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

淀粉样蛋白、白质高信号

• 批准号: 8488366
• 负责人: MERYL A BUTTERS
• 金额: $ 17.05万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-14 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8488366
• 关键词: Accounting; Address; Age; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Amyloid deposition; Area; Award; Binding; Biological Assay; Biological Markers; Blood; Blood Vessels; Brain; Brain scan; Butter; Cerebrovascular Disorders; Classification; Clinical; Cognition; Cognitive; Conflict (Psychology); Data; Data Collection; Dementia; Deposition; Depressed mood; Development; Disease; Education; Elderly; Enrollment; Exhibits; Funding; Goals; Health; Health Services Research; Hippocampus (Brain); Human; Image; Impaired cognition; Individual; Intervention; Joints; Laboratories; Lead; Ligands; Link; Literature; Magnetic Resonance Imaging; Measures; Mental Depression; Methods; Mood Disorders; Natural History; Neurofibrillary Tangles; Outcome; Participant; Pathology; Pathway interactions; Patients; Phenotype; Pittsburgh Compound-B; Play; Population; Positron-Emission Tomography; Preventive Intervention; Price; Program Research Project Grants; Public Health; Recording of previous events; Research; Research Infrastructure; Risk; Risk Factors; Role; Senile Plaques; Series; Source; Staging; Symptoms; TNFRSF5 gene; Testing; Therapeutic Intervention; Time; Universities; Vascular Dementia; Visuospatial; abstracting; aged; amyloid imaging; amyloid pathology; burden of illness; cerebrovascular; cerebrovascular lesion; cognitive function; cohort; follow-up; geriatric depression; improved; in vivo; indexing; information gathering; information processing; injury burden; meetings; mild neurocognitive impairment; neurobehavioral; neurobehavioral disorder; neuroimaging; neuropathology; neuropsychological; novel; processing speed; progressive neurodegeneration; research study; white matter

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.

描述（由申请人提供）：该 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：一种与淀粉样蛋白结合的新型 PET 配体（匹兹堡化合物-B；PiB）和白质高信号 (WMH) 的体积 MRI。指导性假设是，由于明显的潜在神经病理学变化（通常表现为轻度认知障碍（MCI）），患有 LLD 的个体会出现不断发展的认知障碍。淀粉样蛋白和 WMH 是主要的神经病理学特征，会降低大脑储备能力，进而增加临床阿尔茨海默病的风险。为了实现这一目标，利用匹兹堡大学晚年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，缓解抑郁症的个体将接受 PiB-PET 成像以进行淀粉样蛋白病理学和 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，并通过巴特斯博士的 R01（MH072947；“将晚年抑郁症与 MCI 和痴呆症联系起来的途径”）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性 MCI 受试者以及 75 名具有一系列认知分类（50 名认知正常，25 名遗忘性 MCI）的从未抑郁受试者的类似数据进行比较，这些数据是在其他两个资助奖项（计划项目拨款 AG025204“体内 PiB-PET 淀粉样蛋白成像： 正常人、MCI 和痴呆症”和 MERIT 奖 AG025516“正常老年人的脑淀粉样蛋白和认知”）。我们将测试一系列相互关联的假设，这些假设假设老年抑郁症患者出现认知障碍并导致某些人患上阿尔茨海默病的一些途径的神经病理学基础。公共健康相关性：这项研究将收集信息，以加深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，采用新的大脑扫描方法来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有患特定类型痴呆症（例如阿尔茨海默病）风险的个体，那么随着新的痴呆症治疗方法的出现，他们就可以成为在疾病最早阶段接受治疗的候选者。