White matter hyperintensities in former American football players.
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ABSTRACT: Introduction
The presentation, risk factors, and etiologies of white matter hyperintensities (WMH) in people exposed to repetitive head impacts are unknown. We examined the burden and distribution of WMH, and their association with years of play, age of first exposure, and clinical function in former American football players.Methods
A total of 149 former football players and 53 asymptomatic unexposed participants (all men, 45-74 years) completed fluid-attenuated inversion recovery magnetic resonance imaging, neuropsychological testing, and self-report neuropsychiatric measures. Lesion Segmentation Toolbox estimated WMH. Analyses were performed in the total sample and stratified by age 60.Results
In older but not younger participants, former football players had greater total, frontal, temporal, and parietal log-WMH compared to asymptomatic unexposed men. In older but not younger former football players, greater log-WMH was associated with younger age of first exposure to football and worse executive function.Discussion
In older former football players, WMH may have unique presentations, risk factors, and etiologies.Highlights
Older but not younger former football players had greater total, frontal, temporal, and parietal lobe white matter hyperintensities (WMH) compared to same-age asymptomatic unexposed men. Younger age of first exposure to football was associated with greater WMH in older but not younger former American football players. In former football players, greater WMH was associated with worse executive function and verbal memory.
SUBMITTER: Alosco ML
PROVIDER: S-EPMC10351916 | biostudies-literature | 2023 Apr
REPOSITORIES: biostudies-literature
Publications
White matter hyperintensities in former American football players.
Alosco Michael L ML Tripodis Yorghos Y Baucom Zachary H ZH Adler Charles H CH Balcer Laura J LJ Bernick Charles C Mariani Megan L ML Au Rhoda R Banks Sarah J SJ Barr William B WB Wethe Jennifer V JV Cantu Robert C RC Coleman Michael J MJ Dodick David W DW McClean Michael D MD McKee Ann C AC Mez Jesse J Palmisano Joseph N JN Martin Brett B Hartlage Kaitlin K Lin Alexander P AP Koerte Inga K IK Cummings Jeffrey L JL Reiman Eric M EM Stern Robert A RA Shenton Martha E ME Bouix Sylvain S
Alzheimer's & dementia : the journal of the Alzheimer's Association 20220822 4
<h4>Introduction</h4>The presentation, risk factors, and etiologies of white matter hyperintensities (WMH) in people exposed to repetitive head impacts are unknown. We examined the burden and distribution of WMH, and their association with years of play, age of first exposure, and clinical function in former American football players.<h4>Methods</h4>A total of 149 former football players and 53 asymptomatic unexposed participants (all men, 45-74 years) completed fluid-attenuated inversion recove ...[more]
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Project description:BackgroundPatterns of cognitive impairment in former American football players are uncertain because objective neuropsychological data are lacking. This study characterized the neuropsychological test performance of former college and professional football players.MethodsOne hundred seventy male former football players (n=111 professional, n=59 college; 45-74 years) completed a neuropsychological test battery. Raw scores were converted to T-scores using age, sex, and education-adjusted normative data. A T-score ≤ 35 defined impairment. A domain was impaired if 2+ scores fell in the impaired range except for the language and visuospatial domains due to the limited number of tests.ResultsMost football players had subjective cognitive concerns. On testing, rates of impairments were greatest for memory (21.2% two tests impaired), especially for recall of unstructured (44.7%) versus structured verbal stimuli (18.8%); 51.8% had one test impaired. 7.1% evidenced impaired executive functions; however, 20.6% had impaired Trail Making Test B. 12.1% evidenced impairments in the attention, visual scanning, and psychomotor speed domain with frequent impairments on Trail Making Test A (18.8%). Other common impairments were on measures of language (i.e., Multilingual Naming Test [21.2%], Animal Fluency [17.1%]) and working memory (Number Span Backward [14.7%]). Impairments on our tasks of visuospatial functions were infrequent.ConclusionsIn this sample of former football players (most of whom had subjective cognitive concerns), there were diffuse impairments on neuropsychological testing with verbal memory being the most frequently impaired domain.
| S-EPMC9808953 | biostudies-literature
Project description:Recent attention to consequences of head trauma among former professional American-style football players has increased the likelihood that former players and their healthcare providers attribute neurocognitive effects to these exposures. In addition to head trauma, however, many potentially modifiable risk factors are associated with cognitive impairment. We examined the association of self-reported risk factors for cognitive impairment (e.g., cardiovascular health, sleep, pain, depression, anxiety, smoking, physical impairment, and physical activity) with cognition-related quality of life, measured by the Quality of Life in Neurological Disorders, Applied Cognition-General Concerns (Neuro-QOL) among 3803 former National Football League (NFL) players. We examined the prevalence of risk factors among men who had experienced a high number of concussion symptoms during playing years, comparing men with good current cognition-related QOL, the "healthy concussed," to men with poor cognition-related QOL, the "unhealthy concussed." Physical functioning, pain, depression, and anxiety were very strongly associated with poor cognitive-related QOL (risk ratio range, 2.21-2.70, p < 0.0001 for all). Short sleep duration and low physical activity were also strongly associated (RR = 1.69 and 1.57, respectively, p < 0.0001 for both). The largest differences between healthy and unhealthy concussed were in chronic pain (72.0% vs. 21.2%), depressive symptoms (50.3% vs. 6.3%), anxiety symptoms (53.4% vs. 11.6%), and physical impairment (52.4% vs. 12.5%). Substantial differences also existed in prevalence of sleep apnea, short sleep duration, high-intensity exercise, weight training, high blood pressure, and body mass index ≥35 kg/m2 (all differences >10 percentage points). We identified cognitive risk factors, including chronic pain, mood problems, sleep problems, obesity, and lack of exercise, that were commonly present in former football players with cognition-related impairment. Better treatment for these factors may reduce cognitive problems in this population.
| S-EPMC8182470 | biostudies-literature
Project description: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-β. 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-β 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.
| S-EPMC10458363 | biostudies-literature
Project description:BACKGROUND:The long-term health consequences of participation in American style football (ASF) are not well understood. METHODS:We conducted a retrospective cohort study of men who had played in the NFL after 1960. Participants were studied using a standardized self-administered questionnaire designed to determine both the exposure history to ASF and the prevalence of chronic pain, sleep apnea, cardiometabolic disease, and neurocognitive impairment. Logistic regression and negative binomial regression models were used to assess associations between age, ethnicity, body-mass index during professional football career, field position, and football career duration with individual and multiple afflictions. RESULTS:In this cohort of former NFL players (n?=?3745), approximately one quarter of the eligible former players (27%) reported two or more medical afflictions (chronic pain, cardiometabolic disease, sleep apnea, or neurocognitive impairment). Career duration was significantly associated with an increase in the number of comorbidities. Age, race, and body-mass index were associated with all affliction categories, other than neurocognitive impairment, which was similarly prevalent in middle-aged players and older players. Earlier age when first playing the sport was protective against cardiometabolic affliction. CONCLUSIONS:Former NFL players report significant combinations of cross-system afflictions. Future work will be required to determine mechanistic underpinnings. However, attention to the whole player, rather than specific organ systems seems critical to improve long-term health outcomes in former ASF professional athletes.
| S-EPMC6640629 | biostudies-literature
Project description:ImportancePilot studies that involved early imaging of the 18 kDa translocator protein (TSPO) using positron emission tomography (PET) indicated high levels of TSPO in the brains of active or former National Football League (NFL) players. If validated further in larger studies, those findings may have implications for athletes involved in collision sport.ObjectiveTo test for higher TSPO that marks brain injury and repair in a relatively large, unique cohort of former NFL players compared with former elite, noncollision sport athletes.Design, setting, and participantsThis cross-sectional study used carbon 11-labeled N,N-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide positron emission tomography ([11C]DPA-713 PET) data from former NFL players within 12 years of last participation in the NFL and elite noncollision sport athletes from across the US. Participants were enrolled between April 2018 and February 2023.Main outcomes and measuresRegional [11C]DPA-713 total distribution volume from [11C]DPA-713 PET that is a measure of regional brain TSPO; regional brain volumes on magnetic resonance imaging; neuropsychological performance, including attention, executive function, and memory domains.ResultsThis study included 27 former NFL players and 27 former elite, noncollision sport athletes. Regional TSPO levels were higher in former NFL players compared with former elite, noncollision sport athletes (unstandardized β coefficient, 1.08; SE, 0.22; 95% CI, 0.65 to 1.52; P < .001). The magnitude of the group difference depended on region, with largest group differences in TSPO in cingulate and frontal cortices as well as hippocampus. Compared with noncollision sport athletes, former NFL players performed worse in learning (mean difference [MD], -0.70; 95% CI, -1.14 to -0.25; P = .003) and memory (MD, -0.77; 95% CI, -1.24 to -0.30; P = .002), with no correlation between total gray matter TSPO and these cognitive domains.Conclusions and relevanceIn this cross-sectional study using [11C]DPA-713 PET, higher brain TSPO was found in former NFL players compared with noncollision sport athletes. This finding is consistent with neuroimmune activation even after cessation of NFL play. Future longitudinal [11C]DPA-713 PET and neuropsychological testing promises to inform whether neuroimmune-modulating therapy may be warranted.
| S-EPMC10616723 | biostudies-literature
Project description:ImportanceStudies of American-style football players have suggested lower overall mortality rates compared with general populations, but with possibly increased neurodegenerative mortality. However, comparisons with general populations can introduce bias. This study compared mortality between US National Football League (NFL) and US Major League Baseball (MLB) players, a more appropriate comparison group of professional athletes.ObjectiveTo compare all-cause and cause-specific mortality between NFL and MLB players.Design, setting, and participantsIn this retrospective cohort study, the setting was US mortality from January 1, 1979, through December 31, 2013. The dates of analysis were January 2016 to April 2019. Participants were 3419 NFL and 2708 MLB players with at least 5 playing seasons.ExposuresParticipation in the NFL compared with the MLB.Main outcomes and measuresVital status and causes of death from the National Death Index from 1979 through 2013 were obtained. Cox proportional hazards regression models using age as the timescale were used to calculate hazard ratios (HRs) and 95% CIs to examine all-cause and cause-specific mortality among NFL players compared with MLB players, adjusted for race and decade of birth.ResultsBy the end of follow-up, there were 517 deaths (mean [SD] age, 59.6 [13.2] years) in the NFL cohort and 431 deaths (mean [SD] age, 66.7 [12.3] years) in the MLB cohort. Cardiovascular and neurodegenerative conditions, respectively, were noted as underlying or contributing causes in 498 and 39 deaths in the NFL and 225 and 16 deaths in the MLB. Compared with MLB players, NFL players had significantly elevated rates of all-cause (HR, 1.26; 95% CI, 1.10-1.44), cardiovascular disease (HR, 2.40; 95% CI, 2.03-2.84), and neurodegenerative disease (HR, 2.99; 95% CI, 1.64-5.45) mortality. Comparing hypothetical populations of 1000 NFL and 1000 MLB players followed up to age 75 years, there would be an excess 21 all-cause deaths among NFL players, as well as 77 and 11 more deaths with underlying or contributing causes that included cardiovascular and neurodegenerative conditions, respectively.Conclusions and relevanceThis study found that NFL players had elevated all-cause, cardiovascular, and neurodegenerative mortality rates compared with MLB players, although the absolute number of excess neurodegenerative deaths was still small. Factors that vary across these sports (eg, body habitus and head trauma) as opposed to those common across sports (eg, physical activity) could underlie the differences.
| S-EPMC6632140 | biostudies-literature
Project description:Social networks have broad effects on health and quality of life. Biopsychosocial factors may also modify the effects of brain trauma on clinical and pathological outcomes. However, social network characterization is missing in studies of contact sports athletes. Here, we characterized the personal social networks of former National Football League players compared to non-football US males. In 303 former football players and 269 US males, we found that network structure (e.g., network size) did not differ, but network composition (e.g., proportion of family versus friends) did differ. Football players had more men than women, and more friends than family in their networks compared to US males. Black players had more racially diverse networks than White players and US males. These results are unexpected because brain trauma and chronic illnesses typically cause diminished social relationships. We anticipate our study will inform more multi-dimensional study of, and treatment options for, contact sports athletes. For example, the strong allegiances of former athletes may be harnessed in the form of social network interventions after brain trauma. Because preserving health of contact sports athletes is a major goal, the study of social networks is critical to the design of future research and treatment trials.
| S-EPMC7851122 | biostudies-literature
Project description:BackgroundChronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been associated with a history of repetitive head impacts. The neuropathological diagnosis is based on a specific pattern of tau deposition with minimal amyloid-beta deposition that differs from other disorders, including Alzheimer's disease. The feasibility of detecting tau and amyloid deposition in the brains of living persons at risk for CTE has not been well studied.MethodsWe used flortaucipir positron-emission tomography (PET) and florbetapir PET to measure deposition of tau and amyloid-beta, respectively, in the brains of former National Football League (NFL) players with cognitive and neuropsychiatric symptoms and in asymptomatic men with no history of traumatic brain injury. Automated image-analysis algorithms were used to compare the regional tau standardized uptake value ratio (SUVR, the ratio of radioactivity in a cerebral region to that in the cerebellum as a reference) between the two groups and to explore the associations of SUVR with symptom severity and with years of football play in the former-player group.ResultsA total of 26 former players and 31 controls were included in the analysis. The mean flortaucipir SUVR was higher among former players than among controls in three regions of the brain: bilateral superior frontal (1.09 vs. 0.98; adjusted mean difference, 0.13; 95% confidence interval [CI], 0.06 to 0.20; P<0.001), bilateral medial temporal (1.23 vs. 1.12; adjusted mean difference, 0.13; 95% CI, 0.05 to 0.21; P<0.001), and left parietal (1.12 vs. 1.01; adjusted mean difference, 0.12; 95% CI, 0.05 to 0.20; P = 0.002). In exploratory analyses, the correlation coefficients in these three regions between the SUVRs and years of play were 0.58 (95% CI, 0.25 to 0.79), 0.45 (95% CI, 0.07 to 0.71), and 0.50 (95% CI, 0.14 to 0.74), respectively. There was no association between tau deposition and scores on cognitive and neuropsychiatric tests. Only one former player had levels of amyloid-beta deposition similar to those in persons with Alzheimer's disease.ConclusionsA group of living former NFL players with cognitive and neuropsychiatric symptoms had higher tau levels measured by PET than controls in brain regions that are affected by CTE and did not have elevated amyloid-beta levels. Further studies are needed to determine whether elevated CTE-associated tau can be detected in individual persons. (Funded by Avid Radiopharmaceuticals and others.).
| S-EPMC6636818 | biostudies-literature
Project description:IntroductionTau 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.MethodWe 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).ResultsSignificantly 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.DiscussionAdditional studies are needed to further understand tau pathology in CTE and other individuals with a history of RHI.
| S-EPMC10984430 | biostudies-literature
Project description:Neuroticism is a major risk factor for neurodegenerative disorders, such as Alzheimer's disease and related dementias. This study investigates whether neuroticism is associated with white matter hyperintensities and whether this measure of brain integrity is a mediator between neuroticism and cognitive function. Middle-aged and older adults from the UK Biobank (N = 40,602; aged 45-82 years, M = 63.97, SD = 7.66) provided information on demographic and health covariates, completed measures of neuroticism and cognition, and underwent magnetic resonance imaging from which the volume of white matter hyperintensities was derived. Regression analyses that included age and sex as covariates found that participants who scored higher on neuroticism had more white matter hyperintensities (β = 0.024, 95% CI 0.015 to 0.032; p < .001), an association that was consistent across peri-ventricular and deep brain regions. The association was reduced by about 40% when accounting for vascular risk factors (smoking, obesity, diabetes, high blood pressure, heart attack, angina, and stroke). The association was not moderated by age, sex, college education, deprivation index, or APOE e4 genotype, and remained unchanged in sensitivity analyses that excluded individuals with dementia or those younger than 65. The mediation analysis revealed that white matter hyperintensities partly mediated the association between neuroticism and cognitive function. These findings identify white matter integrity as a potential neurobiological pathway that accounts for a small proportion of the association between neuroticism and cognitive health.
| S-EPMC10528519 | biostudies-literature