Exposure to Repetitive Head Impacts Is Associated With Corpus Callosum Microstructure and Plasma Total Tau in Former Professional American Football Players

Background and Objectives:Late neuropathologies of repetitive head impacts from contact sports can include chronic traumatic encephalopathy (CTE) and white matter degeneration. White matter hyperintensities (WMH) on fluid attenuated inversion recovery (FLAIR) MRI scans are often viewed as microvascular disease from vascular risk, but might have unique underlying pathologies and risk factors in the setting of repetitive head impacts. We investigated the neuropathological correlates of antemortem WMH in brain donors exposed to repetitive head impacts. The association between WMH, and repetitive head impact exposure and informant-reported cognitive and daily function were tested.Methods:This imaging-pathological correlation study included symptomatic deceased men exposed to repetitive head impacts. Donors had antemortem FLAIR scans from medical records and were without evidence of CNS neoplasm, large vessel infarcts, hemorrhage, and/or encephalomalacia. WMH were quantified using log-transformed values for total lesion volume (TLV), calculated using the lesion prediction algorithm from the Lesion Segmentation Toolbox. Neuropathological assessments included semi-quantitative ratings of white matter rarefaction, cerebrovascular disease, p-tau severity (CTE stage, dorsolateral frontal cortex), and Aβ. Among football players, years of play was a proxy for repetitive head impact exposure. Retrospective informant-reported cognitive and daily function were assessed using the Cognitive Difficulties Scale (CDS) and Functional Activities Questionnaire (FAQ). Regression models controlled for demographics, diabetes, hypertension, and MRI resolution. Statistical significance was defined as p<0.05.Results:The sample included 75 donors: 67 football players and 8 non-football contact sport athletes and/or military veterans. Dementia was the most common MRI indication (64%). Fifty-three (70.7%) had CTE at autopsy. Log-TLV was associated with white matter rarefaction (OR=2.32, 95% CI=1.03,5.24, p=0.04), arteriolosclerosis (OR=2.38, 95% CI=1.02,5.52, p=0.04), CTE stage (OR=2.58, 95% CI=1.17,5.71, p=0.02), and dorsolateral frontal p-tau severity (OR=3.03, 95% CI=1.32,6.97, p=0.01). There was no association with Aβ. More years of football play was associated with log-TLV (b=0.04, 95% CI=0.01,0.06, p=0.01). Greater log-TLV correlated with higher FAQ (unstandardized beta=4.94, 95% CI=0.42,8.57, p=0.03) and CDS scores (unstandardized beta=15.35, 95% CI=-0.27,30.97, p=0.05).Discussion:WMH might capture long-term white matter pathologies from repetitive head impacts, including those from white matter rarefaction and p-tau, in addition to microvascular disease. Prospective imaging-pathological correlation studies are needed.Classification of Evidence:This study provides Class IV evidence of associations between FLAIR white matter hyperintensities, and neuropathological changes (white matter rarefaction, arteriolosclerosis, p-tau accumulation), years of American football play, and reported cognitive symptoms in symptomatic brain donors exposed to repetitive head impacts.

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Age at First Exposure to Repetitive Head Impacts Is Associated with Smaller Thalamic Volumes in Former Professional American Football Players

Journal of Neurotrauma ◽

10.1089/neu.2017.5145 ◽

2018 ◽

Vol 35 (2) ◽

pp. 278-285 ◽

Cited By ~ 38

Author(s):

Vivian Schultz ◽

Robert A. Stern ◽

Yorghos Tripodis ◽

Julie Stamm ◽

Pawel Wrobel ◽

...

Keyword(s):

American Football ◽

Football Players ◽

Head Impacts ◽

Repetitive Head Impacts

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History of Chronic Traumatic Encephalopathy

Seminars in Neurology ◽

10.1055/s-0040-1713622 ◽

2020 ◽

Vol 40 (04) ◽

pp. 353-358

Author(s):

Robert C. Cantu ◽

Charles Bernick

Keyword(s):

Chronic Traumatic Encephalopathy ◽

Neurological Impairment ◽

American Football ◽

Football Players ◽

Long Term Effects ◽

Public Attention ◽

Head Impacts ◽

Repetitive Head Impacts ◽

History Of ◽

Initial Description

AbstractThe long-term effects of repetitive head impacts have been recognized for close to a century. What is now referred to as chronic traumatic encephalopathy (CTE) was first described by Martland in 1928 in a series of boxers. Over the years, several important articles were published, including Critchley's 1957 report where he introduced the term “chronic traumatic encephalopathy,” Robert's study in 1969 which provided evidence of the prevalence of neurological impairment in retired fighters, and Corsellis' initial description of the pathology of CTE. However, what brought public attention to the issue of CTE in sports were the postmortem findings of CTE pathology in professional American football players, initially reported by Omalu and subsequently in a large series by McKee. There is now standardization of pathological criteria for CTE and recognition that it can be seen across all activities that involve repetitive head impacts.

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Repetitive head impacts in a collegiate football season: Exposure and effects

International Journal of Sports Science & Coaching ◽

10.1177/17479541211027277 ◽

2021 ◽

pp. 174795412110272

Author(s):

Laura D Wilson ◽

Rachel A Hildebrand ◽

Trang Le ◽

Brett A McKinney

Keyword(s):

Reaction Time ◽

American Football ◽

Division I ◽

Football Players ◽

Short Term ◽

Head Impacts ◽

Repetitive Head Impacts ◽

The Past ◽

Acute Increase ◽

Collegiate Football

This study describes exposure to repetitive head impacts (RHI) by player position and activity during a collegiate football season, and investigates the relationship between RHI and acute (i.e., daily and weekly) and short-term (i.e., pre- to post-season) changes in balance, reaction time, symptoms, and cognition. We recorded RHI exposure in twenty Division I collegiate American football players during a single season using the Riddell InSite system. Participants sustained 4,586 impacts (4.20% high impact, i.e., >63 g; 95.79% low impact, i.e., 20–63 g). Greatest exposure to RHI was observed in running backs and defensive ends during games, and tight ends and defensive ends during practices. Running plays and team drills placed players at greatest risk for exposure during practice. Cumulative RHI exposure across the season was associated with short-term declines in reaction time (p = 0.045), but not balance or cognition. Acute decline in balance was associated with the number of impacts sustained in the past week (p < 0.05), but not the past 24 hours (p > 0.05). Acute increase in total symptom score was also associated with the number of impacts sustained in the past week (p < 0.01), but not the past 24 hours (p > 0.05). Reaction time did not decline based on impact exposure in the past 24 hours or week. This study identifies activities and positions that may put players at risk for RHI exposure, and demonstrates that RHI sustained during the course of typical American football play by non-concussed individuals may result in small changes in balance, reaction time, and symptoms, but not cognition.

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Similar head impact acceleration measured using instrumented ear patches in a junior rugby union team during matches in comparison with other sports

Journal of Neurosurgery Pediatrics ◽

10.3171/2015.12.peds15605 ◽

2016 ◽

Vol 18 (1) ◽

pp. 65-72 ◽

Cited By ~ 15

Author(s):

Doug A. King ◽

Patria A. Hume ◽

Conor Gissane ◽

Trevor N. Clark

Keyword(s):

Injury Risk ◽

Linear Acceleration ◽

Rugby Union ◽

Head Impact ◽

American Football ◽

Football Players ◽

Head Impacts ◽

Impact Acceleration ◽

The Impact ◽

Rugby Players

OBJECTIVE Direct impact with the head and the inertial loading of the head have been postulated as major mechanisms of head-related injuries, such as concussion. METHODS This descriptive observational study was conducted to quantify the head impact acceleration characteristics in under-9-year-old junior rugby union players in New Zealand. The impact magnitude, frequency, and location were collected with a wireless head impact sensor that was worn by 14 junior rugby players who participated in 4 matches. RESULTS A total of 721 impacts > 10g were recorded. The median (interquartile range [IQR]) number of impacts per player was 46 (IQR 37–58), resulting in 10 (IQR 4–18) impacts to the head per player per match. The median impact magnitudes recorded were 15g (IQR 12g–21g) for linear acceleration and 2296 rad/sec2 (IQR 1352–4152 rad/sec2) for rotational acceleration. CONCLUSIONS There were 121 impacts (16.8%) above the rotational injury risk limit and 1 (0.1%) impact above the linear injury risk limit. The acceleration magnitude and number of head impacts in junior rugby union players were higher than those previously reported in similar age-group sports participants. The median linear acceleration for the under-9-year-old rugby players were similar to 7- to 8-year-old American football players, but lower than 9- to 12-year-old youth American football players. The median rotational accelerations measured were higher than the median and 95th percentiles in youth, high school, and collegiate American football players.

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Impact on the head during collisions between university American football players - focusing on the number of head impacts and linear head acceleration -

The Journal of Physical Fitness and Sports Medicine ◽

10.7600/jpfsm.6.241 ◽

2017 ◽

Vol 6 (4) ◽

pp. 241-249 ◽

Cited By ~ 1

Author(s):

Takashi Fukuda ◽

Sekiya Koike ◽

Syumpei Miyakawa ◽

Hiroto Fujiya ◽

Yuki Yamamoto

Keyword(s):

American Football ◽

Football Players ◽

Head Acceleration ◽

Head Impacts

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Defining Exposures in Professional Football: Professional American-Style Football Players as an Occupational Cohort

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967119829212 ◽

2019 ◽

Vol 7 (2) ◽

pp. 232596711982921 ◽

Cited By ~ 4

Author(s):

Rachel G. Grashow ◽

Andrea L. Roberts ◽

Ross Zafonte ◽

Alvaro Pascual-Leone ◽

Herman Taylor ◽

...

Keyword(s):

American Football ◽

Epidemiological Methods ◽

Football Players ◽

Professional Football ◽

Head Impacts ◽

Adverse Health Outcomes ◽

Acute Injuries ◽

Full Complement ◽

Occupational Cohort

Studies of professional American football players have shown that football-related activities lead to acute injuries and may have long-term adverse health outcomes including osteoarthritis, neurocognitive impairment, and cardiovascular disease. However, the full complement of what constitutes professional football exposure has yet to be effectively articulated. Most likely, professional football exposure encompasses a multifaceted array of experiences including head impacts and joint stresses, long-term pain medication use, dietary restrictions, and strenuous training regimens. To study the health of professional American football players, characterizing the group as an occupational cohort and taking advantage of methods established within the discipline of occupational epidemiology may be beneficial. We conducted a narrative review of existing football research, occupational epidemiological methods papers, and occupational medicine studies. Here we describe the traditional occupational epidemiological approach to assessing exposure in a novel cohort and show how this framework could be implemented in studies of professional football players. In addition, we identify the specific challenges associated with studying an elite athletic occupational group, including the healthy worker effect and other types of selection and information biases, and explore these in the context of existing studies of football-related health. The application of well-established occupational epidemiological methods to professional football players may yield new insights into the effects of playing exposure and may provide opportunities for interventions to reduce harm.

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Behavioral Tackling Interventions Decrease Head Impact Frequency in American Football Players: A Critically Appraised Topic

International Journal of Athletic Therapy & Training ◽

10.1123/ijatt.2020-0019 ◽

2020 ◽

pp. 1-7

Author(s):

Ashley E. Evans ◽

Madeline Curtis ◽

Marguerite (Meg) Montjoy ◽

Erica Beidler

Keyword(s):

High School ◽

Injury Prevention ◽

Head Impact ◽

American Football ◽

Football Players ◽

Clinical Question ◽

Impact Frequency ◽

Bottom Line ◽

Head Impacts ◽

Different Types

Context: The rate of sport-related concussion diagnosis has significantly increased in recent years, which has created a need for injury prevention initiatives. There have been efforts put forth by researchers and American football organizations to teach athletes how to tackle properly in order to decrease the number of subconcussive head impacts and concussions. Clinical Question: Does the implementation of a behavioral tackling intervention decrease the head impact frequency in American football players? Clinical Bottom Line: There is moderate SORT Level B evidence to support the use of behavioral tackling interventions as a means for reducing head impact frequency in football athletes. All four included studies found a significant reduction in head impacts following a behavioral tackling intervention with study findings ranging from a 26–33% reduction in impact frequency. These findings were consistent in youth, high school, and college football players and for different types of behavioral tackling interventions. Therefore, these results indicate that behavioral tackling interventions have the potential to reduce the number of head impacts sustained by American football players, which may ultimately lead to a reduction in concussion occurrence as well.

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Chronic Traumatic Encephalopathy: Advocacy and Communicating with the Public

Seminars in Neurology ◽

10.1055/s-0040-1713621 ◽

2020 ◽

Vol 40 (04) ◽

pp. 461-468

Author(s):

Madeline Uretsky ◽

Christopher J. Nowinski

Keyword(s):

Chronic Traumatic Encephalopathy ◽

American Football ◽

Football Players ◽

Advocacy Groups ◽

Contact Sport ◽

Head Impacts ◽

The Public ◽

The Past ◽

Raising Awareness ◽

Sports Concussions

AbstractOver the past 40 years, advocacy groups have been instrumental in raising awareness for neurodegenerative diseases such as Alzheimer's disease. More recently, advocates have emerged to educate about sports concussions and chronic traumatic encephalopathy (CTE), including the Concussion Legacy Foundation (CLF). CTE is a neurodegenerative disease caused in part by repetitive head impacts (RHI). While the majority of CTE research has focused on studying former American football players, CTE has also been found in military personnel, victims of domestic violence, and contact sport athletes from high school to professional levels of play. Advocates' many goals include creating a culture of brain donation and modifying youth contact sports to decrease RHI. Here, we provide the first review of CTE advocacy, summarize the accomplishments of the CLF, and consider the connections between CTE advocacy, research, and legislation over the last decade.

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Longitudinal change in regional brain volumes with exposure to repetitive head impacts

Neurology ◽

10.1212/wnl.0000000000008817 ◽

2019 ◽

Vol 94 (3) ◽

pp. e232-e240 ◽

Cited By ~ 2

Author(s):

Charles Bernick ◽

Guogen Shan ◽

Henrik Zetterberg ◽

Sarah Banks ◽

Virendra R. Mishra ◽

...

Keyword(s):

Corpus Callosum ◽

Brain Mri ◽

Brain Regions ◽

Cognitive Testing ◽

Longitudinal Change ◽

Health Study ◽

Brain Volumes ◽

Head Impacts ◽

Repetitive Head Impacts ◽

Regional Brain

ObjectiveThis study tests the hypothesis that certain MRI-based regional brain volumes will show reductions over time in a cohort exposed to repetitive head impacts (RHI).MethodsParticipants were drawn from the Professional Fighters Brain Health Study, a longitudinal observational study of professional fighters and controls. Participants underwent annual 3T brain MRI, computerized cognitive testing, and blood sampling for determination of neurofilament light (NfL) and tau levels. Yearly change in regional brain volume was calculated for several predetermined cortical and subcortical brain volumes and the relationship with NfL and tau levels determined.ResultsA total of 204 participants who had at least 2 assessments were included in the analyses. Compared to controls, the active boxers had an average yearly rate of decline in volumes of the left thalamus (102.3 mm3/y [p = 0.0004], mid anterior corpus callosum (10.2 mm3/y [p = 0.018]), and central corpus callosum (16.5 mm3/y [p = <0.0001]). Retired boxers showed the most significant volumetric declines compared to controls in left (32.1 mm3/y [p = 0.002]) and right (30.6 mm3/y [p = 0.008]) amygdala and right hippocampus (33.5 mm3/y [p = 0.01]). Higher baseline NfL levels were associated with greater volumetric decline in left hippocampus and mid anterior corpus callosum.ConclusionVolumetric loss in different brain regions may reflect different pathologic processes at different times among individuals exposed to RHI.

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