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: 7471170
• 负责人: Bruce Reed
• 金额: $ 29.01万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-15 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7471170
• 关键词: Affect; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Amyloid deposition; Arteriosclerosis; Autopsy; 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; 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