Cumulative Head Research Articles

Dispersion-based cognitive intra-individual variability in former American football players: Association with traumatic encephalopathy syndrome, repetitive head impacts, and biomarkers

Background: Exposure to repetitive head impacts (RHI), such as those experienced in American football, is linked to cognitive dysfunction later in life. Traumatic encephalopathy syndrome (TES) is a proposed clinical syndrome thought to be linked to neuropath­ology of chronic traumatic encephalopathy (CTE), a condition associated with RHI from football. Cognitive intra-individual variability (d-CIIV) measures test-score dispersion, indicating cognitive dysfunction. This study examined d-CIIV in former football players and its associations with TES diagnosis, RHI exposure, and DTI and CSF biomarkers. Methods: Data included 237 males (45–74 years) from DIAGNOSE CTE Research Project, including former professional and college football players (COL) (n = 173) and asymptomatic men without RHI or TBI (n = 55). Participants completed neuropsychological tests. TES diagnosis was based on 2021 NINDS TES criteria. Years of football play and a cumulative head impact index (CHII) measured RHI exposure. Lumipulse technology was used for CSF assays. DTI fractional anisotropy assessed white matter integrity. Coefficient of variation (CoV) measured d-CIIV. ANCOVA compared d-CIIV among groups (football versus control; TES-status). Pearson correlations and linear regressions tested associations between d-CIIV, RHI exposure, and CSF and DTI biomarkers. Results: Former professional players had higher d-CIIV than controls (F(7, 194) = 2.87, p = .007). d-CIIV was associated with TES diagnosis (F(8, 146) = 9.063, p < .001), with highest d-CIIV in TES Possible/Probable-CTE. Higher d-CIIV correlated with higher CHII scores (r = 0.19), reduced CSF Aβ1–42 (β = −0.302), increased p-tau181 (β = 0.374), and reduced DTI FA (β = −0.202). Conclusion: d-CIIV is linked to RHI exposure and TES diagnosis in former football players, with associated changes in CSF biomarkers and white matter integrity.

Associations Between Instrumented Mouthguard-Measured Head Acceleration Events and Post-Match Biomarkers of Astroglial and Axonal Injury in MaleAmateur Australian Football Players.

Advances in instrumented mouthguards (iMGs) allow for accurate quantification of single high-acceleration head impacts and cumulative head acceleration exposure in collision sports. However, relationships between these measures and risk of brain cell injury remain unclear. The purpose of this study was to quantify measures of non-concussive head impact exposure and assess their association with blood glial fibrillary acidic protein (GFAP), neurofilament light (NfL) and phosphorylated-tau-181 (p-tau-181) levels in male Australian football players. A total of 31 athletes underwent in-season (24h post-match) and post-season (> 5weeks) blood collections and/or wore HITIQ Nexus A9 iMGs measuring peak linear (PLA) and rotational (PRA) acceleration. Match footage was used to verify and code impacts. Blood GFAP, NfL, and p-tau-181 were quantified using Simoa and natural log transformed for analysis. Associations between post-match biomarkers and within match maximum single impact and cumulative PLA/PRA were assessed with linear mixed models. In-season versus post-season elevations were found for GFAP (mean difference 0.14, 95% CI 0.01-0.26, p = 0.033), NfL (mean difference = 0.21, 95% CI 0.09-0.32, p = 0.001) and p-tau-181 (mean difference = 0.49, 95% CI 0.33-0.65, p < 0.001). Post-match GFAP was associated with maximum single impact PLA (B = 0.003, 95% CI 0.0002-0.005, p = 0.036), cumulative PLA (B = 0.001, 95% CI 0.0002-0.002, p = 0.017), cumulativePRA (B = 0.01, 95% CI 0.002-0.02, p = 0.014), and impact number (B = 0.03, 95% CI 0.003-0.05, p = 0.029) within a single match. Change in NfL levels between two-matches correlated with cumulative PLA (r = 0.80, 95% CI 0.38-0.95, p = 0.005), PRA (r = 0.71, 95% CI 0.19-0.92, p = 0.019) and impact number (r = 0.63, 95% CI 0.05-0.89, p = 0.038). Maximum and cumulative head accelerations in Australian football, measured by iMGs, were associated with elevated blood biomarkers of brain injury, highlighting the potential of both technologies for head impact management in collision sports.

Cavum Septum Pellucidum in Former American Football Players: Findings From the DIAGNOSE CTE Research Project.

Exposure to repetitive head impacts (RHI) is linked to the development of chronic traumatic encephalopathy (CTE), which can only be diagnosed at post-mortem. The presence of a cavum septum pellucidum (CSP) is a common finding in post-mortem studies of confirmed CTE and in neuroimaging studies of individuals exposed to RHI. This study examines CSP in living former American football players, investigating its association with RHI exposure, traumatic encephalopathy syndrome (TES) diagnosis, and provisional levels of certainty for CTE pathology. Data from the DIAGNOSE CTE Research Project were used to compare the presence and ratio of CSP in former American football players (n = 175), consisting of former college (n = 58) and former professional players (n = 117), and asymptomatic unexposed controls without RHI exposure (n = 55). We further evaluated potential associations between CSP measures and cumulative head impact index (CHII) measures (frequency, linear acceleration, and rotational force), a TES diagnosis (yes/no), and a provisional level of certainty for CTE pathology (suggestive, possible, and probable). Former American football players exhibited a higher CSP presence and ratio than unexposed asymptomatic controls. Among player subgroups, professional players showed a greater CSP ratio than former college players and unexposed asymptomatic controls. Among all football players, CHII rotational forces correlated with an increased CSP ratio. No significant associations were found between CSP measures and diagnosis of TES or provisional levels of certainty for CTE pathology. This study confirms previous findings, highlighting a greater prevalence of CSP and a greater CSP ratio in former American football players compared with unexposed asymptomatic controls. In addition, former professional players showed a greater CSP ratio than college players. Moreover, the relationship between estimates of CHII rotational forces and CSP measures suggests that cumulative frequency and strength of rotational forces experienced in football are associated with CSP. However, CSP does not directly correlate with TES diagnosis or provisional levels of certainty for CTE, indicating that it may be a consequence of RHI associated with rotational forces. Further research, especially longitudinal studies, is needed for confirmation and to explore changes over time.

B - 55 Diffusion Tensor Imaging Analysis of Former American Football Players Exposed to Repetitive Head Impacts

Abstract Objective Exposure to repetitive head impacts (RHI) has been linked to Chronic Traumatic Encephalopathy (CTE) and neuropathological alterations such as white matter shear injuries. In this study, we use diffusion-tensor imaging (DTI) to investigate in vivo white matter alterations among former American football players. We also investigate how age and factors associated with RHI exposure influence white matter integrity. Methods We analyzed data from the DIAGNOSE CTE Research Project, focusing on former American football players (n = 166). The measures included whole-brain Fractional Anisotropy (FA), reflecting water diffusion directionality in white matter, and FreeWater-corrected FA (FAt) accounting for extracellular free water, using FSL Tract-Based Spatial Statistics (TBSS). We performed linear regressions on FA and FAt with age, age of first exposure to football, and estimates of cumulative head impact index (CHII) scores of frequency, linear acceleration, and rotational force controlling for age, body mass index, race, education, and APOE e4 allele presence as covariates. Results Both FA (p &amp;lt; 0.00001) and FAt (p &amp;lt; 0.00001) decreased as age increased. Moreover, FA (p &amp;lt; 0.01) and FAt (p &amp;lt; 0.01) were significantly lower with an earlier age of first exposure to football. Finally, FAt decreased as CHII linear acceleration (p &amp;lt; 0.04) and rotational forces (p &amp;lt; 0.02) increased. Conclusion Our study reveals age-related declines in both FA and FAt and highlights that the duration and intensity of exposure to RHI have an impact on white matter microstructure later in life. Overall, these results underscore the impact of prolonged exposure to RHI on white matter microstructure.

Repetitive Head Impacts and Perivascular Space Volume in Former American Football Players

Exposure to repetitive head impacts (RHI) is associated with increased risk for neurodegeneration. Accumulation of toxic proteins due to impaired brain clearance is suspected to play a role. To investigate whether perivascular space (PVS) volume is associated with lifetime exposure to RHI in individuals at risk for RHI-associated neurodegeneration. This cross-sectional study was part of the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project, a 7-year multicenter study consisting of 4 US study sites. Data were collected from September 2016 to February 2020 and analyses were performed between May 2021 and October 2023. After controlling for magnetic resonance image (MRI) and processing quality, former American football players and unexposed asymptomatic control participants were included in analyses. Prior exposure to RHI while participating in American football was estimated using the 3 cumulative head impact indices (CHII-G, linear acceleration; CHII-R, rotational acceleration; and CHII, number of head impacts). Individual PVS volume was calculated in the white matter of structural MRI. Cognitive impairment was based on neuropsychological assessment. Linear regression models were used to assess associations of PVS volume with neuropsychological assessments in former American football players. All analyses were adjusted for confounders associated with PVS volume. Analyses included 224 participants (median [IQR] age, 57 [51-65] years), with 170 male former football players (114 former professional athletes, 56 former collegiate athletes) and 54 male unexposed control participants. Former football players had larger PVS volume compared with the unexposed group (mean difference, 0.28 [95% CI, 0.00-0.56]; P = .05). Within the football group, PVS volume was associated with higher CHII-R (β = 2.71 × 10-8 [95% CI, 0.50 × 10-8 to 4.93 × 10-8]; P = .03) and CHII-G (β = 2.24 × 10-6 [95% CI, 0.35 × 10-6 to 4.13 × 10-6]; P = .03). Larger PVS volume was also associated with worse performance on cognitive functioning in former American football players (β = -0.74 [95% CI, -1.35 to -0.13]; P = .04). These findings suggest that impaired perivascular brain clearance, as indicated by larger PVS volume, may contribute to the association observed between RHI exposure and neurodegeneration.

A - 59 MEG Power Changes in Non-concussed High School Football Players: Implications of Cumulative Head Impact Risk

Abstract Purpose The purpose of this study was to determine how cumulative repetitive head impacts (RHI) over a single season affects functional brain activity in high school football players that are clinically asymptomatic for concussion. Method Pre-season and post-season magnetoencephalography (275 channel CTF MEG) and MRI were acquired for 88 football participant seasons (mean age = 16.09 yrs, mean BMI = 26.32). Helmet-based accelerometer data was collected for each practice and game. Cumulative risk-weighted exposure from linear acceleration (RWELinear) was calculated for each subject. Standard processing and source localization of 8-minutes eyes-open-resting state MEG data was performed using Brainstorm2. Voxel-wise relative power spectral density (PSD) was calculated for the theta frequency band (5-7 Hz). After transformation to MNI space2, pre-season to post-season percent change in PSD (%theta) was calculated and spatial clusters significantly correlated with RWELinear were identified using SPM8 (a = 0.05 and false discovery correction to account for multiple corrections). Mean cluster values were extracted, and linear regression analysis performed in R 3.21 with covariates of BMI, age, and time between scans. Results After covariate adjustment, there was a significant positive correlation between RWELinear and %Δtheta PSD in the right postcentral gyrus and inferior parietal lobe (p = 9.342e-05, adj. R2 = 0.2092), with no other significant associations noted. Conclusions Changes in functional brain activity may be associated with RHI specifically in the right postcentral gyrus and inferior parietal lobe over a typical football season. Future research will include examining how these affected areas are associated with cognitive performance.

229. Interactive Effects of Depression and Cumulative Head Impacts on Frontal Lobe Thickness in Elite Former Athletes

229. Interactive Effects of Depression and Cumulative Head Impacts on Frontal Lobe Thickness in Elite Former Athletes

Inflammatory biomarkers for neurobehavioral dysregulation in former American football players: findings from the DIAGNOSE CTE Research Project

BackgroundTraumatic encephalopathy syndrome (TES) is defined as the clinical manifestation of the neuropathological entity chronic traumatic encephalopathy (CTE). A core feature of TES is neurobehavioral dysregulation (NBD), a neuropsychiatric syndrome in repetitive head impact (RHI)-exposed individuals, characterized by a poor regulation of emotions/behavior. To discover biological correlates for NBD, we investigated the association between biomarkers of inflammation (interleukin (IL)-1β, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) in cerebrospinal fluid (CSF) and NBD symptoms in former American football players and unexposed individuals.MethodsOur cohort consisted of former American football players, with (n = 104) or without (n = 76) NBD diagnosis, as well as asymptomatic unexposed individuals (n = 55) from the DIAGNOSE CTE Research Project. Specific measures for NBD were derived (i.e., explosivity, emotional dyscontrol, impulsivity, affective lability, and a total NBD score) from a factor analysis of multiple self-report neuropsychiatric measures. Analyses of covariance tested differences in biomarker concentrations between the three groups. Within former football players, multivariable linear regression models assessed relationships among log-transformed inflammatory biomarkers, proxies for RHI exposure (total years of football, cumulative head impact index), and NBD factor scores, adjusted for relevant confounding variables. Sensitivity analyses tested (1) differences in age subgroups (< 60, ≥ 60 years); (2) whether associations could be identified with plasma inflammatory biomarkers; (3) associations between neurodegeneration and NBD, using plasma neurofilament light (NfL) chain protein; and (4) associations between biomarkers and cognitive performance to explore broader clinical symptoms related to TES.ResultsCSF IL-6 was higher in former American football players with NBD diagnosis compared to players without NBD. Furthermore, elevated levels of CSF IL-6 were significantly associated with higher emotional dyscontrol, affective lability, impulsivity, and total NBD scores. In older football players, plasma NfL was associated with higher emotional dyscontrol and impulsivity, but also with worse executive function and processing speed. Proxies for RHI exposure were not significantly associated with biomarker concentrations.ConclusionSpecific NBD symptoms in former American football players may result from multiple factors, including neuroinflammation and neurodegeneration. Future studies need to unravel the exact link between NBD and RHI exposure, including the role of other pathophysiological pathways.

Effect of Repetitive Head Impacts on Saccade Performance in Canadian University Football Players.

Investigate the effect of cumulative head impacts on saccade latency and errors, measured across two successive football seasons. Participants were acquired from a sample of convenience-one Canadian university football team. Head impacts were collected during training camp, practices, eight regular season games, and four playoff games in each season. Saccade measurements were collected at five time points-before and after training camp, at midseason, after regular season, and after playoffs. Two seasons following players from a single USports football team during practices and games. Players who completed a baseline saccade measurement and a minimum of one follow-up measurement were included in the study. A total of 127 players were monitored across two competitive seasons, including 61 players who participated in both seasons. Head impact measurements were collected using helmet-mounted sensors. Saccade latency and number of errors were measured using high-speed video or electro-oculography. On average, each head impact increased prosaccade latency by 5.16 × 10-3 ms (95% confidence interval [CI], 2.26 × 10-4-1.00 × 10-2, P = 0.03) and antisaccade latency by 5.74 × 10-3 ms (95% CI, 7.18 × 10-4-1.06 × 10-2, P = 0.02). These latency increases did not decrease between the two seasons; in fact, prosaccade latencies were 23.20 ms longer (95% CI, 19.40-27.14, P < 0.001) at the second season's baseline measurement than the first. The number of saccade errors was not affected by cumulative head impacts. Repetitive head impacts in Canadian university football result in cumulative declines in brain function as measured by saccade performance. Football organizations should consider implementing policies focused on reducing head impacts to improve player safety.

High magnitude exposure to repetitive head impacts alters female adolescent brain activity for lower extremity motor control

Contact and collision sport participation among adolescent athletes has raised concerns about the potential negative effects of cumulative repetitive head impacts (RHIs) on brain function. Impairments from RHIs and sports-related concussions (SRC) may propagate into lingering neuromuscular control. However, the neural mechanisms that link RHIs to altered motor control processes remain unknown. The purpose of this study was to isolate changes in neural activity for a lower extremity motor control task associated with the frequency and magnitude of RHI exposure. A cohort of fifteen high school female soccer players participated in a prospective longitudinal study and underwent pre- and post-season functional magnetic resonance imaging (fMRI). During fMRI, athletes completed simultaneous bilateral ankle, knee, and hip flexion/extension movements against resistance (bilateral leg press) to characterize neural activity associated with lower extremity motor control. RHI data were binned into continuous categories between 20 g − 120 g (defined by progressively greater intervals), with the number of impacts independently modeled within the fMRI analyses. Results revealed that differential exposure to high magnitude RHIs (≥90 g - < 110 g and ≥ 110 g) was associated with acute changes in neural activity for the bilateral leg press (broadly inclusive of motor, visual, and cognitive regions; all p < 0.05 & z > 3.1). Greater exposure to high magnitude RHIs may impair lower extremity motor control through maladaptive neural mechanisms. Future work is warranted to extend these mechanistic findings and examine the linkages between RHI exposure and neural activity as it relates to subsequent neuromuscular control deficits.

Flortaucipir tau PET findings from former professional and college American football players in the DIAGNOSE CTE research project.

Tau is a key pathology in chronic traumatic encephalopathy (CTE). Here, we report our findings in tau positron emission tomography (PET) measurements from the DIAGNOSE CTE Research Project. We compare flortaucipir PET measures from 104 former professional players (PRO), 58 former college football players (COL), and 56 same-age men without exposure to repetitive head impacts (RHI) or traumatic brain injury (unexposed [UE]); characterize their associations with RHI exposure; and compare players who did or did not meet diagnostic criteria for traumatic encephalopathy syndrome (TES). Significantly elevated flortaucipir uptake was observed in former football players (PRO+COL) in prespecified regions (p<0.05). Association between regional flortaucipir uptake and estimated cumulative head impact exposure was only observed in the superior frontal region in former players over 60 years old. Flortaucipir PET was not able to differentiate TES groups. Additional studies are needed to further understand tau pathology in CTE and other individuals with a history of RHI.

Effects of Cumulative Head Impact Exposure in Adolescent Male Contact and Collision Sport Student Athletes.

This prospective cohort study aimed to investigate the association between head impact exposure (HIE) and neuropsychological sequelae in high school football and ice hockey players over 1 year. Community sample. A cohort of 52 adolescent American football and ice hockey players were enrolled in the study, with a final study sample of 35 included in analyses. The study followed a prospective cohort design, with participants undergoing neuropsychological screening and accelerometer-based measurement of HIE over 1 season. Changes in cognition, emotions, behavior, and reported symptoms were assessed using standardized neuropsychological tests and self-reported questionnaires. Cumulative HIE was not consistently associated with changes in cognition, emotions, behavior, or reported symptoms. However, it was linked to an isolated measure of processing speed, showing inconsistent results based on the type of HIE. History of previous concussion was associated with worsened verbal memory recognition (ImPACT Verbal Memory) but not on a more robust measure of verbal memory (California Verbal Learning Test [CVLT]). Reported attention-deficit/hyperactivity disorder history predicted improved neurocognitive change scores. No associations were found between reported history of anxiety/depression or headaches/migraines and neuropsychological change scores. Overall, our findings do not support the hypothesis that greater HIE is associated with an increase in neuropsychological sequelae over time in adolescent football and ice hockey players. The results align with the existing literature, indicating that HIE over 1 season of youth sports is not consistently associated with significant neuropsychological changes. However, the study is limited by a small sample size, attrition over time, and the absence of performance validity testing for neurocognitive measures. Future studies with larger and more diverse samples, longer follow-up, and integration of advanced imaging and biomarkers are needed to comprehensively understand the relationship between HIE and neurobehavioral outcomes. Findings can inform guidelines for safe youth participation in contact sports while promoting the associated health and psychosocial benefits.

Head Acceleration Events in Male Community Rugby Players: An Observational Cohort Study across Four Playing Grades, from Under-13 to Senior Men

ObjectivesThe aim of this study was to examine the cumulative head acceleration event (HAE) exposure in male rugby players from the Under-13 (U13) to senior club level over 4 weeks of matches and training during the 2021 community rugby season.MethodsThis prospective, observational cohort study involved 328 male rugby players. Players were representative of four playing grades: U13 (N = 60, age 12.5 ± 0.6 years), U15 (N = 100, age 14.8 ± 0.9 years), U19 (N = 78, age 16.9 ± 0.7 years) and Premier senior men (N = 97, age 22.5 ± 3.1 years). HAE exposure was tracked across 48 matches and 113 training sessions. HAEs were recorded using boil-and-bite instrumented mouthguards (iMGs). The study assessed the incidence and prevalence of HAEs by ages, playing positions, and session types (match or training).ResultsFor all age grades, weekly match HAE incidence was highest at lower magnitudes (10–29 g). Proportionally, younger players experienced higher weekly incidence rates during training. The U19 players had 1.36 times the risk of high-magnitude (> 30 g) events during matches, while the U13 players had the lowest risk compared with all other grades. Tackles and rucks accounted for the largest HAE burden during matches, with forwards having 1.67 times the risk of > 30 g HAEs in rucks compared with backs.ConclusionsThis study provides novel data on head accelerations during rugby matches and training. The findings have important implications for identifying populations at greatest risk of high cumulative and acute head acceleration. Findings may guide training load management and teaching of skill execution in high-risk activities, particularly for younger players who may be exposed to proportionally more contact during training and for older players during matches.

Leveraging football accelerometer data to quantify associations between repetitive head impacts and chronic traumatic encephalopathy in males

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHI), but the components of RHI exposure underlying this relationship are unclear. We create a position exposure matrix (PEM), composed of American football helmet sensor data, summarized from literature review by player position and level of play. Using this PEM, we estimate measures of lifetime RHI exposure for a separate cohort of 631 football playing brain donors. Separate models examine the relationship between CTE pathology and players’ concussion count, athletic positions, years of football, and PEM-derived measures, including estimated cumulative head impacts, linear accelerations, and rotational accelerations. Only duration of play and PEM-derived measures are significantly associated with CTE pathology. Models incorporating cumulative linear or rotational acceleration have better model fit and are better predictors of CTE pathology than duration of play or cumulative head impacts alone. These findings implicate cumulative head impact intensity in CTE pathogenesis.

Decreasing the Effects of Cumulative Head Injuries in Adolescent Football Players.

Judy A. Beal is a Professor and Dean Emerita, Simmons University, Boston, MA. Dr. Beal can be reached via email at [email protected] The author declares no conflicts of interest.

Age of first exposure to soccer heading: Associations with cognitive, clinical, and imaging outcomes in the Einstein Soccer Study.

The objective of this study is to assess the role of age at first exposure (AFE) to soccer heading as a predictor of known adverse associations of recent and longer-term heading with brain microstructure, cognitive, and behavioral features among adult amateur soccer players. The sample included 276 active amateur soccer players (196 male and 81 female) aged 18-53 years old. AFE to soccer heading was treated as a binary variable, dichotomized at ≤ 10 years vs. >10 years old, based on a recently promulgated US Soccer policy, which bans heading for athletes ages 10 and under. We found that soccer players who began heading at age 10 or younger performed better on tests of working memory (p = 0.03) and verbal learning (p = 0.02), while accounting for duration of heading exposure, education, sex, and verbal intelligence. No difference in brain microstructure or behavioral measures was observed between the two exposure groups. The findings indicate that, among adult amateur soccer players, AFE to heading before age 10 compared to later start of heading, is not associated with adverse outcomes, and may be associated with better cognitive performance in young adulthood. Cumulative heading exposure across the lifespan, rather than early life exposure, may drive risk for adverse effects and should be the focus of future longitudinal studies to inform approaches to enhance player safety.

Repetitive Transcranial Magnetic Stimulation for Depression and Posttraumatic Stress Disorder in Veterans With Mild Traumatic Brain Injury

ObjectivesMild traumatic brain injury (mTBI) is a signature injury of military conflicts and is prevalent in veterans with major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Although therapeutic transcranial magnetic stimulation (TMS) can reduce symptoms of depression and PTSD, whether traumatic brain injury (TBI) affects TMS responsiveness is not yet known. We hypothesized mTBI would be associated with higher pretreatment symptom burden and poorer TMS response. Materials and MethodsWe investigated a registry of veterans (N = 770) who received TMS for depression across the US Veterans Affairs system. Of these, 665 (86.4%) had data on TBI and lifetime number of head injuries while 658 had complete data related to depression outcomes. Depression symptoms were assessed using the nine-item Patient Health Questionnaire and PTSD symptoms using the PTSD Checklist for DSM-5. Linear mixed effects models and t-tests evaluated whether head injuries predicted symptom severity before treatment, and how TBI status affected clinical TMS outcomes. ResultsOf the 658 veterans included, 337 (50.7%) reported previous mTBI, with a mean of three head injuries (range 1–20). TBI status did not predict depressive symptom severity or TMS-associated changes in depression (all p’s > 0.1). TBI status was associated with a modest attenuation of TMS-associated improvement in PTSD (in patients with PTSD Checklist for DSM-5 scores > 33). There was no correlation between the number of head injuries and TMS response (p > 0.1). ConclusionsContrary to our hypothesis, presence of mTBI did not meaningfully change TMS outcomes. Veterans with mTBI had greater PTSD symptoms, yet neither TBI status nor cumulative head injuries reduced TMS effectiveness. Limitations include those inherent to retrospective registry studies and self-reporting. Although these findings are contrary to our hypotheses, they support the safety and effectiveness of TMS for MDD and PTSD in patients who have comorbid mTBI.

Association Between Head Impact Exposure, Psychological Needs, and Indicators of Mental Health Among U.S. High School Tackle Football Players

PurposeAge of first exposure to tackle football and head impact kinematics have been used to examine the effect of head impacts on mental health outcomes. These measures coupled with retrospective and cross-sectional designs have contributed to conflicting results. The purpose of this study was to identify the effect of one season of head impact exposure, age of first exposure to football, and psychological need satisfaction on acute mental health outcomes in adolescent football players. MethodsThis prospective single-season cohort study used sensor-installed mouthguards to collect head impact exposure along with surveys to assess age of first exposure to football, psychological satisfaction, depressive symptoms, anxiety symptoms, and thriving from football players at four high schools (n = 91). Linear regression was used to test the association of head impact exposure, age of first exposure, and psychological satisfaction with acute mental health outcomes. ResultsA total of 9,428 impacts were recorded with a mean of 102 ± 113 impacts/player. Cumulative head impact exposure and age of first exposure were not associated with acute mental health outcomes at postseason or change scores from preseason to postseason. Greater psychological satisfaction was associated with fewer depressive symptoms (β = −0.035, SE = 0.008, p = < .001), fewer anxiety symptoms (β = −0.021, SE = 0.008, p = .010), and greater thriving scores (β = 0.278, SE = 0.040, p = < .001) at postseason. DiscussionThis study does not support the premise that greater single-season head impact exposure or earlier age of first exposure to tackle football is associated with worse acute mental health indicators over the course of a single season in adolescent football players.

Relating American Football Age of First Exposure to Patient-Reported Outcomes and Medical Diagnoses Among Former National Football League Players: An NFL-LONG study.

The age of first exposure (AFE) to American football participation is a growing concern for late-life function. Mixed evidence exists surrounding AFE and may be attributed to varied methods employed across studies. To examine the associations between AFE to American football participation with measures of cognitive, behavioral, and physical function and brain-related medical diagnoses across age categories among former National Football League players. We conducted a cross-sectional survey of 1784 former players (age: 52.3 ± 16.3years, AFE: 11.3 ± 2.9years, years of football: 17.5 ± 4.5years, 86.9% ≥ one lifetime concussion). Players completed a general health questionnaire recording demographics, football playing history (including AFE), and diagnoses (anxiety, depression, any form of dementia, mild cognitive impairment). Players completed Patient-Reported Outcomes Measurement Information System (PROMIS) measures assessing domains of cognitive and physical function, anxiety, depression, sleep disturbance, pain interference, and emotional-behavioral dyscontrol. Multivariable linear and binomial regression models were used to examine the associations of AFE and age with PROMIS outcomes and diagnoses, respectively. No significant AFE by age interactions were detected for PROMIS outcomes (p ≥ 0.066) or diagnoses (p ≥ 0.147). Younger AFE associated with higher PROMIS scores of anxiety (B = - 0.22, p = 0.016), depression (B = - 0.22, p = 0.010), sleep disturbances (B = - 0.16, p = 0.007), pain interference (B = - 0.19, p = 0.014), and emotional-behavioral dyscontrol (B = - 0.22, p = 0.019). Age was associated with all PROMIS outcomes (p ≤ 0.042). AFE was not associated with the prevalence of anxiety, depression, dementia, or mild cognitive impairment (p ≥ 0.449), while age was (p ≤ 0.013). AFE was significantly associated with PROMIS outcomes, albeit low-strength associations (i.e., effect sizes), but not with diagnoses. Our findings indicate AFE is a significant but minor contributing factor for health-related quality of life in this cohort. Future work should incorporate additional characterizations of cumulative head impacts and related factors when examining long-term outcomes associated with football participation.

Leveraging American football helmet accelerometer data to estimate associations between cumulative repetitive head impact exposure and chronic traumatic encephalopathy

AbstractBackgroundChronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. We previously showed that duration of American football play is associated with risk and severity of CTE pathology. Helmet accelerometers have been used previously to examine frequency, linear acceleration, and rotational acceleration of hits sustained across youth, high school, and college football. Here we projected this data onto former American football playing brain donors to examine the relationship between cumulative frequency of hits, linear acceleration, and rotational acceleration during players’ athletic careers and CTE pathology.Method656 former American football playing brain donors from the Veterans Affairs‐Boston University‐Concussion Legacy Foundation Brain Bank were examined for CTE pathology and severity. Years and position of play at each level (youth, high school, college, professional) were acquired through retrospective clinical interviews with brain donors next‐of‐kin. From a literature search of studies using helmet accelerometers, we calculated the mean frequency of hits, linear acceleration (g‐force), and rotational acceleration (rad/sec2) for one year of play at each level‐position combination. These values were projected onto brain donors’ career exposure to derive cumulative frequency of head impacts (CHII), cumulative linear acceleration (CHII‐G), and cumulative rotational acceleration (CHII‐R). Separate logistic regression models examined the relationship of years of play, CHII, CHII‐G, and CHII‐R on CTE status and severity (low vs. high), adjusting for age at death.ResultThe mean (SD) age at death was 59.7 (20.1) and 451 (68.8%) had CTE pathology. Each cumulative measure was significantly associated with presence of CTE (p’s&lt;.001) and severity of CTE (p’s&lt;.001). Based on ROC analyses, CHII‐R (AUC=0.765, p&lt;.001) and CHII‐G (AUC= 0.758, p&lt;.001) performed significantly better than years of play (AUC=0.716) in classifying CTE pathology, and there was no difference between years of play and CHII (AUC=0.698, p=0.25). Similar relationships were observed for CTE severity. Model fit and cross‐validation statistics were also consistent (Table 2).ConclusionAmong former American football playing brain donors, cumulative linear and rotational acceleration were better predictors of CTE pathology than duration of play or cumulative hits. The findings suggest head impact intensity is an important factor in developing CTE pathology.