AGING BRAIN: VASCULATURE, ISCHEMIA, AND BEHAVIOR

大脑老化：血管、缺血和行为

• 批准号: 6089890
• 负责人: HELENA Chang CHUI
• 金额: $ 187.89万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6089890
• 关键词: Alzheimer's disease; cerebral ischemia /hypoxia; cerebrovascular disorders; neuropathology

This is a revised competing renewal application for a program project grant (PPG) that focuses on subcortical ischemia vascular dementia (SIVD) in comparison to Alzheimer disease (AD). Based upon new findings during the initial funding period, we propose that dementia in both AD and SIVD is associated with changes in cerebral cortex, including atrophy, glucose hypometabolism, and loss of N-acetylaspartate [NAA]. The mechanisms leading to these cortical changes, however, are likely to differ and during the renewal we will further explore the mechanisms operant in SIVD. Using a longitudinal study design, we will also determine whether the regional pattern or rate of structural, metabolic, biochemical and perfusion changes are helpful for differential diagnosis and prognosis. The Central Coordinating Core (CC) will continue to recruit and follow to autopsy 500 subjects representing a spectrum of cognitive impairment, as well as ischemic vascular- and AD- type pathology. The Imaging Core will localize lacunes and measure volumes of lacunes (L), white matter lesions (WML), cortical gray matter (cGM)), and hippocampus (HV). The Pathology Core will determine the nature and rate the severity of neurodegenerative, ischemic, and cerebrovascular lesions. Four research projects are proposed (Note: Project 4 was discontinued): Project 1 (Reed et al.) Will used fluoro deoxyglucose positron emission tomography (FDG-PET) to study the utility of the regional and longitudinal pattern of cerebral metabolic rate for glucose (CMRgic) for differential diagnosis and prognosis. Project 2 (Weiner et al.) will use 1H MRSI and perfusion MR to study the utility of [NAA], myoinositol, and blood flow for diagnosis and prognosis. Project 3 (Chui et al) will co-register the clinical MRI to post-mortem brain to determine the pathological correlates of hippocampal and cortical atrophy, WML, and lacunes. Project 5 (Mungas et al) will use multi- variate random effect analyses to model, over time, the neuropsychological and MRI measures correlates of dementia in SIVD and AD. By integration of multi-dimensional data obtained using state of the art methods, we propose to advance understanding of the pathogenesis of SIVD, and to provide practical tools for diagnosis and prognosis.

这是与阿尔茨海默病(AD)相比，专注于皮质下缺血性血管性痴呆(SIVD)的计划项目赠款(PPG)的修订竞争续签申请。根据最初资助期的新发现，我们认为AD和SIVD的痴呆都与大脑皮层的变化有关，包括萎缩、葡萄糖代谢低下和N-乙酰天冬氨酸[NAA]的丢失。然而，导致这些皮质变化的机制可能不同，在更新过程中，我们将进一步探索SIVD的作用机制。采用纵向研究设计，我们还将确定结构、代谢、生化和血流灌注变化的区域模式或比率是否有助于鉴别诊断和预后。中央协调核心(CC)将继续招募和跟踪500名受试者进行尸检，这些受试者代表了一系列认知障碍以及缺血性血管和AD类型的病理。成像核心将定位腔隙并测量腔隙(L)、白质病变(白质病变)、皮质灰质(CGM)和海马体(HV)的体积。病理学核心将决定神经退行性病变、缺血性病变和脑血管病变的性质和严重程度。提出了四个研究项目(注：项目4已中止)：项目1(Reed等人)Will使用氟脱氧葡萄糖正电子发射断层扫描(FDG-PET)来研究脑葡萄糖代谢率的区域和纵向模式在鉴别诊断和预后中的作用。项目2(Weiner等人)将使用1HMRSI和灌注MR来研究[NAA]、肌醇和血流在诊断和预后中的作用。项目3(Chui等人)将把临床MRI与死后脑共同注册，以确定海马和皮质萎缩、WML和腔隙的病理相关性。项目5(Mungas等人)将使用多变量随机效应分析来模拟随着时间的推移，SIVD和AD中痴呆的神经心理学和MRI测量的相关性。通过综合使用最先进的方法获得的多维数据，我们建议促进对SIVD发病机制的了解，并为诊断和预后提供实用工具。