Amyloid, white matter hyperintensities & outcomes of late-life depression

描述(申请人提供)：本R01申请的目标是通过两种成像方法来研究晚年抑郁(LLD)、认知障碍和进行性神经退行性变之间的关系：一种新型的PET配体(匹兹堡化合物-B；PIB)，它与淀粉样蛋白和体积MRI的白质高信号(WMH)相结合。指导性假设是，发展为LLD的个体具有进行性认知障碍，这是不同的潜在神经病理变化的结果，这些变化经常表现为轻度认知障碍(MCI)。淀粉样蛋白和WMH是降低大脑储备能力的主要神经病理特征，进而增加临床阿尔茨海默病的表达风险。为了实现这一目标，利用匹兹堡大学老年情绪障碍高级干预和服务研究中心(MH071944)和阿尔茨海默病研究中心(AG05133)的联合基础设施，缓解性抑郁症患者将接受淀粉样蛋白病理的PIB-PET成像和MRI以确定WMH体积。我们将研究100名具有不同认知分类的缓解抑郁症受试者(50名认知正常，50名MCI)，并通过巴特斯博士的R01(MH072947；《将晚年抑郁与MCI和痴呆症联系起来的路径》)对他们进行为期3年的纵向临床、认知和实验室数据收集。这些受试者的WMH和PIB-PET数据将与通过拟议研究收集的25名从未抑郁的非遗忘型MCI受试者以及75名具有各种认知分类(50名认知正常，25名遗忘型MCI)的从未抑郁的受试者的类似数据进行比较，这些受试者是在另外两个资助奖项(项目拨款AG025204“in Vivo PIB-PET淀粉样蛋白成像：正常人、MCI与痴呆”和MCI奖AG025516“正常老年人的脑淀粉样蛋白与认知”)下收集的。我们将测试一系列相互关联的假说，这些假说假定老年抑郁症患者发展认知障碍并导致一些阿尔茨海默病的一些途径的神经病理基础。公共卫生相关性：这项研究将收集信息，以提高对为什么老年抑郁症患者患痴呆症的风险增加的理解。为了实现这一目标，我们将对相关研究的参与者进行研究，使用新的脑部扫描方法检测脑血管疾病和淀粉样蛋白，淀粉样蛋白是阿尔茨海默病患者大脑中积累的关键物质之一。如果我们能更好地识别患有特定类型痴呆症(如阿尔茨海默病)的风险个体，那么随着新的痴呆症治疗方法的出现，他们可以在疾病的最早阶段接受治疗。

DESCRIPTION (provided by applicant): The goal of this R01 application is to investigate the relationships among late-life depression (LLD), cognitive impairment and progressive neurodegeneration with two imaging approaches: a novel PET ligand (Pittsburgh Compound-B; PiB) that binds to amyloid and volumetric MRI of white matter hyperintensities (WMH). The guiding hypothesis is that individuals who develop LLD have evolving cognitive impairments as a consequence of distinct underlying neuropathologic changes that frequently are expressed as Mild Cognitive Impairment (MCI). Amyloid and WMH are major neuropathologic features that lower brain reserve capacity, and in turn, increase risk of expressing clinical Alzheimer's disease. To pursue this goal, using the joint infrastructure of the University of Pittsburgh's Advanced Center for Intervention and Services Research for Late-Life Mood Disorders (MH071944) and the Alzheimer's Disease Research Center (AG05133), individuals with remitted depression will undergo PiB-PET imaging for amyloid pathology and MRI to determine WMH volume. We will study 100 remitted depressed subjects with a range of cognitive classifications (50 cognitively normal, 50 MCI) and follow them for 3 years with longitudinal clinical, cognitive and laboratory data collection through Dr. Butters' R01 (MH072947; "Pathways Linking Late-Life Depression to MCI & Dementia"). WMH and PiB-PET data from these subjects will be compared with similar data on 25 never-depressed non-amnestic MCI subjects gathered through the proposed research along with 75 never-depressed subjects with a range of cognitive classifications (50 cognitively normal, 25 amnestic MCI), collected under the auspices of two other funded awards (Program Project Grant AG025204 "In Vivo PiB-PET Amyloid Imaging: Normals, MCI & Dementia" and MERIT Award AG025516 "Brain Amyloid and Cognition in Normal Elderly"). We will test a series of linked hypotheses that postulate the neuropathologic substrates of some of the pathways by which elderly, depressed patients develop cognitive impairment and lead some to Alzheimer's disease. PUBLIC HEALTH RELEVANCE: This research study will gather information that will improve understanding of why elderly depressed individuals have an increased risk of developing dementia. To meet this goal we will study participants from related studies, with new brain scanning methods that detect cerebrovascular disease and amyloid, one of the key substances that accumulates in the brains of individuals with Alzheimer's disease. If we can better identify individuals at risk for developing specific types of dementia, such as Alzheimer's disease, then they can be candidates for treatment at the earliest disease stages, as new dementia treatments become available.