Career duration and later-life health conditions among former professional American-style football players.

OBJECTIVES: Career duration is often used as a metric of neurotrauma exposure in studies of elite athletes. However, as a proxy metric, career length may not accurately represent causal factors, and associations with health outcomes may be susceptible to selection effects. To date, relationships between professional American-style football (ASF) career length and postcareer health remain incompletely characterised. METHODS: We conducted a survey-based cross-sectional cohort study of former professional ASF players. Flexible regression methods measured associations between self-reported career duration and four self-reported health conditions: pain, arthritis, mood and cognitive symptoms. We also measured associations between career duration and four self-reported ASF exposures: prior concussion signs and symptoms (CSS), performance enhancing drugs, intracareer surgeries and average snaps per game. Models were adjusted for age and race. RESULTS: Among 4189 former players (52±14 years of age, 39% black, 34% lineman position), the average career length was 6.7±3.9 professional seasons (range=1-20+). We observed inverted U-shaped relationships between career duration and outcomes (all p<0.001), indicating that adverse health effects were more common among men with intermediate career durations than those with shorter or longer careers. Similar findings were observed for play-related exposures (eg, CSS and snaps). CONCLUSIONS: Relationships between ASF career duration and subsequent health status are non-linear. Attenuation of the associations among longer career players may reflect selection effects and suggest career length may serve as a poor proxy for true causal factors. Findings highlight the need for cautious use of career duration as a proxy exposure metric in studies of former athletes.

Healthspan and chronic disease burden among young adult and middle-aged male former American-style professional football players.

OBJECTIVE: To examine the relationships between age, healthspan and chronic illness among former professional American-style football (ASF) players. METHODS: We compared age-specific race-standardised and body mass index-standardised prevalence ratios of arthritis, dementia/Alzheimer's disease, hypertension and diabetes among early adult and middle-aged (range 25-59 years) male former professional ASF players (n=2864) with a comparator cohort from the National Health and Nutrition Examination Survey and National Health Interview Survey, two representative samples of the US general population. Age was stratified into 25-29, 30-39, 40-49 and 50-59 years. RESULTS: Arthritis and dementia/Alzheimer's disease were more prevalent among ASF players across all study age ranges (all p<0.001). In contrast, hypertension and diabetes were more prevalent among ASF players in the youngest age stratum only (p<0.001 and p<0.01, respectively). ASF players were less likely to demonstrate intact healthspan (ie, absence of chronic disease) than the general population across all age ranges. CONCLUSION: These data suggest the emergence of a maladaptive early ageing phenotype among former professional ASF players characterised by premature burden of chronic disease and reduced healthspan. Additional study is needed to investigate these findings and their impact on morbidity and mortality in former ASF players and other athlete groups.

Premortem Chronic Traumatic Encephalopathy Diagnoses in Professional Football.

OBJECTIVE: American-style football (ASF) has gained attention because of possible links between repetitive head injury and neurodegenerative diseases. Although postmortem pathologic changes consistent with chronic traumatic encephalopathy (CTE) have been reported in ASF players, there are currently no established premortem diagnostic criteria for CTE. Nevertheless, presented with symptoms of cognitive impairment, clinicians treating former players may be inclined to suggest CTE without a thorough exploration of comorbid factors that demonstrate similar clinical phenotypes to putative CTE. METHODS: A survey of 3,913 former ASF players aged 24 to 89 was conducted for those who responded by March 2019. RESULTS: Despite being a postmortem diagnosis, 108 players (2.8%) self-reported clinician-diagnosed CTE. The percentage of players under age 60 years reporting a CTE diagnosis was 2.3% versus 3.7% in participants age 60 or older. Comorbidities in participants self-reporting CTE were significantly more common, including sleep apnea, hypercholesterolemia, obesity, indicators of past or current depression, hypertension, prescription pain medication use, heart conditions, and low testosterone when compared to non-CTE respondents. Patterns of reporting for obesity, hypertension, heart conditions, or hypercholesterolemia differed between older and younger participants. Cognitive impairment symptoms were significantly higher in participants self-reporting CTE. INTERPRETATION: Some former professional football players have been clinically diagnosed with CTE, a postmortem condition. Comorbidities that can affect cognition were associated with CTE diagnoses in both older and younger players. Although underlying neuropathology cannot be ruled out, treatable conditions should be explored in former athletes demonstrating CTE-linked clinical phenotypes or symptoms as a means of improving cognitive health in these patients. ANN NEUROL 2020 ANN NEUROL 2020;88:106-112.

Integrating Exposure Knowledge and Serum Suspect Screening as a New Approach to Biomonitoring: An Application in Firefighters and Office Workers.

Firefighters (FF) are exposed to recognized and probable carcinogens, yet there are few studies of chemical exposures and associated health concerns in women FFs, such as breast cancer. Biomonitoring often requires a priori selection of compounds to be measured, and so, it may not detect relevant, lesser known, exposures. The Women FFs Biomonitoring Collaborative (WFBC) created a biological sample archive and conducted a general suspect screen (GSS) to address this data gap. Using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry, we sought to identify candidate chemicals of interest in serum samples from 83 women FFs and 79 women office workers (OW) in San Francisco. We identified chemical peaks by matching accurate mass from serum samples against a custom chemical database of 722 slightly polar phenolic and acidic compounds, including many of relevance to firefighting or breast cancer etiology. We then selected tentatively identified chemicals for confirmation based on the following criteria: (1) detection frequency or peak area differences between OW and FF; (2) evidence of mammary carcinogenicity, estrogenicity, or genotoxicity; and (3) not currently measured in large biomonitoring studies. We detected 620 chemicals that matched 300 molecular formulas in the WFBC database, including phthalate metabolites, phosphate flame-retardant metabolites, phenols, pesticides, nitro and nitroso compounds, and per- and polyfluoroalkyl substances. Of the 20 suspect chemicals selected for validation, 8 were confirmed-including two alkylphenols, ethyl paraben, BPF, PFOSAA, benzophenone-3, benzyl p-hydroxybenzoate, and triphenyl phosphate-by running a matrix spike of the reference standards and using m/z, retention time, and the confirmation of at least two fragment ions as criteria for matching. GSS provides a powerful high-throughput approach to identify and prioritize novel chemicals for biomonitoring and health studies.

The association between global DNA methylation and telomere length in a longitudinal study of boilermakers.

The objectives of this study were to determine if global DNA methylation, as reflected in LINE-1 and Alu elements, is associated with telomere length and whether it modifies the rate of telomeric change. A repeated-measures longitudinal study was performed with a panel of 87 boilermaker subjects. The follow-up period was 29 months. LINE-1 and Alu methylation was determined using pyrosequencing. Leukocyte relative telomere length was assessed via real-time qPCR. Linear-mixed models were used to estimate the association between DNA methylation and telomere length. A structural equation model (SEM) was used to explore the hypothesized relationship between DNA methylation, proxies of particulate matter exposure, and telomere length at baseline. There appeared to be a positive association between both LINE-1 and Alu methylation levels, and telomere length. For every incremental increase in LINE-1 methylation, there was a statistically significant 1.0 × 10(-1) (95% CI: 4.6 × 10(-2), 1.5 × 10(-1), P < 0.01) unit increase in relative telomere length, controlling for age at baseline, current and past smoking status, work history, BMI (log kg/m(2) ) and leukocyte differentials. Furthermore, for every incremental increase in Alu methylation, there was a statistically significant 6.2 × 10(-2) (95% CI: 1.0 × 10(-2), 1.1 × 10(-1), P = 0.02) unit increase in relative telomere length. The interaction between LINE-1 methylation and follow-up time was statistically significant with an estimate -9.8 × 10(-3) (95% CI: -1.8 × 10(-2), -1.9 × 10(-3), P = 0.02); suggesting that the rate of telomeric change was modified by the degree of LINE-1 methylation. No statistically significant association was found between the cumulative PM exposure construct, with global DNA methylation and telomere length at baseline.

Inverse association between toenail arsenic and body mass index in a population of welders.

Recent data show that arsenic may play a role in obesity-related diseases. However, urinary arsenic studies report an inverse association between arsenic level and body mass index (BMI). We explored whether toenail arsenic, a long-term exposure measure, was associated with BMI in 74 welders with known arsenic exposure. BMI showed significant inverse associations with toenail arsenic (p=0.01), which persisted in models adjusted for demographics, diet and work history. It is unclear whether low arsenic biomarker concentrations in high BMI subjects truly reflect lower exposures, or instead reflect internal or metabolic changes that alter arsenic metabolism and tissue deposition.

Toenail metal concentration as a biomarker of occupational welding fume exposure.

In populations exposed to heavy metals, there are few biomarkers that capture intermediate exposure windows. We sought to determine the correlation between toenail metal concentrations and prior 12-month work activity in welders with variable, metal-rich, welding fume exposures. Forty-eight participants, recruited through a local union, provided 69 sets of toenail clippings. Union-supplied and worker-verified personal work histories were used to quantify hours welded and respirator use. Toenail samples were digested and analyzed for lead (Pb), manganese (Mn), cadmium (Cd), nickel (Ni), and arsenic (As) using ICP-MS. Spearman correlation coefficients were used to examine the correlation between toenail metal concentrations. Using mixed models to account for multiple participation times, we divided hours welded into three-month intervals and examined how weld hours correlated with log-transformed toenail Pb, Mn, Cd, Ni, and As concentrations. Highest concentrations were found for Ni, followed by Mn, Pb and As, and Cd. All the metals were significantly correlated with one another (rho range = 0.28-0.51), with the exception of Ni and As (rho = 0.20, p = 0.17). Using mixed models adjusted for age, respirator use, smoking status, and BMI, we found that Mn was associated with weld hours 7-9 months prior to clipping (p = 0.003), Pb was associated with weld hours 10-12 months prior to clipping (p = 0.03) and over the entire year (p = 0.04). Cd was associated with weld hours 10-12 months prior to clipping (p = 0.05), and also with the previous year's total hours welded (p = 0.02). The association between Ni and weld hours 7-9 months prior to clipping approached significance (p = 0.06). Toenail metal concentrations were not associated with the long-term exposure metric, years as a welder. Results suggest Mn, Pb, and Cd may have particular windows of relevant exposure that reflect work activity. In a population with variable exposure, toenails may serve as useful biomarkers for occupational metal fume exposures to Mn, Pb, and Cd during distinct periods over the year prior to sample collection.

Interaction of Medical Conditions and Football Exposures Associated with Premortem Chronic Traumatic Encephalopathy Diagnosis in Former Professional American Football Players.

BACKGROUND AND OBJECTIVE: Despite being a postmortem diagnosis, former professional American-style football players report receiving chronic traumatic encephalopathy (CTE) diagnoses from medical care providers. However, many players also report other health conditions that manifest with cognitive and psychological symptoms. The purpose of this study was to identify how medical conditions, psychological disorders, and football exposure combinations are associated with former athletes reporting a premortem CTE diagnosis. METHODS: This study was a cross-sectional cohort survey from 2015 to 2019 of 4033 former professional American-style football players. Demographics (age, race, domestic status, primary care recipient), football-related factors (position, years of professional play, burden of symptoms following head impacts, performance-enhancing drug use), and comorbidities (sleep apnea, psychological disorder status [depression and anxiety; either depression or anxiety; neither depression nor anxiety], diabetes mellitus, attention-deficit/hyperactivity disorder, hypertension, heart conditions, high cholesterol, stroke, cancer, low testosterone, chronic pain, current and maximum body mass index) were recorded. A Chi-square automatic interaction detection (CHAID) decision tree model identified interactive effects between demographics, health conditions, and football exposures on the CTE diagnosis. RESULTS: Depression showed the strongest univariate association with premortem CTE diagnoses (odds ratio [OR] = 9.5, 95% confidence interval [CI] 6.0-15.3). CHAID differentiated participants with premortem CTE diagnoses with 98.2% accuracy and area under the curve = 0.81. Participants reporting both depression and anxiety were more likely to have a CTE diagnosis compared with participants who reported no psychological disorders (OR = 12.2; 95% CI 7.3-21.1) or one psychological disorder (OR = 4.5; 95% CI 1.9-13.0). Sleep apnea was also associated with a CTE diagnosis amongst those with both depression and anxiety (OR = 2.7; 95% CI 1.4-5.2). CONCLUSIONS: Clinical phenotypes including psychological disorders and sleep apnea were strongly associated with an increased likelihood of having received a pre-mortem CTE diagnosis in former professional football players. Depression, anxiety, and sleep apnea produce cognitive symptoms, are treatable conditions, and should be distinguished from neurodegenerative disease.

Medical Conditions in Former Professional American-Style Football Players Are Associated With Self-Reported Clinical Features of Traumatic Encephalopathy Syndrome.

Consensus criteria for traumatic encephalopathy syndrome (TES) specify that at least one core clinical feature of cognitive impairment (CI; e.g., difficulties with memory, executive function) or neurobehavioral dysregulation (ND; e.g., explosiveness, rage, and mood lability) be present and not fully accounted for by other health disorders. Associations between self-reported symptoms that mirror the core clinical features of TES-and how they may be related to concomitant medical conditions-remain unclear. The purpose of this study was to evaluate the association of medical conditions and football exposures with TES clinical features (CI+/-, ND+/-) in 1741 former professional American-style football (ASF) players (age, 57.7 ± 13.9 years; professional seasons, 6.6 ± 3.9 years). Demographics (age, race/ethnicity, current body mass index, age of first football exposure, use of performance-enhancing drugs, position played, and past concussion symptoms), self-reported medical conditions (anxiety, depression, attention-deficit hyperactivity disorder [ADHD], sleep apnea, headache, stroke, hypertension, heart disease, high cholesterol, erectile dysfunction, and low testosterone) were collected. Of 1741 participants, 7.4% were CI+ and/or ND+ (n = 129). Participants who were CI+ or ND+ were more likely to report one or more coexisting medical conditions than participants who did not report CI or ND (odds ratio [OR] = 2.04; 95% confidence interval: 1.25-3.47; p = 0.003). Separate general linear models for each medical condition that adjusted for demographics and football-related factors identified significant associations between ADHD, diabetes, erectile dysfunction, headaches, sleep apnea, anxiety, and low testosterone and CI+ and/or ND+ (ORs = 1.8-6.0). Chi-square automatic interaction detection (CHAID) multi-variable decision tree models that incorporated medical conditions and football exposures accurately differentiated former players meeting either CI or ND clinical criteria from those meeting none (accuracy = 91.2-96.6%). CHAID identified combinations of depression, headache, sleep apnea, ADHD, and upper quartiles of concussion symptom history as most predictive of CI+ and/or ND+ status. CI+ and/or ND+ players were more likely to report medical conditions known to cause cognitive symptoms. Concussion exposure and medical conditions significantly increased the likelihood that a former ASF player would demonstrate cognitive or neurobehavioral dysfunction. Clinicians engaged with this population should consider whether treatable coexisting condition(s) could account for some portion of the clinical picture associated with TES presentation.

Concussion burden and later-life cardiovascular risk factors in former professional American-style football players.

OBJECTIVE: Mid-life cardiovascular risk factors are associated with later cognitive decline. Whether repetitive head injury among professional athletes impacts cardiovascular risk is unknown. We investigated associations between concussion burden and postcareer hypertension, high cholesterol, and diabetes among former professional American-style football (ASF) players. METHODS: In a cross-sectional study of 4080 professional ASF players conducted between January 2015 and March 2022, we used an mulitsymptom concussion symptom score (CSS) and the number of loss-of-consciousness (LOC) episodes as a single severe symptom to quantify football-related concussion exposure. Primary outcomes were hypertension, dyslipidemia, and diabetes, defined by current or recommended prescription medication use. RESULTS: The prevalence of hypertension, high cholesterol, and diabetes among former players (52 ± 14 years of age) was 37%, 34%, and 9%. Concussion burden was significantly associated with hypertension (lowest vs. highest CSS quartile, odds ratio (OR) = 1.99; 95%CI: 1.33-2.98; p < 0.01) and high cholesterol (lowest vs. moderate CSS, OR = 1.46, 95%CI, 1.11-1.91; p < 0.01), but not diabetes. In fully adjusted models, the prevalence of multiple CVD was associated with CSS. These results were driven by younger former players (≤ 40 year of age) in which the odds of hypertension were over three times higher in those in the highest CSS quartile (OR = 3.29, 95%CI: 1.39-7.61; p = 0.01). Results were similar for LOC analyses. INTERPRETATION: Prior concussion burden is associated with postcareer atherogenic cardiovascular risk profiles among former professional American football players.

Risk of Long-Term Ischemic Stroke in Patients With Traumatic Brain Injury and Incident Hypertension.

Traumatic brain injury (TBI) is independently associated with hypertension and ischemic stroke. The goal of this study was to determine the interplay between TBI and incident hypertension in the occurrence of post-TBI stroke. This prospective study used a hospital-based registry to identify patients without pre-existing comorbidities. TBI patients (n = 3664) were frequency matched on age, sex, and race to non-TBI patients (n = 1848). Follow-up started 6 months post-TBI or study entry and extended up to 10 years. To examine hypertension's role in post-TBI stroke, we used logistic regression models to calculate the effect estimates for stroke in four exposure categories that included TBI or hypertension in isolation and in combination. Second, we calculated the conditional direct effect (CDE) of TBI in models that considered hypertension as intermediary. Third, we examined whether TBI effect was modified by antihypertensive medication use. The 10-year cumulative incidence of stroke was higher in the TBI group (4.7%) than the non-TBI group (1.3%; p < 0.001). TBI patients who developed hypertension had the highest risk of stroke (odds ratio [OR] = 4.83, 95% confidence interval [CI] = 2.53-9.23, p < 0.001). The combined effect estimates were less than additive, suggesting an overlapping biological pathway. The total effect of TBI (OR = 3.16, 95% CI = 1.94-5.16, p < 0.001) was higher than the CDE that accounted for hypertension (OR = 2.45, 95% CI = 0.93-6.47, p = 0.06). Antihypertensives attenuated the TBI effect, suggesting that the TBI effect on stroke is partially mediated through hypertension. TBI is an independent risk factor for long-term stroke, and the underlying biological pathway may partly operate through TBI-precipitated hypertension. These findings suggest that screening for hypertension may mitigate stroke risk in TBI.

Age of First Exposure Does Not Relate to Post-Career Health in Former Professional American-Style Football Players.

OBJECTIVE: Prior studies examining small samples of symptomatic former professional football players suggest that earlier age of first exposure (AFE) to American football is associated with adverse later life health outcomes. This study examined a larger, more representative sample of former professional American football players to assess associations between AFE before age 12 (AFE < 12) and clinical outcomes compared with those who started at age 12 or older (AFE 12 +). METHODS: Former professional American football players who completed a questionnaire were dichotomized into AFE < 12 and AFE 12 + . AFE groups were compared on outcomes including symptoms of depression and anxiety, perceived cognitive difficulties, neurobehavioral dysregulation, and self-reported health conditions (e.g., headaches, sleep apnea, hypertension, chronic pain, memory loss, dementia/Alzheimer's disease, and others). RESULTS: Among 4189 former professional football players (aged 52 ± 14 years, 39% self-reported as Black), univariable associations with negligible effect sizes were seen with AFE < 12, depressive symptoms (p = 0.03; η2 = 0.001), and anxiety-related symptoms (p = 0.02; η2 = 0.001) only. Multivariable models adjusting for age, race, body mass index, playing position, number of professional seasons, and past concussion burden revealed no significant relationships between AFE < 12 and any outcome. Linear and non-linear models examining AFE as a continuous variable showed similar null results. CONCLUSIONS: In a large cohort of former professional American-style football players, AFE was not independently associated with adverse later life outcomes. These findings are inconsistent with smaller studies of former professional football players. Studies examining AFE in professional football players may have limited utility and generalizability regarding policy implications for youth sports.

Perceived Chronic Traumatic Encephalopathy and Suicidality in Former Professional Football Players.

Importance: Participation in American-style football (ASF) has been linked to chronic traumatic encephalopathy neuropathological change (CTE-NC), a specific neuropathologic finding that can only be established at autopsy. Despite being a postmortem diagnosis, living former ASF players may perceive themselves to have CTE-NC. At present, the proportion and clinical correlates of living former professional ASF athletes with perceived CTE who report suicidality are unknown. Objective: To determine the proportion, clinical correlates, and suicidality of living former professional ASF players with perceived CTE. Design, Setting, and Participants: A cross-sectional study within the Football Players Health Study at Harvard University was conducted from 2017 to 2020. Using electronic and paper surveys, this population-based study included former ASF players who contracted with a professional league from 1960 to 2020 and volunteered to fill out a baseline survey. Data for this study were analyzed from June 2023 through March 2024. Exposures: Data included demographics, football-related exposures (eg, position, career duration), and current health problems (anxiety, attention-deficit/hyperactivity disorder, depression, diabetes, emotional and behavioral dyscontrol symptoms, headache, hyperlipidemia, hypertension, low testosterone level, pain, sleep apnea, and subjective cognitive function). Main Outcomes and Measures: The proportion of participants reporting perceived CTE. Univariable and multivariable models were used to determine clinical and suicidality correlates of perceived CTE. Results: Among 4180 former professional ASF players who volunteered to fill out a baseline survey, 1980 (47.4%) provided follow-up data (mean [SD] age, 57.7 [13.9] years). A total of 681 participants (34.4%) reported perceived CTE. Subjective cognitive difficulties, low testosterone level, headache, concussion signs and symptoms accrued during playing years, depressive/emotional and behavioral dyscontrol symptoms, pain, and younger age were significantly associated with perceived CTE. Suicidality was reported by 171 of 681 participants with perceived CTE (25.4%) and 64 of 1299 without perceived CTE (5.0%). After adjusting for established suicidality predictors (eg, depression), men with perceived CTE remained twice as likely to report suicidality (odds ratio, 2.06; 95% CI, 1.36-3.12; P < .001). Conclusions and Relevance: This study found that approximately one-third of living former professional ASF players reported perceived CTE. Men with perceived CTE had an increased prevalence of suicidality and were more likely to have health problems associated with cognitive impairment compared with men without perceived CTE. Perceived CTE represents a novel risk factor for suicidality and, if present, should motivate the diagnostic assessment and treatment of medical and behavioral conditions that may be misattributed to CTE-NC.

Long-term risk of cardiovascular disease after traumatic brain injury: screening and prevention.

Traumatic brain injury (TBI) is highly prevalent among individuals participating in contact sports, military personnel, and in the general population. Although it is well known that brain injury can cause neurological and psychiatric complications, evidence from studies on individuals exposed to a single or repetitive brain injuries suggests an understudied association between TBI and the risk of developing chronic cardiovascular diseases and risk factors for cardiovascular disease. Several studies have shown that people without pre-existing comorbidities who sustain a TBI have a significantly higher risk of developing chronic cardiovascular disease, than people without TBI. Similar observations made in military and professional American-style football cohorts suggest causal pathways through which modifiable cardiovascular risk factors might mediate the relationship between brain injury and chronic neurological diseases. A better understanding of cardiovascular disease risk after TBI combined with a proactive, targeted screening programme might mitigate long-term morbidity and mortality in individuals with TBI, and improve their quality of life.

Association of Retrospectively Reported Concussion Symptoms with Objective Cognitive Performance in Former American-Style Football Players.

OBJECTIVE: Sustaining concussions has been linked to health issues later in life, yet evidence for associations between contact sports exposure and long-term cognitive performance is mixed. This cross-sectional study of former professional American-style football players tested the association of several measures of football exposure with later life cognitive performance, while also comparing the cognitive performance of former players to nonplayers. METHODS: In total, 353 former professional football players (Mage = 54.3) completed both (1) an online cognitive test battery measuring objective cognitive performance and (2) a survey querying demographic information, current health conditions, and measures of past football exposure, including recollected concussion symptoms playing professional football, diagnosed concussions, years of professional play, and age of first football exposure. Testing occurred an average of 29 years after former players' final season of professional play. In addition, a comparison sample of 5,086 male participants (nonplayers) completed one or more cognitive tests. RESULTS: Former players' cognitive performance was associated with retrospectively reported football concussion symptoms (rp = -0.19, 95% CI -0.09 to -0.29; p < 0.001), but not with diagnosed concussions, years of professional play, or age of first football exposure. This association could be due to differences in pre-concussion cognitive functioning, however, which could not be estimated based on available data. CONCLUSIONS: Future investigations of the long-term outcomes of contact sports exposure should include measures of sports-related concussion symptoms, which were more sensitive to objective cognitive performance than other football exposure measures, including self-reported diagnosed concussions.

Race differences in pain and pain-related risk factors among former professional American-style football players.

ABSTRACT: The burden of pain is unequal across demographic groups, with broad and persisting race differences in pain-related outcomes in the United States. Members of racial and ethnic minorities frequently report more pervasive and severe pain compared with those in the majority, with at least some disparity attributable to differences in socioeconomic status. Whether race disparities in pain-related health outcomes exist among former professional football players is unknown. We examined the association of race with pain outcomes among 3995 former professional American-style football players who self-identified as either Black or White. Black players reported more intense pain and higher levels of pain interference relative to White players, even after controlling for age, football history, comorbidities, and psychosocial factors. Race moderated associations between several biopsychosocial factors and pain; higher body mass index was associated with more pain among White but not among Black players. Fatigue and psychosocial factors were more strongly related to pain among Black players relative to White players. Collectively, the substantial social and economic advantages of working as a professional athlete did not seem to erase race-related disparities in pain. We highlight an increased burden of pain among elite Black professional football players and identify race-specific patterns of association between pain and biopsychosocial pain risk factors. These findings illuminate potential future targets of interventions that may serve to reduce persistent disparities in the experience and impact of pain.

Tau Positron Emission Tomography and Neurocognitive Function Among Former Professional American-Style Football Players.

American-style football (ASF) players experience repetitive head impacts that may result in chronic traumatic encephalopathy neuropathological change (CTE-NC). At present, a definitive diagnosis of CTE-NC requires the identification of localized hyperphosphorylated Tau (p-Tau) after death via immunohistochemistry. Some studies suggest that positron emission tomography (PET) with the radiotracer [18F]-Flortaucipir (FTP) may be capable of detecting p-Tau and thus establishing a diagnosis of CTE-NC among living former ASF players. To assess associations between FTP, football exposure, and objective neuropsychological measures among former professional ASF players, we conducted a study that compared former professional ASF players with age-matched male control participants without repetitive head impact exposure. Former ASF players and male controls underwent structural magnetic resonance imaging and PET using FTP for p-Tau and [11C]-PiB for amyloid-ß. Former players underwent neuropsychological testing. The ASF exposure was quantified as age at first exposure, professional career duration, concussion signs and symptoms burden, and total years of any football play. Neuropsychological testing included measures of memory, executive functioning, and depression symptom severity. P-Tau was quantified as FTP standardized uptake value ratios (SUVR) and [11C]-PiB by distribution volume ratios (DVR) using cerebellar grey matter as the reference region. There were no significant differences in [18F]-FTP uptake among former ASF players (n = 27, age = 50 ± 7 years) compared with control participants (n = 11, age = 55 ± 4 years), nor did any participant have significant amyloid-ß burden. Among ASF participants, there were no associations between objective measures of neurocognitive functioning and [18F]-FTP uptake. There was a marginally significant difference, however, between [18F]-FTP uptake isolated to the entorhinal cortex among players in age-, position-, and race-adjusted models (p = 0.05) that may represent an area of future investigation. The absence of increased [18F]-FTP uptake in brain regions previously implicated in CTE among former professional ASF players compared with controls questions the utility of [18F]-FTP PET for clinical evaluation in this population.

Reliable neuromodulation from circuits with variable underlying structure.

Recent work argues that similar network performance can result from highly variable sets of network parameters, raising the question of whether neuromodulation can be reliable across individuals with networks with different sets of synaptic strengths and intrinsic membrane conductances. To address this question, we used the dynamic clamp to construct 2-cell reciprocally inhibitory networks from gastric mill (GM) neurons of the crab stomatogastric ganglion. When the strength of the artificial inhibitory synapses (g(syn)) and the conductance of an artificial I(h) (g(h)) were varied with the dynamic clamp, a variety of network behaviors resulted, including regions of stable alternating bursting. Maps of network output as a function of g(syn) and g(h) were constructed in normal saline and again in the presence of serotonin or oxotremorine. Both serotonin and oxotremorine depolarize and excite isolated individual GM neurons, but by different cellular mechanisms. Serotonin and oxotremorine each increased the size of the parameter regions that supported alternating bursting, and, on average, increased burst frequency. Nonetheless, in both cases some parameter sets within the sample space deviated from the mean population response and decreased in frequency. These data provide insight into why pharmacological treatments that work in most individuals can generate anomalous actions in a few individuals, and they have implications for understanding the evolution of nervous systems.

Multi-modality human phenotyping to examine subjective and objective health afflictions in former professional American-style football players: The In-Person Assessment (IPA) protocol.

BACKGROUND: Participation in American-style football (ASF), one of the most popular sports worldwide, has been associated with adverse health outcomes. However, prior clinical studies of former ASF players have been limited by reliance on subjective self-reported data, inadequate sample size, or focus on a single disease process in isolation. OBJECTIVE: To determine the burden of objective multi-system pathology and its relationship with subjective health complaints among former professional ASF players. METHODS: The In-Person Assessment is a case-control, multi-day, deep human phenotyping protocol designed to characterize and quantify pathology among former professional ASF players. Participants, recruited from an on-going large-scale longitudinal cohort study, will include 120 men who report either no health conditions, a single health condition, or multiple health conditions across the key domains of cardiometabolic disease, disordered sleep, chronic pain, and cognitive impairment. Data will be collected from validated questionnaires, structured interviews, physical examinations, multi-modality imaging, and functional assessments over a 3-day study period. A pilot study was conducted to assess feasibility and to obtain participant feedback which was used to shape the final protocol. RESULTS: This study provides a comprehensive assessment of objective multi-system pathology and its relationship with subjective health complaints among former professional ASF players. CONCLUSION: The study will determine whether subjective health complaints among former professional ASF players are explained by objective explanatory pathology and will provide novel opportunities to examine the interrelatedness of co-morbidities. It is anticipated that this protocol will be applicable to other clinical and occupational populations.