Novel Neurocognitive Markers of Risk for and Resilience to Cognitive Decline in Preclinical Alzheimer's Disease

项目摘要 在阿尔茨海默病(AD)的早期阶段发现并预测谁是阿尔茨海默病(AD)是公共卫生的一个强烈需求 最容易受到临床进展的影响。这项K23提案的目标是为候选人提供 经验、知识和技术专长，以独立研究新的早期风险预测因素 以及对阿尔茨海默病相关认知能力下降的恢复能力。职业发展计划包括一个补充方案 一套培训和研究活动，以支持候选人向独立的过渡。具体培训 目标包括：1)发展使用脑电(EEG)评估大脑网络的专业知识 老龄化人口的动力学；2)增加功能神经解剖学的知识深度，重点是 额叶网络在AD病程早期受损；3)获得临床研究方面的专门培训 设计和统计，重点是降维和复杂数据分析；以及4)接收 在专业发展方面的正式指导。培训计划利用了一支模范的跨学科团队。 拥有脑电图学(S.Jones)、认知神经科学和功能神经解剖学方面的专长 (Heindel)、统计学方法和认知储备假说(R.Jones)和临床神经心理学 (特雷蒙特)培训活动将通过正式指导、体验式实验室培训、 教学，以及完成一项严谨的研究项目。该研究项目的科学目标是 研究额叶控制网络完整性的行为和电生理标记物 AD相关认知功能下降的风险和恢复能力的新标记物。每个研究目标都对应于 一个相辅相成的培训领域。具体目标包括1)检查行为和电生理 阿尔茨海默病高危老年人额叶网络动力学指标；2)验证行为和 使用额叶网络完整性(即磁共振)的独立测量的电生理标记物 成像)；以及3)验证这些标记作为认知韧性的指标。这项研究项目将利用 罗德岛阿尔茨海默病预防登记处的基础设施，这是一个庞大的老年人队列 他们的认知能力每年都会受到监测。成功完成这些相互关联的培训和研究 活动将促进候选人发展成为一名独立的临床研究人员，具有 早期预测AD相关认知功能衰退的风险和恢复能力。

PROJECT ABSTRACT There is a strong public health need to detect Alzheimer’s disease (AD) in its earliest stages and predict who is most vulnerable to clinical progression. The goal of this K23 proposal is to provide the candidate with the experience, knowledge, and technical expertise to independently investigate novel early predictors of risk for and resilience to AD-associated cognitive decline. The career development plan comprises a complementary set of training and research activities to support the candidate’s transition to independence. Specific training goals include: 1) to develop expertise in using electroencephalography (EEG) to assess brain network dynamics in aging populations; 2) to increase depth of knowledge of functional neuroanatomy, with a focus on frontal networks compromised early in the course of AD; 3) to gain specialized training in clinical research design and statistics, with an emphasis on dimension reduction and analysis of complex data; and 4) to receive formal mentorship in professional development. The training plan draws on an exemplary interdisciplinary team with expertise in the electroencephalography (S. Jones), cognitive neuroscience and functional neuroanatomy (Heindel), statistical methods and the cognitive reserve hypothesis (R. Jones), and clinical neuropsychology (Tremont). Training activities will take place through formal mentorship, experiential laboratory training, didactics, and the completion of a rigorous research project. The scientific objective of the research project is to investigate behavioral and electrophysiological markers of frontal control network integrity that may serve as novel markers of risk for and resilience to AD-associated cognitive decline. Each research aim corresponds to a complementary area of training. Specific aims include 1) to examine behavioral and electrophysiological markers of frontal network dynamics in older adults at risk for AD; 2) to validate the behavioral and electrophysiological markers using independent measures of frontal network integrity (i.e., magnetic resonance imaging); and 3) to validate the markers as indices of cognitive resilience. The research project will leverage the infrastructure of the Rhode Island Alzheimer’s Disease Prevention Registry, a large cohort of older adults whose cognition is monitored annually. Successful completion of these interrelated training and research activities will foster the candidate’s development into an independent clinical researcher with expertise in the early prediction of risk for and resilience to AD-associated cognitive decline.