Farina Nicolas, Llewellyn David, Isaac Mokhtar Gad El Kareem Nasr, Tabet Naji
Centre for Dementia Studies, Brighton and Sussex Medical School, Brighton, UK, BN1 9QH.
Medical School, University of Exeter, Exeter, UK, +44 (0) 1392 726018.
Cochrane Database Syst Rev. 2017 Jan 27;1(1):CD002854. doi: 10.1002/14651858.CD002854.pub4.
Vitamin E occurs naturally in the diet. It has several biological activities, including functioning as an antioxidant to scavenge toxic free radicals. Evidence that free radicals may contribute to the pathological processes behind cognitive impairment has led to interest in the use of vitamin E supplements to treat mild cognitive impairment (MCI) and Alzheimer's disease (AD). This is an update of a Cochrane Review first published in 2000, and previously updated in 2006 and 2012.
To assess the efficacy of vitamin E in the treatment of MCI and dementia due to AD.
We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS as well as many trials databases and grey literature sources on 22 April 2016 using the terms: "Vitamin E", vitamin-E, alpha-tocopherol.
We included all double-blind, randomised trials in which treatment with any dose of vitamin E was compared with placebo in people with AD or MCI.
We used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. Where appropriate we attempted to contact authors to obtain missing information.
Four trials met the inclusion criteria, but we could only extract outcome data in accordance with our protocol from two trials, one in an AD population (n = 304) and one in an MCI population (n = 516). Both trials had an overall low to unclear risk of bias. It was not possible to pool data across studies owing to a lack of comparable outcome measures.In people with AD, we found no evidence of any clinically important effect of vitamin E on cognition, measured with change from baseline in the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) over six to 48 months (mean difference (MD) -1.81, 95% confidence interval (CI) -3.75 to 0.13, P = 0.07, 1 study, n = 272; moderate quality evidence). There was no evidence of a difference between vitamin E and placebo groups in the risk of experiencing at least one serious adverse event over six to 48 months (risk ratio (RR) 0.86, 95% CI 0.71 to 1.05, P = 0.13, 1 study, n = 304; moderate quality evidence), or in the risk of death (RR 0.84, 95% CI 0.52 to 1.34, P = 0.46, 1 study, n = 304; moderate quality evidence). People with AD receiving vitamin E showed less functional decline on the Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory than people receiving placebo at six to 48 months (mean difference (MD) 3.15, 95% CI 0.07 to 6.23, P = 0.04, 1 study, n = 280; moderate quality evidence). There was no evidence of any clinically important effect on neuropsychiatric symptoms measured with the Neuropsychiatric Inventory (MD -1.47, 95% CI -4.26 to 1.32, P = 0.30, 1 study, n = 280; moderate quality evidence).We found no evidence that vitamin E affected the probability of progression from MCI to probable dementia due to AD over 36 months (RR 1.03, 95% CI 0.79 to 1.35, P = 0.81, 1 study, n = 516; moderate quality evidence). Five deaths occurred in each of the vitamin E and placebo groups over the 36 months (RR 1.01, 95% CI 0.30 to 3.44, P = 0.99, 1 study, n = 516; moderate quality evidence). We were unable to extract data in accordance with the review protocol for other outcomes. However, the study authors found no evidence that vitamin E differed from placebo in its effect on cognitive function, global severity or activities of daily living . There was also no evidence of a difference between groups in the more commonly reported adverse events.
AUTHORS' CONCLUSIONS: We found no evidence that the alpha-tocopherol form of vitamin E given to people with MCI prevents progression to dementia, or that it improves cognitive function in people with MCI or dementia due to AD. However, there is moderate quality evidence from a single study that it may slow functional decline in AD. Vitamin E was not associated with an increased risk of serious adverse events or mortality in the trials in this review. These conclusions have changed since the previous update, however they are still based on small numbers of trials and participants and further research is quite likely to affect the results.
维生素E天然存在于饮食中。它具有多种生物学活性，包括作为抗氧化剂清除有毒自由基。有证据表明自由基可能参与认知障碍背后的病理过程，这引发了人们对使用维生素E补充剂治疗轻度认知障碍（MCI）和阿尔茨海默病（AD）的兴趣。这是Cochrane系统评价的更新版，该评价首次发表于2000年，此前于2006年和2012年进行过更新。
评估维生素E治疗MCI及AD所致痴呆的疗效。
2016年4月22日，我们检索了Cochrane痴呆与认知改善小组专业注册库（ALOIS）、Cochrane图书馆、MEDLINE、Embase、PsycINFO、CINAHL、LILACS以及许多试验数据库和灰色文献来源，检索词为：“Vitamin E”、vitamin-E、alpha-tocopherol。
我们纳入了所有双盲随机试验，这些试验将任何剂量的维生素E治疗与AD或MCI患者的安慰剂进行比较。
我们根据Cochrane干预措施系统评价手册使用标准方法程序。我们采用GRADE方法对证据质量进行评级。在适当情况下，我们试图联系作者以获取缺失信息。
四项试验符合纳入标准，但我们只能按照方案从两项试验中提取结局数据，一项针对AD患者（n = 304），一项针对MCI患者（n = 516）。两项试验的总体偏倚风险均为低到不清楚。由于缺乏可比的结局测量指标，无法对各研究的数据进行合并。
在AD患者中，我们没有发现证据表明维生素E对认知有任何临床上重要的影响，以阿尔茨海默病评估量表认知分量表（ADAS-Cog）从基线开始在6至48个月的变化来衡量（平均差（MD）-1.81，95%置信区间（CI）-3.75至0.13，P = 0.07，1项研究，n = 272；中等质量证据）。在6至48个月内发生至少一次严重不良事件的风险方面，维生素E组和安慰剂组之间没有差异的证据（风险比（RR）0.86，95%CI 0.71至1.05，P = 0.13，1项研究，n = 304；中等质量证据），在死亡风险方面也没有差异（RR 0.84，95%CI 0.52至1.34，P = 0.46，1项研究，n = 304；中等质量证据）。在6至48个月时，接受维生素E的AD患者在阿尔茨海默病协作研究/日常生活活动量表上的功能下降比接受安慰剂的患者少（平均差（MD）3.15，95%CI 0.07至6.23，P = 0.04，1项研究，n = 280；中等质量证据）。在使用神经精神科量表测量的神经精神症状方面，没有证据表明有任何临床上重要的影响（MD -1.47，95%CI -4.26至1.32，P = 0.30，1项研究，n = 280；中等质量证据）。
我们没有发现证据表明维生素E会影响MCI患者在36个月内进展为可能的AD痴呆的概率（RR 1.03，95%CI 0.79至1.35，P = 0.81，1项研究，n = 516；中等质量证据）。在36个月内，维生素E组和安慰剂组各有5例死亡（RR 1.01，95%CI 0.30至3.44，P = 0.99，1项研究，n = 516；中等质量证据）。我们无法按照综述方案提取其他结局的数据。然而研究作者没有发现证据表明维生素E在对认知功能、整体严重程度或日常生活活动的影响方面与安慰剂有差异。在更常见报告的不良事件方面，两组之间也没有差异的证据。
我们没有发现证据表明给予MCI患者α-生育酚形式的维生素E可预防进展为痴呆，或改善MCI患者或AD所致痴呆患者的认知功能。然而，有一项研究的中等质量证据表明它可能减缓AD患者的功能下降。在本综述的试验中，维生素E与严重不良事件风险或死亡率增加无关。自上次更新以来这些结论有所变化，然而它们仍然基于少量试验和参与者，进一步的研究很可能会影响结果。
