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

淀粉样蛋白、白质高信号

基本信息

批准号：
7804613
负责人：
MERYL A BUTTERS
金额：
$ 50.77万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-14 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7804613
关键词：
Accounting Address Age Alzheimer&apos s Disease Alzheimer&apos 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 Services Research Hippocampus (Brain)Human Image Impaired cognition Impairment Individual Injury 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 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 cerebrovascular cerebrovascular lesion cognitive function cohort follow-up geriatric depression improved in vivo indexing information gathering information processing meetings mild neurocognitive impairment neurobehavioral neurobehavioral disorder neuroimaging neuropathology neuropsychological novel processing speed progressive neurodegeneration public health relevance research study white matter

项目摘要

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）：此R01应用的目的是研究晚期抑郁症（LLD），认知障碍和进行性神经变性的关系，采用两种成像方法：一种新型的宠物配体（Pittsburgh gompound-b; pib），与白（pittsburgh goled-b; pib）结合，与白（Wmhh）结合白（Wmhh）。指导假设是，发展LLD的个体由于不同的潜在神经病理学变化而经常表示为轻度认知障碍（MCI），因此具有不断发展的认知障碍。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，进而增加表达临床阿尔茨海默氏病的风险。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中心的联合基础设施（MH071944）和阿尔茨海默氏病研究中心（AG05133），具有恢复抑郁症的个体将对PIB-PET进行PIB-PET对淀粉样病理学和MRI的成像，以确定WMH。我们将研究100个通过一系列认知分类（认知正常，50 MCI）的抑郁症受试者，并通过Butters'R01（MH072947）（与MCI抑郁症与MCI＆Dementia连接的途径）通过纵向临床，认知和实验室数据收集3年。将将来自这些受试者的WMH和PIB-PET数据与通过拟议的研究收集的25个从未抑制的非抑制性MCI受试者以及75名具有认知分类的从未抑郁的受试者（50个认知正常，25个amnantic MCI）收集的25个从未抑制的非抑制MCI受试者的数据进行比较。正常的MCI和痴呆症“和功绩奖AG025516“正常老年人的脑淀粉样蛋白和认知”）。我们将测试一系列连接的假设，这些假设假设一些途径的神经病理底物，老年人，抑郁症患者会发展认知障碍并导致一些阿尔茨海默氏病。公共卫生相关性：这项研究将收集信息，以提高人们对为什么老年人沮丧的人患痴呆症的风险增加的理解。为了实现这一目标，我们将使用相关研究的参与者进行研究，新的脑扫描方法检测脑血管疾病和淀粉样蛋白，这是在阿尔茨海默氏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发展特定类型痴呆症（例如阿尔茨海默氏病）风险的人，那么随着新痴呆疗法的可用性，他们可以在最早的疾病阶段进行治疗。