Impact of cerebral anatomical variations on cerebral perfusion, cerebrovascular reactivity, and biomarkers of cognitive decline

脑解剖变异对脑灌注、脑血管反应性和认知衰退生物标志物的影响

基本信息

批准号：
10030849
负责人：
JILL NICOLE BARNES
金额：
$ 192.94万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10030849
关键词：
Acute Address Adult Aerobic Exercise Affect Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Anatomy Architecture Biological Markers Blood Pressure Blood Vessels Blood flow Brain Cerebrospinal Fluid Cerebrovascular Circulation Cerebrovascular system Cerebrum Chronic Clinical Cognition Cognitive Complex Data Development Early identification Elderly Exhibits Functional disorder Genetic Goals Health High Prevalence Human Hypoxia Imaging Techniques Impaired cognition Individual Investigation Knowledge Link Magnetic Resonance Imaging Mediating Medical Mission Modeling Patient Recruitments Perfusion Physiological Pre-Clinical Model Process Public Health Publishing Recommendation Regional Perfusion Regulation Reporting Research Rest Risk Risk Factors Stimulus Subgroup United States National Institutes of Health Universities Variant Vascular Dementia Wisconsin age related brain health cerebral hypoperfusion cerebrovascular cerebrovascular health clinically relevant cognitive testing cohort disability effective intervention high risk hypoperfusion imaging modality imaging study improved middle age neuroimaging novel response vertebral artery

项目摘要

PROJECT SUMMARY Optimal brain health requires effective cerebrovascular function, adequate perfusion, and highly responsive blood flow regulation. If any of these, or a combination of these, are compromised, there are implications for brain health. Previous research demonstrated that cerebral hypoperfusion and inadequate cerebrovascular responses to vasoactive stimuli may precede the onset of cognitive impairment. Indeed, adults with cognitive impairment, including vascular dementia and Alzheimer’s disease, exhibit inadequate cerebral perfusion. Yet, the majority of evidence linking hypoperfusion to cognition comes from preclinical models, and there is minimal research on how chronic cerebral hypoperfusion may impact cerebrovascular control in humans. Accordingly, there is a critical need for more research on the pathophysiology of cognitive decline in humans. Our preliminary data indicate that adults with cerebral anatomical variations demonstrate cerebral hypoperfusion and reduced cerebrovascular reactivity. This finding is important as it presents our investigative team with a group of individuals with a cerebral anatomical variant that may naturally model a state of chronic cerebral hypoperfusion. Our overarching hypothesis is that chronic hypoperfusion, resulting from a specific variation in cerebrovascular architecture, impacts cerebral blood flow regulation which increases the risk of cognitive impairment. Thus, the objectives of this application are to investigate chronic models of hypoperfusion in humans, examine compensatory mechanisms to maintain perfusion, and determine the potential impact on cognitive health. For each aim, we will recruit participants from a unique, risk-enriched cohort of middle-aged and older adults from the University of Wisconsin-Madison Alzheimer’s Disease Research Center. This cohort has extensive longitudinal data on medical health, genetics, and cognitive biomarkers. We will use state-of-the-art imaging modalities to identify differences in cerebrovascular architecture and quantify cerebral blood flow regulation in the following specific aims: In Specific Aim 1, we will examine the compensatory responses to a model of acute hypoperfusion and determine the impact of chronic cerebral hypoperfusion observed in adults with specific cerebral anatomical variations. In Specific Aim 2, we will utilize aerobic exercise to characterize the cerebrovascular responses to acute hyperperfusion and determine the impact of cerebral anatomical variations. In Specific Aim 3 we will determine the impact of cerebral anatomical variations on cerebrovascular control and establish whether adults with cerebral anatomical variations are at a higher risk of cognitive decline. This project will be the first systematic investigation of cerebrovascular control mechanisms in acute and chronic cerebral hypoperfusion in humans, and will address the potential implications of long-term hypoperfusion for cognitive health. Upon completion, we will understand the impact of cerebral anatomical variations on cerebrovascular health and the risk of Alzheimer’s disease and related dementias.

项目概要最佳的大脑健康需要有效的脑血管功能、充足的灌注和高度的反应如果其中任何一个或这些的组合受到损害，就会对血流调节产生影响。先前的研究表明，大脑灌注不足和脑血管不足。事实上，对血管活性刺激的反应可能先于认知障碍的发生。然而，包括血管性痴呆和阿尔茨海默病在内的脑灌注不足。大多数将低灌注与认知联系起来的证据来自临床前模型，并且很少有证据表明关于慢性脑灌注不足如何影响人类脑血管控制的研究因此，我们的初步研究迫切需要对人类认知衰退的病理生理学进行更多研究。数据表明，具有脑解剖变异的成年人表现出脑灌注不足并减少这一发现很重要，因为它为我们的研究团队提供了一组具有脑解剖变异的个体可能自然地模拟慢性脑灌注不足的状态。我们的首要假设是，慢性灌注不足是由脑血管的特定变化引起的。结构，影响脑血流调节，从而增加认知障碍的风险。该应用的目的是研究人类慢性灌注不足模型，检查维持灌注的补偿机制，并确定对认知健康的潜在影响。为了实现每个目标，我们将从独特的、风险丰富的中年和老年人群体中招募参与者威斯康星大学麦迪逊分校阿尔茨海默氏病研究中心对该队列进行了广泛的研究。我们将使用最先进的成像技术来获取有关医疗健康、遗传学和认知生物标志物的纵向数据。识别脑血管结构差异并量化脑血流调节的方法以下具体目标：在具体目标 1 中，我们将研究对急性发作模型的补偿反应低灌注并确定在患有特定疾病的成人中观察到的慢性脑灌注不足的影响在具体目标 2 中，我们将利用有氧运动来描述大脑解剖结构的变化。脑血管对急性过度灌注的反应并确定脑解剖变异的影响。在具体目标 3 中，我们将确定大脑解剖变异对脑血管控制和该项目旨在确定具有大脑解剖变异的成年人是否面临更高的认知能力下降风险。将是首次系统研究急性和慢性脑血管病的脑血管控制机制人类灌注不足，并将解决长期灌注不足对认知的潜在影响完成后，我们将了解大脑解剖变异对脑血管的影响。健康以及阿尔茨海默病和相关痴呆症的风险。