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OBJECTIVE: Altered patterns of brain activity during cognitive tasks have been demonstrated using functional magnetic resonance imaging (fMRI) in mild cognitive impairment and Alzheimer's disease. However, there have been few studies of adults at genetic risk for Alzheimer's disease prior to the onset of symptoms. The purpose of this study was to determine whether brain activation patterns associated with working memory differ as a function of apolipoprotein E (APOE) genotype in cognitively intact adults. METHOD: Participants were cognitively intact, healthy adults who completed genotyping, comprehensive neuropsychological testing, and structural and functional neuroimaging. Twenty-two participants had the APOE epsilon3/epsilon3 genotype, and 13 participants had the APOE epsilon3/epsilon4 genotype. The study employed an auditory verbal N-back task to probe working memory-related brain activity. RESULTS: The epsilon3/epsilon3 and epsilon3/epsilon4 groups did not differ in demographic characteristics, cognitive ability, mood, or in-scanner task performance. The epsilon3/epsilon4 group showed greater activity during working memory in the medial frontal and parietal regions bilaterally and in the right dorsolateral prefrontal cortex. There were no regions in which the epsilon3/epsilon3 group showed greater activation than the epsilon3/epsilon4 group. CONCLUSIONS: These results indicate that differences in brain activity are evident in cognitively intact individuals who are at risk for late-onset Alzheimer's disease by virtue of their APOE allele status. As neuroprotective interventions become available, early detection will increase in importance. The combination of genetic and functional neuroimaging strategies may prove useful for monitoring individuals at risk for Alzheimer's disease before the onset of cognitive symptoms. [ABSTRACT FROM AUTHOR]

Research suggests that up to 45% of individuals with moderate to severe TBI demonstrate reduced awareness or complete lack of awareness of their deficits. We describe dimensions and distinctions within the concept of lack of awareness - including whether an individual has knowledge of a specific deficit, the emotional response an individual manifests to a specific deficit, the ability to comprehend the impact or consequences of the deficit on day to day life, and how an individual explains or accounts for any deficits - and various methods of assessing for lack of awareness in this population. Finally, a review of the literature studying lack of awareness in TBI, its relationship to injury severity, the impact of lack of awareness on outcome, and intervention approaches is presented. [ABSTRACT FROM AUTHOR]

A review of research studies to date suggests that psychosis is a relatively rare, but serious, complication of traumatic brain injury (TBI). Psychotic syndromes occur more frequently in individuals who have had a TBI than in the general population. Onset of symptoms can be early or late. Psychosis can occur during the period of post-traumatic amnesia, in association with post-traumatic epilepsy, in association with TBI-related mood disorders, and as a chronic, schizophrenia-like syndrome. TBI can interact with genetic vulnerability to increase the risk of developing illnesses such as schizophrenia. Thorough diagnostic assessment is the foundation of rational and effective pharmacotherapy for psychosis after TBI. Atypical antipsychotic drugs have emerged as first line drugs for treatment of psychotic disorders from all causes, including TBI. Anticonvulsant, antidepressant or other drugs may also be needed in some cases. Medication approaches must be adjusted for the particular characteristics and vulnerabilities of the patient with a TBI. [ABSTRACT FROM AUTHOR]

Objective: This article describes the design, methods, and participant characteristics of the second phase of the Concussion Assessment, Research, and Education (CARE) Consortium study ("CARE 2.0") of the effects of concussion and repetitive head impact exposure on neuropsychiatric health., Methods: The authors conducted a prospective multisite observational study of male and female collegiate athletes and military service academy cadets and midshipmen participating in the CARE study. Participants were assessed at three time points: undergraduate baseline (UB), before departure from university or service academy (exit), and up to 6 years following graduation (postgrad) via an online battery of brain health assessments. Participant characteristics were compared across the three time points and four levels of head impact exposure., Results: A total of 4,643 participants completed the exit assessment, and 3,981 completed the postgrad assessment. Relative to the UB assessment cohort, the exit and postgrad assessment cohorts differed with respect to the percentage of women, baseline Wechsler Test of Adult Reading scores, National Collegiate Athletic Association division category, sport contact level, and number of previous concussions. The median standardized difference across balancing variables, assessment time points, and degree of head impact exposure was 0.12 (with 90% of effect sizes ≤0.29)., Conclusions: Although there were some statistically significant differences between participants across assessments, the effect sizes were modest, and overall the data suggest that the exit and postgrad cohorts reflect the characteristics of the baseline cohort. The CARE study design and its large, richly characterized sample provide an opportunity to answer important questions about cumulative and persistent effects of concussion and repetitive head impact exposure on neuropsychiatric health., Competing Interests: Dr. McAllister has received research funding from the NCAA, NIH, and the DoD; he has received royalties from American Psychiatric Association Publishing; and he has received support for teaching a Harvard Medical School, Mass General Brigham Neuropsychiatry CME course. Dr. Broglio has received research funding from the Centers for Disease Control and Prevention (CDC), the DoD–U.S. Army Medical Research Acquisition Activity, ElMindA, GE, the National Athletic Trainers’ Association Foundation, the National Football League (NFL), the NCAA, NIH, Simbex, and Under Armour; he has served as a consultant for U.S. Cycling, U.S. Soccer, and the University of Calgary SHRed Concussions external advisory board; he is president-elect of the Concussion in Sport Group; he serves on the scientific advisory board for C3Logix; he has received compensation for medico-legal litigation and speaker honorarium as well as travel reimbursements for talks; he has received royalties from Human Kinetics; he is a patent holder on device used to assess brain metabolism; and he has served on the editorial boards for a number of journals. Dr. McCrea has received research funding to the Medical College of Wisconsin from Abbott Laboratories, the CDC, the Department of Veterans Affairs, the DoD, the NCAA, the NFL, and NIH; he has served as a consultant to Neurotrauma Sciences and is a clinical consultant to the Green Bay Packers professional football club; and he has received honoraria and travel support for professional speaking engagements. The other authors report no financial relationships with commercial interests.

The recovery trajectories of collegiate athletes with sport-related concussion (SRC) are well characterized in contact/collision sports but are less well understood in limited contact sports with lower risk, reducing the ability of clinicians to effectively manage the return-to-play (RTP) process. The current study investigated the time to asymptomatic and RTP across a broad range of male and female collegiate sports and sought to group sports by recovery intervals. Data from the Concussion Assessment, Research and Education (CARE) Consortium included 1049 collegiate athletes who sustained a SRC while participating in game or practice/training of their primary sport. Injury setting and subsequent clinical presentation data were obtained. Survival analysis using the Cox Proportional Hazard model estimated the median recovery times for each sport. Optimal univariate K-means clustering grouped sports into recovery categories. Across all sports, median time to asymptomatic following SRC ranged from 5.9 (female basketball) to 8.6 days (male wrestling). Median RTP protocol duration ranged from 4.9 days (female volleyball) to 6.3 days (male wrestling). Median total RTP days ranged from 11.2 days (female lacrosse) to 16.9 days (male wrestling). Sport clusters based on recovery differences in time to asymptomatic (3) and RTP protocol duration (2) were identified. The findings from this study of a large sample of more than 1000 NCAA collegiate athletes with SRC show there exists ranges in recovery trajectories. Clinicians can thus manage athletes with similar guidelines, with individualized treatment and recovery plans., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Objective : The goal of this study was to characterize normative scores for the Brief Symptom Inventory (BSI-18) in collegiate athletes to inform decision making about the need for psychological health services in this group. Methods : Collegiate student-athletes ( N  = 20,034) from 25 universities completed the BSI-18 at their preseason baseline assessment. A subgroup ( n  = 5,387) underwent multiple baseline assessments. Global Severity Index (GSI) scores were compared to community norms and across multiple timepoints. Results : Collegiate athletes reported significantly lower GSI scores than published community norms ( p <.001). Published GSI threshold scores for "caseness", identified only 2 per 100 athletes (≥ the 98th percentile) as needing further evaluation. Using a GSI score ≥ than the cohort's 90th percentile, 11.4 per 100 athletes would merit additional evaluation. These individuals were more likely to report a history of psychiatric diagnosis (Odds ratio [95% CI] 2.745 [2.480, 3.039]), as well as ≥ 2 prior concussions ( p <.001). GSI scores were not highly correlated across timepoints. Suicidal ideation was rare ( n  = 230; 1.15%). Conclusions : For collegiate student-athletes, published BSI-18 threshold scores identify only extreme outliers who might benefit from additional behavioral health evaluation. Alternatively, use of threshold scores ≥ the 90th percentile identifies a more realistic 11.4% of the population, with higher likelihood of prior concussion and/or psychiatric disorders.

Concussion has been described in the United States (US) collegiate student-athlete population, but female-specific findings are often underrepresented and underreported. Our study aimed to describe female collegiate student-athletes' initial injury characteristics and return to activity outcomes following concussion. Female collegiate student-athletes (n = 1393) from 30-US institutions experienced a concussion and completed standardized, multimodal concussion assessments from pre-injury through unrestricted return to play (uRTP) in this prospective, longitudinal cohort study. Initial injury presentation characteristics, assessment, and return to activity outcomes [<48-h (acute), return to learn, initiate return to play (iRTP), uRTP] were collected. We used descriptive statistics to report injury characteristics, return to activity outcomes, and post-injury assessment performance change categorization (worsened, unchanged, improved) based on change score confidence rank criteria across sport contact classifications [contact (n = 661), limited (n = 446), non-contact (n = 286)]. The median (25th to 75th percentile) days to return to learn was 6.0 (3.0-10.0), iRTP was 8.1 (4.8-13.8), and uRTP was 14.8 (9.9-24.0), but varied by contact classification. Across contact levels, the majority experienced worse SCAT total symptom severity (72.8-82.6%), ImPACT reaction time (91.2-92.6%), and BSI-18 total score (45.2-51.8%) acutely relative to baseline, but unchanged BESS total errors (58.0-60.9%), SAC total score (71.5-76.1%), and remaining ImPACT domains (50.6-66.5%). Our findings provide robust estimates of the typical female collegiate student-athlete presentation and recovery trajectory following concussion, with overall similar findings to the limited female collegiate student-athlete literature. Overall varying confidence rank classification was observed acutely. Our findings provide clinically-relevant insights for athletes, clinicians, researchers, and policymakers to inform efforts specific to females experiencing concussion., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Sporting helmets contain force attenuating materials which reduce traumatic head injury risk and may influence sport-related concussion (SRC) sequelae. The purpose of this study was to examine the association of sport helmet status with SRC-clinical presentation and recovery trajectories in men's collegiate athletes. Sport helmet status was based on the nature of sports being either helmeted/non-helmeted. 1070 SRCs in helmeted (HELM) sports (Men's-Football, Ice Hockey, and Lacrosse), and 399 SRCs in non-helmeted (NOHELM) sports (Men's-Basketball, Cheerleading, Cross Country/Track & Field, Diving, Gymnastics, Soccer, Swimming, Tennis, and Volleyball) were analyzed. Multivariable negative binomial regression models analyzed associations between sport helmet status and post-injury cognition, balance, and symptom severity, adjusting for covariate effects (SRC history, loss of consciousness, anterograde/retrograde amnesia, event type). Kaplan-Meier curves evaluated median days to: initiation of return to play (iRTP) protocol, and unrestricted RTP (URTP) by sport helmet status. Log-rank tests were used to evaluate differential iRTP/URTP between groups. Two independent multivariable Weibull accelerated failure time models were used to examine differential iRTP and URTP between groups, after adjusting for aforementioned covariates and symptom severity score. Overall, the median days to iRTP and URTP was 6.3 and 12.0, respectively, and was comparable across NOHELM- and HELM-SRCs. Post-injury symptom severity was lower (Score Ratio 0.90, 95%CI 0.82, 0.98), and cognitive test performance was higher (Score Ratio 1.03, 95%CI 1.02, 1.05) in NOHELM-compared to HELM-SRCs. Estimated time spent recovering to iRTP/URTP was comparable between sport helmet status groups. Findings suggest that the grouping of sports into helmeted and non-helmeted show slight differences in clinical presentation but not recovery., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Mild traumatic brain injury (mTBI) has been described in the United States (US) military service academy cadet population, but female-specific characteristics and recovery outcomes are poorly characterized despite sex being a confounder. Our objective was to describe female cadets' initial characteristics, assessment performance, and return-to-activity outcomes post-mTBI. Female cadets (n = 472) from the four US military service academies who experienced a mTBI completed standardized mTBI assessments from pre-injury to acute initial injury and unrestricted return-to-duty (uRTD). Initial injury presentation characteristics (e.g., delayed symptoms, retrograde amnesia) and return-to-activity outcomes [i.e., return-to-learn, initiate return-to-duty protocol (iRTD), uRTD] were documented. Descriptive statistics summarized female cadets' injury characteristics, return-to-activity outcomes, and post-mTBI assessment performance change categorization (worsened, unchanged, improved) relative to pre-injury baseline using established change score confidence rank criteria for each assessment score. The median (interquartile range) days to return-to-learn (n = 157) was 7.0 (3.0-14.0), to iRTD (n = 412) was 14.7 (8.6-25.8), and to uRTD (n = 431) was 26.0 (17.7-41.8). The majority experienced worse SCAT total symptom severity (77.8%) and ImPACT reaction time (97.0%) acutely < 24-h versus baseline, but unchanged BESS total errors (75.2%), SAC total score (72%), BSI-18 total score (69.6%), and ImPACT verbal memory (62.3%), visual memory (58.4%), and visual motor speed (52.5%). We observed similar return-to-activity times in the present female cadet cohort relative to the existing female-specific literature. Confidence ranks categorizing post-mTBI performance were heterogenous and indicate multimodal assessments are necessary. Our findings provide clinically relevant insights to female cadets experiencing mTBI across the US service academies for stakeholders providing healthcare., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

The Sport Concussion Assessment Tool (SCAT) is the most widely used tool following sport-related concussion (SRC). Initial SCAT symptom burden is a strong predictor of recovery in collegiate athletes; however, it is unknown if symptom presentation varies within the acute (<48 h) post-SRC phase. The purpose of this cohort study was to examine acute SRC symptom presentation among the National Collegiate Athletic Association (NCAA) athletes. Concussed NCAA varsity athletes ( n = 1,780) from 30 universities across the United States, which participated in the Concussion Assessment, Research, and Education (CARE) Consortium, were included. Time of injury occurrence and SCAT administration data were recorded, from which time-to-SCAT (hours, continuous) was calculated. The main outcome was SCAT total symptom severity [(TSS), 0-126]. Multivariable negative binomial regression was used to examine the association between time (hours) since injury and TSS. Covariates included sex, previous concussion, sport contact level, amnesia/loss of consciousness, immediate reporting of injury, and injury situation. A random effect (person level) accounted for multiple assessments. TSS score ratios (SR) with associated 95% confidence intervals (CI) were provided. The SCAT was administered an average of 14 (25th-75th percentile: 1.2-24) hours post-SRC, and average TSS was 27.35 ± 21.28 across all participants. Time-to-SCAT was associated with a 1% decrease in TSS after adjusting for covariate effects (SR: 0.99, 95% CI: 0.99-0.99, p < 0.001). Overall, we observed a small, but significant decrease in TSS with each hour post-SRC. Assessing a concussed athlete once in the acute phase will likely provide a sufficient sense of their symptomatic well-being, as measures did not fluctuate dramatically. Future research should aim to examine how acute symptom evolution influences recovery metrics.

Background and Purpose: During a season of high school football, adolescents with actively developing brains experience a considerable number of head impacts. Our aim was to determine whether repetitive head impacts in the absence of a clinically diagnosed concussion during a season of high school football produce changes in cognitive performance or functional connectivity of the salience network and its central hub, the dorsal anterior cingulate cortex., Materials and Methods: Football players were instrumented with the Head Impact Telemetry System during all practices and games, and the helmet sensor data were used to compute a risk-weighted exposure metric (RWEcp), accounting for the cumulative risk during the season. Participants underwent MRI and a cognitive battery (ImPACT) before and shortly after the football season. A control group of noncontact/limited-contact-sport athletes was formed from 2 cohorts: one from the same school and protocol and another from a separate, nearly identical study., Results: Sixty-three football players and 34 control athletes were included in the cognitive performance analysis. Preseason, the control group scored significantly higher on the ImPACT Visual Motor ( P = .04) and Reaction Time composites ( P = .006). These differences increased postseason ( P = .003, P < .001, respectively). Additionally, the control group had significantly higher postseason scores on the Visual Memory composite ( P = .001). Compared with controls, football players showed significantly less improvement in the Verbal ( P = .04) and Visual Memory composites ( P = .01). A significantly greater percentage of contact athletes had lower-than-expected scores on the Verbal Memory (27% versus 6%), Visual Motor (21% versus 3%), and Reaction Time composites (24% versus 6%). Among football players, a higher RWEcp was significantly associated with greater increments in ImPACT Reaction Time ( P = .03) and Total Symptom Scores postseason ( P = .006). Fifty-seven football players and 13 control athletes were included in the imaging analyses. Postseason, football players showed significant decreases in interhemispheric connectivity of the dorsal anterior cingulate cortex ( P = .026) and within-network connectivity of the salience network ( P = .018). These decreases in dorsal anterior cingulate cortex interhemispheric connectivity and within-network connectivity of the salience network were significantly correlated with deteriorating ImPACT Total Symptom ( P = .03) and Verbal Memory scores ( P = .04)., Conclusions: Head impact exposure during a single season of high school football is negatively associated with cognitive performance and brain network connectivity. Future studies should further characterize these short-term effects and examine their relationship with long-term sequelae., (© 2024 by American Journal of Neuroradiology.)

Introduction: The purpose of this study was to determine if the time interval between two concussive events influences the number of days to asymptomatic status, days to return to play, or performance on common post-concussion assessments following the second concussion., Methods: Data from 448 collegiate athletes and service academy cadets with two concussions (time between concussions: median 295.0 days [interquartile range: 125.0-438.2]), 40.0% female) were analyzed from Concussion Assessment Research and Education (CARE) Consortium institutions between 2014 and 2020. Days between concussions was the primary predictor variable. Primary outcome measures included time to asymptomatic and time to return to play following the second concussion. Secondary outcome measures included total number of symptoms, total symptom severity, Balance Error Scoring System total score, and Standardized Assessment of Concussion total score within 48 h of their second concussion., Results: Time between concussions did not significantly contribute to the multivariate time to asymptomatic (p = 0.390), time to return to play (p = 0.859), or the secondary outcomes (p-range = 0.165-0.477) models. Time to asymptomatic (p = 0.619) or return to play (p = 0.524) did not differ between same-season and different-season concussions. Sex significantly contributed to the return to play (p = 0.005) multivariate model. Delayed symptom onset and immediate removal from play/competition significantly contributed to the total number of symptoms (p = 0.001, p = 0.014) and symptom severity (p = 0.011, p = 0.022) multivariate models., Conclusion: These results suggest that in a population with a large period between injuries, the time between concussions may not be relevant to clinical recovery., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This retrospective cohort study aims to examine concussion incidence rates (IR) in collegiate soccer players and compare IRs based on risk factors including sex, competition level, games/practices, history of concussion, and playing position. Collegiate soccer players were recruited ( n  = 2,471) from 23 institutions from the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium. Incidence rates for concussion per 1000 athlete exposures (AEs) were calculated across the 2015-16/2016-17 seasons. Incidence rates (IR) comparing risk factor groups were also calculated. A total of 162 concussions occurred during the study, for an IR of 0.08/1000 AEs. Females were more likely to have a concussion than males overall (IR = 1.47) and were more likely to have a concussion in games (IR = 1.42) and practices (IR = 2.91). Concussions were more likely during competition compared to practice (IR = 2.53), and less likely in Division III, compared to Divisions I and II, χ 2  = 6.5, p  > .05. In the concussed group, male sex was associated with 2.47 times higher odds of playing defender and 2.29 times higher odds of a collision mechanism. Results confirm previous findings that females and game exposures have higher concussion IR than males and practice exposures. Findings also supported sex differences in IRs based on exposure type, position, and mechanism.

Objective: To describe sex differences in concussion characteristics in US Service Academy cadets., Design: Descriptive epidemiology study., Setting: Four US service academies., Participants: 2209 cadets (n = 867 females, n = 1342 males)., Independent Variable: Sex., Outcome Measures: Injury proportion ratios (IPR) compared the proportion of injuries by sex (females referent) for injury situation, certainty of diagnosis, prolonged recovery, recurrent injuries, mental status alterations, loss of consciousness (LOC), posttraumatic amnesia (PTA), retrograde amnesia (RGA), motor impairments, delayed symptom presentation, and immediate reporting., Main Results: Concussions from varsity/intercollegiate sports [IPR of 1.73, 95% confidence interval (CI) 1.43-2.10] and intramurals (IPR of 1.53, 95% CI 1.02-2.32) accounted for a larger proportion in males, whereas concussions outside of sport and military activities accounted for a smaller proportion among males (IPR of 0.70, 95% CI 0.58-0.85). The proportion of concussions with prolonged recovery was lower among males (IPR of 0.69, 95% CI 0.60-0.78), while concussions with altered mental status (IPR of 1.23, 95% CI 1.09-1.38), LOC (IPR of 1.67, 95% CI 1.17-2.37), PTA (IPR of 1.94, 95% CI 1.43-2.62), and RGA (IPR of 2.14, 95% CI 1.38-3.31) accounted for a larger proportion among males. A larger proportion of concussions that were immediately reported was observed in males (IPR of 1.15, 95% CI 1.00-2.31). Proportions of other characteristics (e.g., recurrent injuries) were not different between sexes., Conclusions: A higher proportion of concussions occurred outside of sport and military training for female cadets, who also displayed proportionally longer recovery times than males, despite males demonstrating a higher proportion of LOC, PTA, and RGA. Possible factors may include different mechanisms of injury outside of sport and military training, different biopsychosocial states associated with sex or injury context, and delayed injury reporting when outside of an observed environment, possibly secondary to perceived stigma about reporting injuries., (© 2024. The Author(s).)

Identification of genetic alleles associated with both Alzheimer's disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk scores (PRS) and APOE genotypes to investigate any such associations in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset. We assessed six outcomes in 931 total participants. The outcomes were two concussion recovery measures (number of days to asymptomatic status, number of days to return to play (RTP)) and four concussion severity measures (scores on SAC and BESS, SCAT symptom severity, and total number of symptoms). We calculated PRS using a published score [1] and performed multiple linear regression (MLR) to assess the relationship of PRS with the outcomes. We also used t-tests and chi-square tests to examine outcomes by APOE genotype, and MLR to analyze outcomes in European and African genetic ancestry subgroups. Higher PRS was associated with longer injury to RTP in the normal RTP (<24 days) subgroup ( p = 0.024), and one standard deviation increase in PRS resulted in a 9.89 hour increase to the RTP interval. There were no other consistently significant effects, suggesting that high AD genetic risk is not strongly associated with more severe concussions or poor recovery in young adults. Future studies should attempt to replicate these findings in larger samples with longer follow-up using PRS calculated from diverse populations.

Purpose: The aim was to describe the demographic and post-injury factors that influence time to return to learn (RTL) among student-athletes enrolled in the Concussion Assessment, Research and Education (CARE) Consortium., Methods: A total of 47,860 student-athletes enrolled in the National Collegiate Athletic Association-Department of Defense (NCAA-DoD) CARE Consortium study from 2014 to 2020, with 1485 sport-related concussions (SRCs) analyzed in the present dataset. Demographic and post-injury characteristics were calculated using descriptive statistics, followed by Kaplan-Meier estimates to examine median time to return to normal academic performance (i.e., RTL) by sex (male, female), baseline psychiatric conditions (depression, anxiety) and/or learning disorder, NCAA division (I, II, III), SRC history (0, 1, 2, 3+), NCAA sport category (contact, limited contact, non-contact sport), and median difference in baseline/post-injury symptom severity scores (< 21, ≥ 21). Further, a multivariable zero-inflated negative binomial (ZINB) regression model was used to examine their association with RTL., Results: Overall, time to RTL (mean = 4.96 ± 8.24 days, median = 3.0 [interquartile range = 0.0, 6.0] days) was found to be influenced by several factors resulting in earlier trajectories. Notably, nearly 25% of the sample demonstrated immediate RTL (i.e., 0 days). Among student-athletes who did not immediately RTL, males demonstrated a decreased rate in RTL (rate = 0.79; 95% CI 0.66-0.96) compared to females. Further, student-athletes with a ≥ 21 change in symptom severity score (post-injury baseline) demonstrated a higher rate of RTL (rate = 1.47; 95% CI 1.21-1.79) compared to student-athletes with a symptom severity change score < 21. Lastly, male student-athletes demonstrated two times higher odds (odds ratio = 1.95; 95% CI 1.02-3.73) of immediate RTL compared to female student-athletes. No other covariates were associated with time to RTL., Conclusion: Collectively, the present findings suggest a rapid return to the classroom following concussion. Specifically, males demonstrated higher odds of time to RTL, whereas those with greater differences in symptom severity resulted in a higher rate of time to RTL among those who did not immediately RTL. Ultimately, these findings support prior work emphasizing an individualized approach to SRC management., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Concussion evaluations use a multidimensional assessment to evaluate unique patient function dimensions (e.g., subjective symptoms differ from balance assessments), but the overarching latent factor structure has not been empirically substantiated. Our objective was to determine the cumulative latent factor structure of pre-injury baseline and acute (<48-h) post-concussion assessment battery outcomes, and determine measurement equivalence among common factors in collegiate student-athletes. Methods: Collegiate student-athletes at baseline ( n  = 21,865) and post-concussion ( n  = 1,537) across 25-institutions completed standardized assessments. Individual items were used from the baseline and post-concussion assessments and consisted of: Sport Concussion Assessment Tool, Brief Symptom Inventory-18, Standardized Assessment of Concussion, Balance Error Scoring System, Immediate Post-Concussion Assessment and Cognitive Test, and vestibular-ocular motor screening. Exploratory factor analysis was used on half the baseline data, and confirmatory factor analysis on the remaining baseline data and post-concussion data separately. Measurement equivalence was assessed between sex, sport contact classification, concussion history, and time. Results: A 10-factor exploratory model was established and comprised of: depression, somatic, vestibulo-ocular, headache, postural stability, neurocognition, emotional, fatigue, cognitive, consciousness clouding. The 10-factor model was confirmed at baseline and post-concussion with strong measurement equivalence between timepoints. Strong to strict measurement equivalence was observed for sex, sport contact classification, and concussion history at both timepoints separately. Conclusion: Our findings established a robust 10-factor latent factor model equivalent across timepoints and common factors among healthy and concussed collegiate athletes. Clinicians can use these findings to target specific factors while reducing redundant elements to provide efficient, comprehensive post-concussion assessments.

Background: A sport-related concussion (SRC) is a common injury that affects multiple clinical domains such as cognition, balance, and nonspecific neurobehavioral symptoms. Although multidimensional clinical assessments of concussion are widely accepted, there remain limited empirical data on the nature and clinical utility of distinct clinical profiles identified by multimodal assessments., Purpose: Our objectives were to (1) identify distinct clinical profiles discernible from acute postinjury scores on the Sport Concussion Assessment Tool (SCAT), composed of a symptom checklist, a cognitive assessment (Standardized Assessment of Concussion), and a balance assessment (Balance Error Scoring System), and (2) evaluate the clinical utility of the identified profiles by examining their association with injury characteristics, neuropsychological outcomes, and clinical management-related outcomes., Study Design: Cohort study (Prognosis); Level of evidence, 2., Methods: Up to 7 latent profiles were modeled for 1885 collegiate athletes and/or military cadets who completed the SCAT at 0 to 12 hours after an injury. Chi-square tests and general linear models were used to compare identified profiles on outcomes at 12 to 72 hours after the injury. Kaplan-Meier analysis was used to investigate associations between clinical profiles and time to return to being asymptomatic and to return to play., Results: There were 5 latent profiles retained: low impairment (65.8%), high cognitive impairment (5.4%), high balance impairment (5.8%), high symptom severity (16.4%), and global impairment (6.5%). The latent profile predicted outcomes at 12 to 72 hours in expectable ways (eg, the high balance impairment profile demonstrated worse balance at 12 to 72 hours after the injury). Time to return to being asymptomatic and to return to play were different across profiles, with the high symptom severity and global impairment profiles experiencing the longest recovery and the high balance impairment profile experiencing an intermediate-length recovery (vs low impairment profile)., Conclusion: An SRC is a heterogeneous injury that presents in varying ways clinically in the acute injury period and results in different recovery patterns. These data support the clinical prognostic value of diverse profiles of impairment across symptom, cognitive, and balance domains. By identifying distinct profiles of an SRC and connecting them to differing outcomes, the findings support more evidence-based use of accepted multimodal clinical assessment strategies for SRCs., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This secondary analysis project was funded by the National Institute of Neurological Disorders and Stroke (R03NS100691 and R01NS110856). The Concussion Assessment, Research and Education (CARE) Consortium studies were supported in part by the National Collegiate Athletic Association and the DOD. The US Army Medical Research Acquisition Activity is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Combat Casualty Care Research Program, endorsed by the DOD, through the Joint Program Committee 6/Combat Casualty Care Research Program–Psychological Health and Traumatic Brain Injury Research Program (W81XWH1420151 and W81XWH1820047). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: Early medical attention after concussion may minimize symptom duration and burden; however, many concussions are undiagnosed or have a delay in diagnosis after injury. Many concussion symptoms (eg, headache, dizziness) are not visible, meaning that early identification is often contingent on individuals reporting their injury to medical staff. A fundamental understanding of the types and levels of factors that explain when concussions are reported can help identify promising directions for intervention., Purpose: To identify individual and institutional factors that predict immediate (vs delayed) injury reporting., Study Design: Case-control study; Level of evidence, 3., Methods: This study was a secondary analysis of data from the Concussion Assessment, Research and Education (CARE) Consortium study. The sample included 3213 collegiate athletes and military service academy cadets who were diagnosed with a concussion during the study period. Participants were from 27 civilian institutions and 3 military institutions in the United States. Machine learning techniques were used to build models predicting who would report an injury immediately after a concussive event (measured by an athletic trainer denoting the injury as being reported "immediately" or "at a delay"), including both individual athlete/cadet and institutional characteristics., Results: In the sample as a whole, combining individual factors enabled prediction of reporting immediacy, with mean accuracies between 55.8% and 62.6%, depending on classifier type and sample subset; adding institutional factors improved reporting prediction accuracies by 1 to 6 percentage points. At the individual level, injury-related altered mental status and loss of consciousness were most predictive of immediate reporting, which may be the result of observable signs leading to the injury report being externally mediated. At the institutional level, important attributes included athletic department annual revenue and ratio of athletes to athletic trainers., Conclusion: Further study is needed on the pathways through which institutional decisions about resource allocation, including decisions about sports medicine staffing, may contribute to reporting immediacy. More broadly, the relatively low accuracy of the machine learning models tested suggests the importance of continued expansion in how reporting is understood and facilitated., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the DoD through the Psychological Health and Traumatic Brain Injury Research Program under award No. W81XWH-20-2-0044. This publication was also made possible with support from the Grand Alliance Concussion Assessment, Research and Education (CARE) Consortium, funded in part by the National Collegiate Athletic Association (NCAA) and DoD. The US Army Medical Research Acquisition Activity is the awarding and administering acquisition office. E.K-H. has received consulting fees from the NCAA. J.K.R-M. has consulted for Allied Health Education (paid) and has received speaker honoraria and travel reimbursements for talks given. She served previously (unpaid) on USA Football’s Football Development Council. R.C.L. has received current or past funding from the National Operating Committee on Standards for Athletic Equipment and the National Football League (NFL). S.P.B. has received current or past research funding from NFL/Under Armour/GE, Simbex, and ElMindA; has consulted for US Soccer (paid), US Cycling (unpaid), the University of Calgary SHRed Concussions external advisory board (unpaid), and medicolegal litigation; and has received speaker honoraria and travel reimbursements for talks given. He is coauthor of Biomechanics of Injury (3rd ed) and has a patent pending on “Brain Metabolism Monitoring Through CCO Measurements Using All-Fiber-Integrated Super-Continuum Source” (US application No. 17/164,490). M.A.M. has current or past research funding from NFL and Abbott Laboratories. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Objectives: The purpose of this study was to determine sex differences in recovery trajectories of assessments for sport-related concussion using Concussion Assessment, Research and Education (CARE) Consortium data., Methods: National Collegiate Athletic Association athletes (N = 906; 61% female) from sex-comparable sports completed a pre-season baseline assessment and post-sport-related concussion assessments within 6 h of injury, 24-48 h, when they initiated their return to play progression, when they were cleared for unrestricted return to play, and 6 months post-injury. Assessments included the Standardized Assessment of Concussion, Balance Error Scoring System, Brief Symptom Inventory-18, Immediate Post-concussion Assessment and Cognitive Testing (ImPACT), Sport Concussion Assessment Tool-3 symptom evaluation, Clinical Reaction Time, King-Devick test, Vestibular Ocular Motor Screen, 12-item Short-Form Health Survey, Hospital Anxiety and Depression Scale, and Satisfaction with Life Scale., Results: Only the Vestibular Ocular Motor Screen Total Symptom Score at the 24-48 h timepoint (p = 0.005) was statistically significantly different between sexes. Specifically, female athletes (mean = 60.2, 95% confidence interval [CI] 51.5-70.4) had higher Vestibular Ocular Motor Screen Total Symptom Scores than male athletes (mean = 36.9, 95% CI 27.6-49.3), but this difference resolved by the time of return-to-play initiation (female athletes, mean = 1.8, 95% CI 1.1-2.9; male athletes, mean = 4.1, 95% CI 1.5-10.9)., Conclusions: Sport-related concussion recovery trajectories for most assessments were similar for female and male National Collegiate Athletic Association athletes except for Vestibular Ocular Motor Screen symptoms within 48 h of sport-related concussion, which was greater in female athletes. Female athletes had a greater symptom burden across all timepoints, suggesting that cross-sectional observations may indicate sex differences despite similar recovery trajectories., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Neck pain in a concussion population is an emerging area of study that has been shown to have a negative influence on recovery. This effect has not yet been studied in collegiate athletes., Hypothesis: New or worsened neck pain is common after a concussion (>30%), negatively influences recovery, and is associated with patient sex and level of contact in sport., Study Design: Cohort study; Level of evidence, 2., Methods: Varsity-level athletes from 29 National Collegiate Athletic Association member institutions as well as nonvarsity sport athletes at military service academies were eligible for enrollment. Participants completed a preseason baseline assessment and follow-up assessments at 6 and 24 to 48 hours after a concussion, when they were symptom-free, and when they returned to unrestricted play. Data collection occurred between January 2014 and September 2018., Results: A total of 2163 injuries were studied. New or worsened neck pain was reported with 47.0% of injuries. New or worsened neck pain was associated with patient sex (higher in female athletes), an altered mental status after the injury, the mechanism of injury, and what the athlete collided with. The presence of new/worsened neck pain was associated with delayed recovery. Those with new or worsened neck pain had 11.1 days of symptoms versus 8.8 days in those without ( P < .001). They were also less likely to have a resolution of self-reported symptoms in ≤7 days ( P < .001). However, the mean duration of the return-to-play protocol was not significantly different for those with new or worsened neck pain (7.5 ± 7.7 days) than those without (7.4 ± 8.3 days) ( P = .592)., Conclusion: This novel study shows that neck pain was common in collegiate athletes sustaining a concussion, was influenced by many factors, and negatively affected recovery., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This publication was made possible in part by the National Collegiate Athletic Association (NCAA) and the United States DOD. The United States Army Medical Research Acquisition Activity (USAMRAA) is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Combat Casualty Care Research Program, endorsed by the DOD, and the Joint Program Committee 6/Combat Casualty Care Research Program–Psychological Health and Traumatic Brain Injury Research Program (W81XWH-14-2-0151). J.A.K. has received research funding from the National Chiropractic Mutual Insurance Company (NCMIC) and speaking honoraria from the Wisconsin Chiropractic Association. L.D.N. has received funding for unrelated research from the National Institute of Neurological Disorders and Stroke (NINDS), the Centers for Disease Control and Prevention (CDC), the DOD, the Medical Technology Enterprise Consortium, and the Medical College of Wisconsin–Advancing a Healthier Wisconsin Endowment and consulting fees for grant reviewing (DOD) and research (NINDS). B.B. has received grants from the National Institute on Aging and the NINDS, travel reimbursements for presenting at conferences, and a $500 honorarium in 1 instance. J.G. has received funding for unrelated research from the NCMIC and consulting fees for chiropractic education accreditation reviewing from the Council on Chiropractic Education. S.P.B. has received research funding from the National Institutes of Health (NIH), the CDC, the DOD-USAMRAA, the NCAA, the National Athletic Trainers’ Association, National Football League (NFL)/Under Armour/GE, Simbex, and ElMindA; has consulted for US Soccer (paid), USA Cycling (unpaid), the University of Calgary SHRed Concussions external advisory board (unpaid), and medicolegal litigation cases; has received speaker honoraria and travel reimbursements for talks given; is a coauthor of Biomechanics of Injury, 3rd Edition; has a patent on “Brain Metabolism Monitoring Through CCO Measurements Using All-Fiber-Integrated Super-Continuum Source” (US 11,529,091 B2); and is/was on the editorial boards (all unpaid) for the Journal of Athletic Training (2015-present), Concussion (2014-present), Athletic Training & Sports Health Care (2008-present), and the British Journal of Sports Medicine (2008-2019). T.W.M. has received research funding from the NCAA and the DOD to complete this work (travel funds to attend scientific conferences and present data were included in the budget of those grants), has received royalties from American Psychiatric Association Publishing for a textbook on traumatic brain injuries that he coedited, and is a member of the concussion scientific advisory committee for the Australian Football League (uncompensated). M.M. has received research funding through the Medical College of Wisconsin from the NIH, the DOD, the Department of Veterans Affairs, the CDC, NFL, the NCAA, and Abbott Laboratories; is a consultant to NeuroTrauma Sciences and a clinical consultant to the Green Bay Packers; and has received honoraria and travel support for professional speaking engagements. T.B. has received funding from the NCAA/DOD Concussion Assessment, Research and Education (CARE) Consortium as part of this study and industry funding from Statespace (no data from this study are related to that funding). J.T.G. has received honoraria from Pacira. H.J.B. has received support for education from Medwest Associates. C.L.M. has received a grant from DJO. A.K. has received book royalties from APA Books and research funding through the University of Pittsburgh from the CDC, the Chuck Noll Foundation for Brain Injury Research, the DOD (Congressionally Directed Medical Research Program, USAMRAA, Uniformed Services University of the Health Sciences), NFL, the NIH (National Institute of Child Health and Human Development, National Institute of Mental Health, NINDS), and private donors. N.P. has received funding from the NCAA/DOD CARE Consortium (W81XWH-14-2-0151), the DOD (W81XWH-20-1-0717), and the Indiana Spinal Cord and Brain Injury Research Fund and unrestricted funds from Statespace. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Objective: Determine the association of inflammatory biomarkers with clinical measures and recovery in participants with concussion., Setting: Multicenter study in National Collegiate Athletic Association member institutions including military service academies., Participants: Four hundred twenty-two participants with acute concussion., Design: Clinical visits and blood draws were completed preinjury and at multiple visits postconcussion (0-12 hours, 12-36 hours, and 36-60 hours postinjury). Clinical measures included Sport Concussion Assessment Tool (SCAT) symptom severity, Balance Error Scoring System, Standardized Assessment of Concussion (SAC), Brief Symptom Inventory-18 (BSI-18) scores, time to initiation of graduated return-to-play (RTP) protocol, and time to RTP. Interleukin (IL)-6, IL-10, IL-8, IL-1 receptor antagonist (RA), tumor necrosis factor (TNF), c-reactive protein, and vascular endothelial growth factor (VEGF) were measured in serum. Prespecified analyses focused on IL-6 and IL-1RA at 0 to 12 hours; exploratory analyses were conducted with false discovery rate correction., Results: For prespecified analyses, IL-1RA at 0 to 12 hours in female participants was positively associated with more errors on the SAC (B(standard error, SE) = 0.58(0.27), P < .05) and worse SCAT symptom severity (B(SE) = 0.96(0.44), P < .05). For exploratory analyses, higher levels of IL-1RA at 12 to 36 hours were associated with higher global (B(SE) = 0.55(0.14), q < 0.01), depression (B(SE) = 0.45(0.10), q < 0.005), and somatization scores on the BSI (B(SE) = 0.46(0.12), q < 0.01) in participants with concussion; Higher TNF at 12 to 36 hours was associated with fewer errors on the SAC (B(SE) = - 0.46(0.14), q < 0.05). Subanalyses showed similar results for male participants and participants who were athletes. No associations were discovered in nonathlete cadets. Higher IL-8 at 0 to 12 hours was associated with slower RTP in female participants (OR = 14.47; 95% confidence interval, 2.96-70.66, q < 0.05); no other associations with recovery were observed., Conclusions: Peripheral inflammatory markers are associated with clinical symptoms following concussion and potentially represent one mechanism for psychological symptoms observed postinjury. Current results do not provide strong support for a potential prognostic role for these markers., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Few previous studies have investigated how different injury mechanisms leading to sport-related concussion (SRC) in soccer may affect outcomes., Purpose: To describe injury mechanisms and evaluate injury mechanisms as predictors of symptom severity, return to play (RTP) initiation, and unrestricted RTP (URTP) in a cohort of collegiate soccer players., Study Design: Cohort study; Level of evidence, 2., Methods: The Concussion Assessment, Research and Education (CARE) Consortium database was used. The mechanism of injury was categorized into head-to-ball, head-to-head, head-to-body, and head-to-ground/equipment. Baseline/acute injury characteristics-including Sports Concussion Assessment Tool-3 total symptom severity (TSS), loss of consciousness (LOC), and altered mental status (AMS); descriptive data; and recovery (RTP and URTP)-were compared. Multivariable regression and Weibull models were used to assess the predictive value of the mechanism of injury on TSS and RTP/URTP, respectively., Results: Among 391 soccer SRCs, 32.7% were attributed to a head-to-ball mechanism, 27.9% to a head-to-body mechanism, 21.7% to a head-to-head mechanism, and 17.6% to a head-to-ground/equipment mechanism. Event type was significantly associated with injury mechanism [χ 2 (3) = 63; P < .001), such that more head-to-ball concussions occurred in practice sessions (n = 92 [51.1%] vs n = 36 [17.1%]) and more head-to-head (n = 65 [30.8%] vs n = 20 [11.1]) and head-to-body (n = 76 [36%] vs n = 33 [18.3%]) concussions occurred in competition. The primary position was significantly associated with injury mechanism [χ 2 (3) = 24; P < .004], with goalkeepers having no SRCs from the head-to-head mechanism (n = 0 [0%]) and forward players having the least head-to-body mechanism (n = 15 [19.2%]). LOC was also associated with injury mechanism ( P = .034), with LOC being most prevalent in head-to-ground/equipment. Finally, AMS was most prevalent in head-to-ball (n = 54 [34.2%]) and head-to-body (n = 48 [30.4%]) mechanisms [χ 2 (3) = 9; P = .029]. In our multivariable models, the mechanism was not a predictor of TSS or RTP; however, it was associated with URTP ( P = .044), with head-to-equipment/ground injuries resulting in the shortest mean number of days (14 ± 9.1 days) to URTP and the head-to-ball mechanism the longest (18.6 ± 21.6 days)., Conclusion: The mechanism of injury differed by event type and primary position, and LOC and AMS were different across mechanisms. Even though the mechanism of injury was not a significant predictor of acute symptom burden or time until RTP initiation, those with head-to-equipment/ground injuries spent the shortest time until URTP, and those with head-to-ball injuries had the longest time until URTP., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This project was supported, in part, by the Grand Alliance Sport-Related Concussion Assessment, Research, and Education (CARE) Consortium, funded, in part by the National Collegiate Athletic Association (NCAA) and the DoD. The U.S. Army Medical Research Acquisition Activity is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Psychological Health and Traumatic Brain Injury Program under award No. W81XWH-14-2-0151. A.J.B. has been part of projects that have received funding from the DoD, the National Operating Committee on Standards from Athletic Equipment, the National Athletic Trainer's Association (NATA) Research and Education Foundation, and the NCAA. P.F.P. is an employee of the DoD and has previously received other DoD-related grants. T.W.M. has received research support from the NCAA, the US DoD, and the National Institutes of Health (NIH). He also reports textbook royalties from American Psychiatric Press Publishing Inc and serves on the Concussion Committee Scientific Advisory Board for the Australian Football League. M.A.M. has received research funding from the NIH, the Centers for Disease Control and Prevention (CDC), the DoD, the NCAA, the National Football League (NFL), and Abbott Laboratories. S.P.B. has received research funding from the NIH, the CDC, the DoD-USA Medical Research Acquisition Activity, the NCAA, the NATA Research and Education Foundation, the NFL/Under Armour/GE, Simbex, and ElmindA. He has consulted for US Soccer, US Cycling, the University of Calgary SHRed Concussions external advisory board, and medicolegal litigation. S.L.Z. is a member of the NFL Head, Neck, and Spine Committee. D.P.T. serves as a scientific advisor for HitIQ. He previously consulted for REACT Neuro Inc. He has a consulting practice in forensic neuropsychology, including expert testimony, involving individuals who have sustained mild traumatic brain injury (including former athletes). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: Molecular-based approaches to understanding concussion pathophysiology provide complex biological information that can advance concussion research and identify potential diagnostic and/or prognostic biomarkers of injury., Objective: The aim of this study was to identify gene expression changes in peripheral blood that are initiated following concussion and are relevant to concussion response and recovery., Methods: We analyzed whole blood transcriptomes in a large cohort of concussed and control collegiate athletes who were participating in the multicenter prospective cohort Concussion Assessment, Research, and Education (CARE) Consortium study. Blood samples were collected from collegiate athletes at preseason (baseline), within 6 h of concussion injury, and at four additional prescribed time points spanning 24 h to 6 months post-injury. RNA sequencing was performed on samples from 230 concussed, 130 contact control, and 102 non-contact control athletes. Differential gene expression and deconvolution analysis were performed at each time point relative to baseline., Results: Cytokine and immune response signaling pathways were activated immediately after concussion, but at later time points these pathways appeared to be suppressed relative to the contact control group. We also found that the proportion of neutrophils increased and natural killer cells decreased in the blood following concussion., Conclusions: Transcriptome signatures in the blood reflect the known pathophysiology of concussion and may be useful for defining the immediate biological response and the time course for recovery. In addition, the identified immune response pathways and changes in immune cell type proportions following a concussion may inform future treatment strategies., (© 2023. The Author(s).)

Background: Timely and appropriate medical care after concussion presents a difficult public health problem. Concussion identification and treatment rely heavily on self-report, but more than half of concussions go unreported or are reported after a delay. If incomplete self-report increases exposure to harm, blood biomarkers may objectively indicate this neurobiological dysfunction., Purpose/hypothesis: The purpose of this study was to compare postconcussion biomarker levels between individuals with different previous concussion diagnosis statuses and care-seeking statuses. It was hypothesized that individuals with undiagnosed concussions and poorer care seeking would show altered biomarker profiles., Study Design: Cohort study; Level of evidence, 3., Methods: Blood samples were collected from 287 military academy cadets and collegiate athletes diagnosed with concussion in the Advanced Research Core of the Concussion Assessment, Research and Education Consortium. The authors extracted each participant's self-reported previous concussion diagnosis status (no history, all diagnosed, ≥1 undiagnosed) and whether they had delayed or immediate symptom onset, symptom reporting, and removal from activity after the incident concussion. The authors compared the following blood biomarkers associated with neural injury between previous concussion diagnosis status groups and care-seeking groups: glial fibrillary acidic protein, ubiquitin c-terminal hydrolase-L1 (UCH-L1), neurofilament light chain (NF-L), and tau protein, captured at baseline, 24 to 48 hours, asymptomatic, and 7 days after unrestricted return to activity using tests of parallel profiles., Results: The undiagnosed previous concussion group (n = 21) had higher levels of NF-L at 24- to 48-hour and asymptomatic time points relative to all diagnosed (n = 72) or no previous concussion (n = 194) groups. For those with delayed removal from activity (n = 127), UCH-L1 was lower at 7 days after return to activity than that for athletes immediately removed from activity (n = 131). No other biomarker differences were observed., Conclusion: Individuals with previous undiagnosed concussions or delayed removal from activity showed some different biomarker levels after concussion and after clinical recovery, despite a lack of baseline differences. This may indicate that poorer care seeking can create neurobiological differences in the concussed brain., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: All authors received funding from the National Collegiate Athletic Association (NCAA) and/or the Department of Defense (DOD) to complete this investigation and cover travel costs related to the study. This work was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the DOD through the Psychological Health and Traumatic Brain Injury Research Program under award No. W81XWH-20-2-0044. This publication was also made possible with support from the Grand Alliance Concussion Assessment, Research and Education (CARE) Consortium, funded in part by the NCAA and the DOD. The U.S. Army Medical Research Acquisition Activity (820 Chandler Street, Fort Detrick, MD 21702-5014) is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Psychological Health and Traumatic Brain Injury Program under award No. W81XWH-14-2-0151. J.R.M. and R.C.L. have received research funding from the National Operating Committee for the Standards on Athletic Equipment. S.P.B. has consulted for US Soccer (paid), US Cycling (unpaid), and medicolegal litigation; and received speaker honoraria and travel reimbursements for talks given. He is coauthor of Biomechanics of Injury, 3rd edition, and has a patent pending on “Brain Metabolism Monitoring Through CCO Measurements Using All-Fiber-Integrated Super-Continuum Source” (U.S. application No. 17/164,490). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Context: Concussion research has primarily focused on sport-related mechanisms and excluded non-sport-related mechanisms. In adult populations, non-sport-related concussions (non-SRCs) demonstrated worse clinical outcomes compared with sport-related concussions (SRCs); however, investigations of non-SRCs in college-aged patients are limited., Objectives: To examine clinical outcomes in collegiate athletes with non-SRCs compared with SRCs and explore sex differences in outcomes among collegiate athletes with non-SRCs., Design: Prospective cohort study., Setting: Clinical setting., Patients or Other Participants: A total of 3500 athletes were included (n = 555 with non-SRCs, 42.5% female) from colleges or universities and service academies participating in the National Collegiate Athletic Association Department of Defense Concussion Assessment, Research and Education (CARE) Consortium., Main Outcome Measure(s): Dichotomous outcomes (yes or no) consisted of immediate reporting, mental status alterations, loss of consciousness, posttraumatic amnesia, retrograde amnesia, motor impairments, delayed symptom presentation, and required hospital transport. Continuous outcomes were symptom severity, days with concussion symptoms, and days lost to injury. Data were collected within 24 to 48 hours of injury and at return to play. Adjusted relative risks (ARRs) compared the likelihood of dichotomous outcomes by mechanism and by sex within patients with non-SRCs. Multivariate negative binomial regressions were used to assess group differences in continuous variables., Results: Athletes with non-SRCs were less likely to report immediately (ARR = 0.73, 95% CI = 0.65, 0.81) and more likely to report delayed symptom presentation (ARR = 1.17, 95% CI = 1.03, 1.32), loss of consciousness (ARR = 3.15, 95% CI = 2.32, 4.28), retrograde amnesia (ARR = 1.77, 95% CI = 1.22, 2.57), and motor impairment (ARR = 1.45, 95% CI = 1.14, 1.84). Athletes with non-SRCs described greater symptom severity, more symptomatic days, and more days lost to injury (P < .001) compared with those who had SRCs. Within the non-SRC group, female athletes indicated greater symptom severity, more symptomatic days, and more days lost to injury (P < .03) than male athletes., Conclusions: Athletes with non-SRCs had worse postinjury outcomes compared with those who had SRCs, and female athletes with non-SRCs had worse recovery metrics than male athletes. Our findings suggest that further investigation of individuals with non-SRCs is needed to improve concussion reporting and management., (© by the National Athletic Trainers’ Association, Inc.)

Background and Objectives: The objective was to characterize the acute effects of concussion (a subset of mild traumatic brain injury) on serum interleukin (IL)-6 and IL-1 receptor antagonist (RA) and 5 additional inflammatory markers in athletes and military service academy members from the Concussion Assessment, Research, and Education Consortium and to determine whether these markers aid in discrimination of concussed participants from controls., Methods: Athletes and cadets with concussion and matched controls provided blood at baseline and postinjury visits between January 2015 and March 2020. Linear models investigated changes in inflammatory markers measured using Meso Scale Discovery assays across time points (baseline and 0-12, 12-36, 36-60 hours). Subanalyses were conducted in participants split by sex and injury population. Logistic regression analyses tested whether acute levels of IL-6 and IL-1RA improved discrimination of concussed participants relative to brain injury markers (glial fibrillary acidic protein, tau, neurofilament light, ubiquitin c-terminal hydrolase-L1) or clinical data (Sport Concussion Assessment Tool-Third Edition, Standardized Assessment of Concussion, Balance Error Scoring System)., Results: Participants with concussion (total, N = 422) had elevated IL-6 and IL-1RA at 0-12 hours vs controls (n = 345; IL-6: mean difference [MD] (standard error) = 0.701 (0.091), p < 0.0001; IL-1RA: MD = 0.283 (0.042), p < 0.0001) and relative to baseline (IL-6: MD = 0.656 (0.078), p < 0.0001; IL-1RA: MD = 0.242 (0.038), p < 0.0001), 12-36 hours (IL-6: MD = 0.609 (0.086), p < 0.0001; IL-1RA: MD = 0.322 (0.041), p < 0.0001), and 36-60 hours (IL-6: MD = 0.818 (0.084), p < 0.0001; IL-1RA: MD = 0.317 (0.040), p < 0.0001). IL-6 and IL-1RA were elevated in participants with sport (IL-6: MD = 0.748 (0.115), p < 0.0001; IL-1RA: MD = 0.304 (0.055), p < 0.0001) and combative-related concussions (IL-6: MD = 0.583 (0.178), p = 0.001; IL-1RA: MD = 0.312 (0.081), p = 0.0001). IL-6 was elevated in male (MD = 0.734 (0.105), p < 0.0001) and female participants (MD = 0.600 (0.177), p = 0.0008); IL-1RA was only elevated in male participants (MD = 0.356 (0.047), p < 0.0001). Logistic regression showed the inclusion of IL-6 and IL-1RA at 0-12 hours improved the discrimination of participants with concussion from controls relative to brain injury markers (χ 2 (2) = 17.855, p = 0.0001; area under the receiver operating characteristic curve [AUC] 0.73 [0.66-0.80] to 0.78 [0.71-0.84]), objective clinical measures (balance and cognition; χ 2 (2) = 40.661, p < 0.0001; AUC 0.81 [0.76-0.86] to 0.87 [0.83-0.91]), and objective and subjective measures combined (χ 2 (2) = 13.456, p = 0.001; AUC 0.97 [0.95-0.99] to 0.98 [0.96-0.99]), although improvement in AUC was only significantly relative to objective clinical measures., Discussion: IL-6 and IL-1RA (male participants only) are elevated in the early-acute window postconcussion and may aid in diagnostic decisions beyond traditional blood markers and common clinical measures. IL-1RA results highlight sex differences in the immune response to concussion which should be considered in future biomarker work.

Objective: To determine whether alcohol use leads to prolonged clinical recovery or increased severity of concussion symptoms in National Collegiate Athletic Association (NCAA) athletes., Design: Prospective observational study., Setting: Clinical institutions., Participants: Athletes from the NCAA Concussion Assessment Research and Education consortium who sustained a concussion from 2014 to 2021., Interventions: Athletes were divided into 2 groups, those reporting alcohol use postinjury and those reporting no alcohol use postinjury., Main Outcome Measures: Symptom recovery was evaluated as time (in days) from injury to clearance to return to unrestricted play (days until URTP). Severity of concussion symptoms was assessed using the Standardized Sport Concussion Assessment Tool (SCAT3) symptom severity, headache severity, difficulty concentrating, and difficulty remembering scores. These scores were taken a median of 6.6 [interquartile range (IQR) = 4.0-10] and 6 (IQR = 4.0-9.0) days after injury for those who did and did not consume alcohol postinjury respectively and compared with baseline SCAT3 scores., Results: Four hundred eighty four athletes from the data set had complete data for exposure and outcome. The adjusted mean number of days until URTP for athletes reporting alcohol use postinjury [23.3; 95% confidence interval (CI), 20.0-27.2; days] was incidence rate ratio (IRR) 1.32 (95% CI, 1.12-1.55; P < 0.001) times higher than for athletes who reported no alcohol use postinjury [17.7 (95% CI, 16.1-19.3) days]. Postinjury alcohol was not associated with severity of concussion symptoms ( P 's < 0.05)., Conclusion: Self-reported postinjury alcohol use is associated with prolonged recovery but not severity of concussion symptoms in collegiate athletes. This may inform future clinical recommendations regarding alcohol consumption after concussion., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The aim of the present study was to examine the effects of attention-deficit/hyperactivity disorder (ADHD) -related psychostimulant use in the context of concussion risk and symptom recovery. Data were obtained from the National Collegiate Athletic Association Department of Defense Grand Alliance Concussion Assessment, Research, and Education (NCAA-DOD CARE) Consortium from 2014 to 2017. Relative to individuals without diagnosed ADHD (i.e., control), both ADHD diagnosis and the combination of ADHD diagnosis and psychostimulant use were associated with a greater risk of incurring a concussive injury. Following a concussive injury, ADHD diagnosis was associated with longer symptom recovery time relative to the control group. However, individuals with ADHD who use psychostimulants did not take longer to resolve symptoms than controls, suggesting that psychostimulants may have a positive influence on recovery. Regardless of time point, ADHD diagnosis was associated with an elevated number of concussion-related symptoms; however, this effect appears mitigated by having used ADHD-related psychostimulants.

Purpose: The objectives of this study are to 1) describe collegiate student-athlete (SA) race and household income and 2) evaluate time to normal academic performance (i.e., return to learn (RTL)), initiation of the return to play (iRTP) protocol, RTP protocol duration, and time to unrestricted RTP (URTP) after sustaining sport-related concussion (SRC)., Methods: Data were collected between 2014 and 2020 by the Concussion Assessment, Research, and Education Consortium. Baseline data were used to characterize participant demographics ( N = 22,819) and post-SRC outcomes ( n = 5485 SRC) in time to RTL ( n = 1724) and RTP outcomes ( n = 2646) by race. Descriptive statistics and nonparametric tests examined differences across race by demographic and injury characteristics. Kaplan-Meier curves estimated median days to RTL, iRTP protocol, RTP protocol completion, and URTP by race and covariate measures. Multivariable Cox proportional hazards regression assessed the effect of race on risk of RTL and RTP recovery time points., Results: SA largely identified as White (75%) followed by Black (14%), multiracial (7%), and Asian (3%). More than half (53%) of all SA reported a household income of >$120,000, whereas 41% of Black SA reported a household income <$60,000. Race was not associated with relative risk of RTL or iRTP but was associated with RTP protocol completion and URTP. Non-Black/non-White SA were 17% less likely (adjusted hazard ratio = 0.83; 95% confidence interval = 0.71, 0.97) to complete the RTP protocol, and Black SA were 17% more likely (adjusted hazard ratio = 1.17; 95% confidence interval = 1.05, 1.31) to reach the URTP time point compared with White SA., Conclusions: The present findings suggest collegiate SA enrolled in the Concussion Assessment, Research, and Education Consortium are primarily White and come from household incomes well above the US median. Race was not associated with RTL or iRTP but was associated with RTP protocol duration and total time to URTP. Clinicians should be conscientious of how their implicit or preconceived biases may influence SRC management among National Collegiate Athletic Association SA., (Copyright © 2023 by the American College of Sports Medicine.)

Background: A key component of return-to-play (RTP) from sport-related concussion is the symptom-free waiting period (SFWP), i.e., the period during which athletes must remain symptom-free before permitting RTP. Yet, the exact relationship between SFWP and post-RTP injury rates is unclear., Objective: We design computational simulations to estimate the relationship between the SFWP and rates of repeat concussion and non-concussion time-loss injury up to 30 days post-RTP for male and female collegiate athletes across 13 sports., Methods: We leverage N = 735 female and N = 1,094 male post-injury trajectories from the National Collegiate Athletic Association-Department of Defense Concussion Assessment, Research, and Education Consortium., Results: With a 6-day SFWP, the mean [95% CI] rate of repeat concussion per 1,000 simulations was greatest in ice hockey for females (20.31, [20.16, 20.46]) and American football for males (24.16, [24.05, 24.28]). Non-concussion time-loss injury rates were greatest in field hockey for females (153.66, [152.59, 154.74]) and wrestling for males (247.34, [246.20, 248.48]). Increasing to a 13-day SFWP, ice hockey for females (18.88, [18.79, 18.98]) and American football for males (23.16, [23.09, 24.22]) exhibit the greatest decrease in repeat concussion rates across all sports within their respective sexes. Field hockey for females (143.24, [142.53, 143.94]) and wrestling for males (237.73, [236.67, 237.90]) exhibit the greatest decrease in non-concussion time-loss injury rates. Males receive marginally smaller reductions in injury rates for increased SFWP compared to females (OR = 1.003, p ≤ 0.002)., Conclusion: Longer SFWPs lead to greater reductions in post-RTP injury rates for athletes in higher risk sports. Moreover, SFWPs should be tailored to sport-specific post-RTP injury risks., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Growing evidence indicates early exercise may improve symptoms and reduce clinical recovery time after concussion, but research examining collegiate student-athletes is scarce., Objective: The aim of this study was to compare symptom recovery time, clinical recovery time, and persisting post-concussion symptom (i.e., symptoms ≥ 28 days) prevalence by the timing of light exercise initiation before the graded return to play (RTP) protocol among concussed participants., Methods: Collegiate student-athletes (n = 1228; age 18.4 ± 0.9 years; 56.5% male, 76.3% division I; 33.7% ≥ 1 prior concussion) across 30 institutions enrolled in the CARE Consortium completed post-concussion assessments and were monitored over time. Symptom recovery (days from injury to symptom resolution) and clinical recovery (days from injury to return to play protocol completion) was determined by the student-athletes' clinicians. Student-athletes were categorized by timing of light exercise initiation. Early (< 2 days post-concussion; n = 161), typical (3-7 days post-concussion; n = 281), and late exercise (≥ 8 days post-concussion; n = 169) groups were compared with the no-exercise group (n = 617; i.e., did not exercise prior to beginning the RTP protocol) for all analyses. Multivariable Cox regression models with hazard ratios (HR) and survival curves and a multivariable binomial regression model with prevalence ratios (PR) compared recovery outcomes between exercise groups while accounting for covariates., Results: Compared to the no-exercise group, the early exercise group was 92% more probable to experience symptom recovery (HR 1.92; 95% CI 1.57-2.36), 88% more probable to reach clinical recovery (HR 1.88; 95% CI 1.55-2.28) and took a median of 2.4 and 3.2 days less to recover, respectively. The late exercise group relative to the no-exercise group was 57% less probable to reach symptom recovery (HR 0.43; 95% CI 0.35-0.53), 46% less probable to achieve clinical recovery (HR 0.54; 95% CI 0.45-0.66) and took 5.3 days and 5.7 days more to recover, respectively. The typical exercise group did not differ in hazard for symptom or clinical recovery (p ≥ 0.329) compared with the no-exercise group. The prevalence of persisting post-concussion symptoms in the combined sample was 6.6%. Early exercise had 4% lower prevalence (PR 0.96, 95% CI 0.94-0.99) and typical exercise had 3% lower prevalence (PR 0.97, 95% CI 0.94-0.99) of persisting post-concussion symptoms, while the late exercise group had an elevated prevalence (PR 1.11, 95% CI 1.04-1.18) compared with the no-exercise group., Conclusion: Exercise < 2 days post-concussion was associated with more probable and faster symptom and clinical recovery, and lower persisting post-concussion symptom prevalence. When considering our findings and existing literature, qualified clinicians may implement early exercise into their clinical practice to provide therapeutic treatment and improve student-athlete recovery., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Abstract: This prospective cohort study aimed to determine whether preinjury characteristics and performance on baseline concussion assessments predicted future concussions among collegiate student-athletes. Participant cases (concussed = 2529; control = 30,905) completed preinjury: demographic forms (sport, concussion history, sex), Immediate Post-Concussion Assessment and Cognitive Test, Balance Error Scoring System, Sport Concussion Assessment Tool symptom checklist, Standardized Assessment of Concussion, Brief Symptom Inventory-18 item, Wechsler Test of Adult Reading, and Brief Sensation Seeking Scale. We used machine-learning logistic regressions with area under the curve, sensitivity, and positive predictive values statistics for univariable and multivariable analyses. Primary sport was determined to be the strongest univariable predictor (area under the curve = 64.3% ± 1.4, sensitivity = 1.1% ± 1.4, positive predictive value = 4.9% ± 6.5). The all-predictor multivariable model was the strongest (area under the curve = 68.3% ± 1.6, sensitivity = 20.7% ± 2.7, positive predictive value = 16.5% ± 2.0). Despite a robust sample size and novel analytical approaches, accurate concussion prediction was not achieved regardless of modeling complexity. The strongest positive predictive value (16.5%) indicated only 17 of every 100 individuals flagged would experience a concussion. These findings suggest preinjury characteristics or baseline assessments have negligible utility for predicting subsequent concussion. Researchers, healthcare providers, and sporting organizations therefore should not use preinjury characteristics or baseline assessments for future concussion risk identification at this time., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The endorsement of symptoms upon initiation of a graduated return-to-activity (GRTA) protocol has been associated with prolonged protocols. It is unclear whether there are specific symptom clusters affecting protocol durations., Purpose: To describe the endorsement of specific concussion symptom clusters at GRTA protocol initiation and examine the association between symptom cluster endorsement and GRTA protocol duration., Study Design: Cohort study; Level of evidence, 2., Methods: This study was conducted among cadets enrolled at 3 US service academies. Participants completed an evaluation upon GRTA protocol initiation. Participants endorsing symptoms were binarized based on 6 symptom clusters (cognitive, emotional, insomnia, physical, sensitivity, and ungrouped). The primary outcome of interest was GRTA protocol duration based on symptom cluster endorsement severity. Prevalence rates were calculated to describe symptom cluster endorsement. Kaplan-Meier survival estimates and univariate and multivariable Cox proportional hazards regression models were calculated for all 6 symptom clusters to estimate GRTA protocol duration while controlling for significant covariates., Results: Data from 961 concussed participants were analyzed. Of these, 636 participants were asymptomatic upon GRTA protocol initiation. Among the 325 symptomatic participants, the physical symptom cluster (80%) was most endorsed, followed by the cognitive (29%), insomnia (23%), ungrouped (19%), sensitivity (15%), and emotional (9%) clusters. Univariate results revealed a significant association between endorsing cognitive (hazard ratio [HR], 0.79; p = .001), physical (HR, 0.84; p < .001), insomnia (HR, 0.83; p = .013), sensitivity (HR, 0.70; p < .001), and ungrouped (HR, 0.75; p = .005) symptom clusters and GRTA protocol duration. Endorsing physical (HR, 0.84; p < .001) and sensitivity (HR, 0.81; p = .036) clusters maintained a significant association with GRTA protocol duration in the multivariable models., Conclusion: Participants endorsing physical or sensitivity symptom clusters displayed GRTA protocols prolonged by 16% to 19% compared with participants not endorsing that respective cluster after controlling for significant covariates.

The gray matter/white matter (GM/WM) boundary of the brain is vulnerable to shear strain associated with mild traumatic brain injury (mTBI). It is, however, unknown whether GM/WM microstructure is associated with long-term outcomes following mTBI. The diffusion and structural MRI data of 278 participants between 18 and 65 years of age with and without military background from the Department of Defense INTRuST study were analyzed. Fractional anisotropy (FA) was extracted at the GM/WM boundary across the brain and for each lobe. Additionally, two conventional analytic approaches were used: whole-brain deep WM FA (TBSS) and whole-brain cortical thickness (FreeSurfer). ANCOVAs were applied to assess differences between the mTBI cohort ( n = 147) and the comparison cohort ( n = 131). Associations between imaging features and post-concussive symptom severity, and functional and cognitive impairment were investigated using partial correlations while controlling for mental health comorbidities that are particularly common among military cohorts and were present in both the mTBI and comparison group. Findings revealed significantly lower whole-brain and lobe-specific GM/WM boundary FA ( p < 0.011), and deep WM FA ( p = 0.001) in the mTBI cohort. Whole-brain and lobe-specific GM/WM boundary FA was significantly negatively correlated with post-concussive symptoms ( p < 0.039), functional ( p < 0.016), and cognitive impairment ( p < 0.049). Deep WM FA was associated with functional impairment ( p = 0.002). Finally, no significant difference was observed in cortical thickness, nor between cortical thickness and outcome ( p > 0.05). Findings from this study suggest that microstructural alterations at the GM/WM boundary may be sensitive markers of adverse long-term outcomes following mTBI.

Sport-related concussion (SRC) is associated with several post-injury consequences, including neurocognitive decrements and psychological distress. Yet, how these clinical markers interact with each other, the magnitude of their interrelationships, and how they may vary over time following SRC are not well understood. Network analysis has been proposed as a statistical and psychometric method to conceptualize and map the complex interplay of interactions between observed variables (e.g., neurocognitive functioning and psychological symptoms). For each collegiate athlete with SRC ( n  = 565), we constructed a temporal network as a weighted graph, with nodes, edges, and the set of weights associated with each edge at three time-points (baseline, 24-48 h post-injury, and asymptomatic), that graphically depicts the interrelated nature of neurocognitive functioning and symptoms of psychological distress throughout the recovery process. This graph shows that the inter-group relationships between neurocognitive functioning and symptoms of psychological distress were stronger at the 24-48 h time-point than at baseline or at the asymptomatic time-point. Further, all symptoms of psychological distress and neurocognitive functioning significantly improved from the 24-48 h time-point to asymptomatic status. The effect sizes of these changes ranged from 0.126 (small) to 0.616 (medium). This research suggests that significant improvements in symptoms of psychological distress appear necessary to drive related improvements in neurocognitive functioning and vice versa. Therefore, clinical interventions should consider the importance of managing psychological distress during the acute care of individuals with SRC to help ameliorate negative outcomes.

Introduction: The hormonal withdrawal hypothesis suggests that progesterone reduction in women after concussion may lead to greater symptom burden and longer recoveries. Current evidence indicates that hormonal stability after head injury may be an important moderator of postconcussive recovery. Thus, female athletes using hormonal contraceptives (HC) may exhibit better recovery profiles as their hormone levels are artificially stabilized. Our investigation sought to examine the relation between HC use and concussion outcomes in female student-athletes., Methods: This longitudinal study examined concussion outcomes from female student-athletes participating in the NCAA-DoD CARE Consortium Research Initiative, including academic years 2014 to 2020. Eighty-six female collegiate athletes reporting HC use (HC+) were group matched on age, body mass index, race/ethnicity, sport contact level, concussion history, and current injury characteristics (i.e., amnesia, loss of consciousness) to 86 female collegiate athletes reporting no HC use (HC-). All participants had sustained a concussion and completed the Sport Concussion Assessment Tool, 3rd edition Symptom Scale, Brief Symptom Inventory-18, and Immediate Post-concussion Assessment and Cognitive Testing at preinjury baseline, 24 to 48 h postinjury, and when cleared for unrestricted return to play. To provide an index of recovery trajectory, days between injury and unrestricted return to play were calculated., Results: Groups did not differ on length of recovery, postconcussion symptoms, psychological health, or cognitive assessments. No differences were observed between groups on any measure when accounting for baseline levels of performance., Conclusions: Our findings suggest that HC use does not influence recovery trajectory, symptoms, or recovery of cognitive function after concussion., (Copyright © 2023 by the American College of Sports Medicine.)

Background and Objectives: To study longitudinal associations between blood-based neural biomarkers (including total tau, neurofilament light [NfL], glial fibrillary acidic protein [GFAP], and ubiquitin C-terminal hydrolase-L1) and white matter neuroimaging biomarkers in collegiate athletes with sport-related concussion (SRC) from 24 hours postinjury to 1 week after return to play., Methods: We analyzed clinical and imaging data of concussed collegiate athletes in the Concussion Assessment, Research, and Education (CARE) Consortium. The CARE participants completed same-day clinical assessments, blood draws, and diffusion tensor imaging (DTI) at 3 time points: 24-48 hours postinjury, point of becoming asymptomatic, and 7 days after return to play. DTI probabilistic tractography was performed for each participant at each time point to render 27 participant-specific major white matter tracts. The microstructural organization of these tracts was characterized by 4 DTI metrics. Mixed-effects models with random intercepts were applied to test whether white matter microstructural abnormalities are associated with the blood-based biomarkers at the same time point. An interaction model was used to test whether the association varies across time points. A lagged model was used to test whether early blood-based biomarkers predict later microstructural changes., Results: Data from 77 collegiate athletes were included in the following analyses. Among the 4 blood-based biomarkers, total tau had significant associations with the DTI metrics across the 3 time points. In particular, high tau level was associated with high radial diffusivity (RD) in the right corticospinal tract (β = 0.25, SE = 0.07, p FDR-adjusted = 0.016) and superior thalamic radiation (β = 0.21, SE = 0.07, p FDR-adjusted = 0.042). NfL and GFAP had time-dependent associations with the DTI metrics. NfL showed significant associations only at the asymptomatic time point (|β|s > 0.12, SEs <0.09, p s FDR-adjusted < 0.05) and GFAP showed a significant association only at 7 days after return to play (βs > 0.14, SEs <0.06, p s FDR-adjusted < 0.05). The p values for the associations of early tau and later RD were not significant after multiple comparison adjustment, but were less than 0.1 in 7 white matter tracts., Discussion: This prospective study using data from the CARE Consortium demonstrated that in the early phase of SRC, white matter microstructural integrity detected by DTI neuroimaging was associated with elevated levels of blood-based biomarkers of traumatic brain injury. Total tau in the blood showed the strongest association with white matter microstructural changes., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Previous sport-related concussion research highlights post-injury characteristics that influence recovery trajectories; however, there is limited information regarding premorbid factors that affect sport-related concussion risk., Objective: We aimed to (a) compare premorbid demographic factors among a large cohort of collegiate student athletes who did or did not sustain a sport-related concussion and (b) assess differences in acute injury characteristics based on biological sex and contact level., Methods: We conducted a cohort study of university student athletes from 22 sports enrolled in the Concussion Assessment, Research, and Education (CARE) Consortium study from 2014 to 2021 (n = 1804 student athletes with sport-related concussions; n = 21,702 student athletes without sport-related concussions)., Results: Statistical analyses indicated student athletes who self-identified as Black (odds ratio [OR] = 1.61; 95% confidence interval [CI] = 1.42, 1.81) or multiracial (OR = 1.32; 95% CI 1.10, 1.59) demonstrated greater odds of experiencing sport-related concussions than White-identifying student athletes. Additional findings suggest male athletes (OR = 1.47; 95% CI 1.20, 1.81) and contact sport student athletes (OR = 1.40; 95% CI 1.16, 1.70) may be at increased odds for sport-related concussions if they were previously diagnosed with attention deficit hyperactive disorder. Notable post-injury characteristics across sexes included differences in the incident loss of consciousness (male: 5.9%, female: 2.6%; p < 0.001), post-traumatic amnesia (male: 13.6%, female: 5.1%; p < 0.001), and retrograde amnesia (male: 6.8%, female: 2.8%; p < 0.001). A greater proportion of contact-sport student athletes experienced an altered mental status (52.7%) than limited contact (36.2%) and non-contact (48.6%) [p < 0.001]. Last, student athletes participating at lower contact levels were more likely to have a longer delay in removal from activity following injury (contact: 73.6 ± 322.2 min; limited contact: 139.1 ± 560.0 min; non-contact: 461.4 ± 1870.8 min; p = 0.005)., Conclusions: The present study provides contemporary pre- and post-sport-related concussion injury characteristics using a considerably sized cohort of collegiate student athletes. These findings support previous work suggesting sport-related concussion results in complex individualized clinical presentations, which may influence management strategies., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)