Age at First Exposure to Football Is Associated with Altered Corpus Callosum White Matter Microstructure in Former Professional Football Players

Stamm, Julie; Koerte, Inga K.; Muehlmann, Marc; Pasternak, Ofer; Bourlas, Alexandra P.; Baugh, Christine M.; Giwerc, Michelle Y.; Zhu, Angela; Coleman, Michael J.; Bouix, Sylvain; Fritts, Nathan G.; Martin, Brett; Chaisson, Christine E.; McClean, Michael D.; Lin, Alexander P.; Cantu, Robert C.; Tripodis, Yorghos; Stern, Robert; Shenton, Martha E.

doi:10.1089/neu.2014.3822

Cited by 151 publications

(139 citation statements)

References 78 publications

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“…Details of the study protocol can also be found elsewhere. 27,28 The study protocol was approved by the Boston University Medical Center Institutional Review Board, and by the Partners Institutional Review Board. Written informed consent was obtained from all study participants before enrollment into the study.…”

Section: Methodsmentioning

confidence: 99%

Cavum Septi Pellucidi in Symptomatic Former Professional Football Players

Koerte

Hufschmidt

Muehlmann

et al. 2016

Journal of Neurotrauma

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109

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Post-mortem studies reveal a high rate of cavum septi pellucidi (CSP) in chronic traumatic encephalopathy (CTE). It remains, however, to be determined whether or not the presence of CSP may be a potential in vivo imaging marker in populations at high risk to develop CTE. The aim of this study was to evaluate CSP in former professional American football players presenting with cognitive and behavioral symptoms compared with noncontact sports athletes. Seventytwo symptomatic former professional football players (mean age 54.53 years, standard deviation [SD] 7.97) as well as 14 former professional noncontact sports athletes (mean age 57.14 years, SD 7.35) underwent high-resolution structural 3T magnetic resonance imaging. Two raters independently evaluated the CSP, and interrater reliability was calculated. Within National Football League players, an association of CSP measures with cognitive and behavioral functioning was evaluated using a multivariate mixed effects model. The measurements of the two raters were highly correlated (CSP length: rho = 0.98; Intraclass Correlation Coefficient [ICC] 0.99; p < 0.0001; septum length: rho = 0.93; ICC 0.96; p < 0.0001). For presence versus absence of CSP, there was high agreement (Cohen kappa = 0.83, p < 0.0001). A higher rate of CSP, a greater length of CSP, as well as a greater ratio of CSP length to septum length was found in symptomatic former professional football players compared with athlete controls. In addition, a greater length of CSP was associated with decreased performance on a list learning task (Neuropsychological Assessment Battery List A Immediate Recall, p = 0.04) and decreased test scores on a measure of estimate verbal intelligence (Wide Range Achievement Test Fourth Edition Reading Test, p = 0.02). Given the high prevalence of CSP in neuropathologically confirmed CTE in addition to the results of this study, CSP may serve as a potential early in vivo imaging marker to identify those at high risk for CTE. Future research is needed to investigate the pathomechanism underlying the development of CSP after repetitive head impacts, and its potential association with neuropathologically confirmed CTE.

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Section: Methodsmentioning

confidence: 99%

Cavum Septi Pellucidi in Symptomatic Former Professional Football Players

Koerte

Hufschmidt

Muehlmann

et al. 2016

Journal of Neurotrauma

Self Cite

109

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“…Former professional NFL players who played football before the age of 12 years had more severe cognitive loss on neuropsychiatric testing and increased microstructural abnormalities in the corpus callosum on diffusion tensor imaging compared to age-matched subjects who did not play football until after the age of 12 years. 28, 29 Genes, most likely multiple genes, are also likely to modify CTE risk, including the inheritance of the apolipoprotein e4 (APoE e4) allele, MAPT H1 haplotype and TMEM106B. 17 Lifestyle factors (e.g., alcohol, substance abuse, performance enhancing drugs, obesity) might also influence susceptibility or disease progression, but have not yet been tested empirically.…”

Section: Clinical Aspects Of Ctementioning

confidence: 99%

Repetitive Head Impacts and Chronic Traumatic Encephalopathy

McKee

Alosco

Huber

2016

Neurosurgery Clinics of North America

116

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There are growing concerns that cumulative repetitive head impact exposure through routine participation in contact and collision sports is associated with increased risk of long-term problems in memory and cognition, including the development of chronic traumatic encephalopathy (CTE). CTE is a distinctive neurodegenerative disease that occurs as a result of repetitive head impacts (RHI) including concussion and subconcussion. Like most neurodegenerative diseases, CTE can only be diagnosed by postmortem neuropathologic examination of brain tissue. Recently a panel of exerts concluded that CTE is a unique disorder with a pathognomonic lesion that can be reliably distinguished from other neurodegenerative diseases, such as Alzheimer’s disease and frontotemporal lobar degeneration. The pathognomonic lesion of CTE consists of a perivascular accumulation of hyperphosphorylated tau protein in neurons and astrocytes in an irregular pattern, and is typically most prominent at the depths of the cerebral sulci. Clinically CTE is associated with violent behaviors, explosivity, a loss of control, depression, suicide, memory loss and cognitive changes. While the exact incidence and prevalence of CTE remain unknown, there is increasing evidence that CTE affects amateur atheletes as well as professional athletes and military veterans. Given the millions of contact sport athletes and military service members who are exposed to RHI each year, CTE has become a major public health concern. There is a critical need for identification of CTE during life, improved understanding of the epidemiology and pathobiology, and the development of effective prevention and treatment strategies for CTE.

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“…Moreover, studies have suggested that starting to play football at an earlier age (<12 years) was associated with greater cognitive difficulties in later life and altered neurobiology in former National Football League (NFL) players. 63,64 In a small study of 10 collegiate football players who underwent clinical testing and DTI before and after the season, white matter changes in the brain correlated with helmet impact measures (in the absence of a concussion), and these white matter changes persisted at 6-month follow-up. 2 …”

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confidence: 99%

Multiple Past Concussions in High School Football Players

et al. 2016

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Background There is increasing concern about the possible long-term effects of multiple concussions, particularly on the developing adolescent brain. Whether the effect of multiple concussions is detectable in high school football players has not been well studied, although the public health implications are great in this population. Purpose To determine if there are measureable differences in cognitive functioning or symptom reporting in high school football players with a history of multiple concussions. Study Design Cross-sectional study; Level of evidence, 3. Methods Participants included 5232 male adolescent football players (mean [±SD] age, 15.5 ± 1.2 years) who completed baseline testing between 2009 and 2014. On the basis of injury history, athletes were grouped into 0 (n = 4183), 1 (n = 733), 2 (n = 216), 3 (n = 67), or ≥4 (n = 33) prior concussions. Cognitive functioning was measured by the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery, and symptom ratings were obtained from the Post-Concussion Symptom Scale. Results There were no statistically significant differences between groups (based on the number of reported concussions) regarding cognitive functioning. Athletes with ≥3 prior concussions reported more symptoms than did athletes with 0 or 1 prior injury. In multivariate analyses, concussion history was independently related to symptom reporting but less so than developmental problems (eg, attention or learning problems) or other health problems (eg, past treatment for psychiatric problems, headaches, or migraines). Conclusion In the largest study to date, high school football players with multiple past concussions performed the same on cognitive testing as those with no prior concussions. Concussion history was one of several factors that were independently related to symptom reporting.

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Age at First Exposure to Football Is Associated with Altered Corpus Callosum White Matter Microstructure in Former Professional Football Players

Cited by 151 publications

References 78 publications

Cavum Septi Pellucidi in Symptomatic Former Professional Football Players

Cavum Septi Pellucidi in Symptomatic Former Professional Football Players

Repetitive Head Impacts and Chronic Traumatic Encephalopathy

Multiple Past Concussions in High School Football Players

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