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OBJECTIVE: Exposure to repetitive head impacts (RHI) is associated with later-life cognitive symptoms and neuropathologies, including chronic traumatic encephalopathy (CTE). Cognitive decline in community cohorts is often due to multiple pathologies; however, the frequency and contributions of these pathologies to cognitive impairment in people exposed to RHI are unknown. Here, we examined the relative contributions of 13 neuropathologies to cognitive symptoms and dementia in RHI-exposed brain donors. METHODS: Neuropathologists examined brain tissue from 571 RHI-exposed donors and assessed for the presence of 13 neuropathologies, including CTE, Alzheimer disease (AD), Lewy body disease (LBD), and transactive response DNA-binding protein 43 (TDP-43) inclusions. Cognitive status was assessed by presence of dementia, Functional Activities Questionnaire, and Cognitive Difficulties Scale. Spearman rho was calculated to assess intercorrelation of pathologies. Additionally, frequencies of pathological co-occurrence were compared to a simulated distribution assuming no intercorrelation. Logistic and linear regressions tested associations between neuropathologies and dementia status and cognitive scale scores. RESULTS: The sample age range was 18-97 years (median = 65.0, interquartile range = 46.0-76.0). Of the donors, 77.2% had at least one moderate-severe neurodegenerative or cerebrovascular pathology. Stage III-IV CTE was the most common neurodegenerative disease (43.1%), followed by TDP-43 pathology, AD, and hippocampal sclerosis. Neuropathologies were intercorrelated, and there were fewer unique combinations than expected if pathologies were independent (p < 0.001). The greatest contributors to dementia were AD, neocortical LBD, hippocampal sclerosis, cerebral amyloid angiopathy, and CTE. INTERPRETATION: In this sample of RHI-exposed brain donors with wide-ranging ages, multiple neuropathologies were common and correlated. Mixed neuropathologies, including CTE, underlie cognitive impairment in contact sport athletes. ANN NEUROL 2024;95:314-324.
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Doença de Alzheimer , Encefalopatia Traumática Crônica , Esclerose Hipocampal , Doença por Corpos de Lewy , Doenças Neurodegenerativas , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doenças Neurodegenerativas/patologia , Encéfalo/patologia , Doença de Alzheimer/patologia , Doença por Corpos de Lewy/patologia , Encefalopatia Traumática Crônica/patologia , Proteínas de Ligação a DNA/metabolismo , CogniçãoRESUMO
Exposure to repetitive head impacts (RHIs) in contact sports is associated with neurodegenerative disorders including chronic traumatic encephalopathy (CTE) which currently can be diagnosed only at postmortem. American football players are at higher risk of developing CTE given their exposure to RHIs. One promising approach for diagnosing CTE in vivo is to explore known neuropathological abnormalities at postmortem in living individuals using structural magnetic resonance imaging (MRI). MRI brain morphometry was evaluated in 170 male former American football players ages 45-74 years (n = 114 professional; n = 56 college) and 54 same-age unexposed asymptomatic male controls (n = 58 age range 45-74). Cortical thickness and volume of regions of interest were selected based on established CTE pathology findings and were assessed using FreeSurfer. Group differences and interactions with age and exposure factors were evaluated using a generalized least squares model. A separate logistic regression and independent multinomial model were performed to predict each Traumatic Encephalopathy Syndrome (TES) diagnosis core clinical features and provisional level of certainty for CTE pathology using brain regions of interest. Former college and professional American football players (combined) showed significant cortical thickness and/or volume reductions compared to unexposed asymptomatic controls in the hippocampus amygdala entorhinal cortex parahippocampal gyrus insula temporal pole and superior frontal gyrus. Post-hoc analyses identified group-level differences between former professional players and unexposed asymptomatic controls in the hippocampus amygdala entorhinal cortex parahippocampal gyrus insula and superior frontal gyrus. Former college players showed significant volume reductions in the hippocampus amygdala and superior frontal gyrus compared to the unexposed asymptomatic controls. We did not observe age-by-group interactions for brain morphometric measures. Interactions between morphometry and exposure measures were limited to a single significant positive association between the age of first exposure to organized tackle football and right insular volume. We found no significant relationship between brain morphometric measures and the TES diagnosis core clinical features and provisional level of certainty for CTE pathology outcomes. These findings suggest that MRI morphometrics detects abnormalities in individuals with a history of RHI exposure that resemble the anatomic distribution of pathological findings from postmortem CTE studies. The lack of findings associating MRI measures with exposure metrics (except for one significant relationship) or TES diagnosis and core clinical features suggests that brain morphometry must be complemented by other types of measures to characterize individuals with RHIs.
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BACKGROUND: Traumatic encephalopathy syndrome (TES) is defined as the clinical manifestation of the neuropathological entity chronic traumatic encephalopathy (CTE). A core feature of TES is neurobehavioral dysregulation (NBD), a neuropsychiatric syndrome in repetitive head impact (RHI)-exposed individuals, characterized by a poor regulation of emotions/behavior. To discover biological correlates for NBD, we investigated the association between biomarkers of inflammation (interleukin (IL)-1ß, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) in cerebrospinal fluid (CSF) and NBD symptoms in former American football players and unexposed individuals. METHODS: Our cohort consisted of former American football players, with (n = 104) or without (n = 76) NBD diagnosis, as well as asymptomatic unexposed individuals (n = 55) from the DIAGNOSE CTE Research Project. Specific measures for NBD were derived (i.e., explosivity, emotional dyscontrol, impulsivity, affective lability, and a total NBD score) from a factor analysis of multiple self-report neuropsychiatric measures. Analyses of covariance tested differences in biomarker concentrations between the three groups. Within former football players, multivariable linear regression models assessed relationships among log-transformed inflammatory biomarkers, proxies for RHI exposure (total years of football, cumulative head impact index), and NBD factor scores, adjusted for relevant confounding variables. Sensitivity analyses tested (1) differences in age subgroups (< 60, ≥ 60 years); (2) whether associations could be identified with plasma inflammatory biomarkers; (3) associations between neurodegeneration and NBD, using plasma neurofilament light (NfL) chain protein; and (4) associations between biomarkers and cognitive performance to explore broader clinical symptoms related to TES. RESULTS: CSF IL-6 was higher in former American football players with NBD diagnosis compared to players without NBD. Furthermore, elevated levels of CSF IL-6 were significantly associated with higher emotional dyscontrol, affective lability, impulsivity, and total NBD scores. In older football players, plasma NfL was associated with higher emotional dyscontrol and impulsivity, but also with worse executive function and processing speed. Proxies for RHI exposure were not significantly associated with biomarker concentrations. CONCLUSION: Specific NBD symptoms in former American football players may result from multiple factors, including neuroinflammation and neurodegeneration. Future studies need to unravel the exact link between NBD and RHI exposure, including the role of other pathophysiological pathways.
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Lesões Encefálicas Traumáticas , Encefalopatia Traumática Crônica , Futebol Americano , Humanos , Idoso , Pessoa de Meia-Idade , Encefalopatia Traumática Crônica/patologia , Interleucina-6 , BiomarcadoresRESUMO
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head impacts (RHI) and pathologically defined as neuronal phosphorylated tau aggregates around small blood vessels and concentrated at sulcal depths. Cross-sectional studies suggest that tau inclusions follow a stereotyped pattern that begins in the neocortex in low stage disease, followed by involvement of the medial temporal lobe and subcortical regions with significant neocortical burden in high stage CTE. Here, we define a subset of brain donors with high stage CTE and with a low overall cortical burden of tau inclusions (mean semiquantitative value ≤1) and classify them as cortical-sparing CTE (CSCTE). Of 620 brain donors with pathologically diagnosed CTE, 66 (11%) met criteria for CSCTE. Compared to typical high stage CTE, those with CSCTE had a similar age at death and years of contact sports participation and were less likely to carry apolipoprotein ε4 (p < 0.05). CSCTE had less overall tau pathology severity, but a proportional increase of disease burden in medial temporal lobe and brainstem regions compared to the neocortex (p's < 0.001). CSCTE also had lower prevalence of comorbid neurodegenerative disease. Clinically, CSCTE participants were less likely to have dementia (p = 0.023) and had less severe cognitive difficulties (as reported by informants using the Functional Activities Questionnaire (FAQ); p < 0.001, meta-cognitional index T score; p = 0.002 and Cognitive Difficulties Scale (CDS); p < 0.001,) but had an earlier onset age of behavioral (p = 0.006) and Parkinsonian motor (p = 0.013) symptoms when compared to typical high stage CTE. Other comorbid tauopathies likely contributed in part to these differences: when cases with concurrent Alzheimer dementia or frontal temporal lobar degeneration with tau pathology were excluded, differences were largely retained, but only remained significant for FAQ (p = 0.042), meta-cognition index T score (p = 0.014) and age of Parkinsonian motor symptom onset (p = 0.046). Overall, CSCTE appears to be a distinct subtype of high stage CTE with relatively greater involvement of subcortical and brainstem regions and less severe cognitive symptoms.
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Doença de Alzheimer , Encefalopatia Traumática Crônica , Doenças Neurodegenerativas , Humanos , Estudos Transversais , EncéfaloRESUMO
OBJECTIVE: To compare clinical outcomes following steroid injections using the anterior and posterior approaches. DESIGN: Systematic review with meta-analysis. SETTING: Embase, Web of Science, and Cochrane Center Register of Controlled Trials were searched for randomized control trials (RCTs) and prospective comparative studies. PATIENTS: Patients with adhesive capsulitis. INTERVENTIONS: Glenohumeral steroid injections using either anterior or posterior approach. MAIN OUTCOME MEASURES: Pain visual analog scale (VAS) and shoulder range of motion (ROM) at 12 weeks, accuracy, and adverse events. Standardized mean difference (SMD) for VAS and weighted mean difference (WMD) for ROMs. RESULTS: We identified 6 RCTs and one prospective comparative study with a total of 468 patients. While there was no difference in pain VAS at 12 weeks between the 2 approaches (SMD, -0.86; 95% CI, -1.76 to 0.04), the anterior approach resulted in greater improvements in external rotation (WMD, 8.08; 95% CI, 0.79-15.38) and abduction (WMD, 6.76; 95% CI, 3.05-10.48) compared with the posterior approach. Subgroup analysis with RCTs that utilized steroid injection with hydrodilatation for both approaches demonstrated greater reduction in pain VAS at 12 weeks with the anterior approach (SMD, -0.52; 95% CI, -0.98 to -0.07). Overall, procedures were well tolerated without major complications. CONCLUSIONS: While pain reduction is similar, the anterior approach may be more beneficial in restoring shoulder external rotation and abduction compared with the posterior approach at 12 weeks. Steroid injection combined with hydrodilatation may further improve pain control when performed with the anterior approach at 12 weeks.
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INTRODUCTION: Tau is a key pathology in chronic traumatic encephalopathy (CTE). Here, we report our findings in tau positron emission tomography (PET) measurements from the DIAGNOSE CTE Research Project. METHOD: We compare flortaucipir PET measures from 104 former professional players (PRO), 58 former college football players (COL), and 56 same-age men without exposure to repetitive head impacts (RHI) or traumatic brain injury (unexposed [UE]); characterize their associations with RHI exposure; and compare players who did or did not meet diagnostic criteria for traumatic encephalopathy syndrome (TES). RESULTS: Significantly elevated flortaucipir uptake was observed in former football players (PRO+COL) in prespecified regions (p < 0.05). Association between regional flortaucipir uptake and estimated cumulative head impact exposure was only observed in the superior frontal region in former players over 60 years old. Flortaucipir PET was not able to differentiate TES groups. DISCUSSION: Additional studies are needed to further understand tau pathology in CTE and other individuals with a history of RHI.
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Lesões Encefálicas Traumáticas , Carbolinas , Encefalopatia Traumática Crônica , Futebol Americano , Masculino , Humanos , Pessoa de Meia-Idade , Encefalopatia Traumática Crônica/diagnóstico por imagem , Encefalopatia Traumática Crônica/patologia , Futebol Americano/lesões , Proteínas tau , Tomografia por Emissão de Pósitrons , Lesões Encefálicas Traumáticas/complicaçõesRESUMO
Over the last 17 years, there has been a remarkable increase in scientific research concerning chronic traumatic encephalopathy (CTE). Since the publication of NINDS-NIBIB criteria for the neuropathological diagnosis of CTE in 2016, and diagnostic refinements in 2021, hundreds of contact sport athletes and others have been diagnosed at postmortem examination with CTE. CTE has been reported in amateur and professional athletes, including a bull rider, boxers, wrestlers, and American, Canadian, and Australian rules football, rugby union, rugby league, soccer, and ice hockey players. The pathology of CTE is unique, characterized by a pathognomonic lesion consisting of a perivascular accumulation of neuronal phosphorylated tau (p-tau) variably alongside astrocytic aggregates at the depths of the cortical sulci, and a distinctive molecular structural configuration of p-tau fibrils that is unlike the changes observed with aging, Alzheimer's disease, or any other tauopathy. Computational 3-D and finite element models predict the perivascular and sulcal location of p-tau pathology as these brain regions undergo the greatest mechanical deformation during head impact injury. Presently, CTE can be definitively diagnosed only by postmortem neuropathological examination; the corresponding clinical condition is known as traumatic encephalopathy syndrome (TES). Over 97% of CTE cases published have been reported in individuals with known exposure to repetitive head impacts (RHI), including concussions and nonconcussive impacts, most often experienced through participation in contact sports. While some suggest there is uncertainty whether a causal relationship exists between RHI and CTE, the preponderance of the evidence suggests a high likelihood of a causal relationship, a conclusion that is strengthened by the absence of any evidence for plausible alternative hypotheses. There is a robust dose-response relationship between CTE and years of American football play, a relationship that remains consistent even when rigorously accounting for selection bias. Furthermore, a recent study suggests that selection bias underestimates the observed risk. Here, we present the advances in the neuropathological diagnosis of CTE culminating with the development of the NINDS-NIBIB criteria, the multiple international studies that have used these criteria to report CTE in hundreds of contact sports players and others, and the evidence for a robust dose-response relationship between RHI and CTE.
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Encefalopatia Traumática Crônica , Futebol Americano , Tauopatias , Animais , Bovinos , Humanos , Masculino , Austrália , Encéfalo/patologia , Canadá , Encefalopatia Traumática Crônica/patologia , Proteínas tau/metabolismoRESUMO
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 × 10-9 ) and with CTE severity (severe vs mild; OR = 1.14 per year played, 95% CI = 1.07-1.22; p = 3.1 × 10-4 ). 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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Encefalopatia Traumática Crônica/patologia , Futebol Americano/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Idoso , Encéfalo/patologia , Estudos de Casos e Controles , Encefalopatia Traumática Crônica/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Método Simples-Cego , Fatores de TempoRESUMO
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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Autopsia , Lesões Encefálicas Traumáticas/patologia , Encéfalo/patologia , Encefalopatia Traumática Crônica , Doença de Alzheimer/patologia , Encefalopatia Traumática Crônica/diagnóstico , Encefalopatia Traumática Crônica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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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Encéfalo/patologia , Encefalopatia Traumática Crônica/patologia , Tauopatias/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Futebol Americano/lesões , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Tauopatias/etiologia , Adulto Jovem , Proteínas tau/metabolismoRESUMO
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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Fatores Etários , Doença de Alzheimer/etiologia , Encéfalo/patologia , Encefalopatia Traumática Crônica/patologia , Futebol Americano , Adolescente , Doença de Alzheimer/patologia , Encéfalo/fisiopatologia , Encefalopatia Traumática Crônica/fisiopatologia , Humanos , Masculino , Proteínas tau/metabolismoRESUMO
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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Traumatismos em Atletas/patologia , Encéfalo/patologia , Encefalopatia Traumática Crônica/patologia , Futebol Americano/lesões , Adulto , Idoso , Atletas , Traumatismos em Atletas/complicações , Concussão Encefálica/epidemiologia , Causas de Morte , Encefalopatia Traumática Crônica/diagnóstico , Encefalopatia Traumática Crônica/etiologia , Transtornos Cognitivos/etiologia , Humanos , Masculino , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Transtornos Relacionados ao Uso de Substâncias/etiologia , Estados Unidos , Proteínas tau/análiseAssuntos
Encefalopatia Traumática Crônica , Futebol Americano , Tauopatias , Humanos , Estados Unidos , Proteínas tauRESUMO
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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Comportamento/fisiologia , Lesão Encefálica Crônica/metabolismo , Encéfalo/metabolismo , Doenças Neurodegenerativas/etiologia , Neurônios/metabolismo , Animais , Encéfalo/patologia , Lesão Encefálica Crônica/fisiopatologia , Proteínas de Ligação a DNA/metabolismo , Humanos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/fisiopatologiaRESUMO
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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Traumatismos em Atletas , Concussão Encefálica , Educação Continuada/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Tutoria , Medicina Esportiva/educação , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/terapia , Concussão Encefálica/diagnóstico , Concussão Encefálica/etiologia , Concussão Encefálica/terapia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Autorrelato , Estados Unidos , UniversidadesRESUMO
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 ß peptide (Aß) levels, the extent of Aß 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 Aß deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that Aß deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, Aß 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 Aß plaques and those without. Aß 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 (ß = 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 Aß plaques and total levels of Aß1-40 were increased at the depths of the cortical sulcus compared to the gyral crests. Overall, these findings suggest that Aß deposition is altered and accelerated in a cohort of CTE subjects compared to normal aging and that Aß is associated with both pathological and clinical progression of CTE independent of age.
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Peptídeos beta-Amiloides/metabolismo , Lesão Encefálica Crônica/patologia , Encéfalo/patologia , Doenças Neurodegenerativas/patologia , Proteínas tau/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína E4/genética , Atletas , Traumatismos em Atletas/epidemiologia , Traumatismos em Atletas/genética , Traumatismos em Atletas/metabolismo , Traumatismos em Atletas/patologia , Encéfalo/metabolismo , Lesão Encefálica Crônica/epidemiologia , Lesão Encefálica Crônica/genética , Lesão Encefálica Crônica/metabolismo , Estudos de Coortes , Comorbidade , Humanos , Pessoa de Meia-Idade , Doenças Neurodegenerativas/epidemiologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Placa Amiloide/etiologia , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Índice de Gravidade de Doença , Veteranos , Lesões Relacionadas à Guerra/epidemiologia , Lesões Relacionadas à Guerra/genética , Lesões Relacionadas à Guerra/metabolismo , Lesões Relacionadas à Guerra/patologiaRESUMO
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.
Assuntos
Concussão Encefálica , Comunicação , Conhecimentos, Atitudes e Prática em Saúde , Segurança , Esportes , Universidades , Feminino , Humanos , Masculino , Caracteres Sexuais , Inquéritos e Questionários , Estados UnidosRESUMO
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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Concussão Encefálica , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Estudos de Coortes , Hóquei , Humanos , Intenção , Masculino , Projetos Piloto , Adulto JovemRESUMO
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.