Chronic Traumatic Encephalopathy: Detection, Diagnosis, Course, and Risk Factors

慢性创伤性脑病：检测、诊断、病程和危险因素

基本信息

批准号：
10063908
负责人：
JEFFREY L. CUMMINGS
金额：
$ 225.99万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-15 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10063908
关键词：
Address Age Alzheimer&apos s Disease Amygdaloid structure Amyloid Astrocytes Attention Award Behavior Behavioral Biological Markers Boxing Brain Brain Chemistry Brain Concussion Brain Diseases Case Study Clinical Cognitive Consensus Consensus Workshop Control Groups Corpus Callosum Country Data Databases Degenerative Disorder Dementia Deposition Detection Diagnosis Diagnostic Diffusion Magnetic Resonance Imaging Disease Epilepsy Exposure to Frequencies Functional Magnetic Resonance Imaging Genetic Genetic Polymorphism Gold Grant Growth Head Image Impairment Individual Intervention Life Liquid substance Literature Longitudinal Studies Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Manufactured football Measures Methods Modeling Moods Motor Multicenter Studies Nerve Degeneration Neurocognitive Neurodegenerative Disorders Neurologic Neurons Pattern Plasma Play Positron-Emission Tomography Prevention Process Proxy Publishing Recording of previous events Reporting Research Personnel Rest Risk Risk Factors Science Septum Pellucidum Signs and Symptoms Sports Structure Subgroup Symptoms Syndrome Tauopathies Testing Thinness Tracer Trauma Traumatic Brain Injury Validation Validity and Reliability Variant Writing Youth brain abnormalities chronic traumatic encephalopathy clinical Diagnosis clinical diagnostics college contact sports data portal design diagnostic accuracy effective intervention experience follow-up head impact high risk high school in vivo infancy insight men military service multidisciplinary neuroimaging neuropathology novel physical abuse preventive intervention public health relevance service member subconcussion symposium tau Proteins tau-1 tool uptake white matter

项目摘要

DESCRIPTION (provided by applicant): Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by a distinct deposition of an abnormal form of the tau protein in a pattern that is unique from other diseases, including Alzheimer's disease (AD). CTE has been found most often in professional contact sport athletes (e.g., boxing, football) who have been subjected to repetitive blows to the head resulting in concussive and subconcussive trauma. Neuropathologically-confirmed CTE has been reported in individuals as young as 17 and in athletes who only played sports through high school or college. It also has been found in non-athletes who experienced repetitive head impacts, including epileptics, victims of physical abuse, and military service members. In contrast to what may be inferred by the extensive media attention on CTE, the science of CTE remains in its infancy; critical questions remain, such as whether or not it is a common disease. Although the neuropathological features of CTE have become further clarified in recent years, the clinical presentation of CTE is still not well characterized, even though there have been case reports in the literature of "dementia pugilistica" in boxers since the early 1900's. Clinical diagnostic criteria have only recently been published and lack validation. Neuroimaging and fluid biomarkers developed for the diagnosis of other neurodegenerative diseases have only been used in preliminary studies. There is thus an urgent need to develop accurate methods for detecting and diagnosing CTE during life so that effective interventions for prevention and treatment can be developed. Moreover, though a history of repetitive head impacts is a necessary risk factor for CTE, it alone is not sufficient. There is a need to understand what specific aspects of the head impact exposure places an individual at increased risk for CTE and to examine potential genetic modifiers of that risk. To address these needs, we propose a multidisciplinary, multicenter, longitudinal study of former athletes with high exposure to repetitive head impacts (120 former NFL players with and without symptoms) or medium exposure to repetitive head impact (60 former college football players with and without symptoms) and a control group of 60 asymptomatic same-age men without any history of repetitive head impact exposure or traumatic brain injury. The aims of our proposal are: (1) to collect and analyze neuroimaging and fluid biomarkers for the detection of CTE during life, including the use of a novel PET tracer to measure the amount of abnormal brain tau; (2) to characterize the clinical presentation of CTE; (3) to examine the progression of CTE over a three year period; (4) to refine and validate diagnostic criteria for the clinical diagnosisof CTE; (5) to investigate genetic and head impact exposure risk factors for CTE; and (6) to share project data with researchers across the country and abroad in order to expedite growth in our understanding and treatment of this disease.

描述（由适用提供）：慢性创伤性脑病（CTE）是一种神经退行性疾病，其特征是tau蛋白异常形式的明显沉积，其模式与其他疾病独有的模式，包括阿尔茨海默氏病（AD）。 CTE最常在专业接触运动运动员（例如拳击，足球）中被发现，他们受到重复打击，导致脑震荡和亚语创伤。据报道，17岁的个体以及仅通过高中或大学参加体育运动的运动员，已有神经病理学确认的CTE。在非运动员中也发现了这种重复性影响的非运动员，包括癫痫发作，体力虐待的精彩和兵役成员。与广泛的媒体对CTE的关注可能推断出的相反，CTE的科学仍处于起步阶段。仍然存在关键问题，例如它是否是常见疾病。尽管CTE的神经病理学特征在近年来已经进一步阐明，但CTE的临床表现仍未得到很好的特征，尽管自1900年代初以来，“ Pugilistica”的文献中有一些病例报告。临床诊断标准直到最近才发表且缺乏验证。为诊断其他神经退行性疾病而开发的神经影像学和流体生物标志物仅在初步研究中使用。因此，迫切需要开发精确的方法来检测和诊断CTE，以便可以开发出有效的预防和治疗干预措施。此外，尽管重复的头部影响史是CTE的必要风险因素，但仅此而不是需要了解头部影响曝光的哪些特定方面使个人面临CTE的风险增加，并检查该风险的潜在遗传修饰符。为了满足这些需求，我们提出了一项多学科的，多中心的纵向研究，对前运动员高度接触重复性的影响（120名前NFL有和没有症状的前NFL球员）或中等暴露于重复的头部影响（60名前大学橄榄球运动员，具有和没有症状的前大学足球运动员），没有症状的60个非对照组，没有任何重复性的脑海中的对照组，而无效的男性受到重复性影响。我们提案的目的是：（1）收集和分析神经影像学和流体生物标志物在生活中检测CTE，包括使用新型的宠物示踪剂来测量异常的脑tau量；（2）表征CTE的临床表现；（3）检查三年内CTE的进展；（4）用于完善和验证CTE临床诊断的诊断标准；（5）研究CTE的遗传和头部影响暴露风险因素；（6）与全国和国外的研究人员共享项目数据，以加快我们对这种疾病的理解和治疗。