Advanced MR Imaging of Olfactory Impairment in Prodromal Alzheimer's Disease

阿尔茨海默氏病前驱嗅觉障碍的先进 MR 成像

基本信息

批准号：
10377495
负责人：
Arnold Bakker
金额：
$ 78.3万
依托单位：
HUGO W. MOSER RES INST KENNEDY KRIEGER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10377495
关键词：
Address Affect Aging Air Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Alzheimer’s disease biomarker Amyloid beta-Protein Anosmia Area Arteries Behavioral Blood Vessels Blood Volume Brain Brain region Cerebrovascular Circulation Cerebrum Clinical Cognition Cognitive Core-Binding Factor Deltastab Development Diagnosis Disease Dropout Early Diagnosis Early Intervention Early identification Energy Metabolism Foundations Functional disorder Hippocampus (Brain)Homeostasis Human Image Imaging Device Impaired cognition Individual Intervention Investigation Literature Magnetic Resonance Imaging Maintenance Measurement Measures Medial Mediating Memory Memory Loss Metabolic Metabolism Methods Morphologic artifacts Nerve Degeneration Neurobiology Neurons Olfactory Cortex Olfactory Pathways Olfactory dysfunction Oxygen Participant Pathology Patients Physiological Physiology Population Predisposition Psychophysics Resolution Rest Risk Factors Sensitivity and Specificity Severities Signal Transduction Sinus Smell Perception Staging Stimulus Structural defect Structure Sum Symptoms System Temporal Lobe Testing Time Venous Visit Work abeta accumulation accurate diagnosis aging brain arteriole behavior measurement behavior test biomarker development brain dysfunction brain tissue cognitive function design entorhinal cortex follow-up functional decline high risk imaging modality indexing metabolic rate mild cognitive impairment neural circuit neurobiological mechanism neuropathology neurophysiology neurovascular non-invasive imaging novel olfactory stimulus pre-clinical prodromal Alzheimer&apos s disease research clinical testing response sensory system tau Proteins tau-1 tool

Address Affect Aging Air Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Alzheimer’s disease biomarker Amyloid beta-Protein Anosmia Area Arteries Behavioral Blood Vessels Blood Volume Brain Brain region Cerebrovascular Circulation Cerebrum Clinical Cognition Cognitive Core-Binding Factor Deltastab Development Diagnosis Disease Dropout Early Diagnosis Early Intervention Early identification Energy Metabolism Foundations Functional disorder Hippocampus (Brain)Homeostasis Human Image Imaging Device Impaired cognition Individual Intervention Investigation Literature Magnetic Resonance Imaging Maintenance Measurement Measures Medial Mediating Memory Memory Loss Metabolic Metabolism Methods Morphologic artifacts Nerve Degeneration Neurobiology Neurons Olfactory Cortex Olfactory Pathways Olfactory dysfunction Oxygen Participant Pathology Patients Physiological Physiology Population Predisposition Psychophysics Resolution Rest Risk Factors Sensitivity and Specificity Severities Signal Transduction Sinus Smell Perception Staging Stimulus Structural defect Structure Sum Symptoms System Temporal Lobe Testing Time Venous Visit Work abeta accumulation accurate diagnosis aging brain arteriole behavior measurement behavior test biomarker development brain dysfunction brain tissue cognitive function design entorhinal cortex follow-up functional decline high risk imaging modality indexing metabolic rate mild cognitive impairment neural circuit neurobiological mechanism neuropathology neurophysiology neurovascular non-invasive imaging novel olfactory stimulus pre-clinical prodromal Alzheimer&apos s disease research clinical testing response sensory system tau Proteins tau-1 tool

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项目摘要

PROJECT SUMMARY Alzheimer's disease (AD) is a devastating neurodegenerative condition for which accurate and timely diagnosis is key for optimal intervention and for guiding treatment when disease-modifying therapies become available. Olfactory dysfunction is a core preclinical sign of AD that predicts conversion from mild cognitive impairment (MCI) to AD with high sensitivity and specificity. The olfactory system is among the earliest brain regions to demonstrate AD pathology and is the only sensory system that provides direct access to the entorhinal cortex (ERC) and hippocampus, medial temporal lobe (MTL) structures critically important for cognitive and memory decline in AD and MCI. Despite the relevance of olfactory dysfunction to the pathophysiology of AD, the neurobiological underpinnings of olfactory impairment remain poorly understood. To date, clinical evaluation of olfaction has been limited to psychophysical assessment, which is subjective and uninformative regarding underlying physiological abnormalities of the olfactory system. We have developed advanced 7T MRI methods to examine olfactory dysfunction and will use these methods to investigate microvascular and metabolic changes of the olfactory system in prodromal Alzheimer's disease patients and controls. In Aims 1 and 2, we will examine abnormalities in microvascular and metabolic parameters at rest and during olfactory stimulation. Importantly, we will quantify each individual microvascular and metabolic parameter for different blood vessel types (arterioles in particular) separately. These indices will be more biologically meaningful than the relatively global, nonspecific indicators of compromised olfactory function obtained from the behavioral tests. In Aim 3, we will assess the relationship between neurovascular abnormalities of the olfactory system and: olfactory behavioral measures; structural changes measured by MRI; and established CSF biomarkers of AD, including beta amyloid, tau and phosphorylated tau. A longitudinal follow-up of the cognitive measures will be collected after 2 years for all the participants, which will be used to evaluate whether the MRI measures at the initial visit are predictive for cognitive decline in these subjects. This work will significantly advance our understanding of the microvascular and metabolic changes associated with olfactory impairment in MCI. The MRI measures used here are noninvasive, repeatable for longitudinal investigations, and can be performed with high spatial resolution in humans. Results from the proposed studies can facilitate the development of biomarkers for early identification and prediction of AD and also has the potential to inform treatment studies for early intervention in AD.

项目摘要阿尔茨海默氏病（AD）是一种毁灭性的神经退行性疾病，准确及时诊断对于最佳干预和指导治疗的关键是可用的。嗅觉功能障碍是AD的核心临床前迹象，可预测轻度认知障碍的转化（MCI）具有高灵敏度和特异性的广告。嗅觉系统是最早的大脑区域之一演示AD病理学，是唯一可直接访问内嗅皮层的感觉系统（ERC）和海马，内侧颞叶（MTL）结构对认知和记忆至关重要 AD和MCI的下降。尽管嗅觉功能障碍与AD的病理生理相关，但嗅觉障碍的神经生物学基础知之甚少。迄今为止，临床评估嗅觉仅限于心理物理评估，这在嗅觉系统的潜在生理异常。我们已经开发了高级7T MRI方法检查嗅觉功能障碍，并将使用这些方法研究微血管和代谢变化阿尔茨海默氏病患者和对照组中的嗅觉系统。在目标1和2中，我们将检查静止和嗅觉刺激时的微血管和代谢参数异常。重要的是，我们将量化不同血管类型的每个单独的微血管和代谢参数（小动脉特别是）。这些指数在生物学上比相对全球，非特异性更有意义从行为测试获得的嗅觉函数的折衷指标。在AIM 3中，我们将评估嗅觉系统的神经血管异常与：嗅觉行为措施之间的关系； MRI测量的结构变化；并建立了AD的CSF生物标志物，包括β淀粉样蛋白，TAU和磷酸化的tau。 2年后，将收集认知措施的纵向随访参与者，将用于评估初次访问时的MRI措施是否可以预测这些主题的认知能力下降。这项工作将大大提高我们对微血管的理解与MCI中的嗅觉损伤相关的代谢变化。这里使用的MRI措施是无创，可重复进行纵向研究，可以以高空间分辨率进行人类。拟议的研究的结果可以促进生物标志物的发展以早期识别和AD的预测，并且有可能为治疗研究提供早期干预AD的信息。