Browsing by Author "McCrea, Michael"

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    Acute Sport Concussion Assessment Optimization: A Prospective Assessment from the CARE Consortium
    (Springer, 2019) Broglio, Steven P.; Harezlak, Jaroslaw; Katz, Barry; Zhao, Shi; McAllister, Thomas; McCrea, Michael; Biostatistics, School of Public Health
    Background Numerous medical organizations recommend a multifaceted approach to the assessment of concussion occurring during sporting events. A number of tools are available to clinicians, with a wide breadth of sensitivity and specificity; however, little work has been done to evaluate the combined efficiency of these tools in concussed male and female athletes from a broad array of collegiate sports and with variable time from the pre-season baseline evaluation. Objective The aim of this study was to optimize the concussion assessment battery for application within the first 72 h of injury, and to identify the necessary baseline retesting frequency. Methods Between 2014 and 2017, a total of 1458 National Collegiate Athletic Association (NCAA) athletes sustaining 1640 diagnosed concussions completed a baseline assessment each year of the investigation and were evaluated up to three times within the first 72 h of injury using a standardized assessment protocol. Classification and regression tree analyses were implemented to identify the most efficient multifaceted assessment pathway to quantify concussion-related outcomes. Results were optimized for assessments occurring within 1 h post-injury, 1–24 h post-injury, and 24–72 h post-injury when using the raw post-injury assessment performance, difference scores from baseline evaluations occurring in the same year, and difference scores from baseline evaluations occurring the year prior. Results At each of the assessment time points, the analyses indicated that alone or in combination, a symptom evaluation, Balance Error Scoring System (BESS) scores collected on the firm surface, and Standardized Assessment of Concussion (SAC) total score offered the best overall performance when compared with pre-morbid performance captured in the same season. Optimized sensitivity of the multifaceted approach was 61% within 1 h of injury, 67% at the 1–24 h interval, and 55% at the 24–72 h interval when difference scores from the same-season baseline were available. Conclusions This investigation identified key concussion assessments in quantifying post-concussion performance among student athletes, that were maximized when same-season pre-morbid evaluations were available. Consistent with clinical recommendations, medical professionals should continue to focus on symptom reporting, postural control, and neurocognitive screening to support the clinical examination when making a concussion diagnosis.
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    Acute White-Matter Abnormalities in Sports-Related Concussion: A Diffusion Tensor Imaging Study from the NCAA-DoD CARE Consortium
    (Mary Ann Liebert, 2018-11-15) Mustafi, Sourajit Mitra; Harezlak, Jaroslaw; Koch, Kevin M.; Nencka, Andrew S.; Meier, Timothy B.; West, John D.; Giza, Christopher C.; DiFiori, John P.; Guskiewicz, Kevin M.; Mihalik, Jason P.; LaConte, Stephen M.; Duma, Stefan M.; Broglio, Steven P.; Saykin, Andrew J.; McCrea, Michael; McAllister, Thomas W.; Wu, Yu-Chien; Radiology and Imaging Sciences, School of Medicine
    Sports-related concussion (SRC) is an important public health issue. Although standardized assessment tools are useful in the clinical management of acute concussion, the underlying pathophysiology of SRC and the time course of physiological recovery after injury remain unclear. In this study, we used diffusion tensor imaging (DTI) to detect white matter alterations in football players within 48 h after SRC. As part of the NCAA-DoD CARE Consortium study of SRC, 30 American football players diagnosed with acute concussion and 28 matched controls received clinical assessments and underwent advanced magnetic resonance imaging scans. To avoid selection bias and partial volume effects, whole-brain skeletonized white matter was examined by tract-based spatial statistics to investigate between-group differences in DTI metrics and their associations with clinical outcome measures. Mean diffusivity was significantly higher in brain white matter of concussed athletes, particularly in frontal and subfrontal long white matter tracts. In the concussed group, axial diffusivity was significantly correlated with the Brief Symptom Inventory and there was a similar trend with the symptom severity score of the Sport Concussion Assessment Tool. In addition, concussed athletes with higher fractional anisotropy performed better on the cognitive component of the Standardized Assessment of Concussion. Overall, the results of this study are consistent with the hypothesis that SRC is associated with changes in white matter tracts shortly after injury, and these differences are correlated clinically with acute symptoms and functional impairments.
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    Age at First Concussion Influences Number of Subsequent Concussions
    (Elsevier, 2018) Schmidt, Julianne D.; Rizzone, Katherine; Hoffman, Nicole L.; Weber, Michelle L.; Jones, Courtney; Bazarian, Jeff; Broglio, Steven P.; McCrea, Michael; McAllister, Thomas W.; Psychiatry, School of Medicine
    Background: Individuals that sustain their first concussion during childhood may be at greater risk for sustaining multiple concussions throughout their lifetime, due to a longer window of vulnerability. Purpose: To estimate the association between age at first concussion with number of subsequent concussions. Methods: A total of 23,582 collegiate athletes from 26 universities and military cadets from three military academies completed a concussion history questionnaire (65% males, age: 19.9±1.4years). Participants self-reported concussions and age at time of each injury. Participants with a history of concussion (n=3,647, 15.5%) were categorized as having sustained their first concussion during childhood (<10 years old - yo) or adolescence (≥10yo & ≤18yo). Poisson regression was used to model age group (childhood, adolescence) predicting number of subsequent concussions (0, 1, 2+). A second Poisson regression was developed to determine whether age at first concussion predicted number of subsequent concussions. Results: Participants self-reporting their first concussion during childhood had an increased risk of sustaining subsequent concussions (RR=2.19, 95% CI: 1.82, 2.64) compared to participants self-reporting their first concussion during adolescence. For every one-year increase in age at first concussion, we observed a 16% reduction in the risk of subsequent concussion (RR=0.84, 95% CI:0.82,0.86). Conclusion(s): Individuals self-reporting a concussion at a young age sustained a higher number of concussions prior to the age of 18. Concussion prevention, recognition, and reporting strategies are of particular need at the youth level.
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    Age of First Concussion and Cognitive, Psychological, and Physical Outcomes in NCAA Collegiate Student Athletes
    (Springer, 2022-11) Moody, Jena N.; Hayes, Jasmeet P.; Buckley, Thomas A.; Schmidt, Julianne D.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael; Pasquina, Paul F.; Caccese, Jaclyn B.; CARE Consortium Investigators; Psychiatry, School of Medicine
    Objective: Concussions are common among youth athletes and could disrupt critical neurodevelopment. This study examined the association between age of first concussion (AFC) and neurocognitive performance, psychological distress, postural stability, and symptoms commonly associated with concussion in healthy collegiate men and women student athletes. Methods: Participants included 4267 collegiate athletes from various contact, limited-contact, and non-contact sports (1818 women and 2449 men) who completed baseline assessments as part of the Concussion Assessment, Research and Education (CARE) Consortium. Psychological distress was assessed with the Brief Symptom Inventory 18; neurocognitive performance was assessed with the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT); symptoms commonly associated with concussion were assessed with the ImPACT Post-Concussion Symptom Scale; postural stability was assessed with the Balance Error Scoring System. Generalized linear models were used to examine the effects of AFC on clinical outcomes separately in men and women. Results: Later AFC was associated with lower global (Exp(B) = 0.96, P = 0.001) and somatic (Exp(B) = 0.96, P = 0.002) psychological distress on the Brief Symptom Inventory 18 and faster ImPACT reaction time (B = - 0.003, P = 0.001) in women. AFC was not associated with any clinical outcomes in men. Conclusion: Younger AFC was associated with some differences in psychological distress and reaction time among women but not men; however, these results are likely not clinically meaningful. Sociodemographic disparities, pre-existing conditions, and sport type may impact clinical and cognitive outcomes in collegiate athletes more than concussion history. Future work should examine the relationship between AFC and lifespan-related outcomes.
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    Age of First Concussion and Cognitive, Psychological, and Physical Outcomes in NCAA Collegiate Student Athletes
    (Springer, 2022) Moody, Jena N.; Hayes, Jasmeet P.; Buckley, Thomas A.; Schmidt, Julianne D.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael; Pasquina, Paul F.; Caccese, Jaclyn B.; Psychiatry, School of Medicine
    Objective: Concussions are common among youth athletes and could disrupt critical neurodevelopment. This study examined the association between age of first concussion (AFC) and neurocognitive performance, psychological distress, postural stability, and symptoms commonly associated with concussion in healthy collegiate men and women student athletes. Methods: Participants included 4267 collegiate athletes from various contact, limited-contact, and non-contact sports (1818 women and 2449 men) who completed baseline assessments as part of the Concussion Assessment, Research and Education (CARE) Consortium. Psychological distress was assessed with the Brief Symptom Inventory 18; neurocognitive performance was assessed with the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT); symptoms commonly associated with concussion were assessed with the ImPACT Post-Concussion Symptom Scale; postural stability was assessed with the Balance Error Scoring System. Generalized linear models were used to examine the effects of AFC on clinical outcomes separately in men and women. Results: Later AFC was associated with lower global (Exp(B) = 0.96, P = 0.001) and somatic (Exp(B) = 0.96, P = 0.002) psychological distress on the Brief Symptom Inventory 18 and faster ImPACT reaction time (B = - 0.003, P = 0.001) in women. AFC was not associated with any clinical outcomes in men. Conclusion: Younger AFC was associated with some differences in psychological distress and reaction time among women but not men; however, these results are likely not clinically meaningful. Sociodemographic disparities, pre-existing conditions, and sport type may impact clinical and cognitive outcomes in collegiate athletes more than concussion history. Future work should examine the relationship between AFC and lifespan-related outcomes.
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    Assessment of Blood Biomarker Profile After Acute Concussion During Combative Training Among US Military Cadets
    (JAMA, 2021-02) Giza, Christopher C.; McCrea, Michael; Huber, Daniel; Cameron, Kenneth L.; Houston, Megan N.; Jackson, Jonathan C.; McGinty, Gerald; Pasquina, Paul; Broglio, Steven P.; Brooks, Alison; DiFiori, John; Duma, Stefan; Harezlak, Jaroslaw; Goldman, Joshua; Guskiewicz, Kevin; McAllister, Thomas W.; McArthur, David; Meier, Timothy B.; Mihalik, Jason P.; Nelson, Lindsay D.; Rowson, Steven; Gill, Jessica; Foroud, Tatiana; Katz, Barry; Saykin, Andrew; Campbell, Darren E.; Svoboda, Steven; Psychiatry, School of Medicine
    Importance: Validation of protein biomarkers for concussion diagnosis and management in military combative training is important, as these injuries occur outside of traditional health care settings and are generally difficult to diagnose. Objective: To investigate acute blood protein levels in military cadets after combative training-associated concussions. Design, setting, and participants: This multicenter prospective case-control study was part of a larger cohort study conducted by the National Collegiate Athletic Association and the US Department of Defense Concussion Assessment Research and Education (CARE) Consortium from February 20, 2015, to May 31, 2018. The study was performed among cadets from 2 CARE Consortium Advanced Research Core sites: the US Military Academy at West Point and the US Air Force Academy. Cadets who incurred concussions during combative training (concussion group) were compared with cadets who participated in the same combative training exercises but did not incur concussions (contact-control group). Clinical measures and blood sample collection occurred at baseline, the acute postinjury point (<6 hours), the 24- to 48-hour postinjury point, the asymptomatic postinjury point (defined as the point at which the cadet reported being asymptomatic and began the return-to-activity protocol), and 7 days after return to activity. Biomarker levels and estimated mean differences in biomarker levels were natural log (ln) transformed to decrease the skewness of their distributions. Data were collected from August 1, 2016, to May 31, 2018, and analyses were conducted from March 1, 2019, to January 14, 2020. Exposure: Concussion incurred during combative training. Main outcomes and measures: Proteins examined included glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, neurofilament light chain, and tau. Quantification was conducted using a multiplex assay (Simoa; Quanterix Corp). Clinical measures included the Sport Concussion Assessment Tool-Third Edition symptom severity evaluation, the Standardized Assessment of Concussion, the Balance Error Scoring System, and the 18-item Brief Symptom Inventory. Results: Among 103 military service academy cadets, 67 cadets incurred concussions during combative training, and 36 matched cadets who engaged in the same training exercises did not incur concussions. The mean (SD) age of cadets in the concussion group was 18.6 (1.3) years, and 40 cadets (59.7%) were male. The mean (SD) age of matched cadets in the contact-control group was 19.5 (1.3) years, and 25 cadets (69.4%) were male. Compared with cadets in the contact-control group, those in the concussion group had significant increases in glial fibrillary acidic protein (mean difference in ln values, 0.34; 95% CI, 0.18-0.50; P < .001) and ubiquitin C-terminal hydrolase-L1 (mean difference in ln values, 0.97; 95% CI, 0.44-1.50; P < .001) levels at the acute postinjury point. The glial fibrillary acidic protein level remained high in the concussion group compared with the contact-control group at the 24- to 48-hour postinjury point (mean difference in ln values, 0.22; 95% CI, 0.06-0.38; P = .007) and the asymptomatic postinjury point (mean difference in ln values, 0.21; 95% CI, 0.05-0.36; P = .01). The area under the curve for all biomarkers combined, which was used to differentiate cadets in the concussion and contact-control groups, was 0.80 (95% CI, 0.68-0.93; P < .001) at the acute postinjury point. Conclusions and relevance: This study's findings indicate that blood biomarkers have potential for use as research tools to better understand the pathobiological changes associated with concussion and to assist with injury identification and recovery from combative training-associated concussions among military service academy cadets. These results extend the previous findings of studies of collegiate athletes with sport-associated concussions.
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    Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium
    (JAMA Network, 2020-01-03) McCrea, Michael; Broglio, Steven P.; McAllister, Thomas W.; Gill, Jessica; Giza, Christopher C.; Huber, Daniel L.; Harezlak, Jaroslaw; Cameron, Kenneth L.; Houston, Megan N.; McGinty, Gerald; Jackson, Jonathan C.; Guskiewicz, Kevin; Mihalik, Jason; Brooks, M. Alison; Duma, Stephan; Rowson, Steven; Nelson, Lindsay D.; Pasquina, Paul; Meier, Timothy B.; CARE Consortium Investigators; Foroud, Tatiana; Katz, Barry P.; Saykin, Andrew J.; Campbell, Darren E.; Svoboda, Steven J.; Goldman, Joshua; DiFiori, Jon; Psychiatry, School of Medicine
    Importance: There is potential scientific and clinical value in validation of objective biomarkers for sport-related concussion (SRC). Objective: To investigate the association of acute-phase blood biomarker levels with SRC in collegiate athletes. Design, Setting, and Participants: This multicenter, prospective, case-control study was conducted by the National Collegiate Athletic Association (NCAA) and the US Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium from February 20, 2015, to May 31, 2018, at 6 CARE Advanced Research Core sites. A total of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport control athletes completed clinical testing and blood collection at preseason baseline, the acute postinjury period, 24 to 48 hours after injury, the point of reporting being asymptomatic, and 7 days after return to play. Data analysis was conducted from March 1 to November 30, 2019. Main Outcomes and Measures: Glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light chain, and tau were quantified using the Quanterix Simoa multiplex assay. Clinical outcome measures included the Sport Concussion Assessment Tool-Third Edition (SCAT-3) symptom evaluation, Standardized Assessment of Concussion, Balance Error Scoring System, and Brief Symptom Inventory 18. Results: A total of 264 athletes with concussion (mean [SD] age, 19.08 [1.24] years; 211 [79.9%] male), 138 contact sport controls (mean [SD] age, 19.03 [1.27] years; 107 [77.5%] male), and 102 non-contact sport controls (mean [SD] age, 19.39 [1.25] years; 82 [80.4%] male) were included in the study. Athletes with concussion had significant elevation in GFAP (mean difference, 0.430 pg/mL; 95% CI, 0.339-0.521 pg/mL; P < .001), UCH-L1 (mean difference, 0.449 pg/mL; 95% CI, 0.167-0.732 pg/mL; P < .001), and tau levels (mean difference, 0.221 pg/mL; 95% CI, 0.046-0.396 pg/mL; P = .004) at the acute postinjury time point compared with preseason baseline. Longitudinally, a significant interaction (group × visit) was found for GFAP (F7,1507.36 = 16.18, P < .001), UCH-L1 (F7,1153.09 = 5.71, P < .001), and tau (F7,1480.55 = 6.81, P < .001); the interaction for neurofilament light chain was not significant (F7,1506.90 = 1.33, P = .23). The area under the curve for the combination of GFAP and UCH-L1 in differentiating athletes with concussion from contact sport controls at the acute postinjury period was 0.71 (95% CI, 0.64-0.78; P < .001); the acute postinjury area under the curve for all 4 biomarkers combined was 0.72 (95% CI, 0.65-0.79; P < .001). Beyond SCAT-3 symptom score, GFAP at the acute postinjury time point was associated with the classification of athletes with concussion from contact controls (β = 12.298; 95% CI, 2.776-54.481; P = .001) and non-contact sport controls (β = 5.438; 95% CI, 1.676-17.645; P = .005). Athletes with concussion with loss of consciousness or posttraumatic amnesia had significantly higher levels of GFAP than athletes with concussion with neither loss of consciousness nor posttraumatic amnesia at the acute postinjury time point (mean difference, 0.583 pg/mL; 95% CI, 0.369-0.797 pg/mL; P < .001). Conclusions and Relevance: The results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in SRC.
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    Baseline Performance of NCAA Athletes on a Concussion Assessment Battery: A Report from the CARE Consortium
    (Springer, 2018-08) Katz, Barry P.; Kudela, Maria; Harezlak, Jaroslaw; McCrea, Michael; McAllister, Thomas; Broglio, Steven P.; Biostatistics, School of Public Health
    Background Sport-related concussion and repetitive head impact exposure in contact sports continue to receive increased attention in public and medical spheres. The Concussion Assessment, Research and Education (CARE) Consortium, a multicenter cooperative, was established to study the natural history of concussion in National Collegiate Athletic Association (NCAA) collegiate student-athletes across 29 colleges and universities in the United States. The purpose of this investigation is to provide normative data from the CARE Consortium and evaluate for differences between sport categories. Methods NCAA student-athletes were evaluated annually for general demographics and sport-specific characteristics before the start of the competitive season. We collected demographic and medical history information and evaluated each student-athlete’s neurocognitive function, neurological status, postural stability, and self-reported symptoms. Sports were categorized by the amount of contact typically associated with the sport (i.e., contact, limited contact, non-contact). Comparisons between the three sport categories for the evaluated variables were made using linear or zero inflated negative binomial regression models adjusted for gender, concussion history, and household income. Results Over a 2-year period (August 2014–July 2016), 15,681 NCAA athletes completed preseason evaluations. Overall, 53% of the athletes were in the contact sport group, 31% were in the limited contact group and 17% were in the non-contact group. After adjusting for covariates, there were statistically significant differences found between athlete groups, although the differences and effect sizes were small and not clinically significant. The contact sport group had better scores on Immediate Post-Concussion Assessment Testing (ImPACT®) visual and verbal memory, Sport Concussion Assessment Tool (SCAT) symptom checklist, and Brief Symptom Inventory–18 (BSI-18), but slower ImPACT reaction time and worse scores on Standardized Assessment of Concussion (SAC). Further, the data indicate that some ImPACT score distributions were noticeably different from those presented in the technical manual. Conclusions In this large, racially and socio-economically diverse cohort of male and female college athletes, we found no evidence that student-athletes participating in contact sports have clinically meaningful deficits in pre-season cognitive and balance testing. They also did not report significantly more symptoms of psychological distress when compared with student-athletes in non-contact or limited contact sports. In addition, the data suggest potential limitations when using published ImPACT norms when evaluating injured athletes.
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    Clinical Reaction-Time Performance Factors in Healthy Collegiate Athletes
    (Allen Press, 2020-06-23) Caccese, Jaclyn B.; Eckner, James T.; Franco-MacKendrick, Lea; Hazzard, Joseph B.; Ni, Meng; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael; Buckley, Thomas A.; Psychiatry, School of Medicine
    Context: In the absence of baseline testing, normative data may be used to interpret postconcussion scores on the clinical reaction-time test (RTclin). However, to provide normative data, we must understand the performance factors associated with baseline testing. Objective: To explore performance factors associated with baseline RTclin from among candidate variables representing demographics, medical and concussion history, self-reported symptoms, sleep, and sport-related features. Design: Cross-sectional study. Setting: Clinical setting (eg, athletic training room). Patients or other participants: A total of 2584 National Collegiate Athletic Association student-athletes (n = 1206 females [47%], 1377 males [53%], and 1 unreported (<0.1%); mass = 76.7 ± 18.7 kg; height = 176.7 ± 11.3 cm; age = 19.0 ± 1.3 years) from 3 institutions participated in this study as part of the Concussion Assessment, Research and Education Consortium. Main outcome measure(s): Potential performance factors were sex; race; ethnicity; dominant hand; sport type; number of prior concussions; presence of anxiety, learning disability, attention-deficit disorder or attention-deficit/hyperactivity disorder, depression, or migraine headache; self-reported sleep the night before the test; mass; height; age; total number of symptoms; and total symptom burden at baseline. The primary study outcome measure was mean baseline RTclin. Results: The overall RTclin was 202.0 ± 25.0 milliseconds. Female sex (parameter estimate [B] = 8.6 milliseconds, P < .001, Cohen d = 0.54 relative to male sex), black or African American race (B = 5.3 milliseconds, P = .001, Cohen d = 0.08 relative to white race), and limited-contact (B = 4.2 milliseconds, P < .001, Cohen d = 0.30 relative to contact) or noncontact (B = 5.9 milliseconds, P < .001, Cohen d = 0.38 relative to contact) sport participation were associated with slower RTclin. Being taller was associated with a faster RTclin, although this association was weak (B = -0.7 milliseconds, P < .001). No other predictors were significant. When adjustments are made for sex and sport type, the following normative data may be considered (mean ± standard deviation): female, noncontact (211.5 ± 25.8 milliseconds), limited contact (212.1 ± 24.3 milliseconds), contact (203.7 ± 21.5 milliseconds); male, noncontact (199.4 ± 26.7 milliseconds), limited contact (196.3 ± 23.9 milliseconds), contact (195.0 ± 23.8 milliseconds). Conclusions: Potentially clinically relevant differences existed in RTclin for sex and sport type. These results provide normative data adjusting for these performance factors.
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    A cohort study to identify and evaluate concussion risk factors across multiple injury settings: findings from the CARE Consortium
    (Biomed Central, 2019-01-14) Van Pelt, Kathryn L.; Allred, Dain; Cameron, Kenneth L.; Campbell, Darren E.; D’Lauro, Christopher J.; He, Xuming; Houston, Megan N.; Johnson, Brian R.; Kelly, Tim F.; McGinty, Gerald; Meehan, Sean; O’Donnell, Patrick G.; Peck, Karen Y.; Svoboda, Steven J.; Pasquina, Paul; McAllister, Thomas; McCrea, Michael; Broglio, Steven P.; Medicine, School of Medicine
    BACKGROUND: Concussion, or mild traumatic brain injury, is a major public health concern affecting 42 million individuals globally each year. However, little is known regarding concussion risk factors across all concussion settings as most concussion research has focused on only sport-related or military-related concussive injuries. METHODS: The current study is part of the Concussion, Assessment, Research, and Education (CARE) Consortium, a multi-site investigation on the natural history of concussion. Cadets at three participating service academies completed annual baseline assessments, which included demographics, medical history, and concussion history, along with the Sport Concussion Assessment Tool (SCAT) symptom checklist and Brief Symptom Inventory (BSI-18). Clinical and research staff recorded the date and injury setting at time of concussion. Generalized mixed models estimated concussion risk with service academy as a random effect. Since concussion was a rare event, the odds ratios were assumed to approximate relative risk. RESULTS: Beginning in 2014, 10,604 (n = 2421, 22.83% female) cadets enrolled over 3 years. A total of 738 (6.96%) cadets experienced a concussion, 301 (2.84%) concussed cadets were female. Female sex and previous concussion were the most consistent estimators of concussion risk across all concussion settings. Compared to males, females had 2.02 (95% CI: 1.70-2.40) times the risk of a concussion regardless of injury setting, and greater relative risk when the concussion occurred during sport (Odds Ratio (OR): 1.38 95% CI: 1.07-1.78). Previous concussion was associated with 1.98 (95% CI: 1.65-2.37) times increased risk for any incident concussion, and the magnitude was relatively stable across all concussion settings (OR: 1.73 to 2.01). Freshman status was also associated with increased overall concussion risk, but was driven by increased risk for academy training-related concussions (OR: 8.17 95% CI: 5.87-11.37). Medical history of headaches in the past 3 months, diagnosed ADD/ADHD, and BSI-18 Somatization symptoms increased overall concussion risk. CONCLUSIONS: Various demographic and medical history factors are associated with increased concussion risk. While certain factors (e.g. sex and previous concussion) are consistently associated with increased concussion risk, regardless of concussion injury setting, other factors significantly influence concussion risk within specific injury settings. Further research is required to determine whether these risk factors may aid in concussion risk reduction or prevention.