Publications by authors named "Daniel H Daneshvar"

45 Publications

Athlete Enjoyment of Prior Education Moderates change in Concussion-Reporting Intention after Interactive Education.

Inquiry 2021 Jan-Dec;58:469580211022641

Stanford School of Medicine, Palo Alto, CA, USA.

Undiagnosed concussions increase risk of additional injuries and can prolong recovery. Because of the difficulties recognizing concussive symptoms, concussion education must specifically target improving athlete concussion reporting. Many concussion education programs are designed without significant input from athletes, resulting in a less enjoyable athlete experience, with potential implications on program efficacy. Athlete enjoyment of previous concussion education programs moderates the improvement in concussion-reporting intention after experiencing the research version of CrashCourse (CC) concussion education. Prospective cohort study. Level of evidence: Level IV. Quantitative assessment utilizing ANOVA with moderation analysis of 173 male high school football players, aged 13 to 17, who completed baseline assessments of concussion knowledge, concussion reporting, and attitudes about prior educational interventions. Athletes were subsequently shown CC, before a follow-up assessment was administered assessing the same domains. At baseline, only 58.5% of athletes reported that they enjoyed their previous concussion education. After CC, athletes were significantly more likely to endorse that they would report a suspected concussion (from 69.3% of athletes to 85.6%;  < .01). Enjoyment of previous concussion education moderated concussion-reporting intention after CC ( = .02), with CC having a greater effect on concussion-reporting intention in athletes with low enjoyment of previous concussion education ( = 0.21,  = .02), than on individuals with high enjoyment of previous concussion education ( = .99). Enjoyment of CC did not have a moderating effect on concussion-reporting intention. Athletes who previously did not enjoy concussion education exhibited greater gains in concussion-reporting intention than athletes who enjoyed previous education. Given the potential risks associated with undiagnosed concussions, concussion education has sought to improve concussion reporting. Because most athletes participate in concussion education programs due to league or state mandates, improving concussion-reporting intention in these low-enjoyment athletes is of particular relevance to improving concussion-reporting intention broadly.
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http://dx.doi.org/10.1177/00469580211022641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170270PMC
May 2021

Factors Influencing College Football Players' Beliefs About Incurring Football-Related Dementia.

Orthop J Sports Med 2021 Apr 28;9(4):23259671211001129. Epub 2021 Apr 28.

Department of Pediatrics, University of Washington, Seattle, Washington, USA.

Background: Football participation is associated with risks to acute and long-term health, including the possibility of incurring football-related dementia. Concerns have been raised regarding media coverage of these risks, which may have influenced athletes' beliefs. However, little is known about football players' views on football-related dementia. The risk-perception literature suggests that related risk perceptions and features of individual cognition, such as the ability to switch to reasoned, deliberative thinking, may influence individual perception of a long-term risk.

Purpose: To evaluate factors influencing college football players' belief that they are likely to incur football-related dementia in the future.

Study Design: Cross-sectional study.

Methods: Members of 4 National Collegiate Athletic Association Division I Power 5 Football teams participated in this survey-based study, providing responses to demographic, athletic, and risk-posture questions, and completed the cognitive reflection test. Logistic regressions were used to evaluate relationships between beliefs about football-related dementia and factors including athletic and demographic characteristics, football risk posture, health-risk posture, and cognitive reflection test score.

Results: About 10% of the 296 participating athletes thought football-related dementia was likely to occur in their future. Skill players had lower odds than linemen of believing that football-related dementia was likely (odds ratio [OR], 0.35; 95% CI, 0.14-0.89). For each additional suspected concussion in an athlete's career, his odds of believing football-related dementia was likely increased by 24% (OR, 1.24; 95% CI, 1.07-1.45). Acute and chronic football-related risk perceptions, as well as non-football-related health-risk perceptions, were positively associated with athletes' belief that football-related dementia was likely. Higher cognitive reflection test scores, a measure of ability to switch to slow, deliberative thinking, was positively associated with odds of believing football-related dementia was likely (OR, 1.57; 95% CI, 1.12-2.21).

Conclusion: Some athletes view football as generally riskier, while others view football as generally lessri sky. These risk postures are informed by athletes' concussion history, primary playing position, and ability to switch from fast, reactive thinking to slow, deliberative thinking. Ensuring that athletes are appropriately informed of the risks of participation is an ethical obligation of universities; sports medicine clinicians are appropriate facilitators of conversations about athletes' health risks.
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http://dx.doi.org/10.1177/23259671211001129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107942PMC
April 2021

Validity of the 2014 traumatic encephalopathy syndrome criteria for CTE pathology.

Alzheimers Dement 2021 Apr 7. Epub 2021 Apr 7.

Boston University Alzheimer's Disease and CTE Centers, Boston University School of Medicine, Boston, Massachusetts, USA.

Introduction: Validity of the 2014 traumatic encephalopathy syndrome (TES) criteria, proposed to diagnose chronic traumatic encephalopathy (CTE) in life, has not been assessed.

Methods: A total of 336 consecutive brain donors exposed to repetitive head impacts from contact sports, military service, and/or physical violence were included. Blinded to clinical information, neuropathologists applied National Institute on Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering CTE criteria. Blinded to neuropathological information, clinicians interviewed informants and reviewed medical records. An expert panel adjudicated TES diagnoses.

Results: A total of 309 donors were diagnosed with TES; 244 donors had CTE pathology. TES criteria demonstrated sensitivity and specificity of 0.97 and 0.21, respectively. Cognitive (odds ratio [OR] = 3.6; 95% confidence interval [CI]: 1.2-5.1), but not mood/behavior or motor symptoms, were significantly associated with CTE pathology. Having Alzheimer's disease (AD) pathology was significantly associated with reduced TES accuracy (OR = 0.27; 95% CI: 0.12-0.59).

Discussion: TES criteria provided good evidence to rule out, but limited evidence to rule in, CTE pathology. Requiring cognitive symptoms in revised criteria and using AD biomarkers may improve CTE pathology prediction.
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http://dx.doi.org/10.1002/alz.12338DOI Listing
April 2021

Evaluating the Effect of Concussion Education Programs on Intent to Report Concussion in High School Football.

J Athl Train 2021 Jan 6. Epub 2021 Jan 6.

Lecturer and Adjunct Affiliate, Stanford University, School of Education. email:

Context: Concussion underreporting leads to delays in diagnosis and treatment, prolonging recovery time. Athletes' self-report of concussion symptoms therefore reduces risk.

Objective: Evaluate the efficacy of three concussion education programs in improving concussion-reporting intention.

Design: Randomized controlled clinical trial with assessment immediately and one-month after education.

Setting: Three high schools in California.

Patients Or Other Participants: 118 male football players were randomly assigned to receive concussion education via: CrashCourse (CC), Centers for Disease Control (CDC) video educational materials (Vi), or CDC written educational materials (Wr).

Main Outcome Measures: Concussion-reporting intention was assessed at baseline, immediately after education, and at one-month follow-up. Secondary outcomes included concussion knowledge, attitudes, perceived reporting norms, and perceived behavioral control.

Results: Athletes across all educational formats had significant improvement in concussion-reporting intention immediately following education and at one-month follow-up (mean improvement 6.8% and 11.4%, respectively; p<0.001). Similar findings were observed across all education formats in secondary analyses examining knowledge, attitudes, and perceived behavioral control. However, there were significant differences by education and time (p=0.03). On post-hoc analysis, athletes who received CC had increased concussion-reporting intention immediately and at one-month (baseline=4.7, immediate=6.1, one-month=6.0; p=0.007 compared to significant increases only at one-month for CDC-Vi (baseline=4.3, immediate=5.2, one-month=5.8; p=0.001), and no significant improvement for CDC-Wr (p=0.10). Secondary analyses indicated significant differences between CC and both CDC interventions, in concussion knowledge and attitudes, immediately after education and at one-month. There were no significant differences in perceived behavioral control between-interventions or in perceived concussion-reporting norms across or between interventions.

Conclusion: All athletes exhibited improved intent to report concussions, increased concussion knowledge, better concussion attitudes, and more perceived behavioral control, both immediately after education and at one-month follow-up. However, athletes randomized to CC reported greater intent to report concussion, more knowledge, and improved concussion-reporting attitudes, when compared to CDC-Vi and CDC-Wr.

Trial Registry: ClinicalTrials.gov trial ID number is XXX.
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http://dx.doi.org/10.4085/509-20DOI Listing
January 2021

Characterizing tau deposition in chronic traumatic encephalopathy (CTE): utility of the McKee CTE staging scheme.

Acta Neuropathol 2020 10 11;140(4):495-512. Epub 2020 Aug 11.

Department of Neurology, Boston University Alzheimer's Disease and CTE Centers, Boston University School of Medicine, Boston, USA.

Chronic traumatic encephalopathy (CTE) is a tauopathy associated with repetitive head impacts (RHI) that has been neuropathologically diagnosed in American football players and other contact sport athletes. In 2013, McKee and colleagues proposed a staging scheme for characterizing the severity of the hyperphosphorylated tau (p-tau) pathology, the McKee CTE staging scheme. The staging scheme defined four pathological stages of CTE, stages I(mild)-IV(severe), based on the density and regional deposition of p-tau. The objective of this study was to test the utility of the McKee CTE staging scheme, and provide a detailed examination of the regional distribution of p-tau in CTE. We examined the relationship between the McKee CTE staging scheme and semi-quantitative and quantitative assessments of regional p-tau pathology, age at death, dementia, and years of American football play among 366 male brain donors neuropathologically diagnosed with CTE (mean age 61.86, SD 18.90). Spearman's rho correlations showed that higher CTE stage was associated with higher scores on all semi-quantitative and quantitative assessments of p-tau severity and density (p's < 0.001). The severity and distribution of CTE p-tau followed an age-dependent progression: older age was associated with increased odds for having a higher CTE stage (p < 0.001). CTE stage was independently associated with increased odds for dementia (p < 0.001). K-medoids cluster analysis of the semi-quantitative scales of p-tau across 14 regions identified 5 clusters of p-tau that conformed to increasing CTE stage (stage IV had 2 slightly different clusters), age at death, dementia, and years of American football play. There was a predilection for p-tau pathology in five regions: dorsolateral frontal cortex (DLF), superior temporal cortex, entorhinal cortex, amygdala, and locus coeruleus (LC), with CTE in the youngest brain donors and lowest CTE stage restricted to DLF and LC. These findings support the usefulness of the McKee CTE staging scheme and demonstrate the regional distribution of p-tau in CTE.
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http://dx.doi.org/10.1007/s00401-020-02197-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914059PMC
October 2020

Reply to "Chronic Traumatic Encephalopathy and Primary Age-Related Tauopathy".

Ann Neurol 2020 11 22;88(5):1052-1053. Epub 2020 Aug 22.

Boston University Alzheimer's Disease and CTE Centers, Boston University School of Medicine, Boston, MA, USA.

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http://dx.doi.org/10.1002/ana.25858DOI Listing
November 2020

Duration of American Football Play and Chronic Traumatic Encephalopathy.

Ann Neurol 2020 01 23;87(1):116-131. Epub 2019 Nov 23.

Boston University Alzheimer's Disease and Chronic Traumatic Encephalopathy Center, Boston University School of Medicine, Boston, MA.

Objective: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to contact and collision sports, including American football. We hypothesized a dose-response relationship between duration of football played and CTE risk and severity.

Methods: In a convenience sample of 266 deceased American football players from the Veterans Affairs-Boston University-Concussion Legacy Foundation and Framingham Heart Study Brain Banks, we estimated the association of years of football played with CTE pathological status and severity. We evaluated the ability of years played to classify CTE status using receiver operating characteristic curve analysis. Simulation analyses quantified conditions that might lead to selection bias.

Results: In total, 223 of 266 participants met neuropathological diagnostic criteria for CTE. More years of football played were associated with having CTE (odds ratio [OR] = 1.30 per year played, 95% confidence interval [CI] = 1.19-1.41; p = 3.8 × 10 ) and with CTE severity (severe vs mild; OR = 1.14 per year played, 95% CI = 1.07-1.22; p = 3.1 × 10 ). Participants with CTE were 1/10th as likely to have played <4.5 years (negative likelihood ratio [LR] = 0.102, 95% CI = 0.100-0.105) and were 10 times as likely to have played >14.5 years (positive LR = 10.2, 95% CI = 9.8-10.7) compared with participants without CTE. Sensitivity and specificity were maximized at 11 years played. Simulation demonstrated that years played remained adversely associated with CTE status when years played and CTE status were both related to brain bank selection across widely ranging scenarios.

Interpretation: The odds of CTE double every 2.6 years of football played. After accounting for brain bank selection, the magnitude of the relationship between years played and CTE status remained consistent. ANN NEUROL 2020;87:116-131.
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http://dx.doi.org/10.1002/ana.25611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973077PMC
January 2020

Lewy Body Pathology and Chronic Traumatic Encephalopathy Associated With Contact Sports.

J Neuropathol Exp Neurol 2018 09;77(9):757-768

Department of Neurology.

Traumatic brain injury has been associated with increased risk of Parkinson disease and parkinsonism, and parkinsonism and Lewy body disease (LBD) can occur with chronic traumatic encephalopathy (CTE). To test whether contact sports and CTE are associated with LBD, we compared deceased contact sports athletes (n = 269) to cohorts from the community (n = 164) and the Boston University Alzheimer disease (AD) Center (n = 261). Participants with CTE and LBD were more likely to have β-amyloid deposition, dementia, and parkinsonism than CTE alone (p < 0.05). Traditional and hierarchical clustering showed a similar pattern of LBD distribution in CTE compared to LBD alone that was most frequently neocortical, limbic, or brainstem. In the community-based cohort, years of contact sports play were associated with neocortical LBD (OR = 1.30 per year, p = 0.012), and in a pooled analysis a threshold of >8 years of play best predicted neocortical LBD (ROC analysis, OR = 6.24, 95% CI = 1.5-25, p = 0.011), adjusting for age, sex, and APOE ɛ4 allele status. Clinically, dementia was significantly associated with neocortical LBD, CTE stage, and AD; parkinsonism was associated with LBD pathology but not CTE stage. Contact sports participation may increase risk of developing neocortical LBD, and increased LBD frequency may partially explain extrapyramidal motor symptoms sometimes observed in CTE.
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http://dx.doi.org/10.1093/jnen/nly065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097837PMC
September 2018

Age of first exposure to tackle football and chronic traumatic encephalopathy.

Ann Neurol 2018 05;83(5):886-901

Boston University Alzheimer's Disease and CTE Center, Department of Neurology, Boston University School of Medicine, Boston, MA.

Objective: To examine the effect of age of first exposure to tackle football on chronic traumatic encephalopathy (CTE) pathological severity and age of neurobehavioral symptom onset in tackle football players with neuropathologically confirmed CTE.

Methods: The sample included 246 tackle football players who donated their brains for neuropathological examination. Two hundred eleven were diagnosed with CTE (126 of 211 were without comorbid neurodegenerative diseases), and 35 were without CTE. Informant interviews ascertained age of first exposure and age of cognitive and behavioral/mood symptom onset.

Results: Analyses accounted for decade and duration of play. Age of exposure was not associated with CTE pathological severity, or Alzheimer's disease or Lewy body pathology. In the 211 participants with CTE, every 1 year younger participants began to play tackle football predicted earlier reported cognitive symptom onset by 2.44 years (p < 0.0001) and behavioral/mood symptoms by 2.50 years (p < 0.0001). Age of exposure before 12 predicted earlier cognitive (p < 0.0001) and behavioral/mood (p < 0.0001) symptom onset by 13.39 and 13.28 years, respectively. In participants with dementia, younger age of exposure corresponded to earlier functional impairment onset. Similar effects were observed in the 126 CTE-only participants. Effect sizes were comparable in participants without CTE.

Interpretation: In this sample of deceased tackle football players, younger age of exposure to tackle football was not associated with CTE pathological severity, but predicted earlier neurobehavioral symptom onset. Youth exposure to tackle football may reduce resiliency to late-life neuropathology. These findings may not generalize to the broader tackle football population, and informant-report may have affected the accuracy of the estimated effects. Ann Neurol 2018;83:886-901.
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http://dx.doi.org/10.1002/ana.25245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367933PMC
May 2018

Dementia After Moderate-Severe Traumatic Brain Injury: Coexistence of Multiple Proteinopathies.

J Neuropathol Exp Neurol 2018 Jan;77(1):50-63

Department of Neurology; Department of Pathology, F. Edward Hébert School of Medicine; Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland; The Henry M. Jackson Foundation for the Advancement of Military Research (HJF); Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston Massachusetts; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts; Department of Neurology; Alzheimer's Disease Center and CTE Program, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;Department of Rehabilitation Medicine; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York; Radiological Sciences Laboratory, Department of Radiology, Stanford University, Stanford, California; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Boston, Massachusetts; VA Boston Healthcare System, Boston, Massachusetts; and Department of Pathology, Boston University School of Medicine, Boston, Massachusetts.

We report the clinical, neuroimaging, and neuropathologic characteristics of 2 patients who developed early onset dementia after a moderate-severe traumatic brain injury (TBI). Neuropathological evaluation revealed abundant β-amyloid neuritic and cored plaques, diffuse β-amyloid plaques, and frequent hyperphosphorylated-tau neurofibrillary tangles (NFT) involving much of the cortex, including insula and mammillary bodies in both cases. Case 1 additionally showed NFTs in both the superficial and deep cortical layers, occasional perivascular and depth-of-sulci NFTs, and parietal white matter rarefaction, which corresponded with decreased parietal fiber tracts observed on ex vivo MRI. Case 2 additionally showed NFT predominance in the superficial layers of the cortex, hypothalamus and brainstem, diffuse Lewy bodies in the cortex, amygdala and brainstem, and intraneuronal TDP-43 inclusions. The neuropathologic diagnoses were atypical Alzheimer disease (AD) with features of chronic traumatic encephalopathy and white matter loss (Case 1), and atypical AD, dementia with Lewy bodies and coexistent TDP-43 pathology (Case 2). These findings support an epidemiological association between TBI and dementia and further characterize the variety of misfolded proteins that may accumulate after TBI. Analyses with comprehensive clinical, imaging, genetic, and neuropathological data are required to characterize the full clinicopathological spectrum associated with dementias occurring after moderate-severe TBI.
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http://dx.doi.org/10.1093/jnen/nlx101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939622PMC
January 2018

CCL11 is increased in the CNS in chronic traumatic encephalopathy but not in Alzheimer's disease.

PLoS One 2017 26;12(9):e0185541. Epub 2017 Sep 26.

Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, United States of America.

CCL11, a protein previously associated with age-associated cognitive decline, is observed to be increased in the brain and cerebrospinal fluid (CSF) in chronic traumatic encephalopathy (CTE) compared to Alzheimer's disease (AD). Using a cohort of 23 deceased American football players with neuropathologically verified CTE, 50 subjects with neuropathologically diagnosed AD, and 18 non-athlete controls, CCL11 was measured with ELISA in the dorsolateral frontal cortex (DLFC) and CSF. CCL11 levels were significantly increased in the DLFC in subjects with CTE (fold change = 1.234, p < 0.050) compared to non-athlete controls and AD subjects with out a history of head trauma. This increase was also seen to correlate with years of exposure to American football (β = 0.426, p = 0.048) independent of age (β = -0.046, p = 0.824). Preliminary analyses of a subset of subjects with available post-mortem CSF showed a trend for increased CCL11 among individuals with CTE (p = 0.069) mirroring the increase in the DLFC. Furthermore, an association between CSF CCL11 levels and the number of years exposed to football (β = 0.685, p = 0.040) was observed independent of age (β = -0.103, p = 0.716). Finally, a receiver operating characteristic (ROC) curve analysis demonstrated CSF CCL11 accurately distinguished CTE subjects from non-athlete controls and AD subjects (AUC = 0.839, 95% CI 0.62-1.058, p = 0.028). Overall, the current findings provide preliminary evidence that CCL11 may be a novel target for future CTE biomarker studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185541PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614644PMC
October 2017

Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football.

JAMA 2017 07;318(4):360-370

Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, Massachusetts2Department of Neurology, Boston University School of Medicine, Boston, Massachusetts4VA Boston Healthcare System, US Department of Veteran Affairs, Boston, Massachusetts5Department of Veterans Affairs Medical Center, Bedford, Massachusetts12Department of Pathology, Boston University School of Medicine, Boston, Massachusetts23Boston University School of Medicine, Boston, Massachusetts.

Importance: Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE).

Objective: To determine the neuropathological and clinical features of deceased football players with CTE.

Design, Setting, And Participants: Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history.

Exposures: Participation in American football at any level of play.

Main Outcomes And Measures: Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia.

Results: Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre-high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia.

Conclusions And Relevance: In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.
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http://dx.doi.org/10.1001/jama.2017.8334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807097PMC
July 2017

Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy.

Acta Neuropathol Commun 2016 10 28;4(1):112. Epub 2016 Oct 28.

Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA.

The chronic effects of repetitive head impacts (RHI) on the development of neuroinflammation and its relationship to chronic traumatic encephalopathy (CTE) are unknown. Here we set out to determine the relationship between RHI exposure, neuroinflammation, and the development of hyperphosphorylated tau (ptau) pathology and dementia risk in CTE. We studied a cohort of 66 deceased American football athletes from the Boston University-Veteran's Affairs-Concussion Legacy Foundation Brain Bank as well as 16 non-athlete controls. Subjects with a neurodegenerative disease other than CTE were excluded. Counts of total and activated microglia, astrocytes, and ptau pathology were performed in the dorsolateral frontal cortex (DLF). Binary logistic and simultaneous equation regression models were used to test associations between RHI exposure, microglia, ptau pathology, and dementia. Duration of RHI exposure and the development and severity of CTE were associated with reactive microglial morphology and increased numbers of CD68 immunoreactive microglia in the DLF. A simultaneous equation regression model demonstrated that RHI exposure had a significant direct effect on CD68 cell density (p < 0.0001) and ptau pathology (p < 0.0001) independent of age at death. The effect of RHI on ptau pathology was partially mediated through increased CD68 positive cell density. A binary logistic regression demonstrated that a diagnosis of dementia was significantly predicted by CD68 cell density (OR = 1.010, p = 0.011) independent of age (OR = 1.055, p = 0.007), but this effect disappeared when ptau pathology was included in the model. In conclusion, RHI is associated with chronic activation of microglia, which may partially mediate the effect of RHI on the development of ptau pathology and dementia in CTE. Inflammatory molecules may be important diagnostic or predictive biomarkers as well as promising therapeutic targets in CTE.
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http://dx.doi.org/10.1186/s40478-016-0382-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084333PMC
October 2016

Clinical Practices in Collegiate Concussion Management.

Am J Sports Med 2016 Jun 1;44(6):1391-9. Epub 2016 Apr 1.

Micheli Center for Sport Injury Prevention, Division of Sports Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.

Background: In recent years, sports leagues and sports medicine experts have developed guidelines for concussion management. The extent to which current clinical practice is consistent with guideline recommendations is unclear. At the collegiate level, there have been few examinations of concussion management practices and the extent to which meaningful differences across divisions of competition exist.

Purpose: The purposes of this study were to (1) examine current practices in concussion diagnosis and management at National Collegiate Athletic Association (NCAA) member colleges, (2) explore the extent to which current practices reflect current recommendations for concussion diagnosis and management, and (3) determine whether there are differences in management patterns across divisions of competition.

Design: Descriptive epidemiology study.

Methods: An electronic questionnaire was sent to sports medicine clinicians at all NCAA member colleges during September and October 2013. Clinicians were asked about baseline assessments, diagnosis and management practices, return-to-play protocols, the perceived prevalence of underdiagnosis, and basic demographic information.

Results: Approximately 30% (n = 866) of contacted clinicians, representing nearly 50% (n = 527) of NCAA member colleges, responded to the questionnaire. Preparticipation baseline examinations were administered at the majority of schools (95%), but most (87.5%) administered baseline assessments only to selected high-risk athletes. Computerized neurocognitive testing and balance assessments were most commonly used as preseason baseline and postinjury assessments. Multimodal examination in line with NCAA and other guidance was used only at a minority of institutions. Athletic trainers most commonly administered and interpreted the preseason baseline examination. Most clinicians reported that their institutions' practices were in line with NCAA guidelines during the first 24 hours of an athlete's concussion diagnosis, with exact percentages varying across measures. Differences across divisions of competition included shorter return-to-play time at Division I schools than Division III schools (9.13 vs 10.31 days, respectively) and more frequently referring concussed athletes to a physician within 24 hours of diagnosis at Division I schools.

Conclusion: Concussion management at many colleges in the United States incorporates elements recommended by current guidelines; however, there is room to improve. Increasing the use of a multimodal baseline and postinjury examination will elevate the concussion care provided to college athletes and better align with best practice guidance.
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http://dx.doi.org/10.1177/0363546516635639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891296PMC
June 2016

Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players.

J Neurotrauma 2017 01 15;34(2):328-340. Epub 2016 Jun 15.

1 Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine , Boston, Massachusetts.

The term "repetitive head impacts" (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), quantitative analysis of this relationship has not yet been examined because of the lack of validated tools to quantify lifetime RHI exposure. The objectives of this study were: 1) to develop a metric to quantify cumulative RHI exposure from football, which we term the "cumulative head impact index" (CHII); 2) to use the CHII to examine the association between RHI exposure and long-term clinical outcomes; and 3) to evaluate its predictive properties relative to other exposure metrics (i.e., duration of play, age of first exposure, concussion history). Participants included 93 former high school and collegiate football players who completed objective cognitive and self-reported behavioral/mood tests as part of a larger ongoing longitudinal study. Using established cutoff scores, we transformed continuous outcomes into dichotomous variables (normal vs. impaired). The CHII was computed for each participant and derived from a combination of self-reported athletic history (i.e., number of seasons, position[s], levels played), and impact frequencies reported in helmet accelerometer studies. A bivariate probit, instrumental variable model revealed a threshold dose-response relationship between the CHII and risk for later-life cognitive impairment (p < 0.0001), self-reported executive dysfunction (p < 0.0001), depression (p < 0.0001), apathy (p = 0.0161), and behavioral dysregulation (p < 0.0001). Ultimately, the CHII demonstrated greater predictive validity than other individual exposure metrics.
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http://dx.doi.org/10.1089/neu.2016.4413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220530PMC
January 2017

Pathologically Confirmed Chronic Traumatic Encephalopathy in a 25-Year-Old Former College Football Player.

JAMA Neurol 2016 Mar;73(3):353-5

Alzheimer's Disease Center, Chronic Traumatic Encephalopathy Program, Boston University School of Medicine, Boston, Massachusetts2Department of Neurology, Boston University School of Medicine, Boston, Massachusetts4US Department of Veterans Affairs, VA Bo.

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http://dx.doi.org/10.1001/jamaneurol.2015.3998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792748PMC
March 2016

Content, Delivery, and Effectiveness of Concussion Education for US College Coaches.

Clin J Sport Med 2016 Sep;26(5):391-7

*University of Washington, Department of Pediatrics, Seattle, Washington; †Seattle Children's Research Institute, Center for Child Health, Behavior and Development, Seattle, Washington; ‡Harborview Injury Prevention Research Center, Seattle, Washington; §Harvard University, Interfaculty Initiative in Health Policy, Cambridge, Massachusetts; ¶Boston Children's Hospital, Division of Sports Medicine, Boston, Massachusetts; and ‖Center for the Study of Traumatic Encephalopathy, Boston University School of Medicine, Boston, Massachusetts.

Objective: The primary objective of this study was to examine the proportion of US college coaches who receive annual concussion education from their institution and to describe the content and delivery modalities of this education. This study also tested the hypothesis that coaches receiving concussion education from their institution will have greater knowledge about concussions independent of other individual and institutional characteristics.

Design: Cross-sectional online survey.

Setting: US college sport.

Participants: College coaches in National Collegiate Athletic Association Division I, II, and III (n = 1818).

Independent Variables: Self-reported receipt of education from institution, sex, sport coached, division of competition.

Main Outcome Measures: Concussion identification and management knowledge.

Results: Two-thirds of coaches reported receiving informational materials about concussion from their institution. The content of the education most frequently referred to symptoms of a concussion and information about proper management of a concussion. Coaches who received educational materials from their institution were better able to identify symptoms and had more conservative responses to concussion management scenarios. Male coaches of male contact or collision teams less frequently endorsed safe or correct response as compared with female coaches of noncontact or collision teams.

Conclusions: Not all US college coaches receive concussion education from their institution. Male Division I coaches of male contact/collision sport are a population for whom targeted educational outreach may be particularly valuable.

Clinical Relevance: Education for coaches, delivered by clinicians at many institutions, is an important component of ensuring that coaches are prepared to be informed partners in supporting concussion safety.
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http://dx.doi.org/10.1097/JSM.0000000000000272DOI Listing
September 2016

Assessing clinicopathological correlation in chronic traumatic encephalopathy: rationale and methods for the UNITE study.

Alzheimers Res Ther 2015 Oct 12;7(1):62. Epub 2015 Oct 12.

Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, B-7800, Boston, MA, 02118, USA.

Introduction: Chronic traumatic encephalopathy (CTE) is a progressive neurodegeneration associated with repetitive head impacts. Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) is a U01 project recently funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Biomedical Imaging and Bioengineering. The goal of the UNITE project is to examine the neuropathology and clinical presentation of brain donors designated as "at risk" for the development of CTE based on prior athletic or military exposure. Here, we present the rationale and methodology for UNITE.

Methods: Over the course of 4 years, we will analyze the brains and spinal cords of 300 deceased subjects who had a history of repetitive head impacts sustained during participation in contact sports at the professional or collegiate level or during military service. Clinical data are collected through medical record review and retrospective structured and unstructured family interviews conducted by a behavioral neurologist or neuropsychologist. Blinded to the clinical data, a neuropathologist conducts a comprehensive assessment for neurodegenerative disease, including CTE, using published criteria. At a clinicopathological conference, a panel of physicians and neuropsychologists, blinded to the neuropathological data, reaches a clinical consensus diagnosis using published criteria, including proposed clinical research criteria for CTE.

Results: We will investigate the validity of these clinical criteria and sources of error by using recently validated neuropathological criteria as a gold standard for CTE diagnosis. We also will use statistical modeling to identify diagnostic features that best predict CTE pathology.

Conclusions: The UNITE study is a novel and methodologically rigorous means of assessing clinicopathological correlation in CTE. Our findings will be critical for developing future iterations of CTE clinical diagnostic criteria.
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http://dx.doi.org/10.1186/s13195-015-0148-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601147PMC
October 2015

Pressure on Sports Medicine Clinicians to Prematurely Return Collegiate Athletes to Play After Concussion.

J Athl Train 2015 Sep 24;50(9):944-51. Epub 2015 Jul 24.

Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA.

Context: Anecdotal and qualitative evidence has suggested that some clinicians face pressure from coaches and other personnel in the athletic environment to prematurely return athletes to participation after a concussion. This type of pressure potentially can result in compromised patient care.

Objective: To quantify the extent to which clinicians in the collegiate sports medicine environment experience pressure when caring for concussed athletes and whether this pressure varies by the supervisory structure of the institution's sports medicine department, the clinician's sex, and other factors.

Design: Cross-sectional study.

Setting: Web-based survey of National College Athletic Association member institutions.

Patients Or Other Participants: A total of 789 athletic trainers and 111 team physicians from 530 institutions.

Main Outcome Measure(s): We asked participants whether they had experienced pressure from 3 stakeholder populations (other clinicians, coaches, athletes) to prematurely return athletes to participation after a concussion. Modifying variables that we assessed were the position (athletic trainer, physician) and sex of the clinicians, the supervisory structure of their institutions' sports medicine departments, and the division of competition in which their institutions participate.

Results: We observed that 64.4% (n = 580) of responding clinicians reported having experienced pressure from athletes to prematurely clear them to return to participation after a concussion, and 53.7% (n = 483) reported having experienced this pressure from coaches. Only 6.6% (n = 59) reported having experienced pressure from other clinicians to prematurely clear an athlete to return to participation after a concussion. Clinicians reported greater pressure from coaches when their departments were under the supervisory purview of the athletic department rather than a medical institution. Female clinicians reported greater pressure from coaches than male clinicians did.

Conclusions: Most clinicians reported experiencing pressure to prematurely return athletes to participation after a concussion. Identifying factors that are associated with variability in pressure on clinicians during concussion recovery can inform potential future strategies to reduce these pressures.
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http://dx.doi.org/10.4085/1062-6050-50.6.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639885PMC
September 2015

Beta-amyloid deposition in chronic traumatic encephalopathy.

Acta Neuropathol 2015 Jul 6;130(1):21-34. Epub 2015 May 6.

VA Boston Healthcare System, Boston, MA, 02130, USA,

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury. It is defined pathologically by the abnormal accumulation of tau in a unique pattern that is distinct from other tauopathies, including Alzheimer's disease (AD). Although trauma has been suggested to increase amyloid β peptide (Aβ) levels, the extent of Aβ deposition in CTE has not been thoroughly characterized. We studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the hypothesis that Aβ deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that Aβ deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, Aβ deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE compared to a normal aging population (OR = 3.8, p < 0.001). We also found a clear pathological and clinical dichotomy between those CTE cases with Aβ plaques and those without. Aβ deposition was significantly associated with the presence of the APOE ε4 allele (p = 0.035), older age at symptom onset (p < 0.001), and older age at death (p < 0.001). In addition, when controlling for age, neuritic plaques were significantly associated with increased CTE tauopathy stage (β = 2.43, p = 0.018), co-morbid Lewy body disease (OR = 5.01, p = 0.009), and dementia (OR = 4.45, p = 0.012). A subset of subjects met the diagnostic criteria for both CTE and AD, and in these subjects both Aβ plaques and total levels of Aβ1-40 were increased at the depths of the cortical sulcus compared to the gyral crests. Overall, these findings suggest that Aβ deposition is altered and accelerated in a cohort of CTE subjects compared to normal aging and that Aβ is associated with both pathological and clinical progression of CTE independent of age.
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http://dx.doi.org/10.1007/s00401-015-1435-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529056PMC
July 2015

Post-traumatic neurodegeneration and chronic traumatic encephalopathy.

Mol Cell Neurosci 2015 May 7;66(Pt B):81-90. Epub 2015 Mar 7.

Boston University Chronic Traumatic Encephalopathy Program, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Boston University Alzheimer's Disease Center, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Department of Neurology, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; VA Boston Healthcare System, 150 South Huntington Avenue, Jamaica Plain, MA 02130, USA.

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity around the world. Concussive and subconcussive forms of closed-head injury due to impact or blast neurotrauma represent the most common types of TBI in civilian and military settings. It is becoming increasingly evident that TBI can lead to persistent, long-term debilitating effects, and in some cases, progressive neurodegeneration and chronic traumatic encephalopathy (CTE). The epidemiological literature suggests that a single moderate-to-severe TBI may be associated with accelerated neurodegeneration and increased risk of Alzheimer's disease, Parkinson's disease, or motor neuron disease. However, the pathologic phenotype of these post-traumatic neurodegenerations is largely unknown and there may be pathobiological differences between post-traumatic disease and the corresponding sporadic disorder. By contrast, the pathology of CTE is increasingly well known and is characterized by a distinctive pattern of progressive brain atrophy and accumulation of hyperphosphorylated tau neurofibrillary and glial tangles, dystrophic neurites, 43 kDa TAR DNA-binding protein (TDP-43) neuronal and glial aggregates, microvasculopathy, myelinated axonopathy, neuroinflammation, and white matter degeneration. Clinically, CTE is associated with behavioral changes, executive dysfunction, memory deficits, and cognitive impairments that begin insidiously and most often progress slowly over decades. Although research on the long-term effects of TBI is advancing quickly, the incidence and prevalence of post-traumatic neurodegeneration and CTE are unknown. Critical knowledge gaps include elucidation of pathogenic mechanisms, identification of genetic risk factors, and clarification of relevant variables-including age at exposure to trauma, history of prior and subsequent head trauma, substance use, gender, stress, and comorbidities-all of which may contribute to risk profiles and the development of post-traumatic neurodegeneration and CTE. This article is part of a Special Issue entitled 'Traumatic Brain Injury'.
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http://dx.doi.org/10.1016/j.mcn.2015.03.007DOI Listing
May 2015

Determinants of Coach Communication About Concussion Safety in US Collegiate Sport.

Ann Behav Med 2015 Aug;49(4):532-41

Department of Social and Behavioral Sciences, Harvard School of Public Health, 221 Columbus Avenue, Boston, MA, 02116, USA,

Background: Communication between coaches and athletes about concussion safety can reinforce or undermine a sport culture in which concussion under-reporting is often endemic.

Method: This study tested a model in which self-reported coach communication about concussion safety was predicted by factors including concussion knowledge, attitudes and beliefs, sex of the coach, and sex of the team coached. Participants were 997 coaches of contact and collision sports teams competing in National Collegiate Athletic Association Division I, II, or III.

Results: Concussion attitudes and beliefs were the strongest predictors of communication, and the small effect of knowledge on communication was transmitted nearly entirely through its effect on attitudes and beliefs. Much of the variability in communication was attributable to the sex of the coach and the sex of the team coached.

Conclusions: These results serve as a starting point for the design of coach-targeted interventions that encourage communication about health and safety with athletes.
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http://dx.doi.org/10.1007/s12160-014-9683-yDOI Listing
August 2015

The neuropathology of traumatic brain injury.

Handb Clin Neurol 2015 ;127:45-66

VA Boston HealthCare System; Center for the Study of Traumatic Encephalopathy, Alzheimer's Disease Center, and Departments of Neurology and Pathology, Boston University School of Medicine, Boston, MA, USA.

Traumatic brain injury, a leading cause of mortality and morbidity, is divided into three grades of severity: mild, moderate, and severe, based on the Glasgow Coma Scale, the loss of consciousness, and the development of post-traumatic amnesia. Although mild traumatic brain injury, including concussion and subconcussion, is by far the most common, it is also the most difficult to diagnose and the least well understood. Proper recognition, management, and treatment of acute concussion and mild traumatic brain injury are the fundamentals of an emerging clinical discipline. It is also becoming increasingly clear that some mild traumatic brain injuries have persistent, and sometimes progressive, long-term debilitating effects. Evidence indicates that a single traumatic brain injury can precipitate or accelerate multiple age-related neurodegenerations, increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease, and that repetitive mild traumatic brain injuries can provoke the development of a tauopathy, chronic traumatic encephalopathy. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus, septal abnormalities, and abnormal deposits of hyperphosphorylated tau (τ) as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy frequently occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including Alzheimer's disease, Lewy body disease, and motor neuron disease. Currently, chronic traumatic encephalopathy can be diagnosed only at autopsy; however, promising efforts to develop imaging, spinal fluid, and peripheral blood biomarkers are underway to diagnose and monitor the course of disease in living subjects.
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http://dx.doi.org/10.1016/B978-0-444-52892-6.00004-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694720PMC
August 2016

Age of first exposure to football and later-life cognitive impairment in former NFL players.

Neurology 2015 Mar 28;84(11):1114-20. Epub 2015 Jan 28.

From the CTE Center (J.M.S., A.P.B., C.M.B., N.G.F., D.H.D., Y.T., R.A.S.), Department of Anatomy and Neurobiology (J.M.S., R.A.S.), BU Alzheimer's Disease Center (A.P.B., Y.T., R.A.S.), Department of Neurology (C.M.B., R.A.S.), and Department of Neurosurgery (R.A.S.), Boston University School of Medicine; and Data Coordinating Center (B.M.M.), Department of Environmental Health (M.D.M.), and Department of Biostatistics (Y.T.), Boston University School of Public Health, Boston, MA.

Objective: To determine the relationship between exposure to repeated head impacts through tackle football prior to age 12, during a key period of brain development, and later-life executive function, memory, and estimated verbal IQ.

Methods: Forty-two former National Football League (NFL) players ages 40-69 from the Diagnosing and Evaluating Traumatic Encephalopathy using Clinical Tests (DETECT) study were matched by age and divided into 2 groups based on their age of first exposure (AFE) to tackle football: AFE <12 and AFE ≥12. Participants completed the Wisconsin Card Sort Test (WCST), Neuropsychological Assessment Battery List Learning test (NAB-LL), and Wide Range Achievement Test, 4th edition (WRAT-4) Reading subtest as part of a larger neuropsychological testing battery.

Results: Former NFL players in the AFE <12 group performed significantly worse than the AFE ≥12 group on all measures of the WCST, NAB-LL, and WRAT-4 Reading tests after controlling for total number of years of football played and age at the time of evaluation, indicating executive dysfunction, memory impairment, and lower estimated verbal IQ.

Conclusions: There is an association between participation in tackle football prior to age 12 and greater later-life cognitive impairment measured using objective neuropsychological tests. These findings suggest that incurring repeated head impacts during a critical neurodevelopmental period may increase the risk of later-life cognitive impairment. If replicated with larger samples and longitudinal designs, these findings may have implications for safety recommendations for youth sports.
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http://dx.doi.org/10.1212/WNL.0000000000001358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371403PMC
March 2015

Clinical subtypes of chronic traumatic encephalopathy: literature review and proposed research diagnostic criteria for traumatic encephalopathy syndrome.

Alzheimers Res Ther 2014 24;6(5):68. Epub 2014 Sep 24.

Department of Anatomy and Neurobiology, Boston University School of Medicine, 72 East Concord Street, Boston 02118, MA, USA ; BU Alzheimer's Disease Center, Boston University School of Medicine, 72 East Concord Street, Boston 02118, MA, USA ; Department of Neurology, Boston University School of Medicine, 72 East Concord Street, Boston 02118, MA, USA ; Department of Neurosurgery, Boston University School of Medicine, 73 East Concord Street, Boston 02118, MA, USA.

The long-term consequences of repetitive head impacts have been described since the early 20th century. Terms such as punch drunk and dementia pugilistica were first used to describe the clinical syndromes experienced by boxers. A more generic designation, chronic traumatic encephalopathy (CTE), has been employed since the mid-1900s and has been used in recent years to describe a neurodegenerative disease found not just in boxers but in American football players, other contact sport athletes, military veterans, and others with histories of repetitive brain trauma, including concussions and subconcussive trauma. This article reviews the literature of the clinical manifestations of CTE from 202 published cases. The clinical features include impairments in mood (for example, depression and hopelessness), behavior (for example, explosivity and violence), cognition (for example, impaired memory, executive functioning, attention, and dementia), and, less commonly, motor functioning (for example, parkinsonism, ataxia, and dysarthria). We present proposed research criteria for traumatic encephalopathy syndrome (TES) which consist of four variants or subtypes (TES behavioral/mood variant, TES cognitive variant, TES mixed variant, and TES dementia) as well as classifications of 'probable CTE' and 'possible CTE'. These proposed criteria are expected to be modified and updated as new research findings become available. They are not meant to be used for a clinical diagnosis. Rather, they should be viewed as research criteria that can be employed in studies of the underlying causes, risk factors, differential diagnosis, prevention, and treatment of CTE and related disorders.
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http://dx.doi.org/10.1186/s13195-014-0068-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288217PMC
January 2015

Concussion management in United States college sports: compliance with National Collegiate Athletic Association concussion policy and areas for improvement.

Am J Sports Med 2015 Jan 21;43(1):47-56. Epub 2014 Oct 21.

Department of Health Law, Bioethics, and Human Rights, Boston University School of Public Health, Boston, Massachusetts, USA.

Background: In 2010, the National Collegiate Athletic Association (NCAA) adopted its Concussion Policy and Legislation, which applies to more than 450,000 collegiate athletes annually. To date, there has been no examination of school-level compliance with the NCAA Concussion Policy.

Purpose: To examine whether stakeholders at NCAA schools report that their school has a concussion management plan and whether existing plans are consistent with the NCAA policy. Also examined were stakeholders' perceptions regarding concussion management at their institution and possible areas for improvement.

Study Design: Cross-sectional study; Level of evidence, 3.

Methods: Surveys were sent by e-mail to coaches, sports medicine clinicians, and compliance administrators at all 1066 NCAA member institutions. Surveys asked population-specific questions about institutional concussion management. Individuals (N=2880) from 907 unique schools participated in this survey.

Results: Most respondents (n=2607; 92.7%) indicated their school had a concussion management plan. Most schools had all (82.1%) or some (15.2%) respondents indicate a concussion management plan was present. When asked to indicate all individuals who could have final responsibility for returning athletes to play after a concussion, 83.4% selected team doctor, 72.8% athletic trainer, 31.0% specialist physician, 6.8% coach, and 6.6% athlete. Most respondents (76.1%) indicated that their institution had a process for annual athlete concussion education; 91.2% required athletes to acknowledge their responsibility to report concussion symptoms. Nearly all respondents (98.8%) thought their school's concussion management plan protected athletes "well" or "very well." Top categories suggested for improvement included better coach education (39.7%), increasing sports medicine staffing (37.2%), and better athlete education (35.2%).

Conclusion: Although a large majority of respondents indicated that their school has a concussion management plan, improvement is needed. Compliance with specified components (eg, annual athlete education) lags behind the presence of the plan itself, and stakeholders had suggestions for areas in which improvements are needed. Increasing scientific evidence supporting the seriousness of concussion underscores the need for the NCAA to use its regulatory capabilities to ensure that athletes' brains are safe.
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http://dx.doi.org/10.1177/0363546514553090DOI Listing
January 2015

Perceived coach support and concussion symptom-reporting: differences between freshmen and non-freshmen college football players.

J Law Med Ethics 2014 ;42(3):314-22

Clinical Research and Program Coordinator at the Boston University Chronic Traumatic Encephalopathy Center, a Research Instructor in Neurology at the Boston University School of Medicine, and a Lab Fellow at the Edmond J. Safra Center for Ethics at Harvard University.

This paper examines college athletes' perceived support for concussion reporting from coaches and teammates and its variation by year-in-school, finding significant differences in perceived coach support. It also examines the effects of perceived coach support on concussion reporting behaviors, finding that greater perceived coach support is associated with fewer undiagnosed concussions and returning to play while symptomatic less frequently in the two weeks preceding the survey. Coaches play a critical role in athlete concussion reporting.
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http://dx.doi.org/10.1111/jlme.12148DOI Listing
November 2016

Frequency of head-impact-related outcomes by position in NCAA division I collegiate football players.

J Neurotrauma 2015 Mar 16;32(5):314-26. Epub 2014 Dec 16.

1 Harvard Interfaculty Initiative in Health Policy, Harvard University , Cambridge, Massachusetts.

Concussions and subconcussive impacts sustained in American football have been associated with short- and long-term neurological impairment, but differences in head impact outcomes across playing positions are not well understood. The American Medical Society for Sports Medicine has identified playing position as a key risk factor for concussion in football and one for which additional research is needed. This study examined variation in head impact outcomes across primary football playing positions in a group of 730 National Collegiate Athletic Association Division I Football Championship Series athletes, using a self-report questionnaire. Although there were no significant differences between position groups in the number of diagnosed concussions during the 2012 football season, there were significant differences between groups in undiagnosed concussions (p=0.008) and "dings" (p<0.001); offensive linemen reported significantly higher numbers than most other positions. Significant differences were found between position groups in the frequencies of several postimpact symptoms, including dizziness (p<0.001), headache (p<0.001), and seeing stars (p<0.001) during the 2012 football season, with offensive linemen reporting significantly more symptoms compared to most other groups. There were also positional differences in frequency of returning to play while symptomatic (p<0.001) and frequency of participating in full-contact practice (p<0.001). Offensive linemen reported having returned to play while experiencing symptoms more frequently and participating in more full-contact practices than other groups. These findings suggest that offensive linemen, a position group that experiences frequent, but low-magnitude, head impacts, develop more postimpact symptoms than other playing positions, but do not report these symptoms as a concussion.
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http://dx.doi.org/10.1089/neu.2014.3582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628259PMC
March 2015

Pilot randomized evaluation of publically available concussion education materials: evidence of a possible negative effect.

Health Educ Behav 2015 Apr 15;42(2):153-62. Epub 2014 Aug 15.

Boston University School of Medicine, Boston, MA, USA.

Many states and sports leagues are instituting concussion policies aimed at reducing risk of morbidity and mortality; many include mandates about the provision of concussion education to youth athletes. However, there is limited evidence if educational materials provided under these typically vague mandates are in fact effective in changing concussion risk-related behavior or any cognition predictive of risk-related behavior. The purpose of this pilot randomized controlled study was to conduct a theory-driven evaluation of three publically available concussion education materials: two videos and one informational handout. Participants were 256 late adolescent males from 12 teams in a single league of ice hockey competition in the United States. Randomization of educational condition occurred at the team level. Written surveys assessing postimpact symptom reporting behavior, concussion knowledge, and concussion reporting cognitions were completed by participants immediately before receiving their educational intervention, 1 day after, and 1 month after. Results indicated no change in any measure over any time interval, with the exception of perceived underreporting norms. In one of the video conditions, perceived underreporting norms increased significantly 1 day after viewing the video. Possible content and viewing environment-related reasons for this increase are discussed. Across all conditions, perceived underreporting norms increased 1 month after intervention receipt, raising the possibility that late in the competitive season underreporting may be perceived as normative. The need for the development of theory-driven concussion education materials, drawing on best practices from health behavior scholars, is discussed.
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http://dx.doi.org/10.1177/1090198114543011DOI Listing
April 2015

Concussion reporting intention: a valuable metric for predicting reporting behavior and evaluating concussion education.

Clin J Sport Med 2015 May;25(3):243-7

*Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, Massachusetts; †Center for the Study of Traumatic Encephalopathy, Boston University School of Medicine, Boston, Massachusetts; ‡Department of Neurology, Boston University School of Medicine, Boston, Massachusetts; §Sports Legacy Institute, Boston University School of Medicine, Boston, Massachusetts; ¶Department of Neurosurgery, Boston University School of Medicine, Boston, Massachusetts; and ‖Department of Neurosurgery, Emerson Hospital, Concord, Massachusetts.

Objective: This study aimed to evaluate whether preseason concussion knowledge and reporting intention predicted in-season concussion reporting behavior.

Design: Prospective cohort study.

Setting: Collegiate athletic facility of each participating team.

Participants: National Collegiate Athletic Association Division I men's ice hockey players in 1 conference of competition (n = 116).

Independent Variables: Intention to report symptoms of a "minor" concussion and concussion knowledge were assessed at preseason.

Main Outcome Measures: Postseason recall of non-report of postimpact symptoms.

Results: Preseason concussion knowledge was not significantly associated with in-season reporting behavior. Intention to report concussion symptoms was significantly related to in-season reporting behavior. There was a significant interaction between the number of different symptoms experienced and both preseason reporting intention and in-season reporting behavior.

Conclusions: Evaluations of concussion education programs tend to measure concussion knowledge. The present findings suggest that reporting intention may be more strongly predictive of reporting behavior than concussion knowledge and should be included in evaluations of concussion effectiveness. New concussion education initiatives should consider targeting psychosocial constructs that increase reporting intention.

Clinical Relevance: Sports medicine clinicians who are involved in evaluating concussion education programs should measure constructs other than just concussion knowledge. Intention, to report symptoms or to continue play while experiencing symptoms of a concussion, seems to be an important and feasible construct to include as part of proximal evaluations of education effectiveness.
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http://dx.doi.org/10.1097/JSM.0000000000000137DOI Listing
May 2015