MAPPING EARLY NETWORK DYSFUNCTION IN FTD AND AD

绘制 FTD 和 AD 中的早期网络功能障碍

基本信息

批准号：
7624804
负责人：
WILLIAM W SEELEY
金额：
$ 12.62万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7624804
关键词：
Activities of Daily Living Age Alzheimer&apos s Disease Animal Disease Models Animal Model Anomia Atrophic Behavior Behavioral Biological Assay Biological Markers Brain Brain Diseases Broca Aphasia Clinical Cognitive Data Dementia Diagnosis Diffusion Diffusion Magnetic Resonance Imaging Disease Disinhibition Early Diagnosis Empathy Episodic memory Frontotemporal Dementia Functional Magnetic Resonance Imaging Functional disorder Gene Mutation Gliosis Goals Heterogeneity Image Image Analysis Impairment Instruction Knowledge Language Link Magnetic Resonance Imaging Maps Metabolism Methods Molecular Motivation Motor Network-based Neurodegenerative Disorders Neurons Pathogenesis Pathology Patients Pattern Population Positron-Emission Tomography Radioisotopes Research Research Personnel Resolution Rest Semantic Dementias Site Speech Staging Structure Symptoms Synapses Syndrome System Translating Variant Work cerebral atrophy cognitive function diagnostic accuracy gray matter human data improved insight mutation carrier network dysfunction neuroimaging neuron loss neuropsychiatry novel novel strategies programs treatment effect white matter

项目摘要

This project, entitled "Mapping Early Network Dysfunction in FTD and AD" will develop novel network connectivity analyses with the goal of improving early detection and diagnosis of frontotemporal dementia (FTD) and Alzheimer's disease (AD). Normal cognitive and behavioral functions require coordinated activity, within large-scale, distributed networks. Emerging data from human studies and animal disease models suggest that specific networks may develop early, tell-tale aberrations during incipient neurodegenerative disease. To explore this possibility, we will use functional connectivity MRI (fcMRI) and diffusion spectral imaging (DSI) to study 60 patients with FTD, 20 asymptomatic FTD gene mutation carriers, 15 patients with AD, and 30 healthy controls. We hypothesize that network connectivity mapping will link each clinical syndrome to a specific intrinsic brain network, will prove capable of detecting early disease, and will provide new insights into symptom pathogenesis. Our aims are (1) to detect network alterations in early stage FTD and AD, (2) to compare the ability of fcMRI, DSI, and conventional structural MRI to detect network-level dysfunction in presymptomatic FTD gene mutation carriers, and (3) to correlate FTD and AD symptoms with network connectivity disruption. The knowledge gained could provide a first step toward a novel, non- invasive imaging biomarker for early FTD and AD and clarify the network basis for FTD, AD, and other neuropsychiatric disorders that target the brain at the network level. RELEVANCE (See instructions): This project will investigate the specific brain networks disrupted in frontemporal dementia and Alzheimer's disease. The goal of the research is to use neuroimaging to clarify where in the brain these diseases begin and how network dysfunction leads to symptoms. Further developed, these methods could improve early detection and diagnosis and provide a sensitive biomarker for following the effects of treatment.

该项目的标题为“绘制FTD和AD中的早期网络功能障碍”将开发新颖的网络连通性分析的目的是改善额颞痴呆的早期检测和诊断（FTD）和阿尔茨海默氏病（AD）。正常的认知和行为功能需要协调的活动，在大规模的分布式网络中。来自人类研究和动物疾病模型的新兴数据建议在初期神经退行性期间特定的网络可能会早期发展出较早的畸变疾病。为了探索这种可能性，我们将使用功能连通性MRI（FCMRI）和扩散光谱成像（DSI）研究60例FTD患者，20名无症状FTD基因突变载体，15例患者 AD和30个健康对照。我们假设网络连接映射将链接每个临床综合征对特定内在脑网络的综合征，将证明能够检测早期疾病，并将提供对症状发病机理的新见解。我们的目标是（1）检测早期FTD的网络变化和AD，（2）比较FCMRI，DSI和常规结构MRI检测网络级别的能力预性FTD基因突变载体的功能障碍，（3）将FTD和AD症状与网络连接破坏。获得的知识可以提供迈向小说，非 - 早期FTD和AD的侵入性成像生物标志物，并阐明FTD，AD和其他的网络基础针对大脑在网络级别的神经精神疾病。相关性（请参阅说明）：该项目将调查在临时痴呆和阿尔茨海默氏症中破坏的特定大脑网络疾病。该研究的目的是使用神经影像来阐明这些疾病在大脑中开始的何处以及网络功能障碍如何导致症状。进一步发展，这些方法可以提前改善检测和诊断，并为遵循治疗的影响提供了灵敏的生物标志物。