COMBINED FMRI, STRUCTURAL MRI, 18 MPPF PET AND APOE STATUS TO DETECT AD RISK

结合 FMRI、结构 MRI、18 MPPF PET 和 APOE 状态来检测 AD 风险

• 批准号: 8363475
• 负责人: SUSAN Y BOOKHEIMER
• 金额: $ 1.01万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363475
• 关键词: Algorithms; Alzheimer' s Disease; Alzheimer' s disease risk; Amygdaloid structure; Apolipoprotein E; Apolipoproteins; Atrophic; Binding; Brain; Cell Density; Clinical; Clinical assessments; Data; Diagnostic; Early Diagnosis; Elderly; Evaluation; Family; Funding; Future; Genetic Risk; Genotype; Goals; Grant; Hippocampus (Brain); Image; Imaging Techniques; Impaired cognition; Ligands; Magnetic Resonance Imaging; Measures; Memory; Modeling; National Center for Research Resources; Patients; Positron-Emission Tomography; Principal Investigator; Pyramidal Cells; Radial; Recording of previous events; Recruitment Activity; Research; Research Infrastructure; Resolution; Resources; Risk; Source; Structure; Techniques; Thick; Time; United States National Institutes of Health; Work; computational anatomy; cost; entorhinal cortex; high risk; mathematical model; middle age; neuropsychological; new technology; novel

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This is a continuing renewal of our R01 previously titled "Functional MRl for Early Diagnosis of Alzheimer's Disease" (5 R01 AG013308-10). The proposed third grant cycle builds on recent findings from this project and new technologies we have developed for imaging hippocampal structure and function. Our data support the utility of combining genetic risk, structural and functional MRl to identify early manifestations of Alzheimer's disease (AD), and further suggest that brain changes may occur much earlier than previously thought in Apolipoprotein epsilon-4 (APOE-4) carriers. Recently, our group has developed new techniques in high-resolution functional MRl acquisition and analysis, and in mathematical modeling algorithms that identify structural MRl change in Alzheimer's disease subjects over very short time periods. In addition, our group has recently worked with positron emission tomography (PET) using [18F]MPPF imaging, a ligand that measures pyramidal cell density in the hippocampus (HC), entorhinal cortex and amygdala; our preliminary data show that [18F]MPPF binding is decreased in MCI and AD, and correlates with memory in healthy controls, suggesting its potential as an independent assessment of risk for AD. This grant proposes using a combination of four new imaging techniques, two structural (HC cortical thickness and HC radial atrophy), and two functional (FMRI and [18F]MPPF) in control subjects in the 40-80 range at-risk for AD and MCI patients, to determine if there are subtle longitudinal changes in HC structure and function similar to those seen in AD, in cognitively intact at-risk subjects in the late middle age to elderly range. We will recruit 60 younger (40-60) and 36 older (60+) controls, (50% of each with APOE-4), and 35 mild MCI subjects, and follow them for 21/2 years using these novel imaging measures and clinical assessments. Analyses will focus on modeling the rate of change of each measure alone and in combination, with the goal of identifying subjects at highest risk for developing AD. Diagnostic and neuropsychological evaluations will provide clinical corroboration that genotype, family history, and short-term brain changes predict cognitive decline. By combining these different measures of hippocampal structure and function, our primary goal is to develop an approach to identifying those at-risk who are more likely to develop AD, and to determine which of these novel imaging techniques provide the most optimal and independent predictors of future decline.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 这是我们先前标题为“用于阿尔茨海默病早期诊断的功能性MRI”（5 R 01 AG 013308 -10）的R 01的持续更新。拟议的第三个资助周期建立在该项目的最新发现以及我们开发的用于海马结构和功能成像的新技术的基础上。我们的数据支持将遗传风险、结构和功能MRI相结合以识别阿尔茨海默病（AD）的早期表现的效用，并且进一步表明在载脂蛋白A-4（APOE-4）携带者中脑变化可能比先前认为的早得多地发生。最近，我们的小组已经开发了高分辨率功能性MRI采集和分析的新技术，以及在非常短的时间内识别阿尔茨海默病受试者中的结构性MRI变化的数学建模算法。此外，我们的小组最近使用[18 F]MPPF成像进行了正电子发射断层扫描（PET），[18 F]MPPF成像是一种测量海马（HC），内嗅皮层和杏仁核中锥体细胞密度的配体;我们的初步数据显示，[18 F]MPPF结合在MCI和AD中减少，并与健康对照组的记忆相关，表明其作为AD风险独立评估的潜力。这项拨款建议使用四种新的成像技术，两种结构（HC皮质厚度和HC放射状萎缩），以及两个功能性（FMRI和[18 F]MPPF）在AD和MCI患者风险范围为40-80的对照受试者中进行，以确定HC结构和功能是否存在与AD中观察到的类似的细微纵向变化，在中年晚期至老年范围内的认知完整的高危受试者中。我们将招募60名年轻（40-60岁）和36名老年（60岁以上）对照（各50%携带APOE-4）和35名轻度MCI受试者，并使用这些新的成像测量和临床评估对他们进行为期21/2年的随访。分析将侧重于单独和组合的每种测量的变化率建模，目的是确定发展AD的最高风险受试者。诊断和神经心理学评估将提供临床证实，基因型，家族史和短期大脑变化预测认知能力下降。通过结合这些不同的海马结构和功能的措施，我们的主要目标是开发一种方法来识别那些更有可能发展为AD的风险，并确定这些新的成像技术中哪些提供了未来衰退的最佳和独立的预测因子。