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

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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.