Hemodynamic predictors of brain and cognitive aging

描述（由申请人提供）：本研究项目是为了响应国家老龄化研究所（PAR-03-056）的小额赠款计划公告而提出的。具体来说，我们回应了该公告中目标列表中的目标#2（心血管和脑血管老化）和#16（执行功能）。本研究的主要目的是探讨经颅多普勒超声（TCD）用于评估血流动力学因素对不同年龄相关的大脑和认知变化的影响的可行性。我们特别感兴趣的是探索年龄相关的大脑前动脉和中动脉的脑动脉血流速度（CBF-V）减慢（作为脑灌注不足的标志）与白色高信号（WMH）负荷的区域性增加以及皮质和底层白色物质的收缩之间的联系。在认知领域，我们将集中在执行功能，这是不同的敏感老化和前额叶病变。我们的假设是基于身体的临床和临床前研究表明，CBF-V放缓的风险因素发展WMH，我们自己的研究，支持修改脑血管危险因素对年龄相关的脑萎缩的影响的可行性，并在研究表明，执行功能的差异脆弱性轻度高血压。虽然初步报告[5]表明CBF-V降低可能与结构性脑病理学（全球WMH负荷）相关，但尚未确定该指数的区域特异性、认知关系或纵向过程。我们对一组健康成年人（年龄18-85岁）进行了研究，并对100多名个体进行了认知和基于MRI的大脑结构测量。在这个项目中，我们建议使用这些数据作为基线措施，在一个为期两年的纵向研究，并与血流动力学变量的神经解剖和认知变化的速度。因此，拟议的研究符合该计划宣布的目标，因为它代表了一项试点研究，将研究临床上广泛使用的技术应用于健康老龄化研究的可行性，并将受益于现有数据的统计分析。

DESCRIPTION (provided by applicant): This research project is proposed in response to the small grants program announcement of the National Institute on Aging (PAR-03-056). Specifically, we respond to the aims #2 (Cardiovascular and Cerebrovascular Aging), and #16 (Executive Function) on the list of objectives in that announcement. The main goal of the proposed research is to explore the feasibility of using Transcranial Doppler Sonography (TCD) for assessment of the influence exerted by hemodynamic factors on differential age related changes in brain and cognition. We are specifically interested in exploring the links between age-related slowing of cerebral arterial blood velocity (CBF-V) in anterior and middle cerebral arteries, as a marker for cerebral hypoperfusion, and regional increase in white matter hyperintensities (WMH) burden as well as shrinkage of the cortex and the underlying white matter. In cognitive domain we will focus in the executive functions which are differentially sensitive to aging and prefrontal pathology. Our hypotheses are based on the body of clinical and preclinical studies that suggested CBF-V slowing as risk factor for developing WMH, our own studies that support the plausibility of modifying influence of cerebrovascular risk factors on age-related brain shrinkage and on the studies that suggest differential vulnerability of executive functions to mild hypertension. While a preliminary report [5] indicates that reduced CBF-V may be associated with structural brain pathology (global WMH burden), neither regional specificity, nor cognitive relationship nor longitudinal course of that index have been established. We have conducted research on a cohort of healthy adults (age 18-85) and obtained cognitive and MRI-based structural brain measures on more than 100 individuals. In this project, we propose to use these data as baseline measures in a two-year longitudinal study and to relate hemodynamic variables to the rate of neuroanatomical and cognitive change. Thus, the proposed research fits the announced goals of the program in that it represents a pilot study that will examine feasibility of application of a technique widely used in the clinic to research on healthy aging, and it will benefit from statistical analysis of existing data.