What is the relationship between BOLD fMRI and functional MRS in aging and MCI?

BOLD fMRI 和功能性 MRS 在衰老和 MCI 中有何关系？

• 批准号: 9336230
• 负责人: Craig E Stark
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9336230
• 关键词: Age; Aging; Alzheimer' s Disease; Behavioral; Biological Markers; Blood flow; Brain; Brain imaging; Breathing; Cellular Structures; Classification; Code; Cognitive; Coupling; Data; Data Analyses; Dementia; Development; Disease; Dropout; Functional Magnetic Resonance Imaging; Gases; Glutamates; Glutamine; Goals; Hippocampus (Brain); Hyperactive behavior; Imaging Techniques; Impaired cognition; Incidence; Lead; Link; Literature; Location; Longevity; Magnetic Resonance Imaging; Measurement; Measures; Medial; Memory; Memory Loss; Metabolic; Methods; Nature; Neurobiology; Neurocognitive; Oxygen; Participant; Pathologic; Pattern; Population; Prevention; Problem Sets; Public Health; Research; Rest; Risk Factors; Rodent Model; Sampling Biases; Scanning; Signal Transduction; Source; Stress; System; Techniques; Temporal Lobe; Testing; Time; Variant; Vascular Dementia; age effect; age related; aged; aging brain; base; cognitive task; design; experimental study; gamma-Aminobutyric Acid; healthy aging; human data; improved; medical complication; mild cognitive impairment; neuromechanism; novel; pre-clinical; public health relevance; relating to nervous system; response; spectroscopic imaging; success; volunteer

Project Summary Our memory changes as we age. Age-related memory decline in and of itself represents a significant public health impact, but cognitive decline – and in particular memory decline – has been shown to be an important risk factor for Alzheimer's Disease (AD). Examining neurocognitive aging will help us better characterize pathological and non-pathological changes in the brain throughout the lifespan and identify preclinical markers for cognitive decline. The goal of this proposal is to develop and compare a novel method of brain imaging, functional magnetic resonance imaging spectroscopy (fMRS) with the more traditional BOLD functional magnetic resonance imaging (MRI) techniques in healthy aging and mild cognitive impairment (MCI). BOLD fMRI has been used extensively to study differences in neural activity associated with aging and MCI, but it has limitations that may be critical to our interpretation of these data. In particular, the neuro-vasculature coupling ratio (M) is altered in aging, such that age-related changes in BOLD measures may not be due to age-related changes in underlying neural activity, but in vasculature instead. Here, we propose an altogether different approach in fMRS that has the added advantage of providing a measure that may be might be more directly linked to neural activity than the link we have with blood flow. We will develop a novel fMRS technique that will collect metabolite data while participants engage in various cognitive tasks. The fMRS signal will more directly measure cellular activity, energetics, and markers of cellular structure and loss in the aging brain. In particular, excitation and inhibition will be dynamically measured during a memory task by quantifying glutamate, glutamine and GABA while simultaneously measuring BOLD fMRI at the same location. Together, these measurements will allow us to examine the relationship between BOLD fMRI and metabolics and how these are altered with aging and early dementia. It will also give us the opportunity to test whether any of several tasks can serve as an age-invariant baseline in BOLD fMRI tasks as well as to help us more directly link human data and memory decline to the neurobiological models from the rodent. They will also give us the opportunity to explore biomarker / behavioral relationships and to further our understanding of changes in cellular structure related to aging.

项目摘要 随着年龄的增长，我们的记忆会发生变化。与年龄有关的记忆本身就是一个重要的公众 健康影响，但认知能力下降，尤其是记忆下降 - 已被证明是重要的 阿尔茨海默氏病（AD）的危险因素。检查神经认知衰老将有助于我们更好地描述 在整个寿命中，大脑的病理和非病理变化并识别临床前标记 认知能力下降。 该建议的目的是开发和比较一种新颖的脑成像方法，功能磁性 共振成像光谱（FMR）具有更传统的粗体功能磁共振 健康衰老和轻度认知障碍（MCI）的成像（MRI）技术。大胆的fMRI已被使用 广泛研究与衰老和MCI相关的神经活动的差异，但它的局限性可能 对于我们对这些数据的解释至关重要。特别是，神经血脉脉络系统偶联比率（M）在变化 老化，与年龄相关的大胆措施的变化可能不是由于年龄相关的底层变化而引起的 神经活动，但在脉管系统中。在这里，我们在FMR中提出了一种完全不同的方法 提供可能与神经活动更直接相关的措施的额外优势，而不是 我们与血流的联系。 我们将开发一种新颖的FMRS技术，该技术将收集代谢物数据，而参与者参与了各种 认知任务。 FMRS信号将更直接地测量细胞活性，能量和标记 衰老大脑的细胞结构和损失。特别是，兴奋和抑制作用将动态 通过量化谷氨酸，谷氨酰胺和GABA，同时量化在记忆任务中 在同一位置测量大胆的fMRI。这些测量将使我们能够检查 大胆的fMRI与代谢之间的关系以及它们如何随老化和早期痴呆而改变。 还将使我们有机会测试几个任务中的任何一个都可以作为年龄不变的基线 大胆的fMRI任务以及帮助我​​们更直接地将人类数据和记忆降低到 来自啮齿动物的神经生物学模型。他们还将给我们机会探索生物标志物 / 行为关系，并进一步了解与衰老有关的细胞结构变化。