Olfactory and Visual Dysfunction as Potential Predictors of Preclinical Alzheimer's Disease

嗅觉和视觉功能障碍是临床前阿尔茨海默病的潜在预测因素

• 批准号: 10065478
• 负责人: CLAIRE L MURPHY
• 金额: $ 41.71万
• 依托单位: SAN DIEGO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10065478
• 关键词: Address; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Apolipoprotein E; Area; Autopsy; Biological Markers; Clinical Trials; Clinical assessments; Cognitive; Data; Detection; Development; Disease; Early identification; Family history of; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Hippocampus (Brain); Image; Impairment; Individual; Intervention; Magnetic Resonance Imaging; Measures; Memory; Methods; Modality; Nerve Degeneration; Odors; Olfactory Pathways; Olfactory dysfunction; Pathology; Pharmaceutical Preparations; Pharmacologic Substance; Populations at Risk; Process; Research; Retina; Risk Factors; Sensitivity and Specificity; Sensory; Signal Transduction; Smell Perception; Structure; Symptoms; Testing; Thick; Thinness; Tissues; Vision; Visual; apolipoprotein E-4; base; clinical practice; entorhinal cortex; imaging biomarker; improved; magnetic resonance imaging biomarker; memory recognition; multimodality; neural correlate; neural network; neuropathology; normal aging; pre-clinical; pre-clinical assessment; prevent; prodromal Alzheimer' s disease; relating to nervous system; sensory system; tau Proteins; tau-1; visual dysfunction

Simple odor identification tests reveal reduced ability to identify odors in Alzheimer's disease (AD) and in populations at risk for AD because of the ApoE e4 allele, MCI, and a family history of AD. Neuropathology in olfactory areas in AD is well established in post-mortem tissue and in a few structural MRI studies. While impairment in olfaction is known to occur in AD and in those at risk for AD, its sensitivity and specificity, based on simple odor identification tests, has not been sufficient to render it a serious biomarker. Critical research is needed to test the sensitivity of impairment in the olfactory system to signal risk for AD. This will require careful consideration of the methods for testing olfactory system integrity that go beyond simple odor identification tests. Similarly, there is significant evidence to support a difference in retinal thinning between normally aging individuals AD; however whether this measure is predictive of development of MCI or AD in amyloid positive, cognitively normal individuals in unknown. There is a clear need to investigate whether assessment of multiple sensory modalities in conjunction with CSF and imaging markers will improve the detection of preclinical AD. This project aims to address this need using a multimodal approach. It will investigate whether olfactory or visual function or a combination better reflects the presence of CSF biomarkers or structural MRI markers of AD in preclinical AD. Building on a foundation of preliminary data, the project will investigate the underlying cortical structures and neural networks that serve odor recognition memory, remote odor memory and odor identification in individuals with CSF markers that reflect preclinical AD, using fMRI and functional connectivity. The project will develop a deeper understanding of the potential for sensory dysfunction to predict preclinical AD.

简单的气味识别测试揭示了阿尔茨海默氏症患者识别气味的能力降低 在患有AD的人群中，由于ApoE e4等位基因、MCI和一个家族， AD的历史AD嗅觉区的神经病理学在死后组织中得到了很好的证实 以及一些结构性核磁共振研究。虽然已知嗅觉受损发生在AD和AD患者中， 对于那些有AD风险的人来说，它的敏感性和特异性，基于简单的气味识别测试， 不足以使其成为一个重要的生物标志物。需要进行批判性研究来检验 嗅觉系统受损对AD信号风险的敏感性。这将需要小心 对超越简单气味的嗅觉系统完整性测试方法的考虑 鉴定试验。类似地，有显著证据支持视网膜病变的差异。 在正常衰老的个体AD之间变薄;然而，该测量是否预测 在淀粉样蛋白阳性、认知正常的个体中发生MCI或AD，那里 显然需要研究多种感觉方式联合评估是否 与CSF和成像标记物的联合应用将改善临床前AD的检测。该项目旨在 使用多模式方法来满足这一需求。它将调查嗅觉或视觉 功能或组合更好地反映CSF生物标志物或结构MRI的存在 临床前AD中的AD标志物。在初步数据的基础上，该项目将 研究气味识别的皮层结构和神经网络 记忆，远程气味记忆和气味识别的个人与CSF标志物， 反映临床前AD，使用功能磁共振成像和功能连接。该项目将开发更深层次的 了解感觉功能障碍预测临床前AD的潜力。