Relating amyloid pathology to cognition and brain changes in normal elderly indiv

淀粉样蛋白病理学与正常老年人认知和大脑变化的关系

• 批准号: 7546341
• 负责人: ELIZABETH MORMINO
• 金额: $ 3.13万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7546341
• 关键词: Age; Aging; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Amyloid deposition; Area; Atrophic; Autopsy; Binding; Brain; Brain region; CH3OCF2CH(CF3)OCH2F; Characteristics; Clinical; Cognition; Cognitive; Communities; Conflict (Psychology); Dementia; Deposition; Detection; Development; Dissociation; Early Diagnosis; Elderly; Episodic memory; Financial compensation; Functional Magnetic Resonance Imaging; Glucose; High Prevalence; Hippocampus (Brain); Individual; Life; Localized; Magnetic Resonance Imaging; Maps; Measurement; Medial; Metabolic; Neurodegenerative Disorders; Neurofibrillary Tangles; Parietal; Pathology; Pathology, Other; Pattern; Performance; Populations at Risk; Positron-Emission Tomography; Prefrontal Cortex; Public Health; Recruitment Activity; Reporting; Research; Risk; Senile Plaques; Short-Term Memory; Site; Societies; Staging; Structure; Study Subject; Symptoms; Temporal Lobe; Testing; Thinking; amyloid pathology; association cortex; beta amyloid pathology; cognitive function; entorhinal cortex; fluorodeoxyglucose positron emission tomography; glucose metabolism; gray matter; in vivo; memory process; neuromechanism; normal aging; novel; prevent; radiotracer; relating to nervous system; response; uptake

DESCRIPTION (provided by applicant): Normal aging involves decline across multiple cognitive domains, such as episodic and working memory, thought to reflect subtle changes in brain structure and function. Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe episodic memory decline and multiple brain alterations. Interestingly, beta-amyloid plaques, which are the hallmark pathological feature of AD, are commonly found in normal elderly individuals as well, often in amounts comparable to AD. While the impact of beta-amyloid plaques in individuals without dementia remains unclear, it has been hypothesized that they may underlie some of the decline that occurs during aging. Detection of beta-amyloid in normal individuals offers the opportunity to study the earliest stages of AD, as well as to investigate mechanisms of neural compensation that may preserve normal function. To investigate these hypotheses, we have recruited healthy independently-living elderly subjects from the community to undergo neuropyschological testing, PET imaging, and MRI. The recent development of [11C]PIB ('Pittsburg Compound-B'), a PET radiotracer that binds to beta-amyloid plaques allows the unique opportunity to study the deposition of this pathology in vivo. This measurement of pathology will be compared to cognition in multiple domains, gray matter volume, and glucose metabolism. Furthermore, alterations in brain activation are commonly reported in functional MRI studies of aging, and may reflect neural compensation in response to early amyloid deposition. To understand if beta-amyloid pathology leads to functional compensation, normal subjects studied with PIB will undergo functional magnetic resonance imaging (fMRI) while performing an episodic memory task. PUBLIC HEALTH RELEVANCE: The high prevalence of AD poses a great burden to our society. Since AD pathology is thought to accumulate years before dementia onset, early detection may provide an opportunity to halt further accumulation and prevent conversion to AD. Research that strives to understand the initial stages of this pathology may promote the application of novel anti-amyloid treatments to individuals before dementia onset.

描述（由申请人提供）：正常衰老涉及多个认知领域的衰退，如情景记忆和工作记忆，被认为反映了大脑结构和功能的微妙变化。阿尔茨海默病（Alzheimer's disease，AD）是一种进行性神经退行性疾病，以严重的情景记忆减退和多种脑改变为特征。有趣的是，β-淀粉样蛋白斑块，这是AD的标志性病理学特征，通常也在正常老年人中发现，其数量通常与AD相当。虽然β-淀粉样蛋白斑块对没有痴呆的个体的影响尚不清楚，但有人假设它们可能是衰老过程中发生的一些下降的基础。在正常个体中检测β-淀粉样蛋白提供了研究AD的最早阶段以及研究可能保持正常功能的神经补偿机制的机会。为了研究这些假设，我们从社区招募了健康独立生活的老年受试者，进行神经心理学测试，PET成像和MRI。最近开发的[11 C]PIB（“匹兹堡化合物-B”）是一种与β-淀粉样蛋白斑块结合的PET放射性示踪剂，为研究这种病理在体内的沉积提供了独特的机会。 病理学的这种测量将与多个领域、灰质体积和葡萄糖代谢中的认知进行比较。此外，大脑激活的改变通常在功能性MRI衰老研究中报道，并且可能反映了对早期淀粉样蛋白沉积的神经补偿。为了了解β-淀粉样蛋白病理是否导致功能补偿，使用PIB研究的正常受试者将在执行情景记忆任务时进行功能磁共振成像（fMRI）。公共卫生相关性：AD的高患病率给我们的社会带来了巨大的负担。由于AD病理被认为在痴呆发作前数年积累，因此早期检测可能提供阻止进一步积累并防止转化为AD的机会。致力于了解这种病理学的初始阶段的研究可能会促进新的抗淀粉样蛋白治疗在痴呆症发作前应用于个体。