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

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.

项目概要 此 K23 申请提供了一个培训和研究计划，将支持申请人走上通往未来的道路 成为 NIH 资助的独立研究者，专注于了解嗅觉的神经生物学 阿尔茨海默病 (AD) 系统培训：此应用程序中的活动建立在候选人先前的基础上。 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，将 培养他在 1) AD 功能成像原理、2) 机制和神经方面的专业知识的发展 嗅觉系统的电路，3) 生物统计学和心理测量学，以及 4) 负责任的研究行为。 这些培训目标将得到教学、正式咨询计划和实践相结合的支持。 在他的主要导师 Davangere Devanand 博士的指导下进行整个获奖期间的实践。 他的共同导师 Terry Goldberg 博士、科学顾问（Gaurav Patel 博士、Prasanna Karunanayaka、Mark Albers、Jonas Olofsson 和 Scott Small）和同伴导师（Jonathan Overdevest 博士），候选人将 获得神经影像方法、嗅觉评估和 AD 生物标志物力学方面的高级技能 将直接应用于本提案的研究：将进行的研究的总体目标。 该应用程序旨在确定气味记忆缺陷背后的神经机制，并定义 使用气味记忆的新过程纯变体研究气味记忆和 AD 生物标志物之间的关系 目前迫切需要开发增强嗅觉和 AD 早期检测的工具。 气味记忆是 AD 初始阶段出现损伤的系统。 这两个系统有潜力改进现有工具的功能，这些工具通常测量 目前，气味记忆的精确神经基础仍不清楚。 研究涉及气味记忆的大脑激活模式，有望增强我们的能力 该提案将是第一个评估气味检测和气味记忆的提案。 该研究项目的目标 1 将在同一成像范式中共同检查 fMRI 任务相关信号。 AD 患者在功能磁共振成像气味记忆过程中的嗅觉皮层和内侧颞叶， 患有遗忘性轻度认知障碍的患者和认知功能完好的老年人将接受 Aim 扫描。 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 在目标 3 中，气味记忆对于区分群体（AD 患者、患者）的临床效用。 患有轻度认知障碍和认知完好的老年人）将与已确定的气味进行比较 识别和言语记忆测量。