BRAIN MICROVASCULATURE IN AGING AND DEMENTIA

解剖学研究表明，脑微血管系统是 在阿尔茨海默病患者中不正常。三总 已经描述了异常情况。第一，大脑淀粉样蛋白 血管病变(CAA)，其特征是体内存在淀粉样蛋白 脑毛细血管和小动脉壁，是一种常见的 阿尔茨海默病患者。第二，几个 描述了大脑小动脉和毛细血管的“畸形”， 包括毛细管壁和环状结构的增厚。 最后，大脑内已知的神经递质系统会影响 微血管系统，即中枢去甲肾上腺素能和 胆碱能系统，严重影响慢性阻塞性肺疾病患者 阿尔茨海默氏症。尽管存在这些异常现象 脑血管系统的功能是 阿尔茨海默病的损害尚未得到系统的研究 已评估。我们建议通过检验来检验这一假设 应用正电子发射断层扫描(PET)检测微血管功能 研究：1)区域血流的静息状态测量， 血管渗透性-表面积乘积和新陈代谢；2) 血管系统对功能激活的反应(例如，视觉 或躯体感觉刺激)；以及(3) 功能性诱导的血管改变导致局部血糖的变化 利用率。我们将研究50名健康老年人和50名受试者 阿尔茨海默型老年性痴呆(SDAT)及其数据比较 对于健康的年轻人来说。尸检的前景 血管病理的确认是一种额外的力量。虽然 宠物非常适合探索这些它一直困扰着的问题 由于脑萎缩导致的部分体积平均化问题。 作为该项目的一个主要组成部分，我们建议开发和 实施两个新的数据分析创新战略。这个 First旨在对PET进行地区性校正，以应对 使用磁共振成像(MRI)的萎缩。第二 在受试组之间执行PET数据的图像范围比较 在将所有PET数据转换到公共解剖坐标之后 系统使用核磁共振信息。

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.