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 阿尔茨海默氏病（AD）病理可以在大脑中观察到多年甚至几十年 由此产生的痴呆症的发作提供了一个机会统一窗口，白色干预可能最大 成功的机会。 大脑中的网络，不限制内侧时间和parial叶网络。 用功能性磁共振成像（fMRI）观察到的海马激活在患有轻度的受试者中 认知障碍（MCI）似乎会导致记忆功能障碍，并且可能会使用 但是，作为AD病理发展的标志，目前尚不清楚该海马潜水艇是否。 区域规范功能障碍与在早期停滞不前观察到的其他功能磁共振成像变化有关 该疾病，例如副网络变化或内侧时间之间的功能连接器变化 和顶叶网络。 AD病理学的生物标志物（例如脑脊液（CSF））的测量最终 尚不清楚海马，副群或功能连接变化是否可以在认知上观察到变化变化。 何何何何霍何何何何霍何何何何霍何何何何霍何何何何霍Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Habe Habe AD连续性。当前的项目提议直接解决这些问题 海马和顶叶网络功能的神经影像学研究，检查功能连接。 这些网络及其与生产受试者的A，TAU和P-TAU的CSF度量的关联 AD的连续性。 规格功能和副网络功能将拟定高分辨率静止状态fMRI 海马和副网络之间的连通性变化。 网络变化与A，TAU和P-TAU的CSF度量之间的关系。 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）具有早期MCI（EMCI），（3）晚期MCI（LMCI）和（4）健康对照受试者的受试者 与海马和 在LMCI和EMCI受试者中，这些网络之间的隔离网络功能障碍和功能连接连接， 与对照组相比，确定受试者是否表现出相似的异常。 因此，阐明了这些神经网络，认知表现与您之间的变化之间的关系 大脑中的AD病理在受试者的早期疾病中 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。