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

慢性创伤性脑病是一种以明显沉积为特征的神经退行性疾病。 一种异常形式的tau蛋白，其模式与包括阿尔茨海默氏症在内的其他疾病不同 疾病(AD)。CTE最常见于职业接触性运动运动员(如拳击、足球) 头部反复遭受重击，导致脑震荡和亚脑震荡创伤。 据报道，经神经病理证实的CTE患者最小为17岁，运动员仅为 在高中或大学期间参加体育运动。在非运动员身上也发现了这种情况，这些人经历了重复的 头部撞击，包括癫痫患者、身体虐待受害者和服兵役人员。与什么形成对比 可以从媒体对CTE的广泛关注推断，CTE的科学仍处于初级阶段；批判性的 问题仍然存在，比如它是否是一种常见的疾病。虽然脑神经病理特征 CTE的临床表现近年来已进一步明确，但临床表现仍不甚理想。 具有特征性，尽管在拳击手中曾有过“拳击性痴呆症”的病例报道 自20世纪初以来，S。临床诊断标准直到最近才公布，缺乏有效性。 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记物只有 已在初步研究中使用。因此，迫切需要开发准确的方法来检测和 在生活中诊断CTE，以便制定有效的预防和治疗干预措施。 此外，尽管反复头部撞击的病史是CTE的必要危险因素，但它本身不是。 足够了。有必要了解头部撞击暴露的哪些具体方面会使 CTE风险增加的个体，并检查该风险的潜在遗传修饰物。要解决这些问题 需求，我们提出了一项多学科、多中心、纵向研究，研究对象是前运动员，这些运动员曾高度暴露于 重复性头部撞击(120名有症状和无症状的前NFL球员)或中等程度的重复暴露 Head Impact(60名有症状和无症状的前大学橄榄球运动员)和60名对照组 无症状的同龄男性，没有任何重复头部撞击暴露或创伤性脑损伤的病史。 我们建议的目的是：(1)收集和分析神经影像和液体生物标记物，用于检测 生活中的CTE，包括使用一种新的PET示踪剂来测量异常脑tau的数量；(2) 描述CTE的临床表现；(3)检查CTE在三年内的进展情况； (4)完善和验证CTE的临床诊断标准；(5)进行遗传和头颅调查 CTE的影响暴露风险因素；以及(6)与全国各地的研究人员和 为了加快我们对这一疾病的了解和治疗的增长，我们在国外也取得了进展。

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 diagnosis of 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.