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

项目总结 最佳的大脑健康需要有效的脑血管功能、充足的血流灌注和高度的反应能力 血液流动调节。如果其中任何一项受到损害，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，表现出 大脑灌注量不足。迫切需要对认知障碍的病理生理学进行更多的研究。 人类的数量在下降。这个项目调查了脑血管系统、脑血流灌注、 以及中老年人的认知功能。我们的主要假设是慢性低灌注率， 由脑血管结构的特定变化引起的，影响脑血流，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- 相关的脑血流下降，值得进一步研究。我们的初步数据，使用最新情况- ART MRI显示，具有特定大脑解剖变异的个体的脑血流量较低 与大脑解剖正常的对照组相比，脑血管功能降低。因此，目标是 这一应用的目的是研究椎动脉发育不良(VAH)，作为一种慢性低血流灌注模型。 并确定其对大脑健康的潜在影响。对于每个目标，我们将利用现有的核磁共振扫描 来自威斯康星大学麦迪逊分校的一个独特的、风险丰富的中老年人队列 阿尔茨海默病研究中心(ADRC)。这个队列有大量关于医疗健康的纵向数据， 遗传学和认知生物标记物。我们将使用新的神经成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特定目标。在目标1中，我们将 确定威斯康星州认知正常和认知受损成年人中VAH的患病率 ADRC队列。在目标2中，我们将检查VAH对认知正常成年人脑血流的影响。 年龄55-70岁。在目标3中，我们将确定VAH对认知能力下降的生物标志物的影响 完好无损的成年人。此应用程序将提供基本信息，以确定 脑血管结构是认知功能减退的新危险因素并为未来研究提供关键数据 评估慢性低灌流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，我们将对具有明显差异的成年人进行创新的MRI分析 在脑血管结构中。这一方法与NIH最近强调有必要 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 并确定大脑解剖变异是否与风险增加有关 治疗认知功能减退。

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.