A Novel MRI Biomarker for Incipient Alzheimer's Disease

描述(由申请者提供)：这项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将功能成像应用于以患者为导向的临床研究的技能，以便他可以成为痴呆症和神经成像领域的独立研究员。Greicius博士的具体研究目标是熟练掌握神经成像技术在阿尔茨海默病(AD)早期准确诊断中的应用。为了实现这一目标，候选人将接受功能成像、衰老和认知障碍、神经心理学和统计学领域的专家的指导。此外，应聘者将继续学习一个教育项目，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，候选人将开展一项与其研究培训计划密切相关的研究项目。 这项拟议的研究项目的目标是开发一种新的功能磁共振技术，该技术将高度确定地预测哪些有AD风险的受试者随后会发展成这种疾病。这项研究将使用一种新的功能磁共振成像方法，功能连接磁共振成像(FcMRI)，来检查三个受试组：轻度认知障碍(MCI)组，轻-中度AD组，以及一组年龄和性别与AD组和MCI组受试者年龄和性别匹配的健康老年人。MCI组将在基线时进行成像，并纵向进行临床和神经心理学评估。功能连接性分析将重点放在一个特定的静息状态网络(RSN)上，该网络包含在AD病程早期受影响的几个大脑区域，包括后扣带皮质(PCC)、顶叶下叶和海马体。主要的假设是：1)功能连接性分析将显示与年龄匹配的对照组相比，AD组的RSN活动异常；2)RSN的异常活动将可靠地区分转换为AD的MCI患者和不转换为AD的MCI患者。 通过开展这一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领域的独立研究员，为AD和其他老年人痴呆疾病的早期发现和治疗做出贡献。

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.