The Frontotemporal Lobar Degeneration Neuroimaging Initiative

描述(由申请人提供)：这项提案描述了一项利用阿尔茨海默病神经成像倡议(ADNI)建立的基础设施来研究额颞叶变性(FTLD)的计划。FTLD是导致痴呆症的常见原因，尤其是在65岁以下的患者中，会带来巨大的经济和社会代价。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。在为这些临床试验做准备时，重要的是建立准确、可靠和成本效益高的疾病进展标志物，以最大限度地发挥治疗试验的力量，以检测疾病改变的效果。在这项拟议的研究中，120名FTLD患者和120名年龄匹配的对照组将在一年的时间里接受MRI、FDG-PET以及血液、尿液和脑脊液生物标记物的研究，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，识别与阿尔茨海默病相关的β-淀粉样斑块。本研究的具体目的是：1)确定FTLD葡萄糖代谢、脑血流灌注和灰质体积纵向变化最大的区域，方差最小的区域；2)确定FTLD白质束完整性纵向变化最大、方差最小的区域；3)对比FDG-PET、ASL血流灌注、灰质体积和白质束完整性的表现，检测FTLD的纵向变化；4)建立FTLD糖代谢、脑血流灌注、灰质体积和白质完整性纵向变化的临床相关性，5)量化FTLD患者脑脊液tau和A-beta1-42水平及tau/abeta比值随时间的变化；6)明确代谢、结构成像和脑脊液生物标志物特征，预测FTLD的临床诊断价值。如果实现了这些目标，拟议的研究将提供确切的数据，说明哪些区域是跟踪FTLD病程的最敏感指标，以及就这一目的而言，PET是否明显优于MRI，或者反过来。这些数据还将提供估计，根据这些估计可以计算出用于临床研究的能量。所有数据最终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)神经成像计划将提供有关如何使用大脑图像随时间跟踪FTLD进程的信息，以及为此目的最好的技术。这些信息对计划FTLD新药试验的研究人员将是有价值的，这样他们就可以使用大脑成像来帮助决定哪些药物对治疗这种疾病最有希望。

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.