.

At the same time, the accumulation of tau protein in the brain as neurofibrillary tangles is also seen in normal aging. One study identified abnormally phosphorylated tau protein within the brain in 2322 of 2332 cases (99.5%) aged 1-100 years old.¹¹ Also, 90% of those over 10 years and 100% of cases over 30 years of age had abnormally phosphorylated tau.¹¹

Clearly, many factors can initiate tauopathy and subsequent CTE pathology in the brain, some related to head injuries and others unrelated.

Chronic Traumatic Encephalopathy as a Neuroinflammation Problem

Furthermore, anything that causes neuroinflammation, microglial activation, and blood brain barrier disruption can be risk factors for tau accumulation.¹² Head injury can promote these consequences, but so can chronic infections and an inflammatory diet.

Also, individuals who abuse substances like opioid drugs for pain have had elevated levels of hyperphosphorylated tau accumulation and neurofibrillary tangles.^13,14 Both studies state that the microglial activation associated with opioid use is the largest driver of tau pathology.

Opioid drugs are commonly prescribed to people in chronic pain, and they were often abused by professional athletes who need to play to maintain their jobs. This is an overlooked contributing factor related to CTE. More research needs to look at long-term substance abuse and CTE in former NFL players.

CTE-like Pathology Is Not Unique to Athletes or Repetitive Head Trauma

Because accumulation of tau is very common, CTE-like pathology has been found in individuals without previous head trauma exposure.¹⁵ These include people with substance abuse, schizophrenia, temporal lobe epilepsy, and other neurodegenerative diseases.

One study from the Mayo Clinic looked at CTE pathology retrospectively.¹⁶ From 2566 autopsy cases, the researchers selected 300 former athletes and 450 non-athletes to screen the brain tissue for tau pathology and CTE. The athletes mostly played in high school, but some played beyond high school.

For the athletes, 86% had tau pathology versus 76% of the non-athletes, and this statistic was not significant. However, it emphasizes the commonality of tau pathology in aging brains. In total, 42 of the 750 brains had CTE-like pathology or CTE, and this was significantly more present in athletes (9%) verses the non-athletes (3.3%).¹⁶

This shows that a low percentage of people, whether they played contact sports or not, will develop CTE. When breaking down the athletes separately, CTE-like pathology was present in 29% of boxers, 15% football players, 14% baseball players, 12% basketball players, 10% hockey players, and 0% soccer players.¹⁶ Only five soccer players in the study was not a great sample size for an accurate representation.

Overall, this study from the Mayo Clinic exploits that CTE-like pathology is found in athletes more than non-athletes with comparable rates among all contact sports, yet the overall prevalence, especially among high school athletes, is low.

Former Athletes Unnecessarily Believe They Have CTE

Due to all the media attention and lack of scientific clarity on CTE, clinicians are wrongfully diagnosing individuals with CTE.

One study surveyed 3,913 former American-style football players between the ages of 24 and 89.¹⁷ Although CTE can only be diagnosed after death, 108 former players reported clinician-diagnosed CTE. These players were more likely to have comorbidities like sleep apnea, high cholesterol, obesity, depression, use of prescription pain medication, and heart conditions. These multiple comorbidities may be causing their symptoms.

The authors point out that doctors should explore other treatable conditions before any diagnosis of traumatic encephalopathy syndrome (TES) or possible CTE (both symptom-based diagnoses). A premature diagnosis may lead to psychological worsening of the individual and treatment neglect when their symptoms may be treatable.¹⁷

Future Research Projects To Better Diagnose Chronic Traumatic Encephalopathy

With all the lack of clarity, there is extensive research and funding going into methods that may be able to diagnose CTE in living people. In December 2015, the National Institute of Neurological Disorders and Stroke presented a seven-year grant to fund the “Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project.”¹⁸

The objectives of DIAGNOSE CTE are to develop blood, fluid, and neuroimaging biomarkers for CTE; characterize its clinical presentation and refine the diagnostic criteria for TES; and examine repetitive head impact exposure, genetic, and other risk factors. There have been some beneficial results.

A tau-specific positron emission tomography (PET) scan has shown increased tau in former football players compared with controls, but the levels do not correlate with symptoms of TES.¹⁹

In 2024, researchers found higher levels of inflammatory biomarkers IL-6 (in cerebrospinal fluid) and neurofilament light (in blood) correlate with neurobehavioral dysregulation in former football players.²⁰ However, levels were not associated with increasing repetitive head impact exposure. There is likely something else is contributing to the inflammation.

Nutrition as a Modifiable Risk Factor for Chronic Traumatic Encephalopathy

With neuroinflammation playing a role, nutrition may be a significant modifiable risk factor for developing CTE. Diet can play a role in neurodegenerative disease, but its role in CTE is unknown.

A mice study measured the effects of nutrition on preventing CTE.²¹ The researchers induced repetitive mTBIs (4 mTBIs over 7 days) to four groups of mice—no specific nutrient diet, fruit blend, vegetable blend, or combo fruit and vegetable blend diets—for the two months prior. There was also a control group that did not receive either the nutrients or the mTBIs.

The nutrient-specific diets gave the mice similar levels of specific vitamins and minerals. The brains from all the mice did not have gross changes, but the repetitive mTBIs caused a significant neuroinflammatory response, with persistent and widespread microglial activation and increased phosphorylated tau up to 6 months after the injuries.²¹

The mice began developing CTE-like pathology; however, the groups treated with the nutrients had significantly less inflammation and phosphorylated tau that was comparable to the control group.²¹ This study shows how diet may play a significant role in the development of neurodegeneration and CTE-like pathology.

Conclusion

In conclusion, chronic traumatic encephalopathy is a neurodegenerative disease associated with repetitive head trauma and only diagnosed after death. It is a real disease and a risk of playing football; however, there is no evidence that participating in collision sports like football cause CTE.

There are modifiable factors involved in CTE pathology like chronic inflammation, diet, and substance abuse. Therefore, concussion prevention strategies include ways to decrease neuroinflammation.

References

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