Vascular Function, Cognition, and Brain MRI in Atherosclerotic Vascular Disease

动脉粥样硬化性血管疾病的血管功能、认知和脑 MRI

• 批准号: 8306028
• 负责人: DAVID J MOSER
• 金额: $ 46.22万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8306028
• 关键词: Accounting; Address; Aging-Related Process; Arteriosclerosis; Atherosclerosis; Attenuated; Base of the Brain; Biology; Blood Vessels; Brain; Cerebrovascular Disorders; Cognition; Data; Dementia; Developed Countries; Early identification; Elderly; Endothelin; Enrollment; Forearm; Functional disorder; Funding; Goals; Grant; Health; Hippocampus (Brain); Impaired cognition; Individual; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Mediator of activation protein; Morbidity - disease rate; Oxidative Stress; Participant; Patients; Performance; Physiological; Pilot Projects; Population; Process; Publishing; Renin-Angiotensin-Aldosterone System; Research; Research Support; Resistance; Risk; Sampling; Stroke; Structure; Sympathetic Nervous System; Temporal Lobe; Thrombosis; Time; Vascular Diseases; aging population; brain volume; cognitive change; comparison group; design; effective therapy; follow-up; gray matter; innovation; mortality; neuroimaging; neuropsychological; normal aging; prevent; response; therapy development; vasoactive agent; vasoconstriction; white matter

DESCRIPTION (provided by applicant): This is the third submission of an R01 requesting five years of funding to support research on vascular disease, cognition, and brain structure in individuals with atherosclerotic vascular disease (AVD) and healthy comparison participants. AVD is the leading cause of morbidity and mortality in industrialized nations and is a primary or contributing factor in well over half of all cases of dementia. Despite this, there are relatively few longitudinal studies of AVD-related cognitive decline and the factors that are most predictive of this process. The early identification of individuals who are at greatest risk for such decline will have important implications for the development of interventions aimed at preventing or attenuating this important health problem. Our research team is using an innovative physiological measure (forearm vascular function - the degree to which forearm vessels dilate in response to vasoactive agents) as an indicator of vascular health to be examined in relation to cognition and brain structure. We have published cross-sectional findings in Stroke and in Arteriosclerosis, Thrombosis, and Vascular Biology showing that this measure of vascular function is significantly related to cognition in patients with AVD, and we have obtained pilot data that suggest that this measure is also related to frontal/temporal grey and white matter volumes. The proposed research will significantly expand upon our current findings by allowing us to achieve the following goals: 1) Determine whether the relationship between vascular function and cognition is unique to AVD or is also present in the general elderly population, as part of the normal aging process; 2) Determine whether vascular function measured at baseline, and change in vascular function across time, are associated with cognitive decline across time; 3) Determine the relationships among oxidative stress-mediated suppression of vascular function, neurohumoral mediators of vasoconstriction (endothelin levels, indicators of renin-angiotensin- aldosterone system and sympathetic nervous system activation), vascular function, and cognition; 4) Determine the relationship between vascular function and specific MRI-based brain measures (both cross- sectionally and longitudinally) in patients with AVD; 5) Conduct a pilot study on vascular function and MRI- based brain measures in healthy comparison participants. We will study healthy elderly participants (N = 100) as well as those with AVD (N = 135, 85 of whom are already enrolled in our ongoing research). This will allow us to conduct baseline and three-year follow-up assessments on those participants who are newly enrolled, and six-year follow-up assessments on those who are already participating in our research. The proposed research will allow us to make significant strides toward our long-term goals of elucidating the mechanisms by which vascular disease contributes to cognitive decline, finding better ways to identify those individuals who are at greatest risk for vascular-related cognitive decline, and developing more effective treatments to prevent or attenuate this process. Atherosclerotic vascular disease is a major contributing factor to cognitive decline and dementia in the elderly. This study is designed to help clarify the mechanisms by which vascular disease causes cognitive decline and to develop better ways to identify those individuals who are at greatest risk for vascular-related cognitive changes.

描述（由申请人提供）：这是R 01的第三次提交，要求提供五年的资金，以支持动脉粥样硬化性血管疾病（AVD）患者和健康对照受试者的血管疾病、认知和脑结构研究。AVD是工业化国家发病率和死亡率的主要原因，是所有痴呆病例中超过一半的主要或促成因素。尽管如此，有相对较少的纵向研究AVD相关的认知能力下降和最能预测这一过程的因素。及早确定最有可能出现这种下降的人，将对制定旨在预防或减轻这一重要健康问题的干预措施产生重要影响。我们的研究团队正在使用一种创新的生理指标（前臂血管功能--前臂血管对血管活性药物的反应而扩张的程度）作为血管健康的指标，以检查与认知和大脑结构的关系。我们在《卒中》和《动脉硬化、血栓形成和血管生物学》中发表了横断面研究结果，表明血管功能的这种测量与AVD患者的认知显著相关，我们获得的初步数据表明，这种测量也与额叶/颞叶灰质和白色物质体积相关。拟议的研究将显著扩展我们目前的研究结果，使我们能够实现以下目标：1）确定血管功能和认知之间的关系是否是AVD独有的，或者也存在于一般老年人群中，作为正常衰老过程的一部分; 2）确定在基线测量的血管功能以及血管功能随时间的变化是否与随时间的认知下降相关; 3）确定氧化应激介导的血管功能抑制与血管收缩的神经体液介质之间的关系（内皮素水平、肾素-血管紧张素-醛固酮系统和交感神经系统激活的指标）、血管功能和认知; 4）确定血管功能和基于MRI的特定脑测量之间的关系5）在健康对照参与者中进行关于血管功能和基于MRI的脑测量的初步研究。我们将研究健康老年受试者（N = 100）以及AVD受试者（N = 135，其中85例已入组我们正在进行的研究）。这将使我们能够对新入组的参与者进行基线和三年随访评估，并对已经参与我们研究的参与者进行六年随访评估。拟议的研究将使我们能够朝着阐明血管疾病导致认知能力下降的机制的长期目标迈出重大步伐，找到更好的方法来识别那些血管相关认知能力下降风险最大的个体，并开发更有效的治疗方法来预防或减弱这一过程。动脉粥样硬化性血管疾病是导致老年人认知能力下降和痴呆的主要因素。这项研究旨在帮助阐明血管疾病导致认知能力下降的机制，并开发更好的方法来识别那些血管相关认知变化风险最大的个体。