The Frontotemporal Lobar Degeneration Neuroimaging Initiative

描述（由申请人提供）：本提案描述了一项计划，使用阿尔茨海默病神经影像学倡议（ADNI）建立的基础设施研究额颞叶变性（FTLD）。FTLD是痴呆症的常见原因，特别是在65岁以下的患者中，具有巨大的经济和社会成本。在接下来的几年里，FTLD的潜在治疗药物可能会出现，并需要临床测试。在准备这些临床试验时，重要的是建立精确、可靠和具有成本效益的疾病进展标志物，以最大限度地提高治疗试验检测疾病改善效果的能力。在拟议的研究中，120名FTLD患者和120名年龄匹配的对照者将在一年内使用MRI，FDG-PET以及血液，尿液和CSF生物标志物进行研究，以确定跟踪FTLD进展的最佳区域和最佳方法。所有患者还将接受PIB-PET扫描，以识别与阿尔茨海默病相关的β-淀粉样蛋白斑块。这项研究的具体目标是：1）确定FTLD显示葡萄糖代谢、脑灌注和灰质体积最大纵向变化且方差最低的区域，2）确定FTLD显示白色物质束完整性最大纵向变化且方差最低的区域，3）对比FDG-PET、ASL灌注、灰质体积和白色物质束完整性以检测FTLD的纵向变化，4）建立FTLD中葡萄糖代谢、灌注、灰质体积和白色物质完整性的纵向变化的临床相关性，5）量化FTLD中CSF tau和A-β 1 -42水平以及tau/abeta比值随时间的变化，以及6）定义预测FTLD临床诊断的PIB滞留增加的代谢、结构成像和CSF生物标志物特征。如果这些目标得以实现，拟议的研究将提供关于哪些区域是FTLD病程最敏感的指标的可靠数据，以及PET在此方面是否明显优于MRI或反之亦然。这些数据还将提供估计值，据此可以计算临床研究的把握度。所有数据最终都将在一个可公开访问的数据库中提供，供其他研究人员使用。公共卫生相关性：额颞叶变性（FTLD）神经影像学倡议将提供有关如何使用大脑图像随时间推移跟踪FTLD过程的信息，以及什么技术最适合此目的。这些信息对于计划FTLD新药试验的研究人员来说非常有价值，因此他们可以使用脑成像来帮助决定哪些药物最有希望治疗这种疾病。

DESCRIPTION (provided by applicant): This proposal describes a plan to study frontotemporal lobar degeneration (FTLD) using the infrastructure established by the Alzheimer's Disease Neuroimaging Initiative (ADNI). FTLD is a common cause of dementia, especially in patients under the age of 65, with large economic and social costs. Over the next few years, potential therapeutic agents for FTLD will likely emerge and require clinical testing. In preparation for these clinical trials, it is important to establish precise, reliable and cost-effective markers for disease progression, to maximize the power of treatment trials to detect disease modifying effects. In the proposed study, 120 patients with FTLD and 120 age-matched controls will be studied with MRI, FDG-PET, and blood, urine and CSF biomarkers over the course of one year to determine the best regions and best methods for following the progression of FTLD. All patients will also undergo PIB-PET scanning, which identifies beta-amyloid plaques associated with Alzheimer's disease. The specific aims of the study are: 1) To identify the regions where FTLD shows greatest longitudinal changes in glucose metabolism, cerebral perfusion, and gray matter volume with the lowest variance, 2) To identify regions where FTLD shows greatest longitudinal changes with lowest variance in white matter tract integrity, 3) To contrast the performance of FDG-PET, ASL perfusion, gray matter volume and white matter tract integrity to detect longitudinal changes in FTLD, 4) To establish the clinical correlates of longitudinal changes in glucose metabolism, perfusion, gray matter volume and white matter integrity in FTLD, 5) To quantify the changes in CSF tau and A-beta1-42 levels and tau/abeta ratios over time in FTLD, and 6) To define the metabolic, structural imaging and CSF biomarker features predicting increased PIB retention with a clinical diagnosis of FTLD. Should these aims be achieved, the proposed study would provide firm data about which regions are the most sensitive indicators for following the course of disease in FTLD, and whether PET is significantly better than MRI for this purpose or visa-versa. The data would also provide estimates from which power could be calculated for clinical studies. All the data will eventually be available in a publicly accessible database for use by other researchers. PUBLIC HEALTH RELEVANCE: The frontotemporal lobar degeneration (FTLD) neuroimaging initiative will provide information on how to use brain images to follow the course of FTLD over time, and what techniques are best for this purpose. This information will be valuable to researchers planning trials of new medications for FTLD, so they can use brain imaging to help decide which drugs show the most promise for treating the disease.