Repetitive Head Research Articles

6 Association Between American Football Play and Parkinson's Disease: Analysis of the Fox Insight Data Set

Objective:Parkinsonism and Parkinson's disease (PD) have been described as consequences of repetitive head impacts (RHI) from boxing, since 1928. Autopsy studies have shown that RHI from other contact sports can also increase risk for neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Lewy bodies. In vivo research on the relationship between American football play and PD is scarce, with small samples, and equivocal findings. This study leveraged the Fox Insight study to evaluate the association between American football and parkinsonism and/or PD Diagnosis and related clinical outcomes.Participants and Methods:Fox Insight is an online study of people with and without PD who are 18+ years (>50,000 enrolled). Participants complete online questionnaires on motor function, cognitive function, and general health behaviors. Participants self-reported whether they "currently have a diagnosis of Parkinson's disease, or parkinsonism, by a physician or other health care professional." In November 2020, the Boston University Head Impact Exposure Assessment was launched in Fox Insight for large-scale data collection on exposure to RHI from contact sports and other sources. Data used in this abstract were obtained from the Fox Insight database https://foxinsight-info.michaeljfox.org/insight/explore/insight.jsp on 01/06/2022. The sample includes 2018 men who endorsed playing an organized sport. Because only 1.6% of football players were women, analyses are limited to men. Responses to questions regarding history of participation in organized football were examined. Other contact and/or non-contact sports served as the referent group. Outcomes included PD status (absence/presence of parkinsonism or PD) and Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15) for assessment of cognitive symptoms. Binary logistic regression tested associations between history and years of football play with PD status, controlling for age, education, current heart disease or diabetes, and family history of PD. Linear regressions, controlling for these variables, were used for the PDAQ-15.Results:Of the 2018 men (mean age=67.67, SD=9.84; 10, 0.5% Black), 788 (39%) played football (mean years of play=4.29, SD=2.88), including 122 (16.3%) who played youth football, 494 (66.0%) played high school, 128 (17.1%) played college football, and 5 (0.7%) played at the semi-professional or professional level. 1738 (86.1%) reported being diagnosed with parkinsonism/PD, and 707 of these were football players (40.7%). History of playing any level of football was associated with increased odds of having a reported parkinsonism or PD diagnosis (OR=1.52, 95% CI=1.14-2.03, p=0.004). The OR remained similar among those age <69 (sample median age) (OR=1.45, 95% CI=0.97-2.17, p=0.07) and 69+ (OR=1.45, 95% CI=0.95-2.22, p=0.09). Among the football players, there was not a significant association between years of play and PD status (OR=1.09, 95% CI=1.00-1.20, p=0.063). History of football play was not associated with PDAQ-15 scores (n=1980) (beta=-0.78, 95% CI=-1.59-0.03, p=0.059) among the entire sample.Conclusions:Among 2018 men from a data set enriched for PD, playing organized football was associated with increased odds of having a reported parkinsonism/PD diagnosis. Next steps include examination of the contribution of traumatic brain injury and other sources of RHI (e.g., soccer, military service).

57 Traumatic Brain Injury and Concussion in Patients with Frontotemporal Dementia Spectrum Diagnoses

Objective:Traumatic brain injury (TBI) and concussion are associated with increased dementia risk. Accurate TBI/concussion exposure estimates are relatively unknown for less common neurodegenerative conditions like frontotemporal dementia (FTD). We evaluated lifetime TBI and concussion frequency in patients diagnosed with a range of FTD spectrum conditions and related prior head trauma to cavum septum pellucidum (CSP) characteristics observable on MRI.Participants and Methods:We administered the Ohio State University TBI Identification and Boston University Head Impact Exposure Assessment to 108 patients (age 69.5 ± 8.0, 35% female, 93% white or unknown race) diagnosed at the UCSF Memory and Aging Center with one of the following FTD or related conditions: behavioral variant frontotemporal dementia (N=39), semantic variant primary progressive aphasia (N=16), nonfluent variant PPA (N=23), corticobasal syndrome (N=14), or progressive supranuclear palsy (N=16). Data were also obtained from 217 controls (“HC”; age 76.8 ± 8.0, 53% female, 91% white or unknown race). CSP characteristics were defined based on width or “grade” (0-1 vs. 2+) and length of anterior-posterior separation (millimeters). We first describe frequency of any and multiple (2+) prior TBI based on different but commonly used definitions: TBI with loss of consciousness (LOC), TBI with LOC or posttraumatic amnesia (LOC/PTA), TBI with LOC/PTA or other symptoms like dizziness, nausea, “seeing stars,” etc. (“concussion”). TBI/concussion frequency was then compared between FTD and HC using chi-square. Associations between TBI/concussion and CSP characteristics were analyzed with chi-square (CSP grade) and Mann-Whitney U tests (CSP length). We explored sex differences due to typically higher rates of TBI among males.Results:History of any TBI with LOC (FTD=20.0%, HC=19.2%), TBI with LOC/PTA (FTD:32.2%, HC=31.5%), and concussion (FTD: 50.0%, HC=44.3%) was common but not different between study groups (p’s>.4). In both FTD and HC, prior TBI/concussion was nominally more frequent in males but not significantly greater than females. Frequency of repeat TBI/concussion (2+) also did not differ significantly between FTD and HC (repeat TBI with LOC: 6.7% vs. 3.3%, TBI with LOC/PTA: 12.2% vs. 10.3%, concussion: 30.2% vs. 28.7%; p’s>.2). Prior TBI/concussion was not significantly related to CSP grade or length in the total sample or within the FTD or HC groups.Conclusions:TBI/concussion rates depend heavily on the symptom definition used for classifying prior injury. Lifetime symptomatic TBI/concussion is common but has an unclear impact on risk for FTD-related diagnoses. Larger samples are needed to appropriately evaluate sex differences, to evaluate whether TBI/concussion rates differ between specific FTD phenotypes, and to understand the rates and effects of more extensive repetitive head trauma (symptomatic and asymptomatic) in patients with FTD.

Neck Health Metrics and Quality of Life: A Comparative Study in Bike Drivers with and without Neck Pain.

Neck pain is a prevalent musculoskeletal issue among bike drivers, often resulting from extended static postures, repetitive head movements, and exposure to vibrations. This study aims to assess the connection between cervical ROM, neck proprioception, CVA, and QOL in bike drivers with neck pain compared to those without neck pain so that the targeted interventions can be developed to enhance their well-being. A cross-sectional study involving 100 bike drivers aged 20-50 years was conducted, split into two groups: those with neck pain (n=50) and those without neck pain (n=50). Cervical ROM was measured using a smartphone, neck proprioception was assessed through a head repositioning test, and CVA was determined using lateral-view photographs with a plumb line. The Short Form-36 (SF-36) questionnaire was employed to evaluate QOL. Data analysis was conducted using independent t-tests and Pearson's correlation coefficient. Bike drivers with neck pain exhibited significantly reduced cervical ROM (p-value=<0.001), impaired neck proprioception (p-value=<0.001), and decreased CVA (p-value=<0.001) compared to their counterparts without neck pain. A strong negative correlation was found between neck pain and QOL, with lower scores in all eight domains of the SF-36. Cervical ROM, neck proprioception, and CVA showed moderate correlations with various QOL domains (p-value=<0.05). Neck pain in bike drivers is linked to decrease cervical ROM, compromised neck proprioception, and reduced CVA. These factors correlate with a lower quality of life, both physical and mental domains. Interventions addressing these aspects may enhance the quality of life for bike drivers experiencing neck pain.

Head trauma analysis of laboratory reconstructed headers using 1966 Slazenger Challenge and 2018 Telstar 18 soccer balls

Retired soccer players are presenting with early onset neurodegenerative diseases, potentially from heading the ball. It has been proposed that the older composition of soccer balls places higher strains on brain tissues. The purpose of this research was to compare the dynamic head response and brain tissue strain of laboratory reconstructed headers using replicas of the 1966 Slazenger Challenge and 2018 Telstar 18 World Cup soccer balls. Head-to-ball impacts were physically conducted in the laboratory by impacting a Hybrid III head form at three locations and four velocities using dry and wet soccer ball conditions, and computational simulation was used to measure the resulting brain tissue strain. This research showed that few significant differences were found in head dynamic response and maximum principal strain between the dry 1966 and 2018 balls during reconstructed soccer headers. Headers using the wet 1966 soccer ball resulted in higher head form responses at low-velocity headers and lower head responses as velocities increased. This study demonstrates that under dry conditions, soccer ball construction does not have a significant effect on head and brain response during headers reconstructed in the laboratory. Although ball construction didn’t show a notable effect, this study revealed that heading the ball, comparable to goalkeeper kicks and punts at 22 m/s, led to maximum principal strains exceeding the 50% likelihood of injury risk threshold. This has implications for the potential risks associated with repetitive heading in soccer for current athletes.

Psychedelic and nutraceutical interventions as therapeutic strategies for military-related mild traumatic brain injuries

LAY SUMMARY Concussion is a type of acquired brain injury that is common in the military, as well as among civilians and contact sport athletes, and is defined by a transient impairment in mental function. Nevertheless, concussion presents a considerable health burden, and a small minority of people suffer from continued impairment. Repetitive sub-concussive head injury is a known risk factor for neurodegenerative disease, including dementias. Concussions are difficult to treat because symptom profiles vary, but psychedelic therapies may help address some of the neurological issues that occur after brain injury. Classic psychedelics show promise as an emerging pharmacological intervention because they appear to help the brain to rewire, and they have anti-inflammatory effects. Nutraceutical interventions are widely available, cost-effective, and well tolerated, and they could also support recovery when combined with psychedelic compounds. Here, studies presenting classical psychedelics and nutraceuticals that may be combined with psychedelics as therapeutic strategies for the treatment of concussions and persistent symptoms are discussed.

Automated anomalous child repetitive head movement identification through transformer networks.

The increasing prevalence of behavioral disorders in children is of growing concern within the medical community. Recognising the significance of early identification and intervention for atypical behaviors, there is a consensus on their pivotal role in improving outcomes. Due to inadequate facilities and a shortage of medical professionals with specialized expertise, traditional diagnostic methods have been unable to effectively address the rising incidence of behavioral disorders. Hence, there is a need to develop automated approaches for the diagnosis of behavioral disorders in children, to overcome the challenges with traditional methods. The purpose of this study is to develop an automated model capable of analyzing videos to differentiate between typical and atypical repetitive head movements in. To address problems resulting from the limited availability of child datasets, various learning methods are employed to mitigate these issues. In this work, we present a fusion of transformer networks, and Non-deterministic Finite Automata (NFA) techniques, which classify repetitive head movements of a child as typical or atypical based on an analysis of gender, age, and type of repetitive head movement, along with count, duration, and frequency of each repetitive head movement. Experimentation was carried out with different transfer learning methods to enhance the performance of the model. The experimental results on five datasets: NIR face dataset, Bosphorus 3D face dataset, ASD dataset, SSBD dataset, and the Head Movements in the Wild dataset, indicate that our proposed model has outperformed many state-of-the-art frameworks when distinguishing typical and atypical repetitive head movements in children.

Amyloid PET across the cognitive spectrum in former professional and college American football players: findings from the DIAGNOSE CTE Research Project

BackgroundExposure to repetitive head impacts (RHI) in American football players can lead to cognitive impairment and dementia due to neurodegenerative disease, particularly chronic traumatic encephalopathy (CTE). The pathognomonic lesion of CTE consists of perivascular aggregates of hyper-phosphorylated tau in neurons at the depths of cortical sulci. However, it is unclear whether exposure to RHI accelerates amyloid-β (Aβ) plaque formation and increases the risk for Alzheimer’s disease (AD). Although the Aβ neuritic plaques characteristic of AD are observed in a minority of later-stage CTE cases, diffuse plaques are more common. This study examined whether former professional and college American football players, including those with cognitive impairment and dementia, have elevated neuritic Aβ plaque density, as measured by florbetapir PET. Regardless of cognitive and functional status, elevated levels of florbetapir uptake were not expected.MethodsWe examined 237 men ages 45–74, including 119 former professional (PRO) and 60 former college (COL) football players, with and without cognitive impairment and dementia, and 58 same-age men without a history of contact sports or TBI (unexposed; UE) and who denied cognitive or behavioral symptoms at telephone screening. Former players were categorized into four diagnostic groups: normal cognition, subjective memory impairment, mild cognitive impairment, and dementia. Positive florbetapir PET was defined by cortical-cerebellar average SUVR of ≥ 1.10. Multivariable linear regression and analysis of covariance (ANCOVA) compared florbetapir average SUVR across diagnostic and exposure groups. Multivariable logistic regression compared florbetapir positivity. Race, education, age, and APOE4 were covariates.ResultsThere were no diagnostic group differences either in florbetapir average SUVR or the proportion of elevated florbetapir uptake. Average SUVR means also did not differ between exposure groups: PRO-COL (p = 0.94, 95% C.I. = [− 0.033, 0.025]), PRO-UE (p = 0.40, 95% C.I. = [− 0.010, 0.029]), COL-UE (p = 0.36, 95% CI = [0.0004, 0.039]). Florbetapir was not significantly associated with years of football exposure, cognition, or daily functioning.ConclusionsCognitive impairment in former American football players is not associated with PET imaging of neuritic Aβ plaque deposition. These findings are inconsistent with a neuropathological diagnosis of AD in individuals with substantial RHI exposure and have both clinical and medico-legal implications.Trial registrationNCT02798185.

TDP43 pathology in chronic traumatic encephalopathy retinas

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head trauma. Brain pathology in CTE is characterized by neuronal loss, gliosis, and a distinctive pattern of neuronal accumulation of hyper-phosphorylated tau (p-tau) and phospho-TDP43 (p-TDP43). Visual anomalies have been reported by patients with CTE, but the ocular pathology underlying these symptoms is unknown. We evaluated retinal pathology in post-mortem eyes collected from 8 contact sport athletes with brain autopsy-confirmed stage IV CTE and compared their findings to retinas from 8 control patients without CTE and with no known history of head injury. Pupil-optic nerve cross sections were prepared and stained with hematoxylin and eosin (H&E), p-tau, p-TDP43, and total TDP43 by immunohistochemistry. No significant retinal degeneration was observed in CTE eyes compared to control eyes by H&E. Strong cytoplasmic p-TDP43 and total TDP43 staining was found in 6/8 CTE eyes in a subset of inner nuclear layer interneurons (INL) of the retina, while only 1/8 control eyes showed similar p-TDP43 pathology. The morphology and location of these inner nuclear layer interneurons were most compatible with retinal horizontal cells, although other retinal cell types present in INL could not be ruled out. No p-tau pathology was observed in CTE or control retinas. These findings identify novel retinal TDP43 pathology in CTE retinas and support further investigation into the role of p-TDP43 in producing visual deficits in patients with CTE.

Repetitive Head Injury and Cognitive, Physical, and Emotional Symptoms in Women Survivors of Intimate Partner Violence.

Many women survivors of intimate partner violence (IPV) experience repetitive head injuries in their lifetime, but limited research has examined the cumulative effects of multiple head injuries on post-concussion symptom severity in this population. This study examined how number of lifetime head injuries and episodes of loss of consciousness (LOC) due to head injuries were related to current cognitive, physical, and emotional symptoms among women survivors of IPV. Cisgender women from Kentucky were recruited following a protective order against an intimate partner, including 268 women with no reported lifetime head injuries and 250 women with one or more IPV-related head injuries (mean [M] = 17.2 head injuries, standard deviation [SD] = 50.5, median [Mdn] = 4, range = 1-515; M = 1.8 LOC episodes, SD = 4.3, Mdn = 1, range = 0-35, respectively). Participants underwent in-person interviews about lifetime physical and sexual IPV history, head injury history, and current cognitive, physical, and emotional symptoms. Sociodemographic characteristics, physical and sexual IPV severity, and current symptom severity were examined in relation to number of head injuries and LOC episodes. A higher number of head injuries was associated with greater age, White race, less than high school education, unemployment, and rural residence. No sociodemographic variables differed based on number of LOC episodes. Greater number of lifetime head injuries and LOC episodes correlated significantly with physical IPV severity (rho = 0.35, p < 0.001; rho = 0.33, p < 0.001, respectively) and sexual IPV severity (rho = 0.22, p < 0.001; rho = 0.19, p = 0.003). Greater number of head injuries and LOC episodes correlated significantly with greater cognitive (rho = 0.33, p < 0.001; rho = 0.23, p < 0.001, respectively), physical (rho = 0.36, p < 0.001; rho = 0.31, p < 0.001), emotional (rho = 0.36, p < 0.001; rho = 0.18, p = 0.004), and total symptom severity (rho = 0.39, p < 0.001; rho = 0.26, p < 0.001). In group comparisons, participant groups stratified by number of head injuries (i.e., 0, 1-3, 4+) differed in total symptom severity (p < 0.001, η2 = 0.15), with greater symptom burden associated with more head injuries. Participants with and without LOC differed in symptom severity: cognitive (p < 0.001, d = 0.45), physical (p < 0.001, d = 0.60), emotional (p = 0.004, d = 0.37), and total symptom severity (p < 0.001, d = 0.53). Group differences between participants with and without LOC remained significant after controlling for sociodemographic variables and IPV severity. There was no cumulative effect of LOC, in that participants with 1 LOC episode did not differ from participants with 2 + LOC episodes (p > 0.05). Based on hierarchical regression analyses, only physical symptoms were independently related to number of head injuries (p = 0.008, ΔR2 = 0.011) and number of LOC episodes (p = 0.014, ΔR2 = 0.021) after controlling for sociodemographic characteristics and IPV severity. Among women survivors of IPV, cumulative head injuries appear related to greater symptom severity. Greater head injury history was independently related to worse physical symptoms (e.g., headaches, dizziness, sleep problems), whereas cognitive and emotional symptoms were, in part, attributable to cumulative physical and emotional trauma due to IPV. Women survivors of IPV with repetitive head injuries have unmet neurobehavioral health needs that may benefit from targeted interventions.

Repetitive Head Impacts In Youth Tackle Football: First Year Athletes Compared To Experienced Athletes

Repetitive Head Impacts In Youth Tackle Football: First Year Athletes Compared To Experienced Athletes

Single Versus Repetitive Traumatic Brain Injury: Current Knowledge on the Chronic Outcomes, Neuropathology and the Role of TDP-43 Proteinopathy.

Traumatic brain injury (TBI) is one of the most important causes of death and disability in adults and thus an important public health problem. Following TBI, secondary pathophysiological processes develop over time and condition the development of different neurodegenerative entities. Previous studies suggest that neurobehavioral changes occurring after a single TBI are the basis for the development of Alzheimer's disease, while repetitive TBI is considered to be a contributing factor for chronic traumatic encephalopathy development. However, pathophysiological processes that determine the evolvement of a particular chronic entity are still unclear. Human post-mortem studies have found combinations of amyloid, tau, Lewi bodies, and TAR DNA-binding protein 43 (TDP-43) pathologies after both single and repetitive TBI. This review focuses on the pathological changes of TDP-43 after single and repetitive brain traumas. Numerous studies have shown that TDP-43 proteinopathy noticeably occurs after repetitive head trauma. A relatively small number of available preclinical research on single brain injury are not in complete agreement with the results from the human samples, which makes it difficult to draw specific conclusions. Also, as TBI is considered a heterogeneous type of injury, different experimental trauma models and injury intensities may cause differences in the cascade of secondary injury, which should be considered in future studies. Experimental and post-mortem studies of TDP-43 pathobiology should be carried out, preferably in the same laboratories, to determine its involvement in the development of neurodegenerative conditions after one and repetitive TBI, especially in the context of the development of new therapeutic options.

Neuropathologic and Clinical Findings in Young Contact Sport Athletes Exposed to Repetitive Head Impacts

Young contact sport athletes may be at risk for long-term neuropathologic disorders, including chronic traumatic encephalopathy (CTE). To characterize the neuropathologic and clinical symptoms of young brain donors who were contact sport athletes. This case series analyzes findings from 152 of 156 brain donors younger than 30 years identified through the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank who donated their brains from February 1, 2008, to September 31, 2022. Neuropathologic evaluations, retrospective telephone clinical assessments, and online questionnaires with informants were performed blinded. Data analysis was conducted between August 2021 and June 2023. Repetitive head impacts from contact sports. Gross and microscopic neuropathologic assessment, including diagnosis of CTE, based on defined diagnostic criteria; and informant-reported athletic history and informant-completed scales that assess cognitive symptoms, mood disturbances, and neurobehavioral dysregulation. Among the 152 deceased contact sports participants (mean [SD] age, 22.97 [4.31] years; 141 [92.8%] male) included in the study, CTE was diagnosed in 63 (41.4%; median [IQR] age, 26 [24-27] years). Of the 63 brain donors diagnosed with CTE, 60 (95.2%) were diagnosed with mild CTE (stages I or II). Brain donors who had CTE were more likely to be older (mean difference, 3.92 years; 95% CI, 2.74-5.10 years) Of the 63 athletes with CTE, 45 (71.4%) were men who played amateur sports, including American football, ice hockey, soccer, rugby, and wrestling; 1 woman with CTE played collegiate soccer. For those who played football, duration of playing career was significantly longer in those with vs without CTE (mean difference, 2.81 years; 95% CI, 1.15-4.48 years). Athletes with CTE had more ventricular dilatation, cavum septum pellucidum, thalamic notching, and perivascular pigment-laden macrophages in the frontal white matter than those without CTE. Cognitive and neurobehavioral symptoms were frequent among all brain donors. Suicide was the most common cause of death, followed by unintentional overdose; there were no differences in cause of death or clinical symptoms based on CTE status. This case series found that young brain donors exposed to repetitive head impacts were highly symptomatic regardless of CTE status, and the causes of symptoms in this sample are likely multifactorial. Future studies that include young brain donors unexposed to repetitive head impacts are needed to clarify the association among exposure, white matter and microvascular pathologic findings, CTE, and clinical symptoms.

The Longitudinal Relationship Between Concussion History, Years of American Football Participation, and Alcohol Use Among Former National Football League Players: an NFL-LONG Study.

Investigate the relationships between concussion history and years of football participation (repetitive head impact proxy) with alcohol use across multiple decades in former professional football players. Participants (n= 348; mean age = 49.0 ± 9.4) completed health questionnaires in 2001 and 2019, which included self-reported concussion history and years of participation. Alcohol use frequency and amount per occasion were reported for three timepoints: during professional career, 2001, and 2019. Ordinal logistic regression models were fit to test associations of concussion history and years of participation with alcohol use at each timepoint. There were no significant associations between either concussion history or years of football participation with alcohol use (frequency and amount per occasion) at any timepoint. Effect estimates for concussion history and years of football participation with alcohol use were generally comparable across timepoints. Later life alcohol use by former American football players is not associated with concussion history or years of exposure to football.

Increased brain age and relationships with blood-based biomarkers following concussion in younger populations

ObjectiveBrain age is increasingly being applied to the spectrum of brain injury to define neuropathological changes in conjunction with blood-based biomarkers. However, data from the acute/sub-acute stages of concussion are lacking, especially among younger cohorts.MethodsPredicted brain age differences were independently calculated in large, prospectively recruited cohorts of pediatric concussion and matched healthy controls (total N = 446), as well as collegiate athletes with sport-related concussion and matched non-contact sport controls (total N = 184). Effects of repetitive head injury (i.e., exposure) were examined in a separate cohort of contact sport athletes (N = 82), as well as by quantifying concussion history through semi-structured interviews and years of contact sport participation.ResultsFindings of increased brain age during acute and sub-acute concussion were independently replicated across both cohorts, with stronger evidence of recovery for pediatric (4 months) relative to concussed athletes (6 months). Mixed evidence existed for effects of repetitive head injury, as brain age was increased in contact sport athletes, but was not associated with concussion history or years of contact sport exposure. There was no difference in brain age between concussed and contact sport athletes. Total tau decreased immediately (~ 1.5 days) post-concussion relative to the non-contact group, whereas pro-inflammatory markers were increased in both concussed and contact sport athletes. Anti-inflammatory markers were inversely related to brain age, whereas markers of axonal injury (neurofilament light) exhibited a trend positive association.ConclusionCurrent and previous findings collectively suggest that the chronicity of brain age differences may be mediated by age at injury (adults > children), with preliminary findings suggesting that exposure to contact sports may also increase brain age.

American Football Play and Parkinson Disease Among Men

Parkinsonism and Parkinson disease (PD) are known to result from repetitive head impacts from boxing. Repetitive head impacts from American football may also be associated with increased risk of neurodegenerative pathologies that cause parkinsonism, yet in vivo research on the association between football play and PD is scarce and limited by small samples and equivocal findings. To evaluate the association between football participation and self-reported parkinsonism or PD diagnosis. This cross-sectional study leveraged data from the online Fox Insight study. Participants completed online questionnaires and self-reported whether they currently had a diagnosis of Parkinson disease or parkinsonism by a physician or other health care professional. In November 2020, the Boston University Head Impact Exposure Assessment was launched for data collection on repetitive head impacts. Data used for this manuscript were obtained from the Fox Insight database on June 9, 2022. A total of 1875 men who endorsed playing any organized sport were included. Former athletes were divided into those who participated in football (n = 729 [38.9%]) and those who participated in other sports (reference group). Self-reported participation in football, duration and level of football play, age at first exposure. Logistic regression tested associations between PD status and history of football play, duration of football play, highest level played, and age at first exposure, controlling for age, education, history of diabetes or heart disease, body mass index, history of traumatic brain injury with loss of consciousness, and family history of PD. In this sample of 1875 men (mean [SD] age, 67.69 [9.84] years) enriched for parkinsonism or PD (n = 1602 [85.4%]), 729 (38.9%) played football (mean [SD] duration, 4.35 [2.91] years). History of playing football was associated with higher odds of having a parkinsonism or PD diagnosis (odds ratio [OR], 1.61; 95% CI, 1.19-2.17). Among the entire sample, longer duration of play was associated with higher odds of having a parkinsonism or PD diagnosis (OR, 1.12; 95% CI, 1.06-1.19). Among football players, longer duration of football play (OR, 1.12; 95% CI, 1.02-1.23) and higher level of play (OR, 2.93; 95% CI, 1.28-6.73) were associated with higher odds of having parkinsonism or PD. In this cross-sectional study of participants enriched for PD, participation in football was associated with higher odds of having a reported parkinsonism or PD diagnosis.

Exposure assessment for repeated sub-concussive head impacts in soccer: The HEalth and Ageing Data IN the Game of football (HEADING) study

The purpose of this paper was to develop exposure estimates for repetitive sub-concussive head impacts (RSHI) for use in epidemiological analyses. We used a questionnaire to collect lifetime history of heading and other head contacts associated with training and playing football from 159 former footballers all members of the English professional football association. We used linear mixed effect regression with player as the random effect, to model the number of headers, blows to the head and head-to-head impacts as a function of potential exposure affecting factors, which were treated as the fixed effects. Exposure affecting factors included playing position, league, context of play (game vs training) and decade of play. Age at time of response to the questionnaire was also included in the models. In model results, playing position was important, with RSHIs being highest among defenders and lowest among goalkeepers. Players headed the ball more during games than in training, and when playing in amateur or youth leagues compared with semi-professional or professional leagues. The average number of reported head impacts declined linearly throughout the observation period (1949–2015). The derived final model for headers explained 43%, 9% and 36% of the between player, within player and total variance in exposure, respectively with good precision and predictive performance. These findings are generally in agreement with previously published results pointing towards the models forming a valid method for estimating exposure to RSHI among former footballers although some further external validation is still warranted.

Why the Australian Commonwealth Government has a Central Role in Addressing Concussion Concerns in Australian Sport

The neurological sequelae of repetitive head impacts (RHIs) in Australian sport has come under intense public scrutiny. Class action litigation against the Australian Football League (AFL) is shaping up to be a ‘battle of the experts’ and could examine long term neurodegenerative disease. The Australian Parliamentary Inquiry into Concussions and Repeated Head Trauma in Contact Sports has conducted public hearings, due to report its recommendations in August 2023. As a high-profile public health concern, we strongly support a central role for the Australian Commonwealth Government to engage its agencies representing public health, sport and education towards a national approach.

Three dimensional evaluation of cerebrovascular density and branching in chronic traumatic encephalopathy

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI) and characterized by perivascular accumulations of hyperphosphorylated tau protein (p-tau) at the depths of the cortical sulci. Studies of living athletes exposed to RHI, including concussive and nonconcussive impacts, have shown increased blood–brain barrier permeability, reduced cerebral blood flow, and alterations in vasoreactivity. Blood–brain barrier abnormalities have also been reported in individuals neuropathologically diagnosed with CTE. To further investigate the three-dimensional microvascular changes in individuals diagnosed with CTE and controls, we used SHIELD tissue processing and passive delipidation to optically clear and label blocks of postmortem human dorsolateral frontal cortex. We used fluorescent confocal microscopy to quantitate vascular branch density and fraction volume. We compared the findings in 41 male brain donors, age at death 31–89 years, mean age 64 years, including 12 donors with low CTE (McKee stage I–II), 13 with high CTE (McKee stage III–IV) to 16 age- and sex-matched non-CTE controls (7 with RHI exposure and 9 with no RHI exposure). The density of vessel branches in the gray matter sulcus was significantly greater in CTE cases than in controls. The ratios of sulcus versus gyrus vessel branch density and fraction volume were also greater in CTE than in controls and significantly above one for the CTE group. Hyperphosphorylated tau pathology density correlated with gray matter sulcus fraction volume. These findings point towards increased vascular coverage and branching in the dorsolateral frontal cortex (DLF) sulci in CTE, that correlates with p-tau pathology.

Alzheimer’s pathology is associated with altered cognition, brain volume, and plasma biomarker patterns in traumatic encephalopathy syndrome

BackgroundTraumatic encephalopathy syndrome (TES) is a clinical phenotype sensitive but non-specific to underlying chronic traumatic encephalopathy (CTE) neuropathology. However, cognitive symptoms of TES overlap with Alzheimer’s disease (AD), and features of AD pathology like beta-amyloid (Aβ) plaques often co-occur with CTE, making clinical-to-pathological conclusions of TES diagnoses challenging. We investigated how Alzheimer’s neuropathological changes associated with cognition, brain volume, and plasma biomarkers in patients with repetitive head impacts (RHI)/TES, clinical AD, or typically aging controls.MethodsWe studied 154 participants including 33 with RHI/TES (age 61.5 ± 11.5, 100% male, 11/33 Aβ[ +]), 62 with AD and no known prior RHI (age 67.1 ± 10.2, 48% male, 62/62 Aβ[ +]), and 59 healthy controls without RHI (HC; age 73.0 ± 6.2, 40% male, 0/59 Aβ[ +]). Patients completed neuropsychological testing (memory, executive functioning, language, visuospatial) and structural MRI (voxel-based morphometry analysis), and provided plasma samples analyzed for GFAP, NfL, IL-6, IFN-γ, and YKL-40. For cognition and plasma biomarkers, patients with RHI/TES were stratified as Aβ[ +] or Aβ[ −] and compared to each other plus the AD and HC groups (ANCOVA adjusting for age and sex). Differences with at least a medium effect size (Cohen’s d > 0.50) were interpreted as potentially meaningful.ResultsCognitively, within the TES group, Aβ[ +] RHI/TES performed worse than Aβ[-] RHI/TES on visuospatial (p = .04, d = 0.86) and memory testing (p = .07, d = 0.74). Comparing voxel-wise brain volume, both Aβ[ +] and Aβ[ −] RHI/TES had lower medial and anterior temporal lobe volume than HC and did not significantly differ from AD. Comparing plasma biomarkers, Aβ[ +] RHI/TES had higher plasma GFAP than HC (p = .01, d = 0.88) and did not significantly differ from AD. Conversely, Aβ[ −] RHI/TES had higher NfL than HC (p = .004, d = 0.93) and higher IL-6 than all other groups (p’s ≤ .004, d’s > 1.0).ConclusionsPresence of Alzheimer’s pathology in patients with RHI/TES is associated with altered cognitive and biomarker profiles. Patients with RHI/TES and positive Aβ-PET have cognitive and plasma biomarker changes that are more like patients with AD than patients with Aβ[ −] RHI/TES. Measuring well-validated Alzheimer’s biomarkers in patients with RHI/TES could improve interpretation of research findings and heighten precision in clinical management.

Blink-related EEG oscillations are neurophysiological indicators of subconcussive head impacts in female soccer players: a preliminary study.

Repetitive subconcussive head impacts can lead to subtle neural changes and functional consequences on brain health. However, the objective assessment of these changes remains limited. Resting state blink-related oscillations (BROs), recently discovered neurological responses following spontaneous blinking, are explored in this study to evaluate changes in BRO responses in subconcussive head impacts. We collected 5-min resting-state electroencephalography (EEG) data from two cohorts of collegiate athletes who were engaged in contact sports (SC) or non-contact sports (HC). Video recordings of all on-field activities were conducted to determine the number of head impacts during games and practices in the SC group. In both groups, we were able to detect a BRO response. Following one season of games and practice, we found a strong association between the number of head impacts sustained by the SC group and increases in delta and beta spectral power post-blink. There was also a significant difference between the two groups in the morphology of BRO responses, including decreased peak-to-peak amplitude of response over left parietal channels and differences in spectral power in delta and alpha frequency range post-blink. Our preliminary results suggest that the BRO response may be a useful biomarker for detecting subtle neural changes resulting from repetitive head impacts. The clinical utility of this biomarker will need to be validated through further research with larger sample sizes, involving both male and female participants, using a longitudinal design.