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

项目摘要 有一个强烈的公共卫生需要检测阿尔茨海默氏病（AD）的最早阶段，并预测谁是 最容易出现临床进展。本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子， 以及对AD相关认知能力下降的适应能力。职业发展计划包括一个补充性的 一系列培训和研究活动，以支持候选人向独立过渡。具体培训 目标包括：1）发展使用脑电图（EEG）评估大脑网络的专业知识 老年人群的动力学; 2）增加功能神经解剖学知识的深度，重点是 额神经网络在AD病程早期受损; 3）在临床研究中获得专业培训 设计和统计，重点是复杂数据的降维和分析;以及4）接收 专业发展的正式指导。培训计划利用了一个示范性的跨学科团队 具有脑电图方面的专业知识（S。Jones）、认知神经科学与功能神经解剖学 （Heindel）、统计方法和认知储备假设（R.琼斯）和临床神经心理学 （特雷蒙）。培训活动将通过正式指导、体验式实验室培训、 教学法，并完成一个严格的研究项目。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志物， AD相关认知能力下降风险和恢复力的新标志物。每个研究目标对应于 一个互补的训练领域。具体目标包括：1）检查行为和电生理 AD风险老年人的额叶网络动力学标志物; 2）验证行为和 使用额叶网络完整性的独立测量的电生理学标记（即，磁共振 成像）;和3）验证标记物作为认知弹性的指标。该研究项目将利用 罗得岛老年痴呆症预防登记处的基础设施， 他们的认知能力每年都会受到监控成功完成这些相互关联的培训和研究 活动将促进候选人的发展成为一个独立的临床研究人员与专业知识 早期预测AD相关认知功能下降的风险和恢复力。

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.