A Novel MRI Biomarker for Incipient Alzheimer's Disease

描述（由申请人提供）：这个指导以患者为导向的研究职业发展（K23）奖的长期目标是发展候选人的技能，将功能成像应用于以患者为导向的临床研究，使他成为痴呆症和神经影像学领域的独立研究者。Greicius博士的具体研究目标是发展神经影像技术应用于阿尔茨海默病（AD）早期和准确诊断的熟练程度。为了实现这一目标，候选人将由功能成像，衰老和认知障碍，神经心理学和统计学领域的专家指导。此外，候选人将继续学习教育课程，包括行为神经学和功能成像方面的高级研讨会，以及计算机编程，神经心理学和统计学领域的正式课程。最后，候选人将承担一个与他的研究培训计划紧密结合的研究项目。 拟议研究项目的目标是开发一种新的fMRI技术，该技术将以高度的确定性预测哪些有AD风险的受试者随后将发展为该疾病。该研究将使用一种新的fMRI方法，功能连接MRI（fcMRI），检查三个受试者组：轻度认知障碍（MCI）组，轻度-中度AD组，以及一组年龄和性别与AD和MCI组受试者匹配的健康老年人。MCI组将在基线时进行成像，并进行纵向临床和神经心理学评价。功能连接分析将集中在一个特定的静息状态网络（RSN），其中包括几个大脑区域受影响的早期过程中的AD，包括后扣带皮层（PCC），下顶叶和海马。主要假设是：1）功能连接分析将证明与年龄匹配的对照组相比，AD组的RSN活性异常，2）RSN活性异常将可靠地区分转化为AD的MCI患者与未转化为AD的MCI患者。 通过开展这项研究项目和实施研究培训计划，Greicius博士计划成为痴呆症和神经影像学领域的独立研究者，并为早期发现和治疗AD和其他老年痴呆症做出贡献。

DESCRIPTION (provided by applicant): The long-term objective of this Mentored Patient-Oriented Research Career Development (K23) Award is to develop the candidate's skills in applying functional imaging to patient-oriented clinical research so that he may become an independent investigator in the fields of dementia and neuroimaging. Dr. Greicius' specific research goal is to develop proficiency in the application of neuroimaging techniques to the early and accurate diagnosis of Alzheimer's disease (AD). To accomplish this goal, the candidate will be mentored by experts in the fields of functional imaging, aging and cognitive disorders, neuropsychology and statistics. In addition, the candidate will pursue an educational program to include advanced seminars in behavioral neurology and functional imaging as well as formal coursework in the areas of computer programming, neuropsychology and statistics. Finally, the candidate will undertake a research project closely aligned with his research training plan. The goal of the proposed research project is to develop a novel fMRI technique that will predict, with a high degree of certainty, which subjects at risk for AD will subsequently develop the disease. The study will use a novel fMRI approach, functional connectivity MRI (fcMRI), to examine three subject groups: A group with mild cognitive impairment (MCI), a group with mild-moderate AD, and a group of healthy older adults age- and gender-matched to subjects in the AD and MCI groups. The MCI group will be imaged at baseline and followed longitudinally with clinical and neuropsychological evaluations. The functional connectivity analysis will focus on a specific resting-state network (RSN) that incorporates several brain regions affected early in the course of AD including the posterior cingulate cortex (PCC), inferior parietal lobes, and hippocampus. The main hypotheses are that 1) functional connectivity analyses will demonstrate abnormal RSN activity in the AD group compared to age-matched controls and 2) abnormal activity in the RSN will reliably distinguish MCI patients who convert to AD from those MCI patients who do not. By conducting this research project and implementing the research training plan, Dr. Greicius plans to become an independent investigator in the fields of dementia and neuroimaging and contribute to the early detection and treatment of AD and other dementing diseases of the elderly.