MENTAL DISORDERS OF AGING -- ANTIINFLAMMATION IN AD

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 中心，不一定是研究者的机构。 几项观察性流行病学研究表明，抗炎治疗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AD的炎症或免疫机制，包括在AD病变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，需要对照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甾体抗炎药（NSAID）布洛芬是否能有效延缓与年龄相关的认知丧失患者的认知症状进展，这些患者有患AD的风险。共有135例年龄相关性记忆障碍（AAMI）受试者存在进一步认知下降的风险（年龄65 - 90岁，言语和视觉记忆以及言语流畅性测试得分较低），将其随机（双盲设计）分配至两个治疗组之一：布洛芬（1200 mg/d）或安慰剂，并随访2年以获得进一步认知下降的证据。所有随机化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]），以探索基线脑形态学（例如，深部白色物质疾病海马体不对称和萎缩）和AD发病的遗传风险（例如，APOE-4、HLA-A2）影响下降率和治疗结果。预期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。该项目建立在我们小组先前使用脑成像，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希望的早期干预观察研究的逻辑后续行动，并将代表针对年龄相关认知能力下降和最终发展为AD的高风险人群的首批对照抗炎治疗试验之一。

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.