CEREBROVASCULAR FUNCTION IN AGING AND ALZHEIMER'S DISEASE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。目的：本初步研究的目的是验证与同龄健康受试者相比，早期阿尔茨海默病（AD）患者脑血管功能受损的中心假设。具体来说，我们将检验以下假设：(1)AD患者的大脑自动调节功能受损，这种功能是通过脑血流对动脉压变化的反应来量化的。(2)在阿尔茨海默病患者早期，脑氧化代谢储备（由急性脑灌注不足时氧提取分数（OEF）增加的幅度来量化）减弱。研究计划和方法：本先导研究将专门探讨(1)早期AD患者的大脑自调节、脑氧化代谢储备、脑神经活化-血流耦合关系是否受损；(2)这些患者的认知能力快速下降是否与脑血管功能迅速恶化相关。12名受试者（早期AD、健康老年人和健康年轻人各4名）将被研究。3D磁共振图像（MRI）将使用GE/Elscint Prestige 2-Tesla系统获取。正电子发射断层扫描（PET）图像将使用CTI西门子HR+全身PET扫描仪在3D模式下获得。测量脑血流量（CBF）、脑血容量（CBV）、氧提取分数（OEF）和脑氧代谢率。临床相关性：阿尔茨海默病（AD）是一种破坏性的神经退行性疾病，影响着美国和世界各地数百万老年人。对疾病机制的研究可能会导致对这些个体更好的诊断和治疗。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The aim of this pilot study is to test the central hypothesis that cerebrovascular function is compromised in patients at the early state of Alzheimer's disease (AD) as compared to healthy subjects of the same age. Specifically, we will test the following hypotheses: (1) Cerebral autoregulation, as quantified by changes in cerebral blood flow in response to changes in arterial pressure, is impaired in patients with AD. (2) Brain oxidative metabolic reserve, as quantified by the magnitude of increase in oxygen extraction fraction (OEF) in response to acute brain hypoperfusion, is attenuated in patients at the early stage of Alzheimer's disease. RESEARCH PLAN AND METHODS: This pilot study will explore specifically (1) whether cerebral autoregulation, brain oxidative metabolic reserve, and the brain neuronal activation-blood flow coupling relationship are impaired in patients at the early stage of AD, and (2) whether cerebrovascular function deteriorates rapidly associated with rapid cognitive decline observed in these patients. Twelve subjects (4 each early AD, healthy elderly, and healthy young) will be studied. 3D Magnetic Resonance images (MRI) will be acquired using a GE/Elscint Prestige 2-Tesla system. Positron emission tomography (PET) images will be acquired using a CTI Siemens HR+ whole body PET scanner in 3D mode. Cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen will be measured. CLINCAL RELEVANCE: Alzheimer's disease (AD) is a devastating neurodegenerative disease affecting millions of the elderly in the United States and around the world. Research into mechanisms of the disease may lead to better diagnosis and treatment for these individuals.