CEREBROVASCULAR DISEASE AND CEREBRAL AMYLOID: PATHWAYS TO COGNITIVE IMPAIRMENT

脑血管疾病和脑淀粉样蛋白：导致认知障碍的途径

• 批准号: 7848849
• 负责人: Bruce Reed
• 金额: $ 26.62万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7848849
• 关键词: Affect; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Amyloid deposition; Arteriosclerosis; Autopsy; Behavior; Blood Vessels; Brain; Brain Injuries; Cerebrovascular Disorders; Cerebrovascular Trauma; Cerebrum; Clinical; Cognition; Communities; Data; Dementia; Development; Diffuse; Epidemiologic Studies; Failure; Functional disorder; Goals; Image; Impaired cognition; Infarction; Investigation; Ischemia; Lead; Lesion; Life; Literature; Location; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Memory; Metabolism; Methods; Modeling; Nature; Neurons; Neuropsychological Tests; Organ; Pathogenesis; Pathologic Processes; Pathology; Pathway interactions; Patients; Pittsburgh Compound-B; Positron-Emission Tomography; Principal Investigator; Process; Program Research Project Grants; Relative (related person); Reporting; Risk Factors; Role; Route; Sclerosis; Secondary to; Series; Structure; Synapses; System; Testing; abeta deposition; aging brain; amyloid pathology; association cortex; brain volume; cardiovascular risk factor; cerebral atrophy; cognitive function; executive function; fluorodeoxyglucose positron emission tomography; gray matter; hippocampal atrophy; in vivo; mild neurocognitive impairment; novel; programs; tool; white matter

Cerebrovascular disease (CVD) and Alzheimer's Disease (AD) are the two most common pathological processes that affect the aging brain. While generally believed to be the second leading cause of dementia, the impact of CVD on cognition may in fact be far greater than currently recognized. As more autopsy data accrue from community studies it appears that not only is mixed AD/CVD very common, but that this combination of pathologies may be particularly devastating to brain function. Thus, the key question to answer about CVD and AD is how they are related, and how they together and separately impair brain function. We have implemented PET imaging of cerebral beta amyloid using the [11-C] Pittsburgh compound B or "PIB". Deposition of Abeta is believed to be a critical step in the pathogenesis of AD; quantifying Abeta during life opens the possibility of a series of investigations never before possible, creating a unique opportunity to study central issues regarding the role of CVD in dementia. This project takes an encompassing view of CVD, measuring risk factors, the pathogenic factor of both small and large vessel sclerosis, as well as the end-organ damage of vascular brain injury (infarcts and white matter lesions; VBI). The Program Project Grant has defined three pathways through which CVD appears to contribute to brain failure, and this project test specific, core hypotheses generated by each of them: 1) CVD leads to VBI, and VBI causes dementia either alone or in combination with AD. Investigation of both routes has been hampered by the inability to detect and quantify AD during life. Having this capacity will allow us to better elucidate both. 2) CVD may increase Abeta deposition. Evidence that "vascular" risk factors increase the risk of AD suggest arteriosclerosis may be amyloidogenic. Quantifying both CVD and AD permits a direct test of this hypothesis. 3) CVD has direct, difusely damaging effects on brain structure and function. There is strong evidence that CVD is associated with extensive cortical atrophy, the mechanism of which is not understood. By excluding AD as a possible factor we will be able to investigate this novel and important hypothesis. Each idea is important in its own right and the prospect of testing the entire set of mechanisms using the same patients and methods, thus allowing us to say something about their relative strength and importance lends an additional richness to our approach.

脑血管病（CVD）和阿尔茨海默病（AD）是两种最常见的病理性疾病， 影响大脑老化的过程虽然一般认为是痴呆症的第二大原因， 心血管疾病对认知能力的影响实际上可能比目前认识到的要大得多。随着更多的尸检数据 从社区研究中得出，似乎不仅混合AD/CVD非常常见， 病理的组合可能对脑功能特别具有破坏性。因此， 关于CVD和AD的答案是它们是如何相关的，以及它们如何一起和单独损害大脑 功能我们已经使用[11-C] Pittsburgh实施了大脑β淀粉样蛋白的PET成像 化合物B或“PI B”。A β沉积被认为是AD发病机制中的关键步骤; 量化生命中的Abeta开启了一系列前所未有的研究的可能性， 一个独特的机会，研究有关心血管疾病在痴呆症中的作用的核心问题。这个项目需要一个 包括心血管病的观点，测量危险因素，小血管和大血管的致病因素 硬化以及血管性脑损伤的终末器官损伤（梗塞和白色物质病变; VBI）。 该计划项目赠款已经确定了三个途径，通过这些途径，CVD似乎有助于大脑 失败，这个项目测试特定的，核心假设产生的每一个：1）心血管疾病导致VBI， VBI单独或与AD联合引起痴呆。对这两条路线的调查已经 在生活中无法检测和量化AD。拥有这种能力将使我们能够更好地 两个都解释清楚。2)CVD可增加Abeta沉积。有证据表明，“血管”风险因素增加了 AD风险提示动脉硬化可能是淀粉样变性的。量化CVD和AD两者允许直接 对这一假设的检验。3)CVD对脑结构和功能具有直接的、不明确的损害作用。那里 是CVD与广泛皮质萎缩相关的强有力证据，其机制不是 明白通过排除AD作为一个可能的因素，我们将能够研究这种新颖而重要的 假说.每一个想法本身都很重要，测试整套机制的前景也很重要 使用相同的病人和方法，从而使我们能够说一些关于他们的相对优势， 重要性使我们的方法更加丰富。