Odor memory and functional neuroimaging in cognitively impaired older adults and Alzheimer's disease

认知障碍老年人和阿尔茨海默病的气味记忆和功能神经影像

• 批准号: 10590472
• 负责人: Jeffrey Nicholas Motter
• 金额: $ 19.54万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-15 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10590472
• 关键词: Address; Affect; Age; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer’s disease biomarker; Apolipoprotein E; Apolipoproteins; Area; Award; Binding; Biological Markers; Biometry; Brain; Brain region; Classification; Clinical; Clinical Trials; Cognitive; Dementia; Detection; Development; Disease; Disease Progression; Early Diagnosis; Early Intervention; Education; Elderly; Environment; Etiology; Evaluation; Fostering; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Genotype; Goals; Hippocampus; Image; Impaired cognition; Impairment; Individual; Invaded; Knowledge; Measures; Mechanics; Medial; Memory; Memory impairment; Mentored Patient-Oriented Research Career Development Award; Mentors; Methodology; Methods; Monitor; Neurobiology; Neurodegenerative Disorders; Neurofibrillary Tangles; Neuropsychology; Odors; Olfactory Cortex; Olfactory Pathways; Olfactory dysfunction; Participant; Pathology; Patients; Pattern; Plasma; Population; Positioning Attribute; Prevalence; Procedures; Process; Psychometrics; ROC Curve; Reporting; Research; Research Personnel; Research Project Grants; Research Proposals; Resources; Retrieval; Risk; Role; Scanning; Semantics; Signal Transduction; Smell Perception; Stimulus; Structure; Supervision; System; Techniques; Temporal Lobe; Testing; Time; Training; Translating; United States National Institutes of Health; Variant; amnestic mild cognitive impairment; clinical application; diagnostic accuracy; entorhinal cortex; experience; experimental study; functional decline; improved; mild cognitive impairment; mortality; neural; neural circuit; neuroimaging; neuromechanism; neuropathology; normal aging; olfactory bulb; patient screening; peer coaching; piriform cortex; programs; response; responsible research conduct; skill acquisition; skills; tau Proteins; tool; tool development; verbal; Address; Affect; Age; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer’s disease biomarker; Apolipoprotein E; Apolipoproteins; Area; Award; Binding; Biological Markers; Biometry; Brain; Brain region; Classification; Clinical; Clinical Trials; Cognitive; Dementia; Detection; Development; Disease; Disease Progression; Early Diagnosis; Early Intervention; Education; Elderly; Environment; Etiology; Evaluation; Fostering; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Genotype; Goals; Hippocampus; Image; Impaired cognition; Impairment; Individual; Invaded; Knowledge; Measures; Mechanics; Medial; Memory; Memory impairment; Mentored Patient-Oriented Research Career Development Award; Mentors; Methodology; Methods; Monitor; Neurobiology; Neurodegenerative Disorders; Neurofibrillary Tangles; Neuropsychology; Odors; Olfactory Cortex; Olfactory Pathways; Olfactory dysfunction; Participant; Pathology; Patients; Pattern; Plasma; Population; Positioning Attribute; Prevalence; Procedures; Process; Psychometrics; ROC Curve; Reporting; Research; Research Personnel; Research Project Grants; Research Proposals; Resources; Retrieval; Risk; Role; Scanning; Semantics; Signal Transduction; Smell Perception; Stimulus; Structure; Supervision; System; Techniques; Temporal Lobe; Testing; Time; Training; Translating; United States National Institutes of Health; Variant; amnestic mild cognitive impairment; clinical application; diagnostic accuracy; entorhinal cortex; experience; experimental study; functional decline; improved; mild cognitive impairment; mortality; neural; neural circuit; neuroimaging; neuromechanism; neuropathology; normal aging; olfactory bulb; patient screening; peer coaching; piriform cortex; programs; response; responsible research conduct; skill acquisition; skills; tau Proteins; tool; tool development; verbal

Project Summary This K23 application presents a training and research program that will support the applicant on a path towards becoming an NIH-funded independent investigator focused on understanding the neurobiology of the olfactory system in Alzheimer’s disease (AD). Training: The activities in this application build on the candidate’s prior clinical neuropsychology training and research experience and are set in a resource-rich environment that will foster his development of expertise in 1) principles of functional imaging in AD, 2) mechanisms and neural circuitry of the olfactory system, 3) biostatistics and psychometrics, and 4) responsible conduct of research. These training goals will be supported by a combination of didactics, formal advisory plans, and hands-on- practicum throughout the award period. Under the guidance of his primary mentor, Dr. Davangere Devanand, his co-mentor Dr. Terry Goldberg, scientific advisors (Drs. Gaurav Patel, Prasanna Karunanayaka, Mark Albers, Jonas Olofsson, and Scott Small), and peer mentor (Dr. Jonathan Overdevest), the candidate will acquire advanced skills in neuroimaging methodologies, olfactory evaluations, and AD biomarker mechanics that will be directly applied to this proposal. Research: The overarching goal of the research to be carried out in this application is to determine the neural mechanisms underlying odor memory deficits, and to define the relationship between odor memory and AD biomarkers using a new process-pure variant of an odor memory test. There is an urgent and unmet need to develop tools for enhancing early detection of AD. Olfaction and memory are systems in which impairments develop during initial stages of AD. Odor memory, which combines these two systems, has potential for improving upon the capabilities of existing tools which commonly measure either system in isolation. Currently, the precise neural substrates of odor memory remain undefined. By investigating the brain activation patterns involved in odor memory, there is promise for enhancing our ability to identify individuals at risk for decline. This proposal will be the first to evaluate odor detection and odor memory jointly within the same imaging paradigm. Aim 1 of the research project will examine fMRI task-related signal in the olfactory cortex and medial temporal lobe during an fMRI odor memory procedure. Patients with AD, patients with amnestic mild cognitive impairment, and cognitively intact older adults will undergo scanning. Aim 2 strives to establish the association of abnormal odor memory with apolipoprotein genotype and plasma tau biomarkers. In Aim 3, the clinical utility of odor memory for differentiating groups (patients with AD, patients with mild cognitive impairment, and cognitively intact older adults) will be compared against established odor identification and verbal memory measures.

项目摘要 该K23应用程序提供了一项培训和研究计划，该计划将支持该应用程序 成为NIH资助的独立研究者，专注于理解嗅觉的神经生物学 阿尔茨海默氏病（AD）的系统。培训：本申请中的活动基于候选人的先验 临床神经心理学培训和研究经验，并设置在资源丰富的环境中 在1）AD中的功能成像原理中培养他的专业知识，2）机制和神经 嗅觉系统的电路，3）生物统计学和精神计量学，以及4）负责任的研究。 这些培训目标将由教学品，正式咨询计划和动手实践的结合支持 在整个奖励期间实践。在他的主要导师Davangere Devanand博士的指导下 他的同事特里·戈德伯格（Terry Goldberg）博士，科学顾问（Gaurav Patel博士，Prasanna Karunanayaka Albers，Jonas Olofsson和Scott Small）和同行导师（Jonathan Overdevest博士），候选人将 获得神经影像学方法，嗅觉评估和广告生物标志物机制的高级技能 这将直接应用于此提案。研究：将在 该应用是为了确定气味记忆的基础神经机制定义，并定义 气味存储器与广告生物标志物之间的关系使用气味存储器的新过程 - 变体 测试。紧急且未满足的需要开发工具来增强对AD的早期检测。嗅觉和 记忆是在AD初始阶段发展的系统。气味记忆，结合了 这两个系统具有提高现有工具能力的潜力，这些工具通常是衡量的 两种系统孤立。当前，气味记忆的精确神经基板仍然不确定。经过 调查气味记忆中涉及的大脑激活模式，有望增强我们的能力 确定有衰落风险的人。该提案将是第一个评估气味检测和气味记忆的提案 共同在同一成像范式中。研究项目的目标1将检查与fMRI任务相关的信号 fMRI气味记忆过程中的嗅觉皮层和中值临时叶。 AD患者， 柔和的轻度认知障碍患者，认知完整的老年人将接受扫描。目的 2努力建立异常气味记忆与载脂蛋白基因型和血浆TAU的关联 生物标志物。在AIM 3中，气味记忆的临床效用是分化组的（AD患者，患者 将与既定的otor进行轻度认知障碍和认知完整的老年人进行比较 识别和言语记忆措施。