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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 阿尔茨海默病 (AD) 是导致痴呆症的最常见原因，影响 65 岁以上人群中多达十分之一和 85 岁以上人群中三分之一的人。流行病学研究估计，目前美国 AD 患病率约为 400 万人到 2050 年，这一数字预计将达到 1300 万。目前批准的治疗只能提供有限的症状益处，但几种旨在预防疾病发作或进展的药物正在进行临床试验。 由于预防性或治疗性治疗的潜力即将出现，并且人们认识到这种治疗在疾病的最早阶段开始是最有效的，因此研究转向了 AD 的早期（最好是临床前）检测。 尽管为开发 AD 体内诊断测定方法付出了巨大努力，但研究人员仍无法在血清或脑脊液分析中鉴定出具有足够灵敏度和特异性的生物标志物，以值得将其用作临床诊断测试。 许多研究小组已经研究了 MRI 在功能性和结构性方面在检测早期 AD 和预测哪些高危患者将患 AD 方面的潜在作用。 然而，迄今为止，这些成像方法在个体患者水平上还缺乏足够的敏感性和特异性。 我们改进了一种新型功能性 MRI 技术——功能连接性 MRI (fcMRI)——来检测特定的静息态网络 (RSN)，该网络包含 AD 早期受影响的多个大脑区域。 该方法包括向个体受试者分配定量分数，反映他们的RSN与RSN标准模板的匹配程度。 我们开发这种方法的目的是使其具有临床相关性和广泛适用性（即从大学教学医院到社区医院）。 为此，它是自动化的，不需要刺激投射或行为反应记录，并且不需要高场 MRI 扫描仪。 我们的初步数据表明，这种方法有可能在疾病的最早阶段区分健康的老年对照和个体 AD 患者。