A Composite MR NeuroImaging Marker for Alzheimer's Disease

描述（由申请人提供）：该提案是我们当前研究项目的竞争性更新。与阿尔茨海默病（AD）相关的神经病理改变可能在高危人群出现临床症状前20至30年就开始了。据估计，有450万美国人患有阿尔茨海默病，到2050年，随着婴儿潮一代达到患病风险最高的年龄，预计患病人数将达到1600万。探索和开发早期发现阿尔茨海默病的新技术，以促进疾病的预防、诊断和有效治疗，是人们关注的主要问题。本RO1提案的目标是开发一种创新的成像技术，用于早期发现AD。我们提出了一种新的复合MRI神经成像（MRN）指数，该指数通过定量结合两种fMRI测量结果获得：功能连接指数（FCI）和静息状态下的区域脑血流(rCBF)-灌注赤字。为了验证该指标的有效性，我们首先测试了该指标能否横断面区分轻度AD与认知正常（CN）受试者，以及是否能区分轻度AD与其他类型的非AD痴呆，如额颞叶痴呆（FTD）和血管性痴呆（VaD）。其次，我们测试了MRN指数是否可以追溯预测轻度认知障碍（MCI）受试者是否转化为AD。第三，我们将在纵向研究中确定MRN指数预测MCI受试者AD痴呆发病的动态特征。公共卫生相关性：本提案是我们当前研究项目的竞争性更新。与阿尔茨海默病（AD）相关的神经病理改变可能在高危人群出现临床症状前20至30年就开始了。据估计，有450万美国人患有阿尔茨海默病，到2050年，随着婴儿潮一代达到患病风险最高的年龄，预计患病人数将达到1600万。探索和开发早期发现阿尔茨海默病的新技术，以促进疾病的预防、诊断和有效治疗，是人们关注的主要问题。本提案的目标是开发一种创新的成像技术，用于AD的早期检测。我们提出了一种新的复合MRI神经成像（MRN）指数，该指数通过定量结合两种功能性MRI测量：功能连接指数（FCI）和静息状态下的区域脑血流(rCBF)-灌注赤字来获得。我们将使用MRN指数来区分注定会发展为AD的轻度认知障碍受试者与证明正常衰老过程或转化为不同类型痴呆的个体。

DESCRIPTION (provided by applicant): This proposal is a competing renewal of our current research project. Neuropathological changes related to Alzheimer's Disease (AD) may begin 20 to 30 years before the onset of clinical symptoms in individuals at great risk. AD affects an estimated 4.5 million Americans and is expected to affect as many as 16 million Americans by 2050, as the baby boomers reach the age at which they are most at risk. It is of major concern to explore and develop new technologies for the early detection of AD in order to facilitate disease prevention, diagnosis, and effective treatment. The goal of this RO1 proposal is to develop an innovative imaging technology for the early detection of AD. We propose a new composite MRI Neuroimaging (MRN) Index, obtained by quantitatively combining two fMRI measurements: Functional Connectivity Index (FCI) and Regional Cerebral Blood Flow (rCBF)-Perfusion Deficits at the resting-state condition. To validate this Index as a marker, we first test whether it can cross-sectionally distinguish mild AD from cognitive normal (CN) subjects and distinguish mild AD from other types of non-AD dementia, such as frontotemporal dementia (FTD) and vascular dementia (VaD). Second, we test whether the MRN Index can retroactively predict mild cognitive impairment (MCI) subjects who converted to AD from those who did not. Third, we will determine the dynamic characteristics of the MRN Index in predicting the onset of AD dementia in MCI subjects during the longitudinal studies. PUBLIC HEALTH RELEVANCE: This proposal is a competing renewal of our current research project. Neuropathological changes related to Alzheimer's Disease (AD) may begin 20 to 30 years before the onset of clinical symptoms in individuals at great risk. AD affects an estimated 4.5 million Americans and is expected to affect as many as 16 million Americans by 2050, as the baby boomers reach the age at which they are most at risk. It is of major concern to explore and develop new technologies for the early detection of AD in order to facilitate disease prevention, diagnosis, and effective treatment. The goal of this proposal is to develop an innovative imaging technology for the early detection of AD. We propose a new composite MRI Neuroimaging (MRN) Index, obtained by quantitatively combining two functional MRI measurements: Functional Connectivity Index (FCI) and Regional Cerebral Blood Flow (rCBF)-Perfusion Deficits at the resting-state condition. We will employ the MRN index to distinguish mild cognitive impaired subjects who are destined to develop AD from individuals evidencing the normal aging processes or converting to different types of dementia.