Novel metrics of brain dynamics in Alzheimer’s disease

阿尔茨海默病大脑动力学的新指标

• 批准号: 10689827
• 负责人: Jace Bradford King
• 金额: $ 13.01万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10689827
• 关键词: Affect; Aging; Alleles; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease related dementia; Amyloid; Amyloid deposition; Area; Award; Biological; Biological Markers; Brain; Classification; Clinical; Clinical Trials; Cognition; Cognitive; Data; Data Analyses; Data Set; Dedications; Dementia; Diagnosis; Diagnostic; Disease; Early identification; Elderly; Enrollment; Evolution; Fostering; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Healthcare; Hippocampus; Impaired cognition; Individual; International; Intervention; Intuition; Investigation; Knowledge; Lead; Literature; Longitudinal Studies; Machine Learning; Magnetic Resonance Imaging; Maps; Measures; Mentors; Mentorship; Methods; Modeling; Monitor; Neurobiology; Neuropsychological Tests; Neuropsychology; Participant; Patients; Performance; Population; Predictive Factor; Prevention; Prognosis; Research; Research Design; Research Personnel; Rest; Scanning; Statistical Methods; Statistical Models; Technology; Testing; Time; Training; Training Programs; Treatment Efficacy; Universities; Utah; apolipoprotein E-4; behavioral phenotyping; brain abnormalities; career; career development; cognitive testing; daily functioning; design; effective therapy; experience; flexibility; functional MRI scan; hippocampal atrophy; improved; insight; machine learning algorithm; mild cognitive impairment; multidisciplinary; multimodality; nervous system disorder; neural circuit; neuroimaging; neuroimaging marker; neuromechanism; normal aging; novel; pathological aging; predictive marker; response to brain injury; skills; statistics; tool

PROJECT SUMMARY/ABSTRACT Alzheimer’s disease (AD) is a progressive neurological disorder that adversely affects cognition and daily functioning in older adults. Functional MRI is a non-invasive and widely available neuroimaging tool that can be used to identify early manifestations of AD, which can then be used as a complimentary biomarker to enrich clinical trials with those patients most likely to decline. Recent investigations have suggested that the core brain abnormalities in AD may not arise from structural or even functional connectivity, but rather the timing of brain activity. Abnormal brain timing is an intuitive mechanism for decreased cognitive flexibility, and may serve as a biomarker for mild cognitive impairment (MCI) and AD. The purpose of this study is to investigate how changes in the temporal duration of functional connectivity are related to MCI and AD. The specific aims are: 1) Characterize the temporal aspects of functional connectivity in cognitively intact individuals and those with cognitive impairment (MCI and AD); 2) Examine the evolution of sustained and lag-based connectivity in individuals with cognitive impairment and establish which biological and cognitive factors predict change; and 3) Evaluate the predictive performance of sustained and lag-based connectivity as a biomarker for cognitive impairment. This proposal is designed to facilitate the career development of Dr. Jace King in acquiring the necessary training, practical experience, and knowledge to become a lead investigator in brain related dysfunction associated with MCI and AD. To excel as an independent researcher, Dr. King will obtain research skills in the following areas: 1) neuropsychological, neurobiological and clinical manifestations of AD; 2) longitudinal study design and analysis; and 3) advanced statistical methods involved in machine learning with an emphasis on how these tools can be used to conduct behavioral phenotyping. This research will be conducted at the University of Utah and supported by a multidisciplinary mentorship team with collaborative experience but distinct expertise. Dr. Duff (primary mentor) is an expert in the neuropsychological assessment of MCI and AD. Dr. Foster (co-mentor) is an expert in the diagnosis and treatment of AD. Dr. Minoshima (co-mentor) is internationally known for his discovery of early signs of AD and dissemination of diagnostic statistical mapping technology. Dr. Phillips (co-mentor) has expertise in machine learning and advanced statistics. Dr. Zielinski’s (co-mentor) expertise are in multimodal MRI analysis and longitudinal study design. Complimenting this team is a dedicated team of consultants with expertise in AD diagnosis and treatment, advanced statistical modeling, and advanced fMRI data analysis. Successful completion of this award will provide the applicant with the background and training necessary to pursue an R01 application to investigate longitudinal brain function in aging populations. The proposed research makes significant contributions to the field as it has the potential to provide novel insights in the cognitive neural mechanisms underlying AD, which will aid in the implementation of targeted intervention and prevention efforts.

项目总结/摘要 阿尔茨海默病（AD）是一种进行性神经系统疾病，其对认知和日常生活产生不利影响。 在老年人中发挥作用。功能性MRI是一种非侵入性和广泛可用的神经成像工具，可以 用于识别AD的早期表现，然后可以用作补充生物标志物， 最有可能下降的患者的临床试验。最近的研究表明， AD中的异常可能不是由结构甚至功能连接引起的，而是由大脑的时间安排引起的。 活动异常的大脑计时是认知灵活性下降的一种直观机制，并可能作为一种 轻度认知障碍（MCI）和AD的生物标志物。这项研究的目的是调查如何改变 在功能连接时程中的作用与MCI和AD有关。具体目标是：1） 描述认知完整个体和认知障碍个体的功能连接的时间方面。 认知障碍（MCI和AD）; 2）检查持续和滞后连接的演变， 认知障碍的个体，并确定哪些生物和认知因素预测变化;以及3） 评估持续和基于滞后的连接性作为认知障碍的生物标志物的预测性能 损伤本提案旨在促进Jace King博士在获得 必要的培训，实践经验和知识，成为大脑相关领域的首席研究员 与MCI和AD相关的功能障碍。为了成为一名出色的独立研究员，金博士将获得研究 以下领域的技能：1）AD的神经心理学、神经生物学和临床表现; 2） 纵向研究设计和分析;以及3）涉及机器学习的先进统计方法， 强调如何使用这些工具进行行为表型分析。这项研究将在 在犹他州的大学，并由一个多学科的导师团队与合作经验的支持， 独特的专业知识。Duff博士（主要导师）是MCI和AD神经心理学评估的专家。 博士Foster（共同导师）是AD诊断和治疗方面的专家。Minoshima博士（共同导师）是 因发现AD的早期症状和传播诊断统计图而闻名于世 技术.菲利普斯博士（共同导师）在机器学习和高级统计学方面拥有专业知识。Zielinski医生的 （共同导师）的专长是多模态MRI分析和纵向研究设计。赞美这支球队的是 一个专门的顾问团队，在AD诊断和治疗，先进的统计建模， 和先进的功能磁共振成像数据分析成功完成此奖项将为申请人提供 研究R 01应用程序以研究纵向脑功能所需的背景和培训， 人口老龄化。拟议的研究为该领域做出了重大贡献，因为它有可能 提供了新的见解，认知神经机制的基础AD，这将有助于实施 有针对性的干预和预防工作。