Background
Exposure to repetitive head impacts (RHI) is associated with an increased risk of later‐life neurobehavioral dysregulation and neurodegenerative disease. The underlying pathomechanisms are ...largely unknown.
Purpose
To investigate whether RHI exposure is associated with later‐life corpus callosum (CC) microstructure and whether CC microstructure is associated with plasma total tau and neuropsychological/neuropsychiatric functioning.
Study Type
Retrospective cohort study.
Population
Seventy‐five former professional American football players (age 55.2 ± 8.0 years) with cognitive, behavioral, and mood symptoms.
Field Strength/Sequence
Diffusion‐weighted echo‐planar MRI at 3 T.
Assessment
Subjects underwent diffusion MRI, venous puncture, neuropsychological testing, and completed self‐report measures of neurobehavioral dysregulation. RHI exposure was assessed using the Cumulative Head Impact Index (CHII). Diffusion MRI measures of CC microstructure (i.e., free‐water corrected fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD)) were extracted from seven segments of the CC (CC1‐7), using a tractography clustering algorithm. Neuropsychological tests were selected: Trail Making Test Part A (TMT‐A) and Part B (TMT‐B), Controlled Oral Word Association Test (COWAT), Stroop Interference Test, and the Behavioral Regulation Index (BRI) from the Behavior Rating Inventory of Executive Function, Adult version (BRIEF‐A).
Statistical Tests
Diffusion MRI metrics were tested for associations with RHI exposure, plasma total tau, neuropsychological performance, and neurobehavioral dysregulation using generalized linear models for repeated measures.
Results
RHI exposure was associated with increased AD of CC1 (correlation coefficient (r) = 0.32, P < 0.05) and with increased plasma total tau (r = 0.34, P < 0.05). AD of the anterior CC1 was associated with increased plasma total tau (CC1: r = 0.30, P < 0.05; CC2: r = 0.29, P < 0.05). Higher trace, AD, and RD of CC1 were associated with better performance (P < 0.05) in TMT‐A (trace, r = 0.33; AD, r = 0.31; and RD, r = 0.28) and TMT‐B (trace, r = 0.31; RD, r = 0.34). Higher FA and AD of CC2 were associated with better performance (P < 0.05) in TMT‐A (FA, r = 0.36; AD, r = 0.28), TMT‐B (FA, r = 0.36; AD, r = 0.27), COWAT (FA, r = 0.36; AD, r = 0.32), and BRI (AD, r = 0.29).
Data Conclusion
These results suggest an association among RHI exposure, CC microstructure, plasma total tau, and clinical functioning in former professional American football players.
Level of Evidence: 3
Technical Efficacy Stage: 1
Later-life brain alterations in former tackle football players are poorly understood, particularly regarding their relationship with repetitive head impacts (RHIs) and clinical function. We examined ...white matter signal abnormalities (WMSAs) and their association with RHIs and clinical function in former National Football League (NFL) players.
Eighty-six clinically symptomatic former NFL players and 23 same-age reportedly asymptomatic controls without head trauma exposure underwent magnetic resonance imaging and neuropsychological testing. FreeSurfer calculated WMSAs. A cumulative head impact index quantified RHIs.
In former NFL players, increased volume of WMSAs was associated with higher cumulative head impact index scores (P = .043) and worse psychomotor speed and executive function (P = .015). Although former NFL players had greater WMSA volume than controls (P = .046), these findings are inconclusive due to recruitment of controls based on lack of clinical symptoms and head trauma exposure.
In former NFL players, WMSAs may reflect long-term microvascular and nonmicrovascular pathologies from RHIs that negatively impact cognition.
•Repetitive head impact exposure was positively associated with WMSAs in former NFL players.•In former NFL players, greater WMSAs was associated with worse psychomotor speed and executive function.•The pathologies of WMSAs may contribute to the clinical presentation of chronic traumatic encephalopathy.
Factors of increased prevalence among individuals with Black racial identity (e.g., cardiovascular disease, CVD) may influence the association between exposure to repetitive head impacts (RHI) from ...American football and later-life neurological outcomes. Here, we tested the interaction between racial identity and RHI on neurobehavioral outcomes, brain volumetric measures, and cerebrospinal fluid (CSF) total tau (t-tau), phosphorylated tau (p-tau
), and Aβ
in symptomatic former National Football League (NFL) players.
68 symptomatic male former NFL players (ages 40-69;
= 27 Black,
= 41 White) underwent neuropsychological testing, structural MRI, and lumbar puncture. FreeSurfer derived estimated intracranial volume (eICV), gray matter volume (GMV), white matter volume (WMV), subcortical GMV, hippocampal volume, and white matter (WM) hypointensities. Multivariate generalized linear models examined the main effects of racial identity and its interaction with a cumulative head impact index (CHII) on all outcomes. Age, years of education, Wide Range Achievement Test, Fourth Edition (WRAT-4) scores, CVD risk factors, and
ε4 were included as covariates; eICV was included for MRI models.
-values were false discovery rate adjusted.
Compared to White former NFL players, Black participants were 4 years younger (
= 0.04), had lower WRAT-4 scores (mean difference = 8.03,
= 0.002), and a higher BMI (mean difference = 3.09,
= 0.01) and systolic blood pressure (mean difference = 8.15,
= 0.03). With regards to group differences on the basis of racial identity, compared to White former NFL players, Black participants had lower GMV (mean adjusted difference = 45649.00,
= 0.001), lower right hippocampal volume (mean adjusted difference = 271.96,
= 0.02), and higher p-tau
/t-tau ratio (mean adjusted difference = -0.25,
= 0.01). There was not a statistically significant association between the CHII with GMV, right hippocampal volume, or p-tau
/t-tau ratio. However, there was a statistically significant Race x CHII interaction for GMV (
= 2206.29,
= 0.001), right hippocampal volume (
= 12.07,
= 0.04), and p-tau
/t-tau ratio concentrations (
= -0.01,
= 0.004).
Continued research on racial neurological disparities could provide insight into risk factors for long-term neurological disorders associated with American football play.
Health-related quality of life (HRQOL) is an important indicator for recovery after pediatric TBI. To date, there are a few questionnaires available for assessing generic HRQOL in children and ...adolescents, but there are not yet any TBI-specific measures of HRQOL that are applicable to pediatric populations. The aim of the present study was to examine psychometric characteristics of the newly developed Quality of Life After Brain Injury Scale for Kids and Adolescents (QOLIBRI-KID/ADO) questionnaire capturing TBI-specific HRQOL in children and adolescents using an item response theory (IRT) framework. Children (8-12 years;
= 152) and adolescents (13-17 years;
= 148) participated in the study. The final version of the QOLIBRI-KID/ADO, comprising 35 items forming 6 scales, was investigated using the partial credit model (PCM). A scale-wise examination for unidimensionality, monotonicity, item infit and outfit, person homogeneity, and local independency was conducted. The questionnaire widely fulfilled the predefined assumptions, with a few restrictions. The newly developed QOLIBRI-KID/ADO instrument shows at least satisfactory psychometric properties according to the results of both classical test theoretical and IRT analyses. Further evidence of its applicability should be explored in the ongoing validation study by performing multidimensional IRT analyses.
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.
The subjective impact of the consequences of pediatric traumatic brain injury (pTBI) on different life dimensions should be assessed multidimensionally and as sensitively as possible using a ...disease-specific health-related quality of life (HRQoL) instrument. The development and psychometrics of the first such self-report questionnaire for children and adolescents after TBI are reported here. Focus group interviews with children, adolescents, and their parents, cognitive debriefing, item pool generation and reduction using Delphi expert panels were performed. The resulting version was psychometrically tested on 300 individuals aged 8-17 years. After item reduction based on factor analyses, differential item functioning, reliability, and validity were investigated. The final 35 items were associated with six scales (Cognition, Self, Daily Life and Autonomy, Social Relationships, Emotions, Physical Problems). Internal consistency and construct validity were satisfactory. Health-related Quality of life (HRQoL) was significantly lower in older and in female participants, as well as those with cognitive disabilities, anxiety, depression and post-concussion symptoms, than in comparative groups. The new QOLIBRI-KID/ADO is a comprehensive, multidimensional, reliable, and valid instrument, comparable in content and items to the QOLIBRI adult version. Therefore, disease-specific HRQoL can now be measured across the lifespan and may support the amelioration of treatment, care, rehabilitation, and daily life of children and adolescents after TBI.
To test whether 1) concussed athletes demonstrate slower tandem gait times compared to controls and 2) concussed female athletes display greater post-injury deficits than males.
Prospective ...longitudinal
Fifty concussed collegiate student-athletes (32% female, age=20.18±1.27 years) completed tandem gait tests during pre-season (Time 1) and acutely (<72hours) post-concussion (Time 2), and twenty-five controls (52% female, age=21.08±2.22 years) completed tandem gait at two time points, 1.96±0.46 days apart. Participants completed four single-task (ST) and dual-task (DT) trials. During DT trials, they simultaneously completed a cognitive assessment. The best ST and DT times were recorded, along with cognitive accuracy, and the change score between the two assessments was calculated. A positive change in tandem gait time was indicative of worsening performance. A 2×2 (group*sex) ANOVA was used to examine change between pre-injury and post-injury tests for ST/DT tandem gait time and DT cognitive accuracy.
The change in tandem gait time from Time 1 to Time 2 was significantly higher for the concussion group relative to controls during both ST (Concussion: 1.36±2.6 seconds, Controls: -1.16±0.8 seconds, p<0.001) and DT (Concussion: 1.70±3.8 seconds, Controls: -0.94±1.7 seconds, p=0.002) tandem gait. There were no interactions or main effects of sex for tandem gait time or cognitive accuracy.
There were no sex-specific differences in the change in tandem gait performance among concussed collegiate athletes or controls. However, all concussed participants, regardless of sex, performed significantly worse on tandem gait than male and female controls, who both improved between testing time points.
Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age‐related neurogenerative disorders that affect white matter (WM) in the brain. ...However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non‐negative matrix factorization (NMF) is a data‐driven approach that detects covarying patterns (components) within high‐dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self‐reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta‐Analysis) Military Brain Injury working group. Regressions were used to examine TBI‐ and mTBI‐related associations in NMF‐derived components while adjusting for age, sex, post‐traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age‐dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q < 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age‐dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans.
We used NMF, an unsupervised, data‐driven method, to capture patterns of fluctuation across the white matter in the brain in a sample of military personnel accessed through the ENIGMA Military Brain Injury working group. We identified significantly stronger age‐dependent effects of lower FA in the military personnel with a TBI compared to a military non‐TBI group. Use of data‐driven methods may help to uncover the heterogeneous patterns of white matter damage resulting from military‐related mTBI and may uncover injury patterns in the brain unrelated to our current understanding of brain structure.
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