A NOVEL FMRI BIOMARKER OF INCIPIENT ALZHEIMER?S DISEASE

早期阿尔茨海默病的新型 FMRI 生物标志物

• 批准号: 8169828
• 负责人: Michael D Greicius
• 金额: $ 1.85万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169828
• 关键词: Affect; Age; Alzheimer disease detection; Alzheimer' s Disease; Behavioral; Biological Assay; Biological Markers; Brain region; Cerebrospinal Fluid; Clinical; Clinical Trials; Community Hospitals; Computer Retrieval of Information on Scientific Projects Database; Data; Dementia; Diagnostic; Diagnostic tests; Disease; Disease Progression; Drug Design; Elderly; Epidemiologic Studies; Functional Magnetic Resonance Imaging; Funding; Goals; Grant; Image; Individual; Institution; Magnetic Resonance Imaging; Methods; Patients; Prevalence; Preventive; Research; Research Personnel; Resources; Rest; Risk; Role; Sensitivity and Specificity; Serum; Source; Staging; Stimulus; Teaching Hospitals; Techniques; United States; United States National Institutes of Health; Universities; clinically relevant; in vivo; novel; pre-clinical; prevent; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alzheimer's Disease (AD) is the most common cause of dementia affecting as many as 1 in 10 people over age 65 and 1 in 3 people over age 85. Epidemiological studies estimate the prevalence of AD in the United States to be approximately 4 million people currently and this number is expected to reach 13 million by the year 2050. Currently approved therapy only provides modest symptomatic benefit, but several drugs designed to prevent the onset or progression of disease are undergoing clinical trials. With the potential for preventive or curative therapy on the horizon and an understanding that such treatments will be most effective when begun at the earliest stages of the illness, research has turned to the early, and ideally pre-clinical, detection of AD. Despite intensive efforts to develop an in vivo diagnostic assay for AD, researchers have been unable to identify biomarkers in either serum or cerebrospinal fluid analyses with sufficient sensitivity and specificity to merit their use as a clinical diagnostic test. A number of groups have examined the potential role of MRI, both functional and structural, in detecting early AD and predicting which at-risk patients will develop AD. To date, however, these imaging approaches have also lacked sufficient sensitivity and specificity at the individual patient level. We have modified a novel functional MRI technique?functional connectivity MRI (fcMRI)?to detect a specific resting-state network (RSN) that incorporates several brain regions affected in the earliest stages of AD. The method includes assigning a quantitative score to individual subjects reflecting the degree to which their RSN matches a standard template of the RSN. We have developed this method with the goal of making it both clinically relevant and broadly applicable (i.e beyond university teaching hospitals to community hospitals). To this end, it is automated, does not require projection of stimuli or recording of behavioral responses, and does not require a high field MRI scanner. Our preliminary data suggests that this approach has the potential to distinguish healthy elderly controls from individual AD patients at the earliest stage of the disease.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 阿尔茨海默氏病（AD）是痴呆症的最常见原因，多达十分之一的人超过65岁，三分之一的人超过35岁，超过85岁。流行病学研究估计，美国AD的流行率当前约400万人，目前约有400万人，这一数字预计将在2050年中造成的临床效果，但预计在2050年中均可享受临床的效果。试验。 随着预防或治愈治疗的潜力即将到来，并了解这种治疗在疾病最早开始时将是最有效的，因此研究已转变为对AD的早期且理想的临床前检测。 尽管为AD开发体内诊断测定法，但研究人员仍无法以足够的敏感性和特异性来识别血清或脑脊液分析中的生物标志物，以应有其用作临床诊断测试。 许多小组研究了功能和结构性MRI在检测早期AD的潜在作用，并预测哪些高危患者将发展为AD。 但是，迄今为止，这些成像方法在单个患者水平上也缺乏足够的敏感性和特异性。 我们修改了一种新型的功能性MRI技术？功能连通性MRI（FCMRI）？检测特定的静息状态网络（RSN），该网络（RSN）结合了在AD最早阶段影响的几个大脑区域。 该方法包括将定量分数分配给反映其RSN与RSN标准模板与之匹配的程度的单个受试者。 我们已经开发了这种方法，目的是使其既相关又广泛地适用（即超出大学教学医院的社区医院）。 为此，它是自动化的，不需要投影刺激或行为响应的记录，也不需要高场MRI扫描仪。 我们的初步数据表明，这种方法有可能在最早的疾病阶段将健康的老年对照与单个AD患者区分开。