BRAIN MICROVASCULATURE IN AGING AND DEMENTIA

解剖学研究表明，大脑微血管是 在阿尔茨海默病患者中是不正常的。 三个一般 已经描述了异常。 一、大脑淀粉样蛋白 血管病（CAA），其特征在于淀粉样蛋白的存在， 脑毛细血管和小动脉壁，是一个经常发生在 老年痴呆症患者 第二，几个 描述了脑小动脉和毛细血管的"畸形"， 包括毛细管壁的增厚和环的形成。 最后，大脑中的神经递质系统， 微血管系统，即中央去甲肾上腺素能和 胆碱能系统，严重影响患者 老年痴呆症 尽管存在这些异常 脑血管系统的功能 阿尔茨海默氏症的受损并没有系统地 评估。 我们建议通过检查 微血管功能使用正电子发射断层扫描（PET）， 研究：1）局部血流的静息状态测量， 血管通透性-表面积乘积和代谢; 2） 脉管系统对功能激活的响应（例如，视觉 或躯体感觉刺激）;以及（3） 局部葡萄糖变化的功能性诱导血管变化 利用率 我们将研究50名健康老年人和50名患有 老年性痴呆的阿尔茨海默型（SDAT），并比较他们的数据 与健康的年轻人相比。 尸检的前景 血管病变的确认是额外的优势 虽然 PET非常适合探讨这些一直困扰它的问题 由于脑萎缩导致的部分体积平均化的问题。 作为该项目的一个主要组成部分，我们建议开发和 实施两个新的、创新的数据分析策略。 的 第一个是设计来纠正PET区域的存在， 使用磁共振成像（MRI）检查萎缩。 第二 对受试者组之间的PET数据进行图像范围比较 在将所有PET数据转换到公共解剖坐标之后 系统使用MRI信息。

Anatomical studies suggest that the brain microvasculature is abnormal in patients with Alzheimer's disease. Three general abnormalities have been described. First, cerebral amyloid angiopathy (CAA), characterized by the presence of amyloid within brain capillary and arteriolar walls, is a frequent occurrence in patients with Alzheimer's disease. Second, several of "deformities" of cerebral arterioles and capillaries are described, including thickening of the capillary walls and loop formations. Finally, neurotransmitter systems within brain known to influence the microvasculature, namely the central noradrenergic and cholinergic systems, are severely affected in patients with Alzheimer's disease. Despite the presence of these abnormalities the hypothesis that the function of the cerebral vasculature is impaired in Alzheimer's disease has not been systematically evaluated. We propose to test that hypothesis by examining microvascular function using positron emission tomography (PET) to study: 1) resting state measurements of regional blood flow, vascular permeability-surface area product and metabolism; 2) the response of the vasculature to functional activation (e.g., visual or somatosensory stimulation); and (3) the relationship of functionally-induced vascular changes to changes in local glucose utilization. We will study 50 healthy elderly and 50 subjects with senile dementia of the Alzheimer type (SDAT) and compare their data to those of healthy young adults. The prospect of autopsy confirmation of vascular pathology is an added strength. Although PET is ideally suited to explore these issues it has been plagued by the problem of partial volume averaging due to brain atrophy. As a major component of this project we propose to develop and implement two new, innovative strategies of data analysis. The first is designed to correct PET regionally for the presence of atrophy using magnetic resonance imaging (MRI). The second performs image wide comparisons of PET data between subject groups after transforming all PET data to a common anatomical coordinate system using MRI information.