Amyloid Imaging in Frontotemporal Dementia and Alzheimer's Disease

描述(申请人提供)：在过去的十年里，痴呆症的诊断方法已经从一种微妙地转变为一种可以利用特征发现来支持特定痴呆症诊断的方法。这种转变在很大程度上是由脑成像的进步推动的，脑成像使用正电子发射断层扫描(PET)显示了阿尔茨海默病(AD)相对特定的分子和生化变化，并使用磁共振成像(MRI)显示了特征性的解剖变化。最近开发的一种PET成像化合物标记淀粉样蛋白，N-甲基[11C]2-(4‘-甲氨基苯基)-6-羟基苯并噻唑，绰号匹兹堡化合物B，是该领域的另一项重大进展，可能有助于区分不同的痴呆症原因。特别是，一组相对常见的退行性痴呆统称为额颞叶变性(FTLD)，在一生中可能很难与AD区分开来。我们推测，PIB成像与传统的葡萄糖代谢PET成像和[18F]氟脱氧葡萄糖(FDG)的结合将有效地区分这两种疾病。我们计划通过加州大学旧金山分校的记忆和衰老中心招募45名AD患者和45名FTLD患者，该中心是AD和FTLD研究的主要中心。患者将接受密集的临床诊断评估，包括认知测试、基因测试和磁共振成像。他们将在纵向队列中接受大脑捐赠计划的跟踪。受试者将接受PIB-PET和FDG-PET的研究，将使用PIB和FDG摄取的定性评级和定量测量。这些措施将与临床诊断和长期尸检诊断进行比较，以确定这两种技术相对于尽可能高质量的临床诊断的敏感性、特异性和区分能力，以及彼此之间的敏感性、特异性和区分性。这个项目的意义在于，目前还没有实验室测试来区分这两种痴呆症。PIB有可能成为诊断AD和FTLD的有用工具。随着针对这两种疾病的新疗法的开发，这一点将特别重要。

DESCRIPTION (provided by applicant): Over the past decade, approaches to the diagnosis of dementia have subtly shifted from one in which various disorders are "ruled out" to one in which characteristic findings may be used to support a specific dementia diagnosis. This transition has in large part been fueled by advances in brain imaging that show relatively specific molecular and biochemical changes in Alzheimer's disease (AD) using positron emission tomography (PET), and characteristic anatomical changes using magnetic resonance imaging (MRI). The recent development of a PET imaging compound that labels amyloid, N-methyl [11C]2-(4'- methylaminophenyl)-6-hydroxybenzothiazole, nicknamed "PIB" for Pittsburgh compound B, is another major advance for the field that may help differentiate different causes of dementia. In particular, a relatively common group of degenerative dementias collectively known as frontotemporal lobar degeneration (FTLD) may be difficult to differentiate from AD during life. We hypothesize that the combination of PIB imaging along with traditional glucose metabolic PET imaging with [18F]Fluorodeoxyglucose (FDG) will effectively differentiate the two disorders. We plan to recruit a group of 45 patients with AD and 45 patients with FTLD through the Memory and Aging center at the University of California San Francisco, a major center for the study of AD and FTLD. Individuals will receive an intensive clinical diagnostic evaluation including cognitive testing, genetic testing, and MR imaging. They will be followed in a longitudinal cohort with a brain donation program. Subjects will be studied with PIB-PET and FDG-PET and both qualitative ratings and quantitative measurements of PIB and FDG uptake will be utilized. These measures will be compared to clinical diagnosis and, over the long term, autopsy diagnoses to define the sensitivity, specificity, and discriminative ability of the two techniques relative to the highest quality clinical diagnosis possible, and to one another. The significance of this project is that there are no current laboratory tests to differentiate these two dementing disorders. PIB could become a diagnostic tool that is useful in diagnosing AD and FTLD during life. This will be especially important as new treatments for both disorders are developed.