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: 7319494
• 负责人: SUSAN Y BOOKHEIMER
• 金额: $ 58.08万
• 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/7319494
• 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; Clinical; Clinical Data; Clinical assessments; Cognition; Cognitive; Cognitive aging; Collaborations; Consent; Consultations; Data; Data Analyses; Data Set; Databases; Diagnostic; Disease Progression; Disease regression; 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; Range; Rate; 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; Thinking; Time; Work; age group; base; classical conditioning; cognitive change; cohort; data acquisition; data management; density; design; entorhinal cortex; family genetics; follow-up; frontal lobe; gray matter; 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），以确定HC结构和功能是否存在与AD相似的细微纵向变化，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。分析将重点对每项指标单独和组合的变化率进行建模，目标是识别患AD风险最高的受试者。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。