Combined fMRI, structural MRI, 18MPPF PET & APOE to detect Alzheimer's risk

组合功能磁共振成像、结构磁共振成像、18MPPF PET

• 批准号: 7622600
• 负责人: SUSAN Y BOOKHEIMER
• 金额: $ 50.59万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-10 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7622600
• 关键词: Affect; Age; Age-associated memory impairment; Algorithms; Alzheimer' s Disease; Alzheimer' s disease risk; Amygdaloid structure; Apolipoprotein E; Apolipoproteins; Atrophic; Binding; Blood Banks; Brain; Brain Mapping; Brain imaging; Cell Density; Clinical; Clinical Data; Clinical assessments; Cognition; Cognitive; Cognitive aging; Collaborations; Consent; Consultations; Data; Data Analyses; Data Set; Databases; Diagnostic; Disease Progression; Early Diagnosis; Elderly; Evaluation; Family history of; Functional Imaging; Functional Magnetic Resonance Imaging; Funding; Future; Genes; Genetic; Genetic Risk; Genotype; Goals; Grant; Hippocampus (Brain); Housing; Human Resources; Image; Image Analysis; Imaging Techniques; Impaired cognition; Individual; Intervention; Laboratories; Ligand Binding; Ligands; Magnetic Resonance Imaging; Maps; Measures; Memory; Metabolic; Methods; Metric; Modality; Modeling; Neurocognitive; Neuropsychological Tests; Onset of illness; Outcome; Outcome Assessment; Participant; Pathologic Processes; Patients; Pattern; Performance; Positron-Emission Tomography; Program Research Project Grants; Pyramidal Cells; Radial; Recruitment Activity; Relative (related person); Reporting; Research; Research Infrastructure; Research Personnel; Resolution; Retrieval; Risk; Risk Assessment; Series; Serotonin Receptor 5-HT1A; Specificity; Structure; Surface; Symptoms; System; Techniques; Testing; Thick; Time; Work; age group; base; classical conditioning; cognitive change; cohort; data management; density; design; entorhinal cortex; family genetics; follow-up; frontal lobe; gray matter; high risk; mathematical model; middle age; mild neurocognitive impairment; neuroimaging; neuropsychological; new technology; normal aging; novel; programs; sensory cortex; statistics; time interval; tool

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：这是我们先前标题为“用于早期诊断阿尔茨海默氏病的功能性MRL”的R01的持续更新（5 R01 AG013308-10）。拟议的第三个赠款周期建立在该项目的最新发现以及我们为海马结构和功能成像开发的新技术的基础上。我们的数据支持将遗传风险，结构和功能性MRL结合起来，以鉴定阿尔茨海默氏病（AD）的早期表现，并进一步表明大脑变化可能比以前在载脂蛋白Epsilon-4（APOE-4）载体中想到的要早得多。最近，我们的小组开发了高分辨率功能性MRL获取和分析以及数学建模算法的新技术，这些算法在很短的时间段内鉴定了阿尔茨海默氏病的结构MRL变化。此外，我们的小组最近使用[18F] MPPF成像（一种测量海马（HC），Entorhinal Cortex和Amygdala中的锥体细胞密度的配体，使用[18F] MPPF成像（PET）。我们的初步数据表明，在MCI和AD中[18F] MPPF结合降低，并且与健康对照中的记忆相关，这表明其潜力是对AD的独立评估。 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年龄到老年人。我们将招募60名年轻（40-60）和36个年龄较大（60+）对照，（每个APOE-4的50％）和35位温和的MCI受试者，并使用这些新颖的成像指标和临床评估来跟随它们21/2年。分析将集中于单独和组合每种度量的变化率建模，目的是确定开发AD风险最高的受试者。诊断和神经心理学评估将提供临床佐证，基因型，家族病史和短期大脑变化可以预测认知能力下降。通过结合海马结构和功能的这些不同的措施，我们的主要目标是开发一种方法来识别那些更有可能开发AD的高危者，并确定这些新型成像技术中的哪种是最佳和独立的未来下降预测指标。