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

• 批准号: 8960576
• 负责人: JEFFREY L. CUMMINGS
• 金额: $ 257.4万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 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/8960576
• 关键词: Address; Age; Alzheimer' s Disease; Amygdaloid structure; Amyloid; Astrocytes; Attention; Award; Behavior; Behavioral; Biological Markers; Boxing; Brain; Brain Chemistry; 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; Health; Image; Impairment; Individual; Intervention; Life; Liquid substance; Literature; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Manufactured football; Measures; Methods; Military Personnel; 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; Services; Signs and Symptoms; Sports; Subgroup; Symptoms; Syndrome; Tauopathies; Testing; Tracer; Trauma; Traumatic Brain Injury; Validation; Validity and Reliability; Variant; Writing; Youth; chronic traumatic encephalopathy; clinical Diagnosis; college; data sharing; design; diagnostic accuracy; effective intervention; experience; follow-up; head impact; high risk; high school; in vivo; infancy; insight; member; men; multidisciplinary; neuroimaging; neuropathology; novel; physical abuse; symposium; tau Proteins; tau-1; tool; uptake; white matter

 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（由申请人提供）：慢性创伤性脑病（CTE）是一种神经退行性疾病，其特征是异常形式的 tau 蛋白明显沉积，其模式不同于其他疾病，包括阿尔茨海默氏病（AD）。 CTE 最常见于职业接触运动运动员（例如拳击、足球），他们的头部受到反复打击，导致脑震荡和亚脑震荡创伤。据报道，年仅 17 岁的个体以及仅在高中或大学参加过体育运动的运动员中就有神经病理学证实的 CTE。在经历过头部反复撞击的非运动员中也发现了这种情况，包括癫痫患者、身体虐待的受害者和军人。与媒体对 CTE 的广泛关注相反，CTE 科学仍处于起步阶段；关键问题仍然存在，例如它是否是一种常见疾病。尽管近年来CTE的神经病理学特征已得到进一步阐明，但自1900年代初以来文献中已有拳击手“拳击手痴呆”的病例报告，但CTE的临床表现仍不明确。临床诊断标准直到最近才被制定 已发表且缺乏验证。为诊断其他神经退行性疾病而开发的神经影像和液体生物标志物仅用于初步研究。因此，迫切需要开发准确的方法来检测和诊断生命中的CTE，以便制定有效的预防和治疗干预措施。此外，尽管重复性头部撞击史是 CTE 的必要危险因素，但仅凭这一点还不够。有必要了解头部撞击暴露的哪些具体方面会增加个体发生 CTE 的风险，并检查该风险的潜在遗传修饰因素。为了满足这些需求，我们提出一项多学科、多中心、纵向研究，研究对象为高度遭受重复性头部撞击的前运动员（120 名有或没有症状的前 NFL 球员）或中度遭受重复性头部撞击的运动员（60 名有或没有症状的前大学橄榄球运动员），以及由 60 名无症状、没有任何重复性头部撞击或创伤性脑损伤史的同龄男性组成的对照组。我们提案的目的是：（1）收集和分析神经影像和液体生物标志物，以检测生命期间的 CTE，包括使用新型 PET 示踪剂来测量异常脑 tau 的数量； (2) 表征CTE的临床表现； (3) 检查三年内 CTE 的进展情况； (4)完善和验证CTE临床诊断的诊断标准； (5) 调查CTE的遗传和头部撞击暴露风险因素； (6) 与国内外研究人员共享项目数据，以加快我们对该疾病的了解和治疗。