Extended results of the Alzheimer's disease anti-inflammatory prevention trial.
Extended results of the Alzheimer's disease anti-inflammatory prevention trial.
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DOI：
10.1016/j.jalz.2010.12.014
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发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
ADAPT Research Group
中科院分区：
文献类型：
--
作者：
Breitner JC;Baker LD;Montine TJ;Meinert CL;Lyketsos CG;Ashe KH;Brandt J;Craft S;Evans DE;Green RC;Ismail MS;Martin BK;Mullan MJ;Sabbagh M;Tariot PN;ADAPT Research Group
流行病学证据表明，非甾体抗炎药（NSAID）延迟阿尔茨海默氏痴呆症（AD）的发作，但随机试验显示，NSAID对症状性AD没有益处。ADAPT将2，528名老年人随机分配至nacetolen或塞来昔布与安慰剂组，为期两年（s.d. 11个月）。在治疗间隔期间，两个NSAID分配组中有32例AD病例的发生率增加。我们将双盲ADAPT方案继续两年，以研究AD的发病率（主要结局）。然后，我们收集了117名志愿者的脑脊液（CSF），以评估其CSF tau与Aβ1-42的比值。包括在2,071名随机个体（92%的参与者在治疗停止时）的随访期间观察到的40起新事件，现在有72例AD病例。总体而言，NSAID相关的损害不再明显，但次要分析显示，在观察的前2.5年中，风险增加仍然显著，特别是在54名患有认知障碍-无痴呆症（CIND）的患者中。这些相同的分析显示，在无症状的登记者中，服用那普利的AD发病率后来有所降低。CSF生物标志物测定表明，后一结果反映了阿尔茨海默型神经变性减少。这些数据表明，对最初的ADAPT假设进行了修订，即NSAID可降低AD风险，因此：NSAID在AD发病机制的后期阶段具有不良作用，而接受传统NSAID（如萘普生）治疗的无症状个体的AD发病率降低，但仅在2 - 3年后。因此，治疗效果在疾病的不同阶段有所不同。这一假设与试验和流行病学研究的数据一致。
Epidemiologic evidence suggests that non-steroidal anti-inflammatory drugs (NSAIDs) delay onset of Alzheimer’s dementia (AD), but randomized trials show no benefit from NSAIDs in symptomatic AD. ADAPT randomized 2,528 elderly persons to naproxen or celecoxib vs. placebo for two years (s.d. 11 months) before treatments were terminated. During the treatment interval, 32 cases of AD revealed increased rates in both NSAID-assigned groups. We continued the double-masked ADAPT protocol for two additional years to investigate incidence of AD (primary outcome). We then collected cerebrospinal fluid (CSF) from 117 volunteer participants to assess their ratio of CSF tau to Aβ1–42. Including 40 new events observed during follow-up of 2,071 randomized individuals (92% of participants at treatment cessation), there were now 72 AD cases. Overall NSAID-related harm was no longer evident, but secondary analyses showed that increased risk remained notable in the first 2.5 years of observations, especially in 54 persons enrolled with Cognitive Impairment – No Dementia (CIND). These same analyses showed later reduction in AD incidence among asymptomatic enrollees given naproxen. CSF biomarker assays suggested that the latter result reflected reduced Alzheimer-type neurodegeneration. These data suggest a revision of the original ADAPT hypothesis that NSAIDs reduce AD risk, thus: NSAIDs have an adverse effect in later stages of AD pathogenesis, while asymptomatic individuals treated with conventional NSAIDs like naproxen experience reduced AD incidence, but only after 2 – 3 years. Thus, treatment effects differ at various stages of disease. This hypothesis is consistent with data from both trials and epidemiological studies.
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影响因子：
48
作者：
Sonnen, Joshua A.;Montine, Kathleen S.;Quinn, Joseph F.;Kaye, Jeffrey A.;Breitner, John C. S.;Montine, Thomas J.
通讯作者：
Montine, Thomas J.
DOI：
10.1097/01.wad.0000194014.43575.fd
发表时间：
2005-10-01
影响因子：
2.1
作者：
Peskind, ER;Riekse, R;Galasko, D
通讯作者：
Galasko, D
影响因子：
158.5
作者：
in 't Veld, BA;Ruitenberg, A;Stricker, BHC
通讯作者：
Stricker, BHC
影响因子：
9.9
作者：
Li, G.;Sokal, I.;Montine, T. J.
通讯作者：
Montine, T. J.
影响因子：
2.4
作者：
Soininen, Hilkka;West, Christine;Niculescu, Liviu
通讯作者：
Niculescu, Liviu