Hayden K M, Zandi P P, Khachaturian A S, Szekely C A, Fotuhi M, Norton M C, Tschanz J T, Pieper C F, Corcoran C, Lyketsos C G, Breitner J C S, Welsh-Bohmer K A
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA.
Neurology. 2007 Jul 17;69(3):275-82. doi: 10.1212/01.wnl.0000265223.25679.2a.
Epidemiologic studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may be useful for the prevention of Alzheimer disease (AD). By contrast, clinical trials have not supported NSAID use to delay or treat AD. Few studies have evaluated cognitive trajectories of NSAID users over time.
Residents of Cache County, UT, aged 65 or older on January 1, 1995, were invited to participate in the study. At baseline, participants provided a detailed inventory of their medications and completed a revised Modified Mini-Mental State Examination (3MS). Participants (n = 3,383) who were cognitively normal at baseline were re-examined after 3 and 8 years. The association between NSAID use and 3MS scores over time was estimated using random effects modeling.
Associations depended upon when NSAIDs were started and APOE genotype. In participants who started NSAID use prior to age 65, those with no APOE epsilon4 alleles performed similarly to nonusers (a difference of 0.10 points per year; p = 0.19), while those with one or more epsilon4 allele(s) showed more protection (0.40 points per year; p = 0.0005). Among participants who first used NSAIDs at or after age 65, those with one or more epsilon4 alleles had higher baseline scores (0.95 points; p = 0.03) but did not show subsequent difference in change in score over time (0.06 points per year; p = 0.56). Those without an epsilon4 allele who started NSAID use after age 65 showed greater decline than nonusers (-0.16 points per year; p = 0.02).
Nonsteroidal anti-inflammatory drug use may help to prevent cognitive decline in older adults if started in midlife rather than late life. This effect may be more notable in those who have one or more APOE epsilon4 alleles.
流行病学研究表明，非甾体抗炎药（NSAIDs）可能有助于预防阿尔茨海默病（AD）。相比之下，临床试验并不支持使用NSAIDs来延缓或治疗AD。很少有研究评估NSAIDs使用者随时间的认知轨迹。
邀请1995年1月1日时年龄在65岁及以上的犹他州卡什县居民参与研究。在基线时，参与者提供了详细的用药清单，并完成了修订后的改良简易精神状态检查表（3MS）。基线时认知正常的参与者（n = 3383）在3年和8年后再次接受检查。使用随机效应模型估计NSAIDs使用与随时间变化的3MS评分之间的关联。
关联取决于开始使用NSAIDs的时间和APOE基因型。在65岁之前开始使用NSAIDs的参与者中，没有APOE ε4等位基因的参与者表现与未使用者相似（每年差异0.10分；p = 0.19），而有一个或多个ε4等位基因的参与者显示出更多的保护作用（每年0.40分；p = 0.0005）。在65岁及以后首次使用NSAIDs的参与者中，有一个或多个ε4等位基因的参与者基线评分较高（0.95分；p = 0.03），但随时间推移评分变化没有后续差异（每年0.06分；p = 0.56）。65岁以后开始使用NSAIDs且没有ε4等位基因的参与者比未使用者下降得更多（每年-0.16分；p = 0.02）。
如果在中年而非晚年开始使用非甾体抗炎药，可能有助于预防老年人的认知衰退。这种效应在有一个或多个APOE ε4等位基因的人群中可能更显著。
