A Novel MRI Biomarker for Incipient Alzheimer's Disease

描述（由申请人提供）：这个以患者为导向的指导研究职业发展（K23）奖的长期目标是发展候选人在以患者为导向的临床研究中应用功能成像的技能，以便他可能成为痴呆和神经成像领域的独立研究者。Greicius博士的具体研究目标是熟练应用神经成像技术来早期和准确诊断阿尔茨海默病（AD）。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，候选人还将学习一门教育课程，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方面的正式课程。最后，候选人将承担与他的研究培训计划密切相关的研究项目。

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.