MENTAL DISORDERS OF AGING -- ANTIINFLAMMATION IN AD

衰老性精神障碍——AD 中的抗炎药

• 批准号: 8171156
• 负责人: GARY William SMALL
• 金额: $ 0.61万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171156
• 关键词: Age; Age-associated memory impairment; Alzheimer' s Disease; Anti-Inflammatory Agents; Anti-inflammatory; Apolipoprotein E; Atrophic; Attenuated; Brain imaging; Computer Retrieval of Information on Scientific Projects Database; Development; Double-Blind Method; Early Diagnosis; Early treatment; Elderly; Epidemiologic Studies; Funding; Genetic Risk; Genotype; Grant; HLA Antigens; Hippocampus (Brain); Ibuprofen; Immune; Impaired cognition; Inflammatory; Institution; Lesion; Magnetic Resonance Imaging; Mental disorders; Microglia; Neurobehavioral Manifestations; Onset of illness; Persons; Pharmaceutical Preparations; Placebos; Randomized; Research; Research Personnel; Resources; Risk; Source; Symptoms; Testing; Treatment outcome; United States National Institutes of Health; White Matter Disease; Work; age related; brain morphology; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 一些观察性流行病学研究表明，抗炎治疗可以减轻或预防晚年最常见的精神疾病之一——阿尔茨海默病（AD）的症状。神经病理学研究也支持 AD 中的炎症或免疫机制，包括 AD 病变内或附近的反应性小胶质细胞的发现。然而，此类证据是间接的，需要进行对照、随机药物试验来确定疗效。该项目旨在确定常用的非甾体类抗炎药 (NSAID) 布洛芬是否能有效延缓患有与年龄相关的认知丧失且有患 AD 风险的人群的认知症状进展。总共 135 名患有与年龄相关的记忆障碍 (AAMI) 且有进一步认知能力下降风险的受试者（年龄 65 至 90 岁，言语和视觉记忆以及言语流畅性测试得分较低）将被随机分组​​（双盲设计） ）到两个治疗组之一：布洛芬（1200 mg/d）或安慰剂，并随访两年以获取进一步认知能力下降的证据。所有随机受试者将接受磁共振成像 (MRI) 扫描和选择性基因分型（载脂蛋白 E [APOE] 和人类白细胞抗原 [HLA]），以探讨基线脑形态（例如深部白质疾病、海马不对称和萎缩）和遗传风险如何影响AD 发病（例如 APOE-4、HLA-A2）影响衰退率和治疗结果。预计接受布洛芬的受试者比接受安慰剂的受试者表现出更少的认知下降证据。拟议的项目建立在我们小组之前利用脑成像、遗传风险和神经心理学评估早期检测 AD 的工作基础上。该项目也是最近一项有前景的早期干预观察研究的合理后续行动，并将成为针对年龄相关认知能力下降和最终发展为 AD 高风险人群的首批对照抗炎治疗试验之一。