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

描述（由申请人提供）：本R01申请的目标是通过两种成像方法研究晚年抑郁症（LLD），认知障碍和进行性神经变性之间的关系：一种新型PET配体（匹兹堡化合物- b； PiB）与淀粉样蛋白结合，以及白质高强度（WMH）的体积MRI。指导假设是，发展为LLD的个体由于不同的潜在神经病理变化而发展为认知障碍，这些变化通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，反过来，增加临床阿尔茨海默病的表达风险。为了实现这一目标，利用匹兹堡大学晚期情绪障碍干预和服务研究高级中心（MH071944）和阿尔茨海默病研究中心（AG05133）的联合基础设施，抑郁症缓解的个体将接受PiB-PET成像检查淀粉样蛋白病理和MRI以确定WMH体积。我们将研究100名具有一系列认知分类的抑郁症患者（50名认知正常，50名轻度认知障碍），并通过巴特斯博士的R01 （MH072947；“晚期抑郁症与轻度认知障碍和痴呆症的联系途径”）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受试者的类似数据进行比较，以及75名从未抑郁的具有一系列认知分类的受试者（50名认知正常，25名遗忘型MCI），这些数据是在另外两个资助奖项(计划项目资助AG025204“体内PiB-PET淀粉样蛋白成像：正常人、轻度认知障碍和痴呆”和优异奖AG025516“正常老年人的脑淀粉样蛋白与认知”)。我们将测试一系列相关的假设，这些假设是老年抑郁症患者发展认知障碍和导致阿尔茨海默病的一些途径的神经病理学基础。公共卫生相关性：这项研究将收集信息，以提高对老年抑郁症患者患痴呆症风险增加的理解。为了实现这一目标，我们将研究相关研究的参与者，使用新的大脑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。如果我们能够更好地识别出患有特定类型痴呆症（如阿尔茨海默病）的个体，那么随着新的痴呆症治疗方法的出现，他们就可以在疾病的早期阶段接受治疗。

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.