The role of myelin & vascular risk on brain structure and function in aging

描述(由申请人提供)：应聘者的长期目标是成为脑白质微结构完整性和血管风险评估方面的专家，因为它与衰老的认知功能有关。为了实现这一目标，候选人将完成一项培训计划，其中包括课程作业、研讨会和与专家的咨询，重点是正常和病理性衰老中脑白质变化的神经病理学，用于评估脑白质微结构的当前和新的神经成像技术，血管风险评估，老龄和血管风险增加的少数族裔人群中的心血管疾病及其病理生理学。主办机构伊利诺伊大学芝加哥分校提供与该奖项相关的培训活动和资源，包括参加神经放射学、血管神经学、心脏病学和少数族裔研究的研讨会、讲座和期刊俱乐部。主要导师阿南德·库马尔博士对脑白质进行了超过15年的神经成像研究，包括衰老和血管风险中髓鞘完整性的生化研究， 并指导了几位K奖获得者和基金会奖学金获得者。他是精神病学系主任，接受R01和K24治疗晚年抑郁症和终生血管风险的工作。候选人目前对这项研究的神经心理学方面做出了贡献，并处于有利地位，可以利用拟议研究的既定转介来源和科学资源。在拟议的研究中，候选人将结合一种新的MRI技术来询问白质微结构(即髓鞘映射)与其他白质病理(包括脑梗塞和微出血)的成像，以确定在老龄化和少数族裔人群中血管风险和认知的最强大生物标记物。虽然使用目前可用的神经成像方法(包括扩散张量成像(DTI))研究整体白质损伤对衰老大脑的影响已有很长的历史，但对于髓鞘的贡献，它们缺乏敏感性和特异性。鉴于髓鞘破坏早在生命的第四个十年就开始了，并随着年龄的增长而加速，我们将在60-80岁的健康老年人(20名高加索人，20名非洲裔美国人和20名西班牙裔美国人)中使用新的髓鞘映射技术和目前的DTI MRI。试验数据表明，在量化正常白质的微结构损伤和髓鞘含量方面，髓鞘映射比DTI更敏感。老年人将接受全面的认知和血管风险评估。试点数据表明，一系列血管风险(在我们的少数群体中升高)与认知表现有关，即执行措施。这项研究站在当前和未来MRI技术的结合点上，以识别和利用体内脑白质微结构完整性的生物标记物，为新的血管老化模型提供基础，该模型可能是特定干预的基础，以减缓白质损伤的进展和与衰老相关的认知能力下降。

DESCRIPTION (provided by applicant): The candidate's long-term goal is to become expert in the interrogation of cerebral white matter micro- structural integrity and vascular risk assessment as it relates to cognitive functioning in aging. To achieve this goal, the candidate will complete a training program of coursework, workshops and consultations with experts focused on the neuropathology underlying white matter alterations in normal and pathological aging, current and novel neuroimaging techniques for assessing white matter microstructure, vascular risk assessment, cardiovascular disease and its pathophysiology in aging and across minority populations at increased vascular risk. Host institute University of Illinois at Chicago provides training activities and resources relevant to this award including access to seminars, lectures and journal clubs on neuroradiology, vascular neurology, cardiology, and minority research. Primary mentor, Dr. Anand Kumar has performed neuroimaging studies of white matter including the biochemistry of myelin integrity in aging and vascular risk for over 15 years, and has mentored several K awardees and foundation fellowship recipients. He is the Head of the Department of Psychiatry and the recipient of R01s and a K24 to conduct work in late-life depression and vascular risk across the lifespan. The candidate currently contributes to the neuropsychological aspects of this research and is well placed to take advantage of established referral sources and scientific resources for the proposed research. For the proposed research, the candidate will combine a novel MRI technique to interrogate white matter microstructure (i.e., myelin mapping) with the imaging of other white matter pathologies including infarcts and microbleeds to determine the most robust biomarker of vascular risk and cognition in aging and minority populations. While there is a long history of research into the impact of overall white matter damage on the aging brain using currently available neuroimaging methods including diffusion tensor imaging (DTI), they lack sensitivity and specificity as to the contribution of myelin. Given that myelin breakdown begins as early as the fourth decade of life and accelerates with aging, we will perform novel myelin mapping techniques along with current DTI MRI in 60 healthy older adults 60-80 years old (20 Caucasians, 20 African Americans and 20 Hispanic Americans). Pilot data suggests myelin mapping is more sensitive than DTI at quantifying microstructural damage and myelin content in otherwise normal appearing white matter. Older adults will receive comprehensive cognitive and vascular risk assessments. Pilot data suggests a range of vascular risk (elevated in our minority populations) that is associated with cognitive performance, i.e., executive measures. This research stands at the nexus of current and future MRI techniques for identifying and utilizing a biomarker of white matter microstructural integrity in vivo providing a foundation for a new model of vascular aging that may be the basis for specific interventions to slow the progression of white matter damage and associated cognitive decline in aging.