Clinicopathological Correlation in Chronic Traumatic Encephalopathy (CTE) and Chronic Traumatic Brain Injury (cTBI)

项目2侧重于慢性创伤性脑病(CTE)和慢性创伤性脑病的临床特征。 创伤性脑损伤(CTBI)病理学。目前，CTE只能通过神经病理学进行诊断。 诊断生活中的CTE是至关重要的，以便能够估计发病率和患病率、病程和预后 可以被理解，可以开发治疗方法。甚至比CTE更大的程度上，临床 CTBI的相关性(在本项目中定义为中度至 严重的颅脑损伤)是未知的。这个项目的主要假设是，有明显的情绪，行为， CTE和cTBI的认知、运动和影像特征。我们将补充现有的临床和 来自八个脑库中每一个的神经病理数据，以及新收集的数据，以解决三个特定的 目标。在目标1中，我们将检验创伤性脑病综合征(TES)的有效性和可靠性。 临床标准。这些标准以前是用来诊断生活中的CTE的，但也意味着 捕捉其他与脑外伤相关的神经退行性变过程。来自世界各地225名脑捐赠者的家人 年龄和脑外伤，接触和碰撞运动和军事暴露，临床医生将获得半 结构化的历史。一个由多学科专家组成的协商一致小组将评估是否符合工商业污水附加费标准。我们 将首先使用CTE病理学评估评分者间的可靠性和敏感性、特异性和准确性，然后使用 以cTBI病理为金标准。在目标2中，我们将使用临床特征来构建预测模型 CTE和cTBI病理学。对于来自脑库的1500名大脑捐赠者，我们将使用现有数据 并从家庭成员那里收集额外的广泛的结构化临床数据，包括各种认知、 情绪、行为和运动症状。我们将使用临床特征来建立CTE和 CTBI病理学使用知识指导和纯数据驱动(机器学习)方法。在目标3中，我们 将研究结构MRI和神经心理学(NP)与CTE和cTBI病理的相关性。为 来自各个脑库的脑捐赠者，我们将汇编之前获得的活体脑MRI扫描和NP 测试。核磁共振成像将在视觉上评估局部萎缩、白质高信号、腔间隔 透明质变薄，骨痂变薄，少量出血。使用NP报告，我们将对捐赠者进行分类 基于认知和情绪/行为领域的损害，包括记忆、执行功能、 注意力、视觉空间功能、语言、抑郁和焦虑。我们将测试CTE和 颅脑损伤的病理、MRI视力分级和NP测试中的损害类型。该项目将添加 全面协调的临床信息到最大的脑捐赠者样本之一，具有良好的 描述了RHI和TBI的历史。该项目的发现将有助于完善现有的临床诊断 CTE标准，并告知未来cTBI的临床诊断标准。生活中的诊断是咨询的关键 了解家庭的病程和预后，并开发有效的治疗方法。

Project 2 focuses on the clinical features associated with chronic traumatic encephalopathy (CTE) and chronic traumatic brain injury (cTBI) pathologies. Currently, CTE only can be diagnosed neuropathologically. Diagnosing CTE in life is critical so that incidence and prevalence can be estimated, the course and prognosis can be understood and therapies can be developed. To an even greater extent than CTE, the clinical correlates of cTBI (defined for the purposes of this project as a chronic cavitary lesion after a moderate to severe TBI) are unknown. The overarching hypothesis of this project is that there are distinct mood, behavior, cognitive, motor and imaging features of CTE and cTBI. We will supplement existing clinical and neuropathological data from each of the eight brain banks with newly collected data to address three specific aims. In Aim 1, we will test the validity and reliability of the traumatic encephalopathy syndrome (TES) clinical criteria. These criteria were previously proposed to diagnose CTE in life, but are also meant to capture other TBI-related neurodegenerative processes. From family members of 225 brain donors across a range of ages and TBI, contact and collision sport and military exposures, clinicians will obtain a semi- structured history. A multi-disciplinary expert consensus panel will assess whether TES criteria are met. We will assess inter-rater reliability and sensitivity, specificity and accuracy using first CTE pathology and then cTBI pathology as the gold-standard. In Aim 2, we will use clinical features to construct predictive models of CTE and cTBI pathology. For 1,500 brain donors from across the brain banks, we will use existing data and collect from family members additional extensive structured clinical data, including a variety of cognitive, mood, behavior and motor symptoms. We will use the clinical features to build predictive models of CTE and cTBI pathology using knowledge guided and pure data-driven (machine learning) methodologies. In Aim 3, we will investigate structural MRI and neuropsychological (NP) correlates of CTE and cTBI pathology. For brain donors from across the brain banks, we will compile previously obtained in-vivo brain MRI scans and NP testing. MRIs will be visually rated for regional atrophy, white matter hyperintensities, cavum septum pellucidum, corpus callosum thinning and microhemorrhages. Using NP reports, we will categorize donors based on cognitive and mood/behavior domains with impairment, including memory, executive function, attention, visuospatial function, language, depression and anxiety. We will test associations between CTE and cTBI pathology, MRI visual ratings and patterns of impairment on NP testing. This project will add comprehensive harmonized clinical information to one of the largest brain donor samples with well- characterized histories of RHI and TBI. Findings from this project will help refine existing clinical diagnostic criteria for CTE and inform future clinical diagnostic criteria for cTBI. Diagnosis in life is pivotal to counsel families about disease course and prognosis and to develop effective therapies.