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

描述（由申请人提供）：正常的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，其特征是严重的情景记忆衰退和多脑改变。有趣的是，β -淀粉样斑块是阿尔茨海默病的标志性病理特征，在正常老年人中也很常见，其数量通常与阿尔茨海默病相当。虽然β -淀粉样蛋白斑块对无痴呆个体的影响尚不清楚，但有人假设它们可能是衰老过程中出现的一些衰退的基础。正常个体中β -淀粉样蛋白的检测为研究阿尔茨海默病的早期阶段以及研究可能保持正常功能的神经代偿机制提供了机会。为了研究这些假设，我们从社区招募了健康独立生活的老年人受试者进行神经心理学测试、PET成像和MRI。最近发展的[11C]PIB（“匹兹堡化合物- b”），一种结合β -淀粉样斑块的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。

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.