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

项目总结 阿尔茨海默病(AD)的病理生理改变先于临床表现 几十年前。因此，国家阿尔茨海默氏症计划的优先事项之一 ACT是通过使用体内试验来加速识别AD症状前阶段的努力 生物标志物。神经精神症状(NPS)，如抑郁和焦虑 在老年人中很常见。精神分裂症神经精神病学领域的核心研究问题 症状前阿尔茨海默病(AD)是为了确定哪个先来，即， 与阿尔茨海默病相关的神经精神症状(NPS)或脑部病理生理改变。 这样的问题只能通过使用两个极其重要的资源来回答：1)a) 大规模，最好是基于人群的神经成像队列，以及2)一项研究 能够清楚地记录核动力源在参与者中的终身模式的基础设施 在神经成像队列中。从头开始构建这两个资源可能会令人望而却步 费用昂贵，可能需要数十年的时间。在我们提议的为期4年的R01赠款中，我们将进行 深入研究神经影像生物标志物、NPS和NPS之间的联系 使用广泛的神经影像生物标记物资源的认知结果 梅奥衰老临床研究(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-淀粉样蛋白沉积之间的联系， 神经退行性变与偶发性MCI/AD痴呆或轨迹的结局 认知变化，是由NPS修饰的。我们将通过以下方式验证这一假设 在2000多个队列中研究NPS和AD生物标志物之间的联系途径 认知正常的人，年龄60岁，经历过所有这三种情况 成像方式，即淀粉样蛋白PET、FDG-PET和脑MRI，以及精神病学 在基线进行评估，至少有一次后续活动。我们将通过以下方式来衡量NPS 使用两种方法：1)我们访问代表病历链接系统将使 我们将严格筛选每个研究参与者的终身NPS。我们将NPS定义为 其中抑郁和焦虑症状将是初步分析的重点。这个 二级分析将包括其他NPS，如冷漠和激动。代表是 可能是世界上唯一一个捕捉从出生到死亡的医学数据的资源 奥姆斯特德县的居民；2)我们还将利用MCSA使用的评估 (例如，贝克抑郁量表和贝克焦虑量表)，以增加代表 数据。因变量将是认知变化的连续轨迹 结果，以及事件MCI/AD痴呆的明确结果。总之， 在这里，我们提出了一项为期4年的R01研究，最终将解决历史悠久的 对精神症状、阿尔茨海默病和神经影像之间时序的认识差距 生物标记物和偶发MCI/AD痴呆的结果。

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.