补充抗氧化剂维生素E和硒无法预防预防阿尔茨海默病
氧化应激是一种已被确定的痴呆通路，抗氧化剂被认为能减缓导致记忆认知功能障碍的氧化应激作用，多年来医学界对使用抗氧化剂作为认知障碍与痴呆的潜在疗法一直很感兴趣，但是补充抗氧化剂能否预防痴呆仍然未知。
2017年3月20日，《美国医学会杂志神经病学分册》在线发表肯塔基大学、弗雷德哈钦森癌症研究中心、西雅图癌症研究与生物统计学中心的PREADViSE（维生素E和硒预防阿尔茨海默病）研究报告，发现无论单独使用还是联合使用，补充抗氧化剂维生素E与硒可能都无法预防阿尔茨海默病（老年前期痴呆）。
PREADViSE是SELECT（硒和维生素E癌症预防试验）的附加研究，SELECT研究是补充硒和维生素E预防前列腺癌的随机临床试验，由于分析结果为无效，于2009年结束。
PREADViSE是首个调查无症状男性补充抗氧化剂与痴呆发生率的长期相关性研究，始于2002年5月，为双盲随机临床试验，从SELECT研究的130个地点共入组7540位年龄≥60岁男性（入组时平均年龄67.5±5.3岁），随机分入4组分别服用维生素E、硒、维生素E＋硒、安慰剂，并分2阶段进行痴呆筛查。2009年9月～2015年5月，PREADViSE转为队列研究，其中3786位男性继续参加。通过电话进行联系，并使用经过改进的2阶段认知筛查进行评定。在两个研究时期，如果筛查结果显示可能认知障碍，则鼓励男性就诊。使用Cox回归比例风险模型进行经过修改的意向治疗分析，比较研究组之间的风险比。
结果发现，3936人（52.2%）受过高等教育，754人（10.0%）为黑人，505人（6.7%）为西班牙裔。排除失访的201人后，其余7338位男性有325人发生痴呆，占4.4%，4个研究组无显著差异（与安慰剂相比，维生素E、硒、维生素E＋硒的校正风险比分别为0.88、0.83、1.00，95%置信区间分别为0.64～1.20、0.60～1.13、0.75～1.35，P值分别为0.41、0.23、0.98）。
因此，补充维生素E、硒均不能预防痴呆，不建议将这些抗氧化剂作为预防痴呆的营养补充剂。
对此，佛罗里达大学、南加利福尼亚大学的学者发表同期评论：预防痴呆的问题很多、时间不够。
JAMA Neurol. 2017 Mar 20. [Epub ahead of print]
Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer's Disease by Vitamin E and Selenium Trial (PREADViSE).
Kryscio RJ, Abner EL, Caban-Holt A, Lovell M, Goodman P, Darke AK, Yee M, Crowley J, Schmitt FA.
University of Kentucky, Lexington; Fred Hutchinson Cancer Research Center, Seattle, Washington; Cancer Research and Biostatistics, Seattle, Washington.
QUESTION: Can vitamin E or selenium prevent dementia in asymptomatic older men?
FINDINGS: The Prevention of Alzheimer's Disease by Vitamin E and Selenium trial initially enrolled 7540 elderly men who were exposed to the supplements for an average of 5.4 years; a subset of 3786 men agreed to be observed for up to 6 additional years. Dementia incidence (4.4%) did not differ among the 4 study arms.
MEANING: Neither supplement is recommended as a preventive agent for dementia.
IMPORTANCE: Oxidative stress is an established dementia pathway, but it is unknown if the use of antioxidant supplements can prevent dementia.
OBJECTIVE: To determine if antioxidant supplements (vitamin E or selenium) used alone or in combination can prevent dementia in asymptomatic older men.
DESIGN, SETTING, AND PARTICIPANTS: The Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADViSE) trial began as a double-blind randomized clinical trial in May 2002, which transformed into a cohort study from September 2009 to May 2015. The PREADViSE trial was ancillary to the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized clinical trial of the same antioxidant supplements for preventing prostate cancer, which closed in 2009 owing to findings from a futility analysis. The PREADViSE trial recruited 7540 men, of whom 3786 continued into the cohort study. Participants were at least 60 years old at study entry and were enrolled at 130 SELECT sites, and Cox proportional hazards models were used in a modified intent-to-treat analysis to compare hazard rates among the study arms.
INTERVENTIONS: Participants were randomized to vitamin E, selenium, vitamin E and selenium, or placebo. While taking study supplements, enrolled men visited their SELECT site and were evaluated for dementia using a 2-stage screen. During the cohort study, men were contacted by telephone and assessed using an enhanced 2-stage cognitive screen. In both phases, men were encouraged to visit their physician if the screen results indicated possible cognitive impairment.
MAIN OUTCOMES AND MEASURES: Dementia case ascertainment relied on a consensus review of the cognitive screens and medical records for men with suspected dementia who visited their physician for an evaluation or by review of all available information, including a functional assessment screen.
RESULTS: The mean (SD) baseline age of the 7540 participants was 67.5 (5.3) years, with 3936 (52.2%) reporting a college education or better, 754 (10.0%) reporting black race, and 505 (6.7%) reporting Hispanic ethnicity. Dementia incidence (325 of 7338 men [4.4%]) was not different among the 4 study arms. A Cox model, which adjusted incidence for participant demographic information and baseline self-reported comorbidities, yielded hazard ratios of 0.88 (95% CI, 0.64-1.20) for vitamin E, 0.83 (0.60-1.13) for selenium, and 1.00 (0.75-1.35) for the combination compared with placebo.
CONCLUSIONS AND RELEVANCE: Neither supplement prevented dementia. To our knowledge, this is the first study to investigate the long-term association of antioxidant supplement use and dementia incidence among asymptomatic men.
PMID: 28319243
DOI: 10.1001/jamaneurol.2016.5778
JAMA Neurol. 2017 Mar 20. [Epub ahead of print]
Preventing Dementia: Many Issues and Not Enough Time.
DeKosky ST, Schneider LS.
McKnight Brain Institute, Florida Alzheimer's Disease Research Center, Department of Neurology, University of Florida, Gainesville; Alzheimer's Disease Research Center, Departments of Psychiatry and the Behavioral Sciences and Neurology, Keck School of Medicine of the University of Southern California, Los Angeles.
PMID: 28319236
DOI: 10.1001/jamaneurol.2017.0045