Hemodynamic predictors of brain and cognitive aging

项目描述（由申请人提供）：本研究项目是应美国国家老龄研究所小额资助计划公告（PAR-03-056）而提出的。具体来说，我们回应了公告中目标清单上的目标#2（心脑血管老化）和#16（执行功能）。本研究的主要目的是探讨使用经颅多普勒超声（TCD）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与年龄相关的大脑前动脉和大脑中动脉血流速度（CBF-V）减慢（作为大脑灌注不足的标志）与白质高强度（WMH）负担的区域性增加以及皮层和潜在白质的萎缩之间的联系。在认知领域，我们将重点关注对衰老和前额叶病理差异敏感的执行功能。我们的假设是基于大量临床和临床前研究，这些研究表明CBF-V减慢是发生WMH的危险因素，我们自己的研究支持脑血管危险因素对年龄相关脑萎缩的调节影响的可行性，以及表明执行功能对轻度高血压的不同易感性的研究。虽然一份初步报告[5]表明CBF-V减少可能与结构性脑病理（全球WMH负担）有关，但该指数的区域特异性、认知关系或纵向过程均未确定。我们对一组健康成年人（18-85岁）进行了研究，并对100多人进行了认知和基于mri的脑结构测量。在这个项目中，我们建议在为期两年的纵向研究中使用这些数据作为基线测量，并将血流动力学变量与神经解剖学和认知变化的速率联系起来。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，将检验在临床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.