Developing an evidence base for trials in genetic frontotemporal dementia - measures of disease onset and progression

额颞叶痴呆（FTD）是年轻发病痴呆的常见原因。目前已知的FTD的唯一危险因素是遗传因素，三个基因占家族性FTD的大部分，分别是前颗粒蛋白、tau和9号染色体开放阅读框72。现在有治疗这些疾病的有希望的途径，但我们仍然不知道什么时候应该开始使用药物，或者我们应该如何衡量对治疗的反应。这项研究计划调查患有遗传性FTD的人，包括已经出现症状的人，也包括携带异常基因突变的人，他们将来有出现症状的风险。这为了解疾病过程中最早的变化提供了一个窗口。来自遗传性FTD家庭的30名研究对象将在每年的三个时间点进行心理测试、脑成像、血液测试和脊髓液采集，以调查这些不同测试在该疾病不同阶段的变化模式。脑成像将不仅包括磁共振成像，还包括新的tau正电子发射断层扫描技术，这可能能够在生命中首次识别tau突变患者大脑中tau病理的存在。研究对象将成为一项更大的多中心研究的一部分，该研究被称为遗传额颞叶痴呆倡议（GENFI），数据将用于分析参与该倡议的300多名受试者。这项研究的关键成果将是开发有助于在早期阶段识别疾病的标志物，以及允许追踪疾病进展的标志物。这些标记物可用于未来的遗传性FTD药物临床试验。

Frontotemporal dementia (FTD) is a common cause of young onset dementia. The only known risk factors for FTD at present are genetic with three genes accounting for the majority of familial FTD, called progranulin, tau and chromosome 9 open reading frame 72. There are now promising avenues for treatment of these disorders but we still do not know when drugs should be started or how we should measure the response to treatment. This study plans to investigate people who have genetic FTD, including both people who have developed symptoms and also people who have a risk of developing symptoms in the future because they carry the abnormal genetic mutation. This allows a window into the earliest changes in the disease process. 30 study subjects from families with genetic FTD will have psychology testing, brain imaging, blood tests and spinal fluid collection annually at three time-points in order to investigate the patterns of change in these different tests at different stages of the disorder. Brain imaging will include not only magnetic resonance imaging but also the novel technique of tau positron emission tomography which may be able to identify the presence of tau pathology in the brains of people with tau mutations for the first time during life. The study subjects will be part of a larger multicentre study called the Genetic Frontotemporal dementia Initiative (GENFI) and data will be available for analysis from over 300 subjects who take part in that initiative. The key outcomes of the study will be to develop markers which help identify the disease at its earliest stage as well as markers that allow the progression of the disease to be tracked. These markers can then be used in future clinical trials of drugs in genetic FTD.