CEREBROVASCULAR DISEASE AND CEREBRAL AMYLOID: PATHWAYS TO COGNITIVE IMPAIRMENT

脑血管疾病(CVD)和阿尔茨海默病(AD)是最常见的两种病理 影响大脑老化的过程。虽然人们普遍认为这是导致痴呆症的第二大原因， 事实上，心血管疾病对认知的影响可能远远大于目前人们所认识到的。随着更多的尸检数据 社区研究表明，不仅AD/CVD混合型非常常见，而且 多种病理因素的结合可能会对大脑功能造成特别严重的破坏。因此，关键问题是 关于CVD和AD的答案是，它们是如何联系在一起的，以及它们是如何一起和单独损害大脑的 功能。我们已经使用匹兹堡的[11-C]实现了大脑β淀粉样蛋白的PET成像 化合物B或“PIB”。Abeta的沉积被认为是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，创造了 这是一个研究心血管疾病在痴呆症中作用的中心问题的独特机会。这个项目需要一个 包括心血管疾病的观点，测量危险因素，小血管和大血管的致病因素 硬化症以及血管性脑损伤的终末器官损害(脑梗塞和脑白质损害；VBI)。 该计划项目拨款定义了心血管疾病对大脑有贡献的三条途径 失败，本项目测试了它们各自产生的特定核心假设：1)CVD导致VBI，以及 VBI会单独或与AD合并导致痴呆症。已经对这两条路线进行了调查 在生活中无法检测和量化AD的障碍。拥有这种能力将使我们能够更好地 两者都要解释清楚。2)CVD可增加Aβ沉积。有证据表明“血管”危险因素会增加 阿尔茨海默病的风险提示动脉硬化可能是淀粉样变性。同时量化CVD和AD允许直接 对这一假设的检验。3)脑血管病对脑结构和功能有直接、严重的损害作用。那里 是CVD与广泛性皮质萎缩相关的有力证据，其机制与 明白了。通过排除AD作为一个可能的因素，我们将能够研究这一新颖而重要的 假设。每个想法本身都很重要，测试整套机制的前景也很重要 使用相同的患者和方法，从而使我们能够谈论他们的相对实力和 重要性为我们的方法增添了额外的丰富性。

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.