Dr. Dan Daneshvar received a Bachelor of Sciences from the Massachusetts Institute of Technology in Brain and Cognitive Sciences with Concentrations in Cognitive Neuroscience and Poetry. He completed his M.D./Ph.D. at Boston University School of Medicine. He joined the CTE Center in January 2009. He began residency at Stanford in Physical Medicine and Rehabilitation in June 2017.

All Publications

  • Age of first exposure to tackle football and chronic traumatic encephalopathy ANNALS OF NEUROLOGY Alosco, M. L., Mez, J., Tripodis, Y., Kiernan, P. T., Abdolmohammadi, B., Murphy, L., Kowall, N. W., Stein, T. D., Huber, B., Goldstein, L. E., Cantu, R. C., Katz, D. I., Chaisson, C. E., Martin, B., Solomon, T. M., McClean, M. D., Daneshvar, D. H., Nowinski, C. J., Stern, R. A., McKee, A. C. 2018; 83 (5): 886–901


    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.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.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.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.

    View details for PubMedID 29710395

  • Dementia After Moderate-Severe Traumatic Brain Injury: Coexistence of Multiple Proteinopathies JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY Kenney, K., Iacono, D., Edlow, B. L., Katz, D. I., Diaz-Arrastia, R., Dams-O'Connor, K., Daneshvar, D. H., Stevens, A., Moreau, A. L., Tirrell, L. S., Varjabedian, A., Yendiki, A., van der Kouwe, A., Mareyam, A., McNab, J. A., Gordon, W. A., Fischl, B., McKee, A. C., Perl, D. P. 2018; 77 (1): 50–63


    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.

    View details for PubMedID 29155947

  • Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players. Journal of neurotrauma Montenigro, P. H., Alosco, M. L., Martin, B. M., Daneshvar, D. H., Mez, J., Chaisson, C. E., Nowinski, C. J., Au, R., McKee, A. C., Cantu, R. C., McClean, M. D., Stern, R. A., Tripodis, Y. 2017; 34 (2): 328-340


    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.

    View details for DOI 10.1089/neu.2016.4413

    View details for PubMedID 27029716

    View details for PubMedCentralID PMC5220530

  • Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football. JAMA Mez, J., Daneshvar, D. H., Kiernan, P. T., Abdolmohammadi, B., Alvarez, V. E., Huber, B. R., Alosco, M. L., Solomon, T. M., Nowinski, C. J., McHale, L., Cormier, K. A., Kubilus, C. A., Martin, B. M., Murphy, L., Baugh, C. M., Montenigro, P. H., Chaisson, C. E., Tripodis, Y., Kowall, N. W., Weuve, J., McClean, M. D., Cantu, R. C., Goldstein, L. E., Katz, D. I., Stern, R. A., Stein, T. D., McKee, A. C. 2017; 318 (4): 360–70


    Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE).To determine the neuropathological and clinical features of deceased football players with CTE.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.Participation in American football at any level of play.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.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.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.

    View details for PubMedID 28742910

  • Cognitive Reserve as a Modifier of Clinical Expression in Chronic Traumatic Encephalopathy: A Preliminary Examination. journal of neuropsychiatry and clinical neurosciences Alosco, M. L., Mez, J., Kowall, N. W., Stein, T. D., Goldstein, L. E., Cantu, R. C., Katz, D. I., Solomon, T. M., Kiernan, P. T., Murphy, L., Abdolmohammadi, B., Daneshvar, D., Montenigro, P. H., Nowinski, C. J., Stern, R. A., McKee, A. C. 2017; 29 (1): 6-12


    This study conducted a preliminary examination on cognitive reserve (CR) as a modifier of symptom expression in subjects with autopsy-confirmed chronic traumatic encephalopathy (CTE). The sample included 25 former professional football players neuropathologically diagnosed with CTE stage III or IV. Next of kin interviews ascertained age at cognitive and behavioral/mood symptom onset and demographic/athletic characteristics. Years of education and occupational attainment defined CR. High occupational achievement predicted later age at cognitive (p=0.02) and behavioral/mood (p=0.02) onset. Education was not an individual predictor. These preliminary findings suggest that CR may forestall the clinical manifestation of CTE.

    View details for DOI 10.1176/appi.neuropsych.16030043

    View details for PubMedID 27539377

    View details for PubMedCentralID PMC5288278

  • Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy. Acta neuropathologica communications Cherry, J. D., Tripodis, Y., Alvarez, V. E., Huber, B., Kiernan, P. T., Daneshvar, D. H., Mez, J., Montenigro, P. H., Solomon, T. M., Alosco, M. L., Stern, R. A., McKee, A. C., Stein, T. D. 2016; 4 (1): 112-?


    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.

    View details for PubMedID 27793189

    View details for PubMedCentralID PMC5084333

  • Content, Delivery, and Effectiveness of Concussion Education for US College Coaches CLINICAL JOURNAL OF SPORT MEDICINE Kroshus, E., Baugh, C. M., Daneshvar, D. H. 2016; 26 (5): 391-397


    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.Cross-sectional online survey.US college sport.College coaches in National Collegiate Athletic Association Division I, II, and III (n = 1818).Self-reported receipt of education from institution, sex, sport coached, division of competition.Concussion identification and management knowledge.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.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.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.

    View details for DOI 10.1097/JSM.0000000000000272

    View details for Web of Science ID 000383906800010

    View details for PubMedID 26540598

  • Clinical Practices in Collegiate Concussion Management AMERICAN JOURNAL OF SPORTS MEDICINE Baugh, C. M., Kroshus, E., Stamm, J. M., Daneshvar, D. H., Pepin, M. J., Meehan, W. P. 2016; 44 (6): 1391-1399


    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.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.Descriptive epidemiology study.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.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.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.

    View details for DOI 10.1177/0363546516635639

    View details for Web of Science ID 000377821700011

    View details for PubMedID 27037282

    View details for PubMedCentralID PMC4891296

  • Pathologically Confirmed Chronic Traumatic Encephalopathy in a 25-Year-Old Former College Football Player JAMA NEUROLOGY Mez, J., Solomon, T. M., Daneshvar, D. H., Stein, T. D., McKee, A. C. 2016; 73 (3): 353-355

    View details for DOI 10.1001/jamaneurol.2015.3998

    View details for Web of Science ID 000372757700020

    View details for PubMedID 26747562

    View details for PubMedCentralID PMC4792748

  • Assessing clinicopathological correlation in chronic traumatic encephalopathy: rationale and methods for the UNITE study ALZHEIMERS RESEARCH & THERAPY Mez, J., Solomon, T. M., Daneshvar, D. H., Murphy, L., Kiernan, P. T., Montenigro, P. H., Kriegel, J., Abdolmohammadi, B., Fry, B., Babcock, K. J., Adams, J. W., Bourlas, A. P., Papadopoulos, Z., McHale, L., Ardaugh, B. M., Martin, B. R., Dixon, D., Nowinski, C. J., Chaisson, C., Alvarez, V. E., Tripodis, Y., Stein, T. D., Goldstein, L. E., Katz, D. I., Kowall, N. W., Cantu, R. C., Stern, R. A., McKee, A. C. 2015; 7


    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.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.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.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.

    View details for DOI 10.1186/s13195-015-0148-8

    View details for Web of Science ID 000362629500001

    View details for PubMedID 26455775

    View details for PubMedCentralID PMC4601147

  • Pressure on Sports Medicine Clinicians to Prematurely Return Collegiate Athletes to Play After Concussion JOURNAL OF ATHLETIC TRAINING Kroshus, E., Baugh, C. M., Daneshvar, D. H., Stamm, J. M., Laursen, R. M., Austin, S. B. 2015; 50 (9): 944-951


    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.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.Cross-sectional study.Web-based survey of National College Athletic Association member institutions.A total of 789 athletic trainers and 111 team physicians from 530 institutions.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.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.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.

    View details for DOI 10.4085/1062-6050-50.6.03

    View details for Web of Science ID 000365183700007

    View details for PubMedID 26207440

    View details for PubMedCentralID PMC4639885

  • Determinants of Coach Communication About Concussion Safety in US Collegiate Sport ANNALS OF BEHAVIORAL MEDICINE Kroshus, E., Baugh, C. M., Hawrilenko, M. J., Daneshvar, D. H. 2015; 49 (4): 532-541


    Communication between coaches and athletes about concussion safety can reinforce or undermine a sport culture in which concussion under-reporting is often endemic.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.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.These results serve as a starting point for the design of coach-targeted interventions that encourage communication about health and safety with athletes.

    View details for DOI 10.1007/s12160-014-9683-y

    View details for Web of Science ID 000357695400005

    View details for PubMedID 25712480

  • Beta-amyloid deposition in chronic traumatic encephalopathy ACTA NEUROPATHOLOGICA Stein, T. D., Montenigro, P. H., Alvarez, V. E., Xia, W., Crary, J. F., Tripodis, Y., Daneshvar, D. H., Mez, J., Solomon, T., Meng, G., Kubilus, C. A., Cormier, K. A., Meng, S., Babcock, K., Kiernan, P., Murphy, L., Nowinski, C. J., Martin, B., Dixon, D., Stern, R. A., Cantu, R. C., Kowall, N. W., McKee, A. C. 2015; 130 (1): 21-34


    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.

    View details for DOI 10.1007/s00401-015-1435-y

    View details for Web of Science ID 000356245500002

    View details for PubMedID 25943889

    View details for PubMedCentralID PMC4529056

  • Concussion Reporting Intention: A Valuable Metric for Predicting Reporting Behavior and Evaluating Concussion Education CLINICAL JOURNAL OF SPORT MEDICINE Kroshus, E., Baugh, C. M., Daneshvar, D. H., Nowinski, C. J., Cantu, R. C. 2015; 25 (3): 243-247


    This study aimed to evaluate whether preseason concussion knowledge and reporting intention predicted in-season concussion reporting behavior.Prospective cohort study.Collegiate athletic facility of each participating team.National Collegiate Athletic Association Division I men's ice hockey players in 1 conference of competition (n = 116).Intention to report symptoms of a "minor" concussion and concussion knowledge were assessed at preseason.Postseason recall of non-report of postimpact symptoms.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.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.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.

    View details for Web of Science ID 000353911700008

    View details for PubMedID 25051193

  • Post-traumatic neurodegeneration and chronic traumatic encephalopathy MOLECULAR AND CELLULAR NEUROSCIENCE Daneshvar, D. H., Goldstein, L. E., Kiernan, P. T., Stein, T. D., McKee, A. C. 2015; 66: 81-90


    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'.

    View details for DOI 10.1016/j.mcn.2015.03.007

    View details for Web of Science ID 000356398900003

    View details for PubMedID 25758552

  • Pilot Randomized Evaluation of Publically Available Concussion Education Materials: Evidence of a Possible Negative Effect HEALTH EDUCATION & BEHAVIOR Kroshus, E., Baugh, C. M., Hawrilenko, M., Daneshvar, D. H. 2015; 42 (2): 153-162


    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.

    View details for DOI 10.1177/1090198114543011

    View details for Web of Science ID 000352228000003

    View details for PubMedID 25128434

  • Age of first exposure to football and later-life cognitive impairment in former NFL players NEUROLOGY Stamm, J. M., Bourlas, A. P., Baugh, C. M., Fritts, N. G., Daneshvar, D. H., Martin, B. M., McClean, M. D., Tripodis, Y., Stern, R. A. 2015; 84 (11): 1114-1120


    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.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.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.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.

    View details for DOI 10.1212/WNL.0000000000001358

    View details for Web of Science ID 000351458600013

    View details for PubMedID 25632088

    View details for PubMedCentralID PMC4371403

  • Frequency of Head-Impact-Related Outcomes by Position in NCAA Division I Collegiate Football Players JOURNAL OF NEUROTRAUMA Baugh, C. M., Kiernan, P. T., Kroshus, E., Daneshvar, D. H., Montenigro, P. H., McKee, A. C., Stern, R. A. 2015; 32 (5): 314-326


    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.

    View details for DOI 10.1089/neu.2014.3582

    View details for Web of Science ID 000350045700004

    View details for PubMedID 25155288

    View details for PubMedCentralID PMC4628259

  • The neuropathology of traumatic brain injury. Handbook of clinical neurology McKee, A. C., Daneshvar, D. H. 2015; 127: 45-66


    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.

    View details for DOI 10.1016/B978-0-444-52892-6.00004-0

    View details for PubMedID 25702209

    View details for PubMedCentralID PMC4694720

  • Concussion Management in United States College Sports Compliance With National Collegiate Athletic Association Concussion Policy and Areas for Improvement AMERICAN JOURNAL OF SPORTS MEDICINE Baugh, C. M., Kroshus, E., Daneshvar, D. H., Filali, N. A., Hiscox, M. J., Glantz, L. H. 2015; 43 (1): 47-56


    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.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.Cross-sectional study; Level of evidence, 3.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.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%).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.

    View details for DOI 10.1177/0363546514553090

    View details for Web of Science ID 000347159300005

    View details for PubMedID 25336600

  • Perceived Coach Support and Concussion Symptom-Reporting: Differences between Freshmen and Non-Freshmen College Football Players JOURNAL OF LAW MEDICINE & ETHICS Baugh, C. M., Kroshus, E., Daneshvar, D. H., Stern, R. A. 2014; 42 (3): 314-322


    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.

    View details for DOI 10.1111/jlme.12148

    View details for Web of Science ID 000342745000006

    View details for PubMedID 25264089

  • Understanding Concussion Reporting Using a Model Based on the Theory of Planned Behavior JOURNAL OF ADOLESCENT HEALTH Kroshus, E., Baugh, C. M., Daneshvar, D. H., Viswanath, K. 2014; 54 (3): 269-?


    Athlete's report of concussion symptoms to coaching or medical personnel is an important component of concussion risk reduction. This study applies a model based on the Theory of Planned Behavior (TPB) to the prediction of concussive symptom underreporting among late adolescent and young adult male ice hockey players.Participants were members of an American Tier III Junior A ice hockey league (ages 18-21 years; male; n = 256). Twelve of 14 league teams and 97% of players within these teams agreed to participate. Written survey items assessed symptom reporting behavior, intention, perceived norms, self-efficacy, perceived outcomes of reporting, and concussion knowledge. Structural equation modeling was used to assess the significance of relationships hypothesized by the TPB-based model and the overall model fit. Data were collected in January 2013.Results supported the fit of the TPB-based model in explaining reporting behavior; all model pathways were significant in the hypothesized direction. Of the perceived reporting outcomes assessed, those related to athletic performance were identified as most strongly associated with reporting intention.Results of this study suggest the importance of considering factors such as perceived outcomes of reporting, perceived norms, and self-efficacy, in addition to knowledge, when analyzing concussion underreporting among adolescent athletes. As concussion education for athletes becomes increasingly mandated, testing and applying psychosocial theories such as TPB may help increase program efficacy.

    View details for DOI 10.1016/j.jadohealth.2013.11.011

    View details for Web of Science ID 000331722800006

    View details for PubMedID 24560034

  • Clinical subtypes of chronic traumatic encephalopathy: literature review and proposed research diagnostic criteria for traumatic encephalopathy syndrome ALZHEIMERS RESEARCH & THERAPY Montenigro, P. H., Baugh, C. M., Daneshvar, D. H., Mez, J., Budson, A. E., Au, R., Katz, D. I., Cantu, R. C., Stern, R. A. 2014; 6 (5)


    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.

    View details for DOI 10.1186/s13195-014-0068-z

    View details for Web of Science ID 000343200300013

    View details for PubMedID 25580160

    View details for PubMedCentralID PMC4288217

  • Self-reported concussion history: impact of providing a definition of concussion. Open access journal of sports medicine Robbins, C. A., Daneshvar, D. H., Picano, J. D., Gavett, B. E., Baugh, C. M., Riley, D. O., Nowinski, C. J., McKee, A. C., Cantu, R. C., Stern, R. A. 2014; 5: 99-103


    In recent years, the understanding of concussion has evolved in the research and medical communities to include more subtle and transient symptoms. The accepted definition of concussion in these communities has reflected this change. However, it is unclear whether this shift is also reflected in the understanding of the athletic community.Self-reported concussion history is an inaccurate assessment of someone's lifetime exposure to concussive brain trauma. However, unfortunately, in many cases it is the only available tool.We hypothesize that athletes' self-reported concussion histories will be significantly greater after reading them the current definition of concussion, relative to the reporting when no definition was provided. An increase from baseline to post-definition response will suggest that athletes are unaware of the currently accepted medical definition.Cross-sectional study of 472 current and former athletes.Investigators conducted structured telephone interviews with current and former athletes between January 2010 and January 2013, asking participants to report how many concussions they had received in their lives. Interviewers then read participants a current definition of concussion, and asked them to re-estimate based on that definition.THE TWO ESTIMATES WERE SIGNIFICANTLY DIFFERENT (WILCOXON SIGNED RANK TEST: z=15.636, P<0.001). Comparison of the baseline and post-definition medians (7 and 15, respectively) indicated that the post-definition estimate was approximately twice the baseline. Follow-up analyses indicated that this effect was consistent across all levels of competition examined and across type of sport (contact versus non-contact).Our results indicate that athletes' current understandings of concussions are not consistent with a currently accepted medical definition. We strongly recommend that clinicians and researchers preface requests for self-reported concussion history with a definition. In addition, it is extremely important that researchers report the definition they used in published manuscripts of their work.Our study shows that unprompted reporting of concussion history produces results that are significantly different from those provided after a definition has been given, suggesting one possible mechanism to improve the reliability of self-reported concussion history across multiple individuals.

    View details for DOI 10.2147/OAJSM.S58005

    View details for PubMedID 24891816

    View details for PubMedCentralID PMC4019619

  • The neuropathology of sport ACTA NEUROPATHOLOGICA McKee, A. C., Daneshvar, D. H., Alvarez, V. E., Stein, T. D. 2014; 127 (1): 29-51


    The benefits of regular exercise, physical fitness and sports participation on cardiovascular and brain health are undeniable. Physical activity reduces the risk for cardiovascular disease, type 2 diabetes, hypertension, obesity, and stroke, and produces beneficial effects on cholesterol levels, antioxidant systems, inflammation, and vascular function. Exercise also enhances psychological health, reduces age-related loss of brain volume, improves cognition, reduces the risk of developing dementia, and impedes neurodegeneration. Nonetheless, the play of sports is associated with risks, including a risk for mild TBI (mTBI) and, rarely, catastrophic traumatic injury and death. There is also growing awareness that repetitive mTBIs, such as concussion and subconcussion, can occasionally produce persistent cognitive, behavioral, and psychiatric problems as well as lead to the development of a neurodegeneration, chronic traumatic encephalopathy (CTE). In this review, we summarize the beneficial aspects of sports participation on psychological, emotional, physical and cognitive health, and specifically analyze some of the less common adverse neuropathological outcomes, including concussion, second-impact syndrome, juvenile head trauma syndrome, catastrophic sudden death, and CTE. CTE is a latent neurodegeneration clinically associated with behavioral changes, executive dysfunction and cognitive impairments, and pathologically characterized by frontal and temporal lobe atrophy, neuronal and axonal loss, and abnormal deposits of paired helical filament (PHF)-tau and 43 kDa TAR deoxyribonucleic acid (DNA)-binding protein (TDP-43). CTE often occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including motor neuron disease (CTE-MND). Although the incidence and prevalence of CTE are not known, CTE has been reported most frequently in American football players and boxers. Other sports associated with CTE include ice hockey, professional wrestling, soccer, rugby, and baseball.

    View details for DOI 10.1007/s00401-013-1230-6

    View details for Web of Science ID 000329225300003

    View details for PubMedID 24366527

    View details for PubMedCentralID PMC4255282

  • NCAA concussion education in ice hockey: an ineffective mandate BRITISH JOURNAL OF SPORTS MEDICINE Kroshus, E., Daneshvar, D. H., Baugh, C. M., Nowinski, C. J., Cantu, R. C. 2014; 48 (2): 135-U146


    Despite concussion education being increasingly mandated by states and sports leagues, there has been limited evaluation of what education is in fact effective. The National Collegiate Athletic Association (NCAA) currently mandates that institutions provide concussion education, without specifying content or delivery. The present study evaluated the effectiveness of this general mandate, as enacted for male collegiate ice hockey teams within one conference of competition.In a prospective cohort design, 146 players from 6 male collegiate ice hockey teams in one Division 1 conference completed written surveys before and after receiving their institution-determined concussion education. Knowledge, attitudes, perceived norms and behavioural intention were assessed using validated measures. Education content and delivery was assessed by open-ended responses and consultation with team athletic trainers.All teams received concussion education material; however, content and delivery varied. Rates of material recall differed by delivery format. Considering all teams together, there were no significant improvements in knowledge and only a very small decrease in intention to continue playing while experiencing symptoms of a concussion. Pre-education and post-education, there were significant between-team differences in attitudes towards concussion reporting and behavioural intention.The NCAA's general education mandate was divergently enacted; it did not significantly change the constructs of interest nor did it mitigate the pre-education team differences in these constructs. Existing educational materials should be evaluated, theory and evidence-driven materials developed, and mandates extended to, at a minimum, recommend materials found to be effective in changing concussion-reporting behaviour.

    View details for DOI 10.1136/bjsports-2013-092498

    View details for Web of Science ID 000328749000016

    View details for PubMedID 23956336

  • Clinical presentation of chronic traumatic encephalopathy NEUROLOGY Stern, R. A., Daneshvar, D. H., Baugh, C. M., Seichepine, D. R., Montenigro, P. H., Riley, D. O., Fritts, N. G., Stamm, J. M., Robbins, C. A., McHale, L., Simkin, I., Stein, T. D., Alvarez, V. E., Goldstein, L. E., Budson, A. E., Kowall, N. W., Nowinski, C. J., Cantu, R. C., McKee, A. C. 2013; 81 (13): 1122-1129


    The goal of this study was to examine the clinical presentation of chronic traumatic encephalopathy (CTE) in neuropathologically confirmed cases.Thirty-six adult male subjects were selected from all cases of neuropathologically confirmed CTE at the Boston University Center for the Study of Traumatic Encephalopathy brain bank. Subjects were all athletes, had no comorbid neurodegenerative or motor neuron disease, and had next-of-kin informants to provide retrospective reports of the subjects' histories and clinical presentations. These interviews were conducted blind to the subjects' neuropathologic findings.A triad of cognitive, behavioral, and mood impairments was common overall, with cognitive deficits reported for almost all subjects. Three subjects were asymptomatic at the time of death. Consistent with earlier case reports of boxers, 2 relatively distinct clinical presentations emerged, with one group whose initial features developed at a younger age and involved behavioral and/or mood disturbance (n = 22), and another group whose initial presentation developed at an older age and involved cognitive impairment (n = 11).This suggests there are 2 major clinical presentations of CTE, one a behavior/mood variant and the other a cognitive variant.

    View details for Web of Science ID 000330768000010

    View details for PubMedID 23966253

    View details for PubMedCentralID PMC3795597

  • Profile of Self-Reported Problems with Executive Functioning in College and Professional Football Players JOURNAL OF NEUROTRAUMA Seichepine, D. R., Stamm, J. M., Daneshvar, D. H., Riley, D. O., Baugh, C. M., Gavett, B. E., Tripodis, Y., Martin, B., Chaisson, C., McKee, A. C., Cantu, R. C., Nowinski, C. J., Stern, R. A. 2013; 30 (14): 1299-1304


    Repetitive mild traumatic brain injury (mTBI), such as that experienced by contact-sport athletes, has been associated with the development of chronic traumatic encephalopathy (CTE). Executive dysfunction is believed to be among the earliest symptoms of CTE, with these symptoms presenting in the fourth or fifth decade of life. The present study used a well-validated self-report measure to study executive functioning in football players, compared to healthy adults. Sixty-four college and professional football players were administered the Behavior Rating Inventory of Executive Function, adult version (BRIEF-A) to evaluate nine areas of executive functioning. Scores on the BRIEF-A were compared to published age-corrected normative scores for healthy adults Relative to healthy adults, the football players indicated significantly more problems overall and on seven of the nine clinical scales, including Inhibit, Shift, Emotional Control, Initiate, Working Memory, Plan/Organize, and Task Monitor. These symptoms were greater in athletes 40 and older, relative to younger players. In sum, football players reported more-frequent problems with executive functioning and these symptoms may develop or worsen in the fifth decade of life. The findings are in accord with a growing body of evidence that participation in football is associated with the development of cognitive changes and dementia as observed in CTE.

    View details for DOI 10.1089/neu.2012.2690

    View details for Web of Science ID 000321821100010

    View details for PubMedID 23421745

    View details for PubMedCentralID PMC3713446

  • The spectrum of disease in chronic traumatic encephalopathy BRAIN McKee, A. C., Stein, T. D., Nowinski, C. J., Stern, R. A., Daneshvar, D. H., Alvarez, V. E., Lee, H., Hall, G., Wojtowicz, S. M., Baugh, C. M., Riley, D. O., Kubilus, C. A., Cormier, K. A., Jacobs, M. A., Martin, B. R., Abraham, C. R., Ikezu, T., Reichard, R. R., Wolozin, B. L., Budson, A. E., Goldstein, L. E., Kowall, N. W., Cantu, R. C. 2013; 136: 43-64


    Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I-IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I-III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy was the sole diagnosis in 43 cases (63%); eight were also diagnosed with motor neuron disease (12%), seven with Alzheimer's disease (11%), 11 with Lewy body disease (16%) and four with frontotemporal lobar degeneration (6%). There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in chronic traumatic encephalopathy that occurs in conjunction with widespread axonal disruption and loss. The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein.

    View details for DOI 10.1093/brain/aws307

    View details for Web of Science ID 000314909900006

    View details for PubMedID 23208308

    View details for PubMedCentralID PMC3624697

  • Effectiveness of the SLICE Program for Youth Concussion Education CLINICAL JOURNAL OF SPORT MEDICINE Bagley, A. F., Daneshvar, D. H., Schanker, B. D., Zurakowski, D., d'Hemecourt, C. A., Nowinski, C. J., Cantu, R. C., Goulet, K. 2012; 22 (5): 385-389


    To analyze the effectiveness of the Sports Legacy Institute Community Educators (SLICE) curriculum for student-athletes on recognition and appropriate responses to concussions.Prospective cohort study, level II.The SLICE concussion workshop.All students ranging from 9 to 18 years (n = 636) taking the SLICE concussion education program.The SLICE concussion education program featuring interactive demonstrations, discussion, and case studies of athletes delivered by medical students and others in health-related fields.Evaluations assessing knowledge of concussion recognition and appropriate response were administered before and after participating in the SLICE concussion education program.Students displayed significant improvements in absolute mean score on the concussion knowledge quiz between prepresentation and postpresentation (P < 0.0001). Significant improvements in mean score were observed among both male and female students within each age group. The proportion of students who passed the quiz increased from 34% prepresentation to 80% postpresentation (P < 0.0001). However, the percentage who passed the quiz postpresentation was significantly higher among female students compared with male students (P < 0.0001) and among students 13 years of age or older compared with students less than 13 years (P < 0.0001). Using multivariable logistic regression, we identified age group and gender as the most significant factors associated with passing the quiz postpresentation.The SLICE program promotes effective learning and knowledge about concussion recognition and response among students ranging from 9 to 18 years. Lessons from the SLICE program may be broadly applicable to youth concussion education.

    View details for DOI 10.1097/JSM.0b013e3182639bb4

    View details for Web of Science ID 000308694400002

    View details for PubMedID 22929042

  • Diagnostic Accuracy Statistics for Seven Neuropsychological Assessment Battery (NAB) Test Variables in the Diagnosis of Alzheimer's Disease APPLIED NEUROPSYCHOLOGY-ADULT Gavett, B. E., Lou, K. R., Daneshvar, D. H., Green, R. C., Jefferson, A. L., Stern, R. A. 2012; 19 (2): 108-115


    Neuropsychological tests are useful for diagnosing Alzheimer's disease (AD), yet for many tests, diagnostic accuracy statistics are unavailable. We present diagnostic accuracy statistics for seven variables from the Neuropsychological Assessment Battery (NAB) that were administered to a large sample of elderly adults (n = 276) participating in a longitudinal research study at a national AD Center. Tests included Driving Scenes, Bill Payment, Daily Living Memory, Screening Visual Discrimination, Screening Design Construction, and Judgment. Clinical diagnosis was made independent of these tests, and for the current study, participants were categorized as AD (n = 65) or non-AD (n = 211). Receiver operating characteristics curve analysis was used to determine each test's sensitivity and specificity at multiple cut points, which were subsequently used to calculate positive and negative predictive values at a variety of base rates. Of the tests analyzed, the Daily Living Memory test provided the greatest accuracy in the identification of AD and the two Screening measures required a significant tradeoff between sensitivity and specificity. Overall, the seven NAB subtests included in the current study are capable of excellent diagnostic accuracy, but appropriate understanding of the context in which the tests are used is crucial for minimizing errors.

    View details for DOI 10.1080/09084282.2011.643947

    View details for Web of Science ID 000304596100005

    View details for PubMedID 23373577

    View details for PubMedCentralID PMC3857936

  • Long-Term Consequences: Effects on Normal Development Profile After Concussion PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA Daneshvar, D. H., Riley, D. O., Nowinski, C. J., McKee, A. C., Stern, R. A., Cantu, R. C. 2011; 22 (4): 683-?


    Each year in the United States, approximately 1.7 million people are diagnosed with a traumatic brain injury (TBI), about 75% of which are classified as mild TBIs or concussions. Although symptoms typically resolve in a matter of weeks, both children and adults may suffer from postconcussion syndrome for months or longer. A progressive tauopathy, chronic traumatic encephalopathy, is believed to stem from repeated brain trauma. Alzheimer-like dementia, Parkinsonism, and motor neuron disease are also associated with repetitive brain trauma. Effective diagnoses, treatments, and education plans are required to reduce the future burden and incidence of long-term effects of head injuries.

    View details for DOI 10.1016/j.pmr.2011.08.009

    View details for Web of Science ID 000297822600009

    View details for PubMedID 22050943

    View details for PubMedCentralID PMC3208826

  • Long-term Consequences of Repetitive Brain Trauma: Chronic Traumatic Encephalopathy PM&R Stern, R. A., Riley, D. O., Daneshvar, D. H., Nowinski, C. J., Cantu, R. C., McKee, A. C. 2011; 3 (10): S460-S467


    Chronic traumatic encephalopathy (CTE) has been linked to participation in contact sports such as boxing and American football. CTE results in a progressive decline of memory and cognition, as well as depression, suicidal behavior, poor impulse control, aggressiveness, parkinsonism, and, eventually, dementia. In some individuals, it is associated with motor neuron disease, referred to as chronic traumatic encephalomyelopathy, which appears clinically similar to amyotrophic lateral sclerosis. Results of neuropathologic research has shown that CTE may be more common in former contact sports athletes than previously believed. It is believed that repetitive brain trauma, with or possibly without symptomatic concussion, is responsible for neurodegenerative changes highlighted by accumulations of hyperphosphorylated tau and TDP-43 proteins. Given the millions of youth, high school, collegiate, and professional athletes participating in contact sports that involve repetitive brain trauma, as well as military personnel exposed to repeated brain trauma from blast and other injuries in the military, CTE represents an important public health issue. Focused and intensive study of the risk factors and in vivo diagnosis of CTE will potentially allow for methods to prevent and treat these diseases. Research also will provide policy makers with the scientific knowledge to make appropriate guidelines regarding the prevention and treatment of brain trauma in all levels of athletic involvement as well as the military theater.

    View details for DOI 10.1016/j.pmrj.2011.08.008

    View details for Web of Science ID 000305873100015

    View details for PubMedID 22035690

  • The Epidemiology of Sport-Related Concussion CLINICS IN SPORTS MEDICINE Daneshvar, D. H., Nowinski, C. J., McKee, A. C., Cantu, R. C. 2011; 30 (1): 1-?


    Concussions and head injuries may never be completely eliminated from sports. However, with better data comes an improved understanding of the types of actions and activities that typically result in concussions. With this knowledge can come improved techniques and rule changes to minimize the rate and severity of concussions in sports. This article identifies the factors that affect concussion rate.

    View details for DOI 10.1016/j.csm.2010.08.006

    View details for Web of Science ID 000285114800003

    View details for PubMedID 21074078

    View details for PubMedCentralID PMC2987636

  • Helmets and Mouth Guards: The Role of Personal Equipment in Preventing Sport-Related Concussions CLINICS IN SPORTS MEDICINE Daneshvar, D. H., Baugh, C. M., Nowinski, C. J., McKee, A. C., Stern, R. A., Cantu, R. C. 2011; 30 (1): 145-?


    Millions of athletes in the United States experience concussions annually. Although helmets and mouth guards have decreased the risk of catastrophic head injuries, their protective effects on concussions are less clear. This article evaluates the current literature on the effect of equipment on concussions. Understanding the role that these equipment play in preventing concussions is complicated by many factors, such as selection bias in nonrandomized studies, variations in playing style, and risk compensation in sports with mandatory protective equipment. Improving coach and player education about proper concussion management, encouraging neck-strengthening exercises, and minimizing high-risk impacts may reduce concussions in sports.

    View details for DOI 10.1016/j.csm.2010.09.006

    View details for Web of Science ID 000285114800014

    View details for PubMedID 21074089

    View details for PubMedCentralID PMC2987604

  • TDP-43 Proteinopathy and Motor Neuron Disease in Chronic Traumatic Encephalopathy JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY McKee, A. C., Gavett, B. E., Stern, R. A., Nowinski, C. J., Cantu, R. C., Kowall, N. W., Perl, D. P., Hedley-Whyte, E. T., Price, B., Sullivan, C., Morin, P., Lee, H., Kubilus, C. A., Daneshvar, D. H., Wulff, M., Budson, A. E. 2010; 69 (9): 918-929


    Epidemiological evidence suggests that the incidence of amyotrophic lateral sclerosis is increased in association with head injury. Repetitive head injury is also associated with the development of chronic traumatic encephalopathy (CTE), a tauopathy characterized by neurofibrillary tangles throughout the brain in the relative absence of β-amyloid deposits. We examined 12 cases of CTE and, in 10, found a widespread TAR DNA-binding protein of approximately 43kd (TDP-43) proteinopathy affecting the frontal and temporal cortices, medial temporal lobe, basal ganglia, diencephalon, and brainstem. Three athletes with CTE also developed a progressive motor neuron disease with profound weakness, atrophy, spasticity, and fasciculations several years before death. In these 3 cases, there were abundant TDP-43-positive inclusions and neurites in the spinal cord in addition to tau neurofibrillary changes, motor neuron loss, and corticospinal tract degeneration. The TDP-43 proteinopathy associated with CTE is similar to that found in frontotemporal lobar degeneration with TDP-43 inclusions, in that widespread regions of the brain are affected. Akin to frontotemporal lobar degeneration with TDP-43 inclusions, in some individuals with CTE, the TDP-43 proteinopathy extends to involve the spinal cord and is associated with motor neuron disease. This is the first pathological evidence that repetitive head trauma experienced in collision sports might be associated with the development of a motor neuron disease.

    View details for DOI 10.1097/NEN.0b013e3181ee7d85

    View details for Web of Science ID 000281712300005

    View details for PubMedID 20720505

    View details for PubMedCentralID PMC2951281

  • At the crossroads: development and evaluation of a dementia caregiver group intervention to assist in driving cessation. Gerontology & geriatrics education Stern, R. A., D'Ambrosio, L. A., Mohyde, M., Carruth, A., Tracton-Bishop, B., Hunter, J. C., Daneshvar, D. H., Coughlin, J. F. 2008; 29 (4): 363-382


    Deciding when an individual with dementia must reduce or stop driving can be a stressful issue for family caregivers. The purpose of this study was to develop a group intervention to assist these caregivers with driving issues and to provide a preliminary evaluation of the comparative effectiveness of this At the Crossroads intervention. Participants were randomized to one of three arms: (1) active intervention (four 2-hour manualized educational/support group meetings; n = 31); (2) written materials only (participants received written materials after a pretest; n = 23); and (3)control (participants received written materials after a posttest; n = 12).Participants were administered a battery of self-report and interview-based questionnaires at baseline and again 2 months later. At follow-up, the active intervention group scored significantly better than both other groups on key outcome variables, including self-efficacy, communication, and preparedness. The At the Crossroads caregiver intervention appears to effectively provide education and support needed for caregivers to address driving-related issues with their loved ones.

    View details for DOI 10.1080/02701960802497936

    View details for PubMedID 19064472

    View details for PubMedCentralID PMC2679525