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

额颞性痴呆(FTD)是青年起病痴呆的常见原因。目前唯一已知的FTD的危险因素是遗传，有三个基因占家族性FTD的大部分，分别是原颗粒蛋白、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用药，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，既包括已经出现症状的人，也包括因为携带异常基因突变而有可能在未来出现症状的人。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家族的30名研究对象将每年在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，还将包括tau正电子发射断层扫描这一新技术，该技术可能在一生中首次识别tau突变患者大脑中是否存在tau病理。这些研究对象将是一项名为遗传性额颞叶痴呆倡议(GENFI)的更大规模多中心研究的一部分，参与该倡议的300多名受试者的数据将可供分析。这项研究的关键成果将是开发有助于在疾病早期识别的标记，以及允许跟踪疾病进展的标记。然后，这些标记可以用于未来遗传FTD药物的临床试验。

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.