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Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates.

ABSTRACT: Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum, signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces and periventricular white matter disease. Given the partial overlapping of the clinical expression, epidemiology and pathogenesis of CTE and Alzheimer's disease (AD), as well as the close association between traumatic brain injuries (TBIs) and neurofibrillary tangle formation, a mixed pathology promoted by pathogenetic cascades resulting in either CTE or AD has been postulated. Molecular studies suggested that TBIs increase the neurotoxicity of the TAR DNA-binding protein 43 (TDP-43) that is a key pathological marker of ubiquitin-positive forms of frontotemporal dementia (FTLD-TDP) associated or not with motor neurone disease/amyotrophic lateral sclerosis (ALS). Similar patterns of immunoreactivity for TDP-43 in CTE, FTLD-TDP and ALS as well as epidemiological correlations support the presence of common pathogenetic mechanisms. The present review provides a critical update of the evolution of the concept of CTE with reference to its neuropathological definition together with an in-depth discussion of the differential diagnosis between this entity, AD and frontotemporal dementia.

SUBMITTER: Costanza A

PROVIDER: S-EPMC3166385 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates.

Costanza A A Weber K K Gandy S S Bouras C C Hof P R PR Giannakopoulos P P Canuto A A

Neuropathology and applied neurobiology 20111001 6

Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality ...[more]

PMID: 21696410

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Project description:Cerebral amyloid angiopathy (CAA) consists of beta-amyloid deposition in the walls of the cerebrovasculature and is commonly associated with Alzheimer's disease (AD). However, the association of CAA with repetitive head impacts (RHI) and with chronic traumatic encephalopathy (CTE) is unknown. We evaluated the relationship between RHI from contact sport participation, CTE, and CAA within a group of deceased contact sport athletes (n?=?357), a community-based cohort (n?=?209), and an AD cohort from Boston University AD Center (n?=?241). Unsupervised hierarchal cluster analysis demonstrated a unique cluster (n?=?11) with increased CAA in the leptomeningeal vessels compared to the intracortical vessels (p?<?0.001) comprised of participants with significantly greater frequencies of CTE (7/11) and history of RHI. Overall, participants with CTE (n?=?251) had more prevalent (p?<?0.001) and severe (p?=?0.010) CAA within the frontal leptomeningeal vessels compared to intracortical vessels. Compared to those with AD, participants with CTE had more severe CAA in frontal than parietal lobes (p?<?0.001) and more severe CAA in leptomeningeal than intracortical vessels (p?=?0.002). The overall frequency of CAA in participants with CTE was low, and there was no significant association between contact sport participation and the presence of CAA. However, in those with CAA, a history of contact sports was associated with increased CAA severity in the frontal leptomeningeal vessels (OR?=?4.01, 95% CI 2.52-6.38, p?<?0.001) adjusting for AD, APOE ?4 status, and age. Participants with CAA had increased levels of sulcal tau pathology and decreased levels of the synaptic marker PSD-95 (p's?<?0.05), and CAA was a predictor of dementia (OR?=?1.75, 95% CI 1.02-2.99, p?=?0.043) adjusting for age, sex, and comorbid pathology. Overall, contact sport participation and CTE were associated with more severe frontal and leptomeningeal CAA, and CAA was independently associated with worse pathological and clinical outcomes.

Project description:Chronic traumatic encephalopathy is a debilitating neurodegenerative disorder associated with repetitive traumatic brain injuries often sustained through prior contact sport participation. The frequency of this disorder in a diverse population, including amateur athletes, is unknown. Primary historical obituary and yearbook records were queried for 2566 autopsy cases in the Mayo Clinic Tissue Registry resulting in identification of 300 former athletes and 450 non-athletes. In these cases, neocortical tissue was screened for tau pathology with immunohistochemistry, including pathology consistent with chronic traumatic encephalopathy, blinded to exposure or demographic information. Using research infrastructure of the Rochester Epidemiology Project, a comprehensive and established medical records-linkage system of care providers in southern Minnesota and western Wisconsin, medical diagnostic billing codes pertaining to head trauma, dementia, movement disorders, substance abuse disorders and psychiatric disorders were recorded for cases and controls in a blinded manner. A total of 42 individuals had pathology consistent with, or features of, chronic traumatic encephalopathy. It was more frequent in athletes compared to non-athletes (27 cases versus 15 cases) and was largely observed in men (except for one woman). For contact sports, American football had the highest frequency of chronic traumatic encephalopathy pathology (15% of cases) and an odds ratio of 2.62 (P-value = 0.005). Cases with chronic traumatic encephalopathy pathology had higher frequencies of antemortem clinical features of dementia, psychosis, movement disorders and alcohol abuse compared to cases without chronic traumatic encephalopathy pathology. Understanding the frequency of chronic traumatic encephalopathy pathology in a large autopsy cohort with diverse exposure backgrounds provides a baseline for future prospective studies assessing the epidemiology and public health impact of chronic traumatic encephalopathy and sports-related repetitive head trauma.

Project description:The United States Department of Defense Blast Injury Research Program Coordinating Office organized the 2015 International State-of-the-Science meeting to explore links between blast-related head injury and the development of chronic traumatic encephalopathy (CTE). Before the meeting, the planning committee examined articles published between 2005 and October 2015 and prepared this literature review, which summarized broadly CTE research and addressed questions about the pathophysiological basis of CTE and its relationship to blast- and nonblast-related head injury. It served to inform participants objectively and help focus meeting discussion on identifying knowledge gaps and priority research areas. CTE is described generally as a progressive neurodegenerative disorder affecting persons exposed to head injury. Affected individuals have been participants primarily in contact sports and military personnel, some of whom were exposed to blast. The symptomatology of CTE overlaps with Alzheimer's disease and includes neurological and cognitive deficits, psychiatric and behavioral problems, and dementia. There are no validated diagnostic criteria, and neuropathological evidence of CTE has come exclusively from autopsy examination of subjects with histories of exposure to head injury. The perivascular accumulation of hyperphosphorylated tau (p-tau) at the depths of cortical sulci is thought to be unique to CTE and has been proposed as a diagnostic requirement, although the contribution of p-tau and other reported pathologies to the development of clinical symptoms of CTE are unknown. The literature on CTE is limited and is focused predominantly on head injuries unrelated to blast exposure (e.g., football players and boxers). In addition, comparative analyses of clinical case reports has been challenging because of small case numbers, selection biases, methodological differences, and lack of matched controls, particularly for blast-exposed individuals. Consequently, the existing literature is not sufficient to determine whether the development of CTE is associated with head injury frequency (e.g., single vs. multiple exposures) or head injury type (e.g., impact, nonimpact, blast-related). Moreover, the incidence and prevalence of CTE in at-risk populations is unknown. Future research priorities should include identifying additional risk factors, pursuing population-based longitudinal studies, and developing the ability to detect and diagnose CTE in living persons using validated criteria.

Dataset Information

Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates.

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Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates.

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