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

描述（由申请人提供）：该R 01申请的目的是使用两种成像方法研究晚年抑郁症（LLD）、认知障碍和进行性神经退行性变之间的关系：一种与淀粉样蛋白结合的新型PET配体（匹兹堡化合物-B; PiB）和白色高信号（WMH）的体积MRI。指导性假设是，发展LLD的个体由于不同的潜在神经病理学变化而具有不断发展的认知障碍，这些神经病理学变化经常被表达为轻度认知障碍（MCI）。淀粉样蛋白和WMH是降低脑储备能力的主要神经病理学特征，并且反过来增加表达临床阿尔茨海默病的风险。为了实现这一目标，使用匹兹堡大学晚期情绪障碍干预和服务研究高级中心（MH 071944）和阿尔茨海默病研究中心（AG 05133）的联合基础设施，患有缓解抑郁症的个体将接受淀粉样蛋白病理学的PiB-PET成像和MRI以确定WMH体积。我们将研究100名具有一系列认知分类（50名认知正常，50名MCI）的缓解抑郁症受试者，并通过Butters博士的R 01（MH 072947;“将晚年抑郁症与MCI和痴呆症联系起来的途径”）进行纵向临床，认知和实验室数据收集，并对其进行为期3年的随访。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，沿着75名具有一系列认知分类的从未抑郁的受试者（50名认知正常，25名遗忘型MCI），在其他两个资助奖项的赞助下收集（计划项目资助AG 025204“体内PiB-PET淀粉样蛋白成像：正常、MCI和痴呆”和MERIT奖AG 025516“正常老年人的脑淀粉样蛋白和认知”）。我们将测试一系列相关的假设，这些假设假定了一些通路的神经病理学底物，老年抑郁症患者通过这些通路发展认知障碍并导致一些阿尔茨海默病。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原因的理解。为了实现这一目标，我们将研究相关研究的参与者，采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。如果我们能更好地识别出有患特定类型痴呆症（如阿尔茨海默病）风险的个体，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.