Hemodynamic predictors of brain and cognitive aging

描述(由申请者提供)：本研究项目是为了响应国家老龄研究所的小额拨款计划(PAR-03-056)而提出的。具体地说，我们对该公告中目标清单上的AIMS#2(心脑血管老龄化)和#16(执行功能)做出回应。本研究的主要目的是探讨经颅多普勒超声(TCD)评估血流动力学因素对不同年龄的脑和认知改变的影响的可行性。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(作为大脑低灌注的标志)与脑白质高信号(WMH)负荷的区域性增加以及皮质和基础白质的收缩之间的联系。在认知领域，我们将重点研究对衰老和前额叶病变具有不同敏感性的执行功能。我们的假设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修改脑血管危险因素对年龄相关性脑萎缩的影响的合理性，以及表明执行功能对轻度高血压的不同易感性的研究。虽然初步报告[5]表明CBF-V降低可能与结构性脑病理(全球WMH负担)有关，但该指标的区域特异性、认知关系或纵向过程尚未确定。我们对一群健康的成年人(18-85岁)进行了研究，并对100多个人进行了认知和基于MRI的结构脑测量。在这个项目中，我们建议在一项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改变的比率联系起来。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，将检验一项在临床上广泛使用的技术应用于健康老龄化研究的可行性，并将受益于对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.