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和最近的研究相反，选择性降低Aβ-42制剂(SALAs) — 其中一类的非类固醇消炎药(NSAIDs)，包括ibuprofen —对于预防阿兹海默氏症(AD)的效果并未优于其他的NSAIDs。
六篇共13,499人使用NSAID的共同研究分析显示，相较于未曾使用NSAIDs者，使用这些药物的人发生AD的风险平均减少23%，不过，减少的风险与使用的NSAID类型无关。
约翰霍普金斯Bloomberg公共卫生学院的研究者Peter P. Zandi博士在美国神经医学会的声明中表示，这是有趣的发现，看来挑战了现有理论所认为的：NSAID以及ibuprofen可以减少阿兹海默氏症风险的看法。
根据该研究的主要作者、Cedars Sinai医学中心的Chris Szekely博士表示，对于本研究和有关AD预防及治疗的一些NSAIDs负面临床试验都需要后续探讨。
本研究发表于5月28日的Neurology期刊。
【SALAs和非SALAs的比较】
为了进行研究，研究人员整合了六个前溯世代研究的资料，以获得足够样本检视SALA使用者与其他非SALA之NSAIDs使用者的AD风险。
这六个研究的纳入规范包括了使用临床研究规范进行的偶发AD诊断；研究对象使用NSAIDs成药和处方药的整体资料；且在失智症诊断之前搜集暴险衡量资料。
在体内或体外模式中，如果可以降低Aβ-42之NSAIDs，即被归类为SALAs，如果没有选择性降低Aβ-42，则被归类为非SALAs。
根据此研究，SALAs包括diclofenac、diflunisal、fenoprofen、flurbiprofen、ibuprofen、indomethacin、meclofenamate、piroxicam以及sulindac；非SALAs包括celecoxib、etodolac、ketoprofen、ketorolac、mefenamic acid、nabumetone、naproxen与 phenylbutazone。
研究者也以乙醯胺酚作为控制药物，因为此药的适应症与NSAIDs类似，但是作用机转不同；由于药物的剂量资讯并未纳入，因此无法检视。
【还有许多需要研究】
在追踪期间，NSAID的随时使用频率为29.6%；阿斯匹灵使用率为47.0%，乙醯胺酚为25.3%；Ibuprofen 是最常被使用的 SALA，占 52.9%的NSAID使用量；Naproxen是最常被使用的非SALA，占24.0%的NSAID使用量；研究对象只有不到1%使用选择性COX-2 抑制剂。
使用任何NSAID减少AD风险达23%，不过，SALAs和非SALAs对于AD风险之降低的比较，并未指出有较大的差异；研究者发现，阿斯匹灵使用者有较低的AD风险，即使是只有使用阿斯匹灵且未使用其他NSAID；乙醯胺酚与降低AD风险无关。
他们写道，有关NSAIDs在AD病理的角色仍有许多需要研究，包括NSAIDs是否有传说中的神经保护效果，还需要时间、使用者的人数以及时间来加以验证，同时也必须探讨服用这些药物的病患类型与特征。
该研究接受美国国家健康研究中心以及加拿大健康研究中心的支持；作者之一，杜克大学的Kathleen A. Welsh-Bohmer医师表示拥有使用NSAIDs作为AD预防/治疗的许多专利的专利权。无其他利益冲突宣告。
SALAs Offer No Edge Over Other NSAIDs in Reducing Alzheimer's Risk
By Caroline Cassels
Medscape Medical News
Contrary to recent reports, selective Aβ-42–lowering agents (SALAs) — a subgroup of nonsteroidal anti-inflammatory drugs (NSAIDs) that includes ibuprofen — offer no greater protection against Alzheimer's disease (AD) than other NSAIDs.
A pooled analysis that included data from 6 studies on NSAID use in 13,499 individuals showed those who used these medications had an overall 23% lower risk of developing AD than individuals who never used NSAIDs. However, the reduction in risk was not associated with the type of NSAID used.
"This is an interesting finding, because it seems to challenge a current theory that the NSAID group that includes ibuprofen may work better in reducing a person's risk of Alzheimer's," study investigator Peter P. Zandi, PhD, from Johns Hopkins Bloomberg School of Public Health, in Baltimore, Maryland, said in a statement from the American Academy of Neurology.
According to the study's lead author Chris Szekely, PhD, from Cedars Sinai Medical Center, in Los Angeles, California, the discrepancy between studies such as this and the negative clinical trials of NSAIDs in the treatment or prevention of AD need further exploration.
The study is published May 28 in Neurology.
SALAs vs Non-SALAs
For the study, the researchers pooled individual-level data from 6 prospective cohort studies to obtain a sufficient sample to examine AD risk in users of SALA vs non-SALA NSAIDs.
Inclusion criteria for the 6 studies included diagnoses of incident AD made using clinical research criteria; systematic data on individual over-the-counter and prescription NSAIDs; and exposure measurements collected prior to dementia diagnosis.
NSAIDs were categorized as SALAs if they had been shown either in in vivo or in vitro models to lower Aβ-42 or as non-SALAs if they did not show selective Aβ-42 lowering.
According to the study, SALAs included diclofenac, diflunisal, fenoprofen, flurbiprofen, ibuprofen, indomethacin, meclofenamate, piroxicam, and sulindac. Non-SALAs included celecoxib, etodolac, ketoprofen, ketorolac, mefenamic acid, nabumetone, naproxen, and phenylbutazone.
The investigators also examined acetaminophen as a "control" medication because it is used for indications similar to those for NSAIDs but has a different mechanism of action. Dose information was not consistently available for medications and therefore was not examined.
More to Learn
The frequency of NSAID use at any time in the follow-up interval was 29.6%; aspirin was used by 47.0% and acetaminophen by 25.3%. Ibuprofen was the most commonly used SALA, accounting for 52.9% of NSAID use. Naproxen was the most commonly used non-SALA, accounting for 24.0% of NSAID use. Less than 1% of study participants reported use of selective COX-2 inhibitors.
Any NSAID use was associated with a 23% reduced risk of AD. However, there was no suggestion of greater AD risk reduction for SALAs vs non-SALAs. The investigators found aspirin users had a lower risk of AD, even among those who used aspirin alone and no other NSAID. Acetaminophen use was not linked to a lower AD risk.
"There is much to learn about the role of NSAIDs in the pathogenesis of AD, including whether the putative neuroprotective effects of NSAIDs depend upon the timing, amount, or duration of their use or on particular characteristics of the subgroups of people who take them," they write.
The study was supported by the National Institutes of Health and the Canadian Institutes of Health Research. One of the authors, Dr. Kathleen A. Welsh-Bohmer, from Duke University, in Durham, North Carolina, reports having a royalty interest in several patents on the use of NSAIDs as a prevention/treatment for AD. No other conflicts of interest are reported.
Neurology. 2008;70:2291-2298.