Dynamic Functional Connectivity MRI in Preclinical AD

临床前 AD 中的动态功能连接 MRI

• 批准号: 9088289
• 负责人: Thomas J. Grabowski
• 金额: $ 22.6万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9088289
• 关键词: Abbreviations; Address; Adult; Alzheimer' s Disease; Amyloid beta-Protein; Amyloid deposition; Anatomy; Apolipoprotein E; Area; Attenuated; Auditory; Autopsy; Biological Markers; Brain; Cerebrum; Clinical; Cognition; Communities; Computer software; Data; Dementia; Detection; Development; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Echo-Planar Imaging; Effectiveness; Equation; Functional Magnetic Resonance Imaging; Future; Health; Healthcare; Hippocampus (Brain); Image; Impaired cognition; Impairment; Individual; Inherited; Institutes; Lesion; Libraries; Linear Models; Liquid substance; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medial; Memory; Memory Loss; Metabolic; Metabolism; Microvascular Dysfunction; Modeling; Molecular; Monitor; Neurologic; Paired Comparison; Participant; Pathologic; Pathologic Processes; Physiological; Population Attributable Risks; Positron-Emission Tomography; Predisposition; Process; Protocols documentation; Proxy; Radiation; Recovery; Research; Sampling; Specificity; Spin Labels; Spinal Puncture; Staging; Structure; System; Target Populations; Testing; Thick; Universities; Verbal Learning; Visual; Washington; Weight; White Matter Hyperintensity; Width; aging brain; base; blood oxygen level dependent; brain health; cardiovascular health; cerebrovascular; cingulate cortex; cognitive reserve; cohort; independent component analysis; memory encoding; memory retrieval; mild cognitive impairment; neuroimaging; novel; novel strategies; pre-clinical; precision medicine; prevent; resilience; study population; tau aggregation; tool

PROJECT 3 - ABSTRACT Alzheimer's disease (AD) pathologic change develops in an orderly anatomic sequence but the level of pathologic change varies among and within preclinical and dementia stages of AD. Moreover, multiple pathological processes, primarily AD and cerebral microvascular disease, varyingly conspire to cause memory problems and dementia. Although very successful and critically important in research settings, and likely to remain part of tiered assessment protocols, CSF biomarkers and PET imaging are likely to encounter barriers as initial screens or serial treatment monitors for millions of people. We seek to address this anticipated barrier to health care effectiveness by developing functional MRI (fMRI)-based approaches that are informative in preclinical stages of dementia. Functional connectivity fMRI (fcMRI) studies show altered functional connectivity in the default mode network (DMN) as a marker of preclinical AD, but it is not known how specific the changes are to AD, or how predictive DMN functional connectivity is of memory decline or AD progression. Moreover, current data derive mostly from research cohorts and have not focused on the likely large contribution from cerebral microvascular disease as indicated by autopsy. Indeed, the Adult Changes in Thought (ACT) study, a community-based study of brain aging and incident dementia in the Seattle area, has demonstrated in large autopsy studies that the population-attributable risk of dementia in ACT was 45% from AD and 33% from cerebral microvascular disease. Using a cohort of ACT participants that is part of the UW ADRC Clinical Core (ACT-Plus), we will evaluate the specificity of DMN functional connectivity changes in preclinical AD, as well as MRI measures of the impact of cerebral microvascular disease. Specific Aim 1. By determining novel fcMRI correlates of preclinical AD as defined by CSF biomarkers in participants without dementia, we will test the hypothesis that functional connectivity measures can discriminate individuals with CSF profiles of AD from those without, and will compare functional connectivity measures to commonly used parameters including hippocampal volume and cortical thickness, as well as to proxy measures of regional cerebral metabolism. Specific Aim 2. By determining novel fcMRI correlates of cognitive impairment and decline in individuals without dementia at baseline, and analyzing them with respect to established and experimental leading measures of cognitive decline, we will test the hypothesis that dynamic functional connectivity, using an approach we developed, is a more sensitive and informative biomarker than existing imaging approaches or stationary functional connectivity for identifying present and predicting future cognitive impairment. When successfully completed, this Project will have determined the utility of novel fMRI approaches to brain aging and preclinical AD in a sample that more closely reflects the ultimate target population.

项目3--摘要 阿尔茨海默病(AD)的病理变化是按解剖顺序发展的，但 阿尔茨海默病的临床前阶段和痴呆阶段之间的病理变化各不相同。此外，多个 病理过程，主要是阿尔茨海默病和脑微血管疾病，以各种方式共同导致记忆 问题和痴呆症。尽管在研究环境中非常成功和至关重要，而且很可能 仍是分级评估方案的一部分，脑脊液生物标记物和PET成像可能会遇到障碍 作为数百万人的初始屏幕或系列治疗监测器。我们试图解决这一预期的障碍 通过开发基于功能磁共振成像(FMRI)的方法来提高医疗保健效率 痴呆的临床前阶段。功能连接功能磁共振成像(FcMRI)研究显示功能改变 默认模式网络(DMN)中的连通性作为临床前AD的标志，但具体程度尚不清楚 这些变化是关于AD的，或者DMN功能连接对记忆衰退或AD进展的预测性。 此外，目前的数据大多来自研究队列，并没有关注可能的大范围 尸检显示脑微血管疾病的贡献。事实上，成年人的变化 思想(ACT)研究，一项基于社区的西雅图地区大脑老化和痴呆症事件研究，已经 大型尸检研究表明，ACT中患痴呆症的人群归因风险为45% AD和33%的患者来自脑微血管疾病。使用作为UW一部分的ACT参与者队列 ADRC临床核心(ACT-Plus)，我们将评估DMN功能连接性变化的特异性 临床前期AD，以及MRI测量脑微血管疾病的影响。具体目标1.由 在没有脑脊液生物标志物的参与者中确定临床前AD的新的fcMRI相关性 对于痴呆症，我们将测试功能连通性测量可以区分个体与 非AD患者的脑脊液图谱，并将功能连接性测量与常用的进行比较 参数包括海马体体积和皮质厚度，以及局部区域的替代测量 大脑新陈代谢。具体目标2.通过确定新的功能磁共振成像与认知障碍和 基线时非痴呆症患者的下降，并分析他们与已建立的和 认知衰退的实验领先指标，我们将检验动态函数的假设 使用我们开发的方法，连接性是一种比现有的更敏感和更有信息量的生物标志物 用于识别现在和预测未来认知的成像方法或固定功能连接 减损。成功完成后，该项目将确定新型功能磁共振成像的用途 更能反映终极目标的样本中脑老化和临床前AD的研究方法 人口。