By Ulrike W. Kaunzner, MD
Assistant Professor of Clinical Neurology, Weill Cornell Medical College
SYNOPSIS: A recent study evaluated the connection between head impact and chronic traumatic encephalopathy (CTE) in male athletes and found that the total number and severity of head impacts throughout life better predicted CTE than the number of symptomatic concussions.
SOURCE: Daneshvar DH, Nair ES, Baucom ZH, et al. Leveraging football accelerometer data to quantify associations between repetitive head impacts and chronic traumatic encephalopathy in males. Nat Commun 2023;14:3470.
Chronic traumatic encephalopathy (CTE) is a degenerative brain disorder found in people with a history of repetitive brain trauma. CTE has been described in athletes who played contact sports, including football and boxing, but it also can occur in military members or domestic violence victims. The clinical picture first was described in 1927 in boxers; however, only in the last 15 years have major studies further investigated the disease.
In 2008, the founding of the brain bank, in collaboration with the CTE Center at Boston University (BU), has led to major investigations, and significant knowledge has been gained about the pathophysiology of this disease. In CTE, there is a progressive buildup of tau protein in the brain, eventually leading to atrophy. Tau buildup in CTE is different from other tauopathies, such as Alzheimer’s disease, and other forms of neurodegenerative dementias. It is characterized by accumulation in the superficial cortex and by irregular patchy distribution in the frontal and temporal cortices. Moreover, the distribution mainly is perivascular, periventricular, and subpial, and accumulation of tau within astrocytes is characteristic.
CTE cannot be definitively diagnosed during a person’s lifetime. However, it is highly suspected in people with high-risk exposures. Different diagnostic biomarkers for CTE are in development but have not yet been validated. Currently, a definitive diagnosis can be made only at autopsy. The condition probably develops years to decades after head trauma, but cases in younger patients have been described recently. The resulting brain damage can lead to cognitive, mood, behavioral, sleep, and motor changes, and has been described in four stages, ranging from dizziness and headache in stage 1 to significant personality changes and dementia in stage 4.
The CTE center at BU reported in 2023 that 345 (91.7%) out of 376 former National Football League (NFL) players who had donated their brain to the center had CTE. The CTE center cautions that brain bank samples are subject to high selection bias, and do not indicate that more than 90% of NFL players have CTE. Assessing CTE in the general population, in a 2018 study evaluating autopsies from the Framingham Study, one person (0.6%) had CTE and, reportedly, this person was a former college football player.
The causes for CTE are not fully understood. Self-reported or informant-reported symptomatic concussions have been suspected, but this might not be the only contributing factor. In general, the development of CTE probably is associated with second impact syndrome, in which a second head injury happens before previous head injury symptoms have fully healed. Years of play have been associated with the development of CTE, and this study further evaluated contributing factors to this possible etiology.
Daneshvar et al identified 34 published helmet sensor studies specifying field positions and levels of play to quantify a player’s lifetime exposure to repetitive head impacts (RHI), including linear accelerations and rotational accelerations. Based on these studies, they developed a positional-exposure matrix (PEM) to match RHI exposure to a different cohort of 631 brain donors.
All donors were male former football players from the UNITE and Framingham Heart Study brain banks. The study group died at a mean age of 59.7 years and played, on average, 12.5 years of football. About 28%, or 180 subjects, did not have evidence of CTE. Another 163 subjects had low-stage CTE, and 288 had high-stage CTE. Mean duration of play for athletes without CTE was 9.5 years, 11.6 years for low-stage CTE, and 15 years for high-stage CTE. The mean cumulative head impact index was 4,515 (standard deviation [SD], 3,199) hits for no diagnosis of CTE, 5,553 (SD, 3,410) hits for low-grade CTE, and 7,641 (SD, 3,870) hits for severe CTE.
The number of symptomatic head injuries, reported as concussions, was not associated with CTE incidence or severity. However, the number of years playing football as well as factors measured by the PEM (cumulative head impacts, linear acceleration, rotational acceleration) were associated with CTE. Each additional year playing football was associated with a 15% increased odds of a CTE diagnosis and, for those with CTE, a 14% increased odds of severe CTE. In summary, the study showed that CTE was related to cumulative head impacts and the severity of the impacts.
COMMENTARY
This important study sheds more light on the field of CTE, a disease that has been investigated frequently over the last few years. It is known that RHI plays a role; however, the exact etiology and different components of RHI still are unclear. The study team developed a PEM similar to a job-exposure matrix to assess occupational risks, which enabled the assessment of lifetime RHI and correlated this matrix to donors’ brain pathology. The study indicates that repeated head injuries are a major driver of CTE pathology, and the accumulation and severity of all the hits to the head are the contributing factors. This is important knowledge, since small repetitive hits seem to have a major effect, rather than the previously suspected symptomatic concussions.
There are limitations, since the brain bank donors consisted of a selection of football players. However, professional league helmet data are not available and, therefore, data from helmet accelerometers studies of mostly collegiate players were matched to a cohort where 49.3% were semi-professional or professional football players. The brain donors have played at different times, and new helmet sensory data might not reflect the possible different practice and playing style of the donor cohort. Also, helmet technology and safety have changed over the last decades.
In addition, characterization and measurement of head hits were different throughout these 34 studies. Although reported concussions were not associated with CTE, the authors cautioned that diagnostic criteria for concussions have changed over time. There might also have been a recall bias of symptomatic head impacts, and concussions might not have been estimated correctly, and therefore no significant result was seen. CTE risk potentially could be lowered through play and practice changes, with the goal to minimize, and ideally prevent, the number of cumulative head impacts. However, this might require a major shift in the rules of play of a proactive contact sport such as football.
