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

描述(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细微变化。阿尔茨海默病(AD)是一种进行性神经退行性疾病，以严重的间歇性记忆减退和多发性脑改变为特征。有趣的是，作为AD标志性病理特征的β-淀粉样斑块在正常老年人中也很常见，其数量通常与AD相当。虽然β-淀粉样斑块对非痴呆症患者的影响尚不清楚，但据推测，它们可能是衰老过程中发生的一些下降的原因。检测正常人的β-淀粉样蛋白为研究阿尔茨海默病的早期阶段提供了机会，也为研究可能保持正常功能的神经代偿机制提供了机会。为了研究这些假说，我们从社区招募了健康的独立生活的老年受试者进行神经心理测试、PET成像和MRI。[11C]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，其最近的发展为研究这种病理在体内的沉积提供了独特的机会。 这种病理测量将与多个领域的认知、灰质体积和葡萄糖代谢进行比较。此外，脑激活的改变在衰老的功能磁共振研究中经常被报道，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-淀粉样蛋白病变是否会导致功能代偿，对PIB进行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)。与公共卫生相关：AD的高患病率给我们的社会带来了巨大的负担。由于阿尔茨海默病的病理被认为在痴呆症发病前多年积累，早期发现可能提供一个机会来阻止进一步积累并防止转化为阿尔茨海默病。致力于了解这种病理的初始阶段的研究可能会促进新型抗淀粉样蛋白治疗在痴呆症发病前应用于个体。

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.