de Jong Daniëlle, Jansen René, Hoefnagels Willibrord, Jellesma-Eggenkamp Marja, Verbeek Marcel, Borm George, Kremer Berry
Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
PLoS One. 2008 Jan 23;3(1):e1475. doi: 10.1371/journal.pone.0001475.
The objective of this study was to determine whether treatment with the nonselective nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows cognitive decline in patients with Alzheimer's disease (AD).
METHODOLOGY/PRINCIPAL FINDINGS: This double-blind, randomized, placebo-controlled trial was conducted between May 2000 and September 2005 in two hospitals in the Netherlands. 51 patients with mild to moderate AD were enrolled into the study. Patients received 100 mg indomethacin or placebo daily for 12 months. Additionally, all patients received omeprazole. The primary outcome measure was the change from baseline after one year of treatment on the cognitive subscale of the AD Assessment Scale (ADAS-cog). Secondary outcome measures included the Mini-Mental State Examination, the Clinician's Interview Based Impression of Change with caregiver input, the noncognitive subscale of the ADAS, the Neuropsychiatric Inventory, and the Interview for Deterioration in Daily life in Dementia. Considerable recruitment problems of participants were encountered, leading to an underpowered study. In the placebo group, 19 out of 25 patients completed the study, and 19 out of 26 patients in the indomethacin group. The deterioration on the ADAS-cog was less in the indomethacin group (7.8+/-7.6), than in the placebo group (9.3+/-10.0). This difference (1.5 points; CI -4.5-7.5) was not statistically significant, and neither were any of the secondary outcome measures.
CONCLUSIONS/SIGNIFICANCE: The results of this study are inconclusive with respect to the hypothesis that indomethacin slows the progression of AD.
本研究的目的是确定使用非选择性非甾体抗炎药（NSAID）吲哚美辛治疗是否能减缓阿尔茨海默病（AD）患者的认知衰退。
方法/主要发现：这项双盲、随机、安慰剂对照试验于2000年5月至2005年9月在荷兰的两家医院进行。51例轻度至中度AD患者纳入研究。患者每天接受100mg吲哚美辛或安慰剂治疗，为期12个月。此外，所有患者均接受奥美拉唑治疗。主要结局指标是治疗一年后阿尔茨海默病评估量表（ADAS-cog）认知子量表相对于基线的变化。次要结局指标包括简易精神状态检查表、基于临床医生访谈并结合照料者意见的变化印象、ADAS的非认知子量表、神经精神科问卷以及痴呆患者日常生活能力衰退访谈。研究遇到了严重的受试者招募问题，导致研究效能不足。在安慰剂组，25例患者中有19例完成研究，吲哚美辛组26例患者中有19例完成研究。吲哚美辛组ADAS-cog的恶化程度（7.8±7.6）低于安慰剂组（9.3±10.0）。这种差异（1.5分；可信区间-4.5至7.5）无统计学意义，次要结局指标也均无统计学意义。
结论/意义：关于吲哚美辛能减缓AD进展这一假设，本研究结果尚无定论。
