Cerebral blood flow, connectivity and cognition: the effect of age and exercise

脑血流量、连通性和认知：年龄和运动的影响

• 批准号: 9115699
• 负责人: JILL NICOLE BARNES
• 金额: $ 24.5万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-12 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9115699
• 关键词: Acute; Adult; Affect; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Biological Markers; Blood Flow Velocity; Blood flow; Brain; Brain imaging; Carbon Dioxide; Cardiovascular system; Cerebrovascular Circulation; Cerebrum; Chemicals; Cognition; Cognitive; Complement; Cyclooxygenase Inhibitors; Data Analyses; Data Collection; Dementia; Development; Early identification; Elderly; Exercise; Exercise Physiology; Fostering; Foundations; Functional Magnetic Resonance Imaging; Funding; Future; Goals; Human; Hyperemia; Image Analysis; Imaging Techniques; Impaired cognition; Indium; Indomethacin; Learning; Link; Magnetic Resonance Imaging; Measures; Mentors; Mentorship; Metabolic; Metabolism; Microvascular Dysfunction; Myocardium; Neuropsychological Tests; Observational Study; Pathway interactions; Perfusion; Phase; Physical activity; Physiology; Prevention; Process; Prostaglandin-Endoperoxide Synthase; Prostaglandins; Regulation; Research Personnel; Risk; Series; Skeletal Muscle; Staging; Stimulus; Techniques; Testing; Training; Vascular Diseases; Vasodilation; Vasodilator Agents; White Matter Hyperintensity; Work; age effect; age related; aging population; brain volume; career; career development; cerebrovascular; cognitive function; executive function; exercise training; follow-up; improved; insight; multidisciplinary; neurovascular coupling; normal aging; novel; potential biomarker; relating to nervous system; research study; response; sedentary; skills; young adult

PROJECT SUMMARY/ABSTRACT The overall goal of this K99/R00 application is to examine the age-related changes in cerebral vasodilatory capacity, and how this is mechanistically linked to cognition. This application will explore the potential beneficial effect of physical activity on the relationships between vasodilatory capacity and emerging biomarkers of cognitive decline. Furthermore, this project will serve as a vehicle to build upon the applicant's training in cardiovascular aging and exercise physiology and her recently completed F32 funded work by allowing her to learn additional techniques including fMRI image analysis and interpretation of neuropsychological testing. Recent evidence suggests that cerebral microvascular dysfunction declines with advancing age, and may precede the onset of cognitive impairment. Aging is associated with greater white matter hyperintensity (WMH) volume and also alters functional connectivity of the default mode network (DMN) which is linked to executive functioning processes. Additionally, physical activity is associated with higher cerebral blood flow velocity and improved cognitive function which may be linked to the ability to match metabolism and perfusion. However, information mechanistically linking cerebral vasodilator function and cognition is lacking. It is currently unclear if aging or exercise training status alters the neurovascular coupling of blood flow with neural activity in the brain. Therefore, we aim to systematically test the hypothesis that cerebral microvascular function is blunted in aging humans and improved with habitual exercise. We will also determine if cerebral vasodilator responses are associated with WMH volume and functional connectivity of the DMN. Collectively, these studies will offer insight into the underlying changes in cerebral microvascular function and explore how they are functionally linked to cognition with potential relevance to the development and prevention of cognitive impairment. In Aim 1, we will compare cerebral vasodilator responses to chemical and metabolic stimuli before and after cyclooxygenase inhibition and determine how these correlate with cognitive function in: 1) young healthy adults; 2) sedentary older adults; and 3) exercise trained older adults. In Aim 2, we will determine if WMH volume in the brain is affected by aging and habitual exercise and if the cerebral vasodilator responses are associated with WMH volume in the same three groups as in Aim 1. In Aim 3, we will determine if aging and habitual physical activity affects DMN connectivity in the brain in the same three groups studied in Aim 1. In summary, we have proposed a sequence of experiments that focus on the mechanistic link between cerebral vasodilator responses, WMH volume, and functional connectivity of the DMN, all of which are potential biomarkers of risk of cognitive decline. These projects will extend the applicant's training by incorporating neuropsychological testing interpretation and advanced fMRI image analysis. In addition, potential follow-up studies have been identified that will be key elements in the applicant's career progression and foster her development as an independent investigator.

项目摘要/摘要 这个K99/R00应用程序的总体目标是检查脑血管舒张性的年龄相关变化 能力，以及这与认知是如何机械联系在一起的。这个应用程序将探索潜在的 体力活动对血管舒张力与新生之间关系的有益影响 认知衰退的生物标志物。此外，该项目将作为一个工具，以建立在申请者的 心血管衰老和运动生理学方面的培训和她最近完成的F32工作由 使她能够学习其他技术，包括fMRI图像分析和解释 神经心理测试。最近的证据表明，脑微血管功能障碍随着 年龄增大，可能先于认知功能障碍的出现。衰老与更白的皮肤有关 物质超强度(WMH)体积，还改变了默认模式网络(DMN)的功能连接 这与行政运作过程有关。此外，体力活动与更高的 脑血流速度和认知功能的改善可能与匹配能力有关 新陈代谢和灌流。然而，将脑血管扩张剂功能和 缺乏认知力。目前尚不清楚衰老或运动训练状态是否会改变神经血管偶联 血液流动与大脑神经活动的关系。因此，我们的目标是系统地检验这一假设 老年人的大脑微血管功能会变得迟钝，而习惯性运动会改善脑微血管功能。我们还将 确定脑血管扩张剂反应是否与WMH容量和功能连接性有关 DMN。总而言之，这些研究将提供对大脑微血管潜在变化的洞察 功能，并探索它们如何在功能上与认知联系起来，与发展有潜在的相关性 和预防认知障碍。在目标1中，我们将比较脑血管扩张剂对化学物质的反应 以及环氧合酶抑制前后的代谢刺激，并确定它们如何与 认知功能：1)年轻健康的成年人；2)久坐的老年人；3)运动训练的老年人。在……里面 目标2，我们将确定大脑中的WMH容量是否受到衰老和习惯性运动的影响，以及 在相同的三组中，脑血管扩张剂反应与WMH容量有关，与Aim 1相同。 3，我们将确定衰老和习惯性体力活动是否会影响大脑中DMN的连接 在目标1中研究了三个小组。总而言之，我们提出了一系列实验，重点是 脑血管扩张剂反应、WMH容量和脑血管功能连接性之间的机制联系 DMN，所有这些都是认知衰退风险的潜在生物标志物。这些项目将延长 将神经心理测试解释和先进的功能磁共振成像相结合的申请者培训 分析。此外，已经确定了潜在的后续研究，这些研究将是申请人 职业发展和培养她作为一名独立调查员的发展。