163 research outputs found

    Self-Reported Cognitive Function and Mental Health Diagnoses among Former Professional American-Style Football Players

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    Clinical practice strongly relies on patients' self-report. Former professional American-style football players are hesitant to seek help for mental health problems, but may be more willing to report cognitive symptoms. We sought to assess the association between cognitive symptoms and diagnosed mental health problems and quality of life among a cohort of former professional players. In a cross-sectional design, we assessed self-reported cognitive function using items from the Quality of Life in Neurological Disorders (Neuro-QOL) Item Bank. We then compared mental health diagnoses and quality of life, assessed by items from the Patient-Reported Outcome Measurement Information System (PROMIS ®), between former professional players reporting daily problems in cognitive function and former players not reporting daily cognitive problems. Of the 3758 former professional players included in the analysis, 40.0% reported daily problems due to cognitive dysfunction. Former players who reported daily cognitive problems were more likely to also report depression (18.0% vs. 3.3%, odds ratio [OR] = 6.42, 95% confidence interval [CI] [4.90-8.40]) and anxiety (19.1% vs. 4.3%, OR = 5.29, 95% CI [4.14-6.75]) than those without daily cognitive problems. Further, former players reporting daily cognitive problems were more likely to report memory loss and attention deficit(/hyperactivity) disorder and poorer general mental health, lower quality of life, less satisfaction with social activities and relationships, and more emotional problems. These findings highlight the potential of an assessment of cognitive symptoms for identifying former players with mental health, social, and emotional problems

    Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae

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    Traumatic brain injury (TBI) is characterized by acute neurological dysfunction and asso- ciated with the development of chronic traumatic encephalopathy (CTE) and Alzheimer’s disease. We previously showed that cis phosphorylated tau (cis P-tau), but not the trans form, contributes to tau pathology and functional impairment in an animal model of severe TBI. Here we found that in human samples obtained post TBI due to a variety of causes, cis P-tau is induced in cortical axons and cerebrospinal fluid and positively correlates with axonal injury and clinical outcome. Using mouse models of severe or repetitive TBI, we showed that cis P-tau elimination with a specific neutralizing antibody administered immediately or at delayed time points after injury, attenuates the development of neuropathology and brain dysfunction during acute and chronic phases including CTE-like pathology and dysfunction after repetitive TBI. Thus, cis P-tau contributes to short-term and long-term sequelae after TBI, but is effectively neutralized by cis antibody treatment

    Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions

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    Background: Age-associated epigenetic changes are implicated in aging. Notably, age-associated DNA methylation changes comprise a so-called aging “clock”, a robust biomarker of aging. However, while genetic, dietary and drug interventions can extend lifespan, their impact on the epigenome is uncharacterised. To fill this knowledge gap, we defined age-associated DNA methylation changes at the whole-genome, single-nucleotide level in mouse liver and tested the impact of longevity-promoting interventions, specifically the Ames dwarf Prop1 df/df mutation, calorie restriction and rapamycin. Results: In wild-type mice fed an unsupplemented ad libitum diet, age-associated hypomethylation was enriched at super-enhancers in highly expressed genes critical for liver function. Genes harbouring hypomethylated enhancers were enriched for genes that change expression with age. Hypermethylation was enriched at CpG islands marked with bivalent activating and repressing histone modifications and resembled hypermethylation in liver cancer. Age-associated methylation changes are suppressed in Ames dwarf and calorie restricted mice and more selectively and less specifically in rapamycin treated mice. Conclusions: Age-associated hypo- and hypermethylation events occur at distinct regulatory features of the genome. Distinct longevity-promoting interventions, specifically genetic, dietary and drug interventions, suppress some age-associated methylation changes, consistent with the idea that these interventions exert their beneficial effects, in part, by modulation of the epigenome. This study is a foundation to understand the epigenetic contribution to healthy aging and longevity and the molecular basis of the DNA methylation clock

    Role of biomarkers and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion: a systematic review

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    OBJECTIVE: Determine the role of fluid-based biomarkers, advanced neuroimaging, genetic testing and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion (SRC). DESIGN: Systematic review. DATA SOURCES: Searches of seven databases from 1 January 2001 through 24 March 2022 using keywords and index terms relevant to concussion, sports and neurobiological recovery. Separate reviews were conducted for studies involving neuroimaging, fluid biomarkers, genetic testing and emerging technologies. A standardised method and data extraction tool was used to document the study design, population, methodology and results. Reviewers also rated the risk of bias and quality of each study. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they: (1) were published in English; (2) represented original research; (3) involved human research; (4) pertained only to SRC; (5) included data involving neuroimaging (including electrophysiological testing), fluid biomarkers or genetic testing or other advanced technologies used to assess neurobiological recovery after SRC; (6) had a minimum of one data collection point within 6 months post-SRC; and (7) contained a minimum sample size of 10 participants. RESULTS: A total of 205 studies met inclusion criteria, including 81 neuroimaging, 50 fluid biomarkers, 5 genetic testing, 73 advanced technologies studies (4 studies overlapped two separate domains). Numerous studies have demonstrated the ability of neuroimaging and fluid-based biomarkers to detect the acute effects of concussion and to track neurobiological recovery after injury. Recent studies have also reported on the diagnostic and prognostic performance of emerging technologies in the assessment of SRC. In sum, the available evidence reinforces the theory that physiological recovery may persist beyond clinical recovery after SRC. The potential role of genetic testing remains unclear based on limited research. CONCLUSIONS: Advanced neuroimaging, fluid-based biomarkers, genetic testing and emerging technologies are valuable research tools for the study of SRC, but there is not sufficient evidence to recommend their use in clinical practice. PROSPERO REGISTRATION NUMBER: CRD42020164558

    Examining racial and ethnic disparities in adult emergency department patient visits for concussion in the United States

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    Background Racial and ethnic differences in emergency department (ED) visits have been reported among adolescent patients but are unsubstantiated among adults. Therefore, our purpose in this study was to examine the relationship between race/ethnicity and adult ED visits for concussions, their injury mechanisms, and computed tomography (CT) scan use among a nationally representative sample. Methods We used the National Hospital Ambulatory Medical Care Survey database from 2010–2015 to examine 63,725 adult (20–45 years old) patient visits, representing an estimated 310.6 million visits presented to EDs. Of these visits, 884 (4.5 million national estimate) were diagnosed with a concussion. Visit records detailed patient information (age, sex, race/ethnicity, geographic region, primary payment type), ED visit diagnoses, injury mechanism (sport, motor vehicle, fall, struck by or against, “other”), and head CT scan use. The primary independent variable was race/ethnicity (non-Hispanic Asian, non-Hispanic Black or African American, Hispanic/Latinx, non-Hispanic multiracial or another, and non-Hispanic White). We used multivariable logistic and multinomial regression models with complex survey sampling design weighting to examine the relationship between concussion ED visits, injury mechanisms, and CT scan use separately by race/ethnicity while accounting for covariates. Results There were no associations between race/ethnicity and concussion diagnosis among adult ED visits after accounting for covariates. Relative to sports-related injuries, non-Hispanic Black or African American patient visits were associated with a motor vehicle (OR = 2.69, 95% CI: 1.06–6.86) and “other” injury mechanism (OR = 4.58, 95% CI: 1.34–15.69) compared to non-Hispanic White patients. Relative to sports-related injuries, non-Hispanic Asian, multiracial, or patients of another race had decreased odds of falls (OR = 0.20, 95% CI: 0.04–0.91) and “other” injuries (OR = 0.09, 95% CI: 0.01–0.55) compared to non-Hispanic White patients. The odds of a CT scan being performed were significantly lower among Hispanic/Latinx patient visits relative to non-Hispanic White patients (OR = 0.52, 95% CI: 0.30–0.91), while no other race/ethnicity comparisons differed. Conclusion Our findings indicate that the overarching concussion ED visit likelihood may not differ by race/ethnicity in adults, but the underlying mechanism causing the concussion and receiving a CT scan demonstrates considerable differences. Prospective future research is warranted to comprehensively understand and intervene in the complex, multi-level race/ethnicity relationships related to concussion health care to ensure equitable patient treatment

    Clinical risk score for persistent postconcussion symptomsamong children with acute concussion in the ED

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    IMPORTANCE Approximately one-third of children experiencing acute concussion experience ongoing somatic, cognitive, and psychological or behavioral symptoms, referred to as persistent postconcussion symptoms (PPCS). However, validated and pragmatic tools enabling clinicians to identify patients at risk for PPCS do not exist. OBJECTIVE To derive and validate a clinical risk score for PPCS among children presenting to the emergency department. DESIGN, SETTING, AND PARTICIPANTS Prospective, multicenter cohort study (Predicting and Preventing Postconcussive Problems in Pediatrics [5P]) enrolled young patients (aged 5-\u3c18 years) who presented within 48 hours of an acute head injury at 1 of 9 pediatric emergency departments within the Pediatric Emergency Research Canada (PERC) network from August 2013 through September 2014 (derivation cohort) and from October 2014 through June 2015 (validation cohort). Participants completed follow-up 28 days after the injury. EXPOSURES All eligible patients had concussions consistent with the Zurich consensus diagnostic criteria. MAIN OUTCOMES AND MEASURES The primary outcomewas PPCS risk score at 28 days, which was defined as 3 or more new or worsening symptoms using the patient-reported Postconcussion Symptom Inventory compared with recalled state of being prior to the injury. RESULTS In total, 3063 patients (median age, 12.0 years [interquartile range, 9.2-14.6 years]; 1205 [39.3%] girls) were enrolled (n = 2006 in the derivation cohort; n = 1057 in the validation cohort) and 2584 of whom (n = 1701 [85%] in the derivation cohort; n = 883 [84%] in the validation cohort) completed follow-up at 28 days after the injury. Persistent postconcussion symptoms were present in 801 patients (31.0%) (n = 510 [30.0%] in the derivation cohort and n = 291 [33.0%] in the validation cohort). The 12-point PPCS risk score model for the derivation cohort included the variables of female sex, age of 13 years or older, physician-diagnosed migraine history, prior concussion with symptoms lasting longer than 1 week, headache, sensitivity to noise, fatigue, answering questions slowly, and 4 or more errors on the Balance Error Scoring System tandem stance. The area under the curve was 0.71 (95%CI, 0.69-0.74) for the derivation cohort and 0.68 (95%CI, 0.65-0.72) for the validation cohort. CONCLUSIONS AND RELEVANCE A clinical risk score developed among children presenting to the emergency department with concussion and head injury within the previous 48 hours had modest discrimination to stratify PPCS risk at 28 days. Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility

    A comparison in a youth population between those with and without a history of concussion using biomechanical reconstruction

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    OBJECTIVE: Concussion is a common topic of research as a result of the short- and long-term effects it can have on the affected individual. Of particular interest is whether previous concussions can lead to a biomechanical susceptibility, or vulnerability, to incurring further head injuries, particularly for youth populations. The purpose of this research was to compare the impact biomechanics of a concussive event in terms of acceleration and brain strains of 2 groups of youths: those who had incurred a previous concussion and those who had not. It was hypothesized that the youths with a history of concussion would have lower-magnitude biomechanical impact measures than those who had never suffered a previous concussion. METHODS: Youths who had suffered a concussion were recruited from emergency departments across Canada. This pool of patients was then separated into 2 categories based on their history of concussion: those who had incurred 1 or more previous concussions, and those who had never suffered a concussion. The impact event that resulted in the brain injury was reconstructed biomechanically using computational, physical, and finite element modeling techniques. The output of the events was measured in biomechanical parameters such as energy, force, acceleration, and brain tissue strain to determine if those patients who had a previous concussion sustained a brain injury at lower magnitudes than those who had no previously reported concussion. RESULTS: The results demonstrated that there was no biomechanical variable that could distinguish between the concussion groups with a history of concussion versus no history of concussion. CONCLUSIONS: The results suggest that there is no measureable biomechanical vulnerability to head impact related to a history of concussions in this youth population. This may be a reflection of the long time between the previous concussion and the one reconstructed in the laboratory, where such a long period has been associated with recovery from injury
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