Long-term outcomes of traumatic brain injury in veterans: a clinical, neuropsychological, and neuropathological study

脑损伤是一种头部损伤，会对大脑造成损害。每两个人中就有一个会在一生中经历脑损伤。它是年轻人死亡和残疾的主要原因，并增加了患痴呆症、中风、癫痫和抑郁症等疾病的风险。需要更多的研究来了解这些风险并帮助降低它们。我们的目标是通过研究二战期间遭受脑损伤的退伍军人的健康状况来实现这一点。我们可以访问一个独特的档案，其中包含2000多名退伍军人一生中收集的信息。这包括他们在受伤后经历的症状和疾病，他们在认知测试中的表现，在某些情况下，他们死后捐赠的脑组织。该研究项目有三个目标：第一个目标是研究脑损伤如何影响导致痴呆症的过程。痴呆症是由大脑某些区域的受损蛋白质堆积引起的。然而，目前还不清楚为什么受损的蛋白质会以这种方式积累。在动物身上的实验表明，受损的蛋白质可能会从一个大脑区域传播到另一个区域，切断区域之间的连接可以阻止这种传播。但很难测试这种情况是否也发生在人类身上。在这个项目中，我们将研究22名退伍军人捐赠的脑组织，他们每个人在枪击和炮弹爆炸造成的脑损伤后都存活了50多年。对于每个大脑，我们将计算和绘制左右两侧受损的蛋白质。然后，我们将比较双方的蛋白质水平。由于退伍军人遭受的每一次损伤只切断了大脑一侧的连接，我们的比较将揭示，当大脑区域之间的连接被切断时，受损蛋白质的传播是否被阻止了。这项研究将提供关于受损蛋白质如何在人类体内积累的有价值的信息，支持针对这一过程的新药的开发，以预防和治疗痴呆。第二个目标是评估不同类型的脑损伤是否会增加发展某些健康状况的长期风险。我们将比较从1000多名脑损伤和颅骨骨折的退伍军人中收集的健康信息和1000多名脑损伤而没有颅骨骨折的退伍军人的健康信息。这项研究将是此类研究中规模最大的。这一结果将被用来为脑损伤管理指南提供参考，目前该指南并未为受颅骨骨折影响的脑损伤患者提供指导。第三个目标是评估现有的理论是否可以用来预测脑损伤后的认知功能(如记忆、语言和注意力)。这些现有的理论描述了不同的大脑区域如何执行特定的认知功能，但它们是基于没有大脑损伤的人。使用这些理论和80名退伍军人脑部扫描显示的损伤区域，我们将预测他们的认知特征。然后，我们将把我们的预测与伤病后几十年收集的退伍军人认知测试分数进行比较。这种比较将使我们能够确定现有的理论是否可以用来预测特定大脑区域受损后的认知功能，以及大脑在受损后是否适应以新的方式执行功能。然后，这些结果可以为特定大脑区域受损患者的个性化康复提供参考。这项研究将作为牛津大学的博士进行。这名博士生是一名学术神经学实习生。他打算利用通过这个项目获得的技能，成为创伤性脑损伤治疗和研究方面的领先专家。博士学位将由一名高级学术神经学家和一名高级神经心理学家指导，前者是脑组织研究方面的专家，后者是研究脑损伤的长期影响的专家。

A brain injury is a head injury which causes damage to the brain. One in two people will experience a brain injury during their life. It is the leading cause of death and disability in young people, and increases the risk of developing diseases like dementia, stroke, epilepsy, and depression. More research is needed to understand these risks and help reduce them. We aim to do this by studying the health of veterans who sustained brain injuries during World War II. We have access to a unique archive of information that was collected over the lifetime of more than 2,000 veterans. This includes the symptoms and diseases they experienced after injury, their performance in cognitive tests, and, in some cases, brain tissue which was donated when they died. The research project has three aims:The first aim is to investigate how brain injuries affect the processes which cause dementia. Dementia is caused by the build up of damaged proteins in certain brain regions. However, it is not clear why damaged proteins accumulate in this way. Experiments in animals suggest that damaged proteins may spread from one brain region to another and that cutting connections between regions stops the spread. But it has been difficult to test whether this also happens in humans. In this project, we will study brain tissue donated by 22 veterans who each survived for more than fifty years after brain injuries caused by gunshots and shell explosions. For each brain, we will count and map the damaged proteins in both the left and right side. Then, we will compare the levels of proteins between the two sides. Because each injury sustained by the veterans only cut connections on one side of the brain, our comparisons will reveal whether the spread of damaged proteins was stopped when connections between brain regions were cut. This study will provide valuable information about how damaged proteins accumulate in humans, supporting the development of new drugs that target this process to prevent and treat dementia.The second aim is to assess whether different types of brain injury increase the long-term risk of developing certain health conditions. We will compare health information collected from more than 1,000 veterans who survived brain injury with skull fracture to more than 1,000 veterans who survived brain injury without skull fracture. This study will be the largest of its kind ever performed. The results will be used to inform brain injury management guidelines, which currently do not provide guidance for people affected by brain injury with skull fracture. The third aim is to evaluate whether existing theories can be used to predict cognitive functions (such as memory, language, and attention) after brain injury. These existing theories describe how different brain regions perform specific cognitive functions, but they are based on people without brain injury. Using these theories and the regions of damage shown on brain scans of 80 veterans, we will predict their cognitive traits. Then, we will compare our predictions with the veterans' cognitive test scores that were collected several decades after injury. This comparison will enable us to determine whether existing theories can be used to predict cognitive function after damage to specific brain regions, and whether the brain adapts to perform functions in new ways after it has been damaged. These results can then inform the personalised rehabilitation of people living with damage to specific brain regions.This research will be conducted as a PhD at Oxford University. The PhD student is an academic neurology trainee. He intends to use the skills that he gains through this project to become a leading specialist in treatment and research of traumatic brain injury. The PhD will be supervised by a senior academic neurologist who is an expert in the study of brain tissue, and a senior neuropsychologist who is an expert in the study of the long-term effects of brain injuries.