Pathways linking neuropsychiatric symptoms with Alzheimer's disease neuroimaging biomarkers and the outcome of incident Mild Cognitive Impairment/ Dementia

将神经精神症状与阿尔茨海默病神经影像生物标志物以及轻度认知障碍/痴呆事件结果联系起来的途径

• 批准号: 10200420
• 负责人: Yonas E Geda
• 金额: $ 39.6万
• 依托单位: ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200420
• 关键词: Address; Aging; Agitation; Alzheimer' s Disease; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Amyloid deposition; Antidepressive Agents; Anxiety; Apolipoprotein E; Attention; Back; Beck depression inventory; Biological Markers; Birth; Brain; Brain imaging; Categories; Cessation of life; Clinic; Clinical; Cognitive; County; Data; Dementia; Education; Elderly; Epidemiology; Equipment and supply inventories; Event; Family history of; Genotype; Grant; Impaired cognition; Individual; Investigation; Knowledge; Language; Life; Link; Magnetic Resonance Imaging; Measures; Medical; Medical Record Linkage; Memory; Mental Depression; Nerve Degeneration; Outcome; Participant; Pathway interactions; Pattern; Persons; Pharmaceutical Preparations; Positron-Emission Tomography; Prospective cohort study; Research; Research Infrastructure; Resources; Risk Factors; Role; System; Testing; Theoretical model; Time; Visuospatial; abeta deposition; aged; anxiety symptoms; brain abnormalities; cognitive change; cohort; comorbidity; depressive symptoms; executive function; fluorodeoxyglucose positron emission tomography; follow-up; imaging modality; in vivo; mild cognitive impairment; neuroimaging; neuroimaging marker; neuropsychiatric symptom; neuropsychiatry; population based; pre-clinical; prospective; psychiatric symptom; public health relevance; secondary analysis; sex; skills

PROJECT SUMMARY Pathophysiological changes in Alzheimer's disease (AD) precede clinical manifestations by several decades. Accordingly, one of the priorities of the National Alzheimer's Plan Act is to accelerate efforts to identify the presymptomatic stages of AD by using in-vivo biomarkers. Neuropsychiatric symptoms (NPS) such as depression and anxiety are common in the elderly. The key research question of the field of neuropsychiatry of presymptomatic Alzheimer's disease (AD) is to determine as to which came first, i.e., neuropsychiatric symptoms (NPS) or pathophysiological brain changes related to AD. Such a question can only be answered by using two critically important resources: 1) a large scale, preferably population-based, neuroimaging cohort, and 2) a research infrastructure that can clearly document the lifelong pattern of NPS among participants in the neuroimaging cohort. Building both resources from scratch can be prohibitively expensive and may take decades. In our proposed 4-years R01 grant, we will conduct an in-depth investigation of the pathways linking neuroimaging biomarkers, NPS and cognitive outcomes by using the extensive neuroimaging biomarker resource of the Mayo Clinic Study of Aging (MCSA) and we will link this with longitudinal psychiatric data by using the unique resource of the Rochester Epidemiology Project (REP). We hypothesize that the association between β-amyloid deposition, neurodegeneration and the outcome of incident MCI/ AD dementia or trajectories of cognitive changes, is modified by NPS. We will test this hypothesis by examining the pathways linking NPS and AD biomarkers in a cohort of over 2000 cognitively normal persons aged ≥ 60 years that have undergone all three modalities of imaging, i.e. amyloid PET, FDG-PET and brain MRI, and psychiatric assessment at baseline with at least one follow-up event. We will measure NPS by using two approaches: 1) Our access to REP medical record linkage system will enable us to rigorously screen for life-time NPS of each study participant. We define NPS as depressive and anxiety symptoms which will be the focus of the primary analysis. The secondary analysis will include other NPS such as apathy and agitation. REP is perhaps the only resource in the world that captures medical data from birth to death on residents of Olmsted County; 2) We will also utilize the assessments used by MCSA (e.g., Beck Depression Inventory and Beck Anxiety Inventory) to augment the REP data. The dependent variables will be trajectories of cognitive changes as continuous outcomes, as well as categorical outcomes of incident MCI/ AD dementia. In conclusion, here we propose a 4-years R01 study that will eventually address the time-honored knowledge gap on time sequence between psychiatric symptoms, AD neuroimaging biomarkers and the outcome of incident MCI/ AD dementia.

项目摘要 阿尔茨海默病（AD）的病理生理变化先于临床表现 几十年了。因此，国家老年痴呆症计划的优先事项之一 该法案旨在通过使用体内试验， 生物标志物。神经精神症状（Neuropsychiatric symptoms，缩写为ESTA），如抑郁症和焦虑症。 常见于老年人。神经精神病学领域的关键研究问题 症状前阿尔茨海默氏病（AD）是为了确定哪个先出现，即， 神经精神症状（AD）或与AD相关的病理生理脑变化。 这样的问题只能通过使用两个至关重要的资源来回答：1） 大规模，优选基于人群的神经成像队列，和2）研究 基础设施，可以清楚地记录参与者之间的终身模式 在神经影像学队列中。从零开始构建这两种资源可能会让人望而却步 价格昂贵，可能需要几十年。在我们建议的4年R 01赠款中，我们将进行 一项关于神经影像学生物标志物、神经胶质瘤和 认知结果，通过使用广泛的神经影像学生物标志物资源， 马约临床衰老研究（MCSA），我们将把它与纵向精神病学联系起来， 通过使用罗切斯特流行病学项目（REP）的独特资源获得数据。我们 假设β-淀粉样蛋白沉积， 神经退行性变和MCI/ AD痴呆或轨迹事件的结局 认知变化的一部分，是由认知改变来修改的。我们将通过以下方式检验这一假设： 在超过2000名患者的队列中检查了连接阿尔茨海默病和AD生物标志物的途径 年龄≥ 60岁的认知正常人，接受了所有三种治疗 成像方式，即淀粉样蛋白PET、FDG-PET和脑MRI，以及精神病学 基线评估，至少有一次随访事件。我们将测量 采用两种方法：1）我们接入REP病历联动系统， 我们要严格筛选每个研究参与者的终身患病情况。我们定义为“ 抑郁和焦虑症状，这将是主要分析的重点。的 二次分析将包括其他缺陷，如冷漠和激动。REP是 也许是世界上唯一一个可以从出生到死亡收集医疗数据的资源。 奥姆斯特德县的居民; 2）我们还将利用MCSA使用的评估 (e.g., Beck抑郁量表和Beck焦虑量表），以增加REP 数据因变量将认知变化的轨迹作为连续的 结果，以及事件MCI/ AD痴呆的分类结果。最后，我谨指出， 在这里，我们提出了一项为期4年的R 01研究，最终将解决历史悠久的 对精神症状、AD神经影像学之间时间顺序的认识差距 生物标志物和MCI/ AD痴呆事件的结果。