Prevalence and impact of cerebral anatomical variations: a risk factor for cognitive decline?

大脑解剖变异的患病率和影响：认知能力下降的危险因素？

• 批准号: 10477190
• 负责人: JILL NICOLE BARNES
• 金额: $ 15.5万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10477190
• 关键词: Address; Adult; Affect; Age; Age-Years; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Anatomy; Architecture; Biological Markers; Blood Vessels; Blood flow; Brain; Cerebrospinal Fluid; Cerebrovascular Circulation; Cerebrovascular system; Cerebrum; Characteristics; Chronic; Clinical; Cognition; Cognitive; Data; Dementia; Early identification; Elderly; Exhibits; Functional disorder; Future; Genetic; Goals; Health; High Prevalence; Human; Impaired cognition; Individual; Investigation; Knowledge; Link; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Medical; Mission; Modeling; Participant; Perfusion; Pre-Clinical Model; Prevalence; Process; Public Health; Publishing; Recommendation; Regional Perfusion; Regulation; Reporting; Research; Risk; Risk Factors; Scanning; Stimulus; Structure; Subgroup; Techniques; United States National Institutes of Health; Universities; Variant; Vascular Dementia; Wisconsin; age related; brain health; cerebral hypoperfusion; cerebrovascular; clinically relevant; cognitive function; cognitive testing; cohort; disability; hypoperfusion; imaging study; improved; innovation; middle age; neuroimaging; novel; response; sex; successful intervention; vertebral artery

PROJECT SUMMARY Optimal brain health requires effective cerebrovascular function, adequate perfusion, and highly responsive blood flow regulation. If any of these are compromised, there are negative implications for brain and cognitive health. Adults with cognitive impairment, including vascular dementia and Alzheimer’s disease, exhibit inadequate cerebral perfusion. There is a critical need for more research on the pathophysiology of cognitive decline in humans. This project investigates the connection between the cerebral vasculature, cerebral perfusion, and cognitive function in middle-aged and older adults. Our overarching hypothesis is that chronic hypoperfusion, resulting from a specific variation in cerebrovascular architecture, impacts cerebral blood flow, and increases the risk of cognitive impairment. Variations in cerebrovascular architecture likely influence the trajectory of age- related declines in cerebral blood flow and warrant further investigation. Our preliminary data, using state-of-the- art MRI, indicates that individuals with a specific cerebral anatomical variation have lower cerebral blood flow and reduced cerebrovascular function compared to controls with normal cerebral anatomy. Thus, the objectives of this application are to investigate vertebral artery hypoplasia (VAH), as a chronic model of hypoperfusion in humans, and determine the potential impact on brain health. For each aim, we will utilize existing MRI scans from a unique, risk-enriched cohort of middle-aged and older adults from the University of Wisconsin-Madison Alzheimer’s Disease Research Center (ADRC). This cohort has extensive longitudinal data on medical health, genetics, and cognitive biomarkers. We will use novel neuroimaging analysis techniques to identify differences in cerebrovascular anatomy and quantify cerebral blood flow in the following specific aims. In Aim 1 we will determine the prevalence of VAH in cognitively unimpaired and cognitively impaired adults in the Wisconsin ADRC cohort. In Aim 2 we will examine the impact of VAH on cerebral blood flow in cognitively unimpaired adults 55-70 years of age. In Aim 3 we will determine the impact of VAH on biomarkers of cognitive decline in cognitively unimpaired adults. This application will provide essential information to determine the potential of variations in cerebrovascular architecture as a novel risk factor for cognitive decline and support critical data for future studies evaluating the impact of chronic hypoperfusion on cognitive function and the risk of Alzheimer’s disease and other dementias. To achieve these aims, we will employ innovative MRI analysis in adults with distinct differences in cerebrovascular architecture. This approach aligns with recent NIH recommendations emphasizing the need for human studies to identify and confirm biomarkers of vascular processes related to cognitive impairment. Upon completion, we will have identified a unique cohort for future large-scale studies, understand the impact on cognitive health and determine whether cerebral anatomical variations are associated with an increase in risk for cognitive decline.

项目摘要 最佳的大脑健康需要有效的脑血管功能，充足的灌注和高度反应性。 血流调节如果其中任何一个受到损害，都会对大脑和认知产生负面影响。 健康患有认知障碍的成年人，包括血管性痴呆和阿尔茨海默病， 脑灌注不足。有一个迫切需要更多的研究的病理生理学的认知 人类的衰落。本项目研究脑血管系统，脑灌注， 和认知功能的影响。我们首要的假设是慢性低灌注， 由于脑血管结构的特殊变化，影响脑血流量，并增加 认知障碍的风险。脑血管结构的变化可能会影响年龄的轨迹- 相关的脑血流量下降，需要进一步研究。我们的初步数据，使用国家的- 磁共振成像技术表明，具有特定脑解剖变异的个体具有较低的脑血流量， 并且与具有正常脑解剖结构的对照组相比降低了脑血管功能。因此，目标 本申请的目的是研究椎动脉发育不全（VAH），作为慢性低灌注模型， 人类，并确定对大脑健康的潜在影响。对于每个目标，我们将利用现有的MRI扫描 来自威斯康星大学麦迪逊分校的一个独特的、风险丰富的中年和老年人群体 阿尔茨海默病研究中心（ADRC）。该队列拥有广泛的医疗健康纵向数据， 遗传学和认知生物标志物。我们将使用新的神经影像分析技术来识别差异 在脑血管解剖学和量化脑血流量在以下具体目标。在目标1中， 确定VAH在威斯康星州认知未受损和认知受损成人中的患病率 ADRC队列。在目标2中，我们将研究VAH对认知未受损成人脑血流的影响 55-70岁。在目标3中，我们将确定VAH对认知功能下降的生物标志物的影响， 未成年人。该应用程序将提供必要的信息，以确定 脑血管结构作为认知能力下降的一个新的危险因素，并为未来的研究提供关键数据 评估慢性低灌注对认知功能和阿尔茨海默病风险的影响， 其他痴呆症为了实现这些目标，我们将在具有明显差异的成人中采用创新的MRI分析。 在脑血管结构中。这种方法符合最近NIH的建议，强调需要 用于人类研究，以识别和确认与认知障碍相关的血管过程的生物标志物。 完成后，我们将为未来的大规模研究确定一个独特的队列，了解其影响 认知健康，并确定大脑解剖结构的变化是否与风险增加有关 认知能力下降