A Composite MR NeuroImaging Marker for Alzheimer's Disease

描述(由申请人提供)：本提案是对我们当前研究项目的竞争性更新。与阿尔茨海默病(AD)相关的神经病理变化可能在高危个体临床症状出现前20至30年开始。据估计，AD影响了450万美国人，预计到2050年，随着婴儿潮一代达到他们面临风险最大的年龄，AD将影响多达1600万美国人。为了促进疾病的预防、诊断和有效治疗，探索和开发早期发现AD的新技术是人们非常关注的问题。这项RO1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综合磁共振神经成像(MRN)指数，该指数是通过定量结合两种功能MRI测量方法得到的：功能连接指数(FCI)和局部脑血流(RCBF)-静息状态下的灌流缺陷。为了验证这一指标作为一种标记物的有效性，我们首先测试了它是否可以横断面区分轻度AD和认知正常(CN)受试者，并将轻度AD与其他类型的非AD痴呆区分开来，如额颞叶痴呆(FTD)和血管性痴呆(VAD)。其次，我们测试MRN指数是否可以追溯预测那些没有转变为AD的轻度认知障碍(MCI)受试者。第三，在纵向研究中，我们将确定MRN指数在预测MCI受试者AD痴呆发病中的动态特征。公共卫生相关性：这项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)相关的神经病理变化可能在高危个体临床症状出现前20至30年开始。据估计，AD影响了450万美国人，预计到2050年，随着婴儿潮一代达到他们面临风险最大的年龄，AD将影响多达1600万美国人。为了促进疾病的预防、诊断和有效治疗，探索和开发早期发现AD的新技术是人们非常关注的问题。这项提议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综合磁共振神经成像(MRN)指数，该指数是通过定量结合两种功能MRI测量方法得到的：功能连接指数(FCI)和局部脑血流(RCBF)-静息状态下的灌流缺陷。我们将使用MRN指数来区分注定要发展为AD的轻度认知障碍受试者与证明正常衰老过程或转变为不同类型痴呆症的个人。

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.