Hippocampal and parietal network changes among subjects in the early phases of AD and relationship with CSF biomarkers

AD 早期受试者海马和顶叶网络的变化及其与脑脊液生物标志物的关系

• 批准号: 9263869
• 负责人: Arnold Bakker
• 金额: $ 18.51万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 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/9263869
• 关键词: Address; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease risk; Anatomy; Animal Model; Area; Biological Markers; Biological Neural Networks; Brain; Brain imaging; Brain region; Cerebrospinal Fluid; Cognitive; Data; Dementia; Development; Diagnosis; Disease; Disease Progression; Episodic memory; Functional Magnetic Resonance Imaging; Functional disorder; Genetic Status; Hippocampus (Brain); Hyperactive behavior; Individual; Intervention; Light; Location; Measures; Medial; Memory; Memory impairment; Methods; Parietal; Parietal Lobe; Pathology; Patients; Pattern; Phase; Play; Reporting; Research; Resolution; Rest; Role; Sampling; Seeds; Specimen; Structure; Taxes; Temporal Lobe; Therapeutic Intervention; Time; Work; amnestic mild cognitive impairment; base; cingulate cortex; cognitive performance; covert attention; dentate gyrus; design; imaging modality; insight; mild cognitive impairment; network dysfunction; neuroimaging; success; tau Proteins

PROJECT 1 PROJECT SUMMARY / ABSTRACT Alzheimer s disease (AD) pathology can be observed in the brain many years or even decades before the onset of the resulting dementia providing a window of opportunity where intervention may have the greatest chance of success. Observed alterations in this prodromal stage involve multiple distinguishable neural networks in the brain, including the medial temporal and parietal lobe networks. Particularly, increased hippocampal activation observed with functional magnetic resonance imaging (fMRI) in subjects with mild cognitive impairment (MCI) appears to contribute to memory dysfunction and may therefore potentially be used as a marker for the early development of AD pathology. However, it remains unclear if this hippocampal sub region specific dysfunction is associated with other fMRI changes commonly observed in the early stages of the disease, such as parietal network changes or functional connectivity changes between medial temporal and parietal lobe networks. Additionally, it remains unclear how these fMRI changes relate to established biomarkers of AD pathology such as cerebrospinal fluid (CSF) measures of A�, tau and p-tau. Finally, it remains unclear if hippocampal, parietal or functional connectivity changes can be observed in cognitively normal individuals who have a significant memory concern and may represent an even earlier phase along the AD continuum. The current project proposes to directly address these questions in a high-resolution neuroimaging study of hippocampal and parietal network function, examining functional connectivity between these networks and their association with CSF measures of A�, tau and p-tau in subjects along the prodromal continuum of AD. Targeted fMRI activation tasks will be employed designed to tax hippocampal sub region specific function and parietal network function. High-resolution resting state fMRI will be employed to assess connectivity changes between hippocampal and parietal networks. CSF samples will be collected to assess the relationship between these network changes and CSF measures of A�, tau and p-tau. These methods will be employed in four groups of subjects: (1) cognitively normal subjects with subjective memory concerns (SMC), (2) subjects with early MCI (EMCI), (3) late MCI (LMCI), and (4) healthy control subjects. Together the proposed studies will provide insight into the functional brain changes associated with hippocampal and parietal network dysfunction and functional connectivity between these networks in LMCI and EMCI subjects, compared to controls, and determine whether SMC subjects display similar abnormalities. These studies will thus shed light on the relationship between changes in these neural networks, cognitive performance and the accumulation of AD pathology in the brain in subjects across the early spectrum of disease. Finally, this work may provide evidence of whether fMRI measures of hippocampal network dysfunction can serve as a marker for the early development of AD pathology.

项目1项目摘要 /摘要 在大脑中可以观察到阿尔茨海默氏病（AD）病理多年甚至几十年 由此产生的痴呆症的发作提供了一个机会之窗，干预可能最大 成功的机会。观察到的前驱阶段的改变涉及多个独特的中性 大脑中的网络，包括中位临时和顶叶网络。特别是增加 使用功能性磁共振成像（fMRI）观察到的海马激活 认知障碍（MCI）似乎会导致记忆功能障碍，因此可能会使用 作为AD病理早期发展的标志。但是，尚不清楚该海马子是否 区域特异性功能障碍与在早期的早期阶段通常观察到的其他功能磁共振成像变化有关 媒体临时性之间的疾病，例如顶网络变化或功能连通性的变化 和顶叶网络。此外，尚不清楚这些功能磁共振成像的变化与已建立的变化如何相关 A，TAU和P-TAU的AD病理学的生物标志物，例如脑脊液（CSF）。最后，它 尚不清楚海马，顶叶或功能连通性是否可以在认知上观察到 正常人有很大的记忆问题，并且可能代表沿着的更早阶段 广告继续。当前的项目建议直接以高分辨率直接解决这些问题 海马和顶叶网络功能的神经影像学研究，检查功能连通性 这些网络及其与沿前驱主体中A，TAU和P-TAU的CSF测量的关联 广告的连续性。有针对性的FMRI激活任务将旨在征税海马次区域 特定功能和顶网络功能。高分辨率休息状态fMRI将被雇用以评估 海马和顶叶网络之间的连通性变化。将收集CSF样品以评估 这些网络变化与A，TAU和P-TAU的CSF度量之间的关系。这些方法将是 在四组受试者中使用：（1）具有主观记忆问题的认知正常受试者（SMC）， （2）患有早期MCI（EMCI），（3）晚期MCI（LMCI）和（4）健康对照受试者的受试者。在一起 拟议的研究将洞悉与海马和海马相关的功能性大脑变化 LMCI和EMCI受试者中这些网络之间的顶点网络功能障碍和功能连接， 与对照组相比，并确定SMC受试者是否表现出相似的异常。这些研究会 因此，阐明了这些神经网络的变化，认知表现与 早期疾病早期范围的受试者中AD病理学的积累。最后，这项工作 可以提供证据表明fMRI是否可以用作标志物的海马网络功能障碍 为了早期发展AD病理学。