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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 几项观察性流行病学研究表明，抗炎治疗可以减轻或预防老年最常见的精神障碍之一-阿尔茨海默病(AD)的症状。神经病理学研究也支持阿尔茨海默病的炎症或免疫机制，包括在阿尔茨海默病皮损内或附近发现反应性小胶质细胞。然而，这样的证据是间接的，需要受控的随机药物试验来确定疗效。拟议的项目旨在确定常用的非类固醇抗炎药(NSAID)布洛芬是否有效地延缓了年龄相关认知障碍患者的认知症状的进展，这些人有患AD的风险。共有135名年龄相关性记忆障碍(AAMI)的受试者面临进一步认知能力下降的风险(年龄在65岁至90岁之间，在言语和视觉记忆以及语言流利性测试中得分较低)，他们将被随机(双盲设计)分成两个治疗组：布洛芬(1200 mg/d)或安慰剂，并追踪两年，以寻找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[HL A])，以探索基线脑形态(如深部白质病、海马区不对称和萎缩)和AD发病的遗传风险(如APOE-4、HL A-A2)如何影响下降率和治疗结果。与服用安慰剂的受试者相比，服用布洛芬的受试者预计表现出较少的认知能力下降的证据。拟议的项目建立在我们小组使用脑成像、遗传风险和神经心理学评估早期检测AD方面的先前工作的基础上。该项目也是对最近一项有希望的早期干预的观察研究的合乎逻辑的后续行动，并将代表着针对与年龄相关的认知能力下降和最终发展为阿尔茨海默病的高风险人群的首批受控抗炎治疗试验之一。