MENTAL DISORDERS OF AGING -- ANTIINFLAMMATION IN AD

衰老性精神障碍——AD 中的抗炎药

• 批准号: 8363471
• 负责人: GARY William SMALL
• 金额: $ 1.01万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363471
• 关键词: Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Anti-Inflammatory Agents; Anti-inflammatory; Apolipoprotein E; Atrophic; Attenuated; Brain imaging; Development; Double-Blind Method; Early Diagnosis; Early treatment; Elderly; Epidemiologic Studies; Funding; Genetic Risk; Genotype; Grant; HLA Antigens; HLA-A2 Antigen; Hippocampus (Brain); Ibuprofen; Immune; Impaired cognition; Inflammatory; Lesion; Magnetic Resonance Imaging; Mental disorders; Microglia; Modeling; National Center for Research Resources; Neurobehavioral Manifestations; Onset of illness; Persons; Pharmaceutical Preparations; Placebos; Principal Investigator; Randomized; Research; Research Infrastructure; Resources; Risk; Source; Symptoms; Testing; Treatment outcome; United States National Institutes of Health; White Matter Disease; Work; age related; apolipoprotein E-4; brain morphology; computational anatomy; cost; design; follow-up; high risk; neuropsychological; prevent; treatment trial; visual memory

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Several observational epidemiological studies indicate that anti- inflammatory treatments attenuate or prevent the symptoms of one of the most common mental disorders of late life, Alzheimer disease (AD). Neuropathological studies also support inflammatory or immune mechanisms in AD, including findings of reactive microglia within or near AD lesions. Such evidence, however, is circumstantial, and controlled, randomized drug trials are needed to determine efficacy. The proposed project is designed to determine if the commonly used non-steroidal anti-inflammatory drug (NSAID), ibuprofen, is efficacious in delaying progression of cognitive symptoms in people with age-related cognitive losses who are at risk for developing AD. A total of 135 subjects with age-associated memory impairment (AAMI) who are at risk for further cognitive decline (age 65 to 90 years, low scores on tests of verbal and visual memory and verbal fluency) will be randomized (double-blind design) to one of two treatment groups: ibuprofen (1200 mg/d) or placebo, and followed for two years for evidence of further cognitive decline. All randomized subjects will receive magnetic resonance imaging (MRI) scans and selective genotyping (apolipoprotein E [APOE] and human leukocyte antigen [HLA) to explore how baseline brain morphology (e.g., deep white matter disease hippocampal asymmetry and atrophy) and genetic risk for AD onset (e.g., APOE-4, HLA- A2) influence decline rates and treatment outcome. Subjects receiving ibuprofen are expected to show less evidence of cognitive decline than those receiving placebo. The proposed project builds upon our group's prior work on early detection of AD using brain imaging, genetic risk, and neuropsychological assessments. This project also is a logical follow-up to recent observation studies of a promising early intervention and will represent one of the first controlled, anti-inflammatory treatment trials for persons at high risk for age-related cognitive decline and the eventual development of AD.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 几项观察性流行病学研究表明，抗炎症治疗可减轻或预防晚期生活中最常见的精神疾病之一，阿尔茨海默氏病（AD）的症状。神经病理学研究还支持AD中的炎症或免疫机制，包括在AD病变内或附近的反应性小胶质细胞的发现。然而，这种证据是间接的，需要受控的随机药物试验来确定功效。拟议的项目旨在确定常用的非甾体类抗炎药（NSAID）是否有效地在延迟与年龄相关的认知损失的人的认知症状进展方面有效，他们有可能发展AD的风险。共有135名患有年龄相关记忆障碍（AAMI）的受试者面临进一步认知能力下降的风险（65至90岁，口头和视觉记忆测试的得分较低，并且在两种治疗组中的评分（双盲设计）将被随机化（双盲设计）：Ibuprofen（Ibuprofen（Ibuprofen）（Ibuprofen）（Ibuprofen（1200 mg/d）或lote boar and Glotbo和blotbo和blotbo和seltbo bo and laster cojection for两年All randomized subjects will receive magnetic resonance imaging (MRI) scans and selective genotyping (apolipoprotein E [APOE] and human leukocyte antigen [HLA) to explore how baseline brain morphology (e.g., deep white matter disease hippocampal asymmetry and atrophy) and genetic risk for AD onset (e.g., APOE-4, HLA- A2) influence decline rates and treatment 结果。预计接受布洛芬的受试者比接受安慰剂的受试者显示出认知能力下降的证据更少。拟议的项目建立在我们小组先前使用大脑成像，遗传风险和神经心理学评估的AD检测的工作。该项目也是对有希望的早期干预的最新观察研究的逻辑随访，它将代表对年龄相关认知能力下降的高风险和AD最终发展的第一个受控的抗炎治疗试验之一。