Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial
Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial
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DOI：
10.1016/s1474-4422(17)30040-6
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发表时间：
2017-05-01
期刊：
影响因子：
48
通讯作者：
Vellas, Bruno
中科院分区：
文献类型：
--
作者：
Andrieu, Sandrine;Guyonnet, Sophie;Vellas, Bruno
背景与安慰剂相比，目前还没有进行大型试验来研究一种特定化合物和几种生活方式干预相结合的干预措施在预防认知衰退方面的有效性。与安慰剂相比，我们测试了补充omega 3多不饱和脂肪酸和多领域干预(体力活动、认知训练和营养建议)单独或联合使用对认知下降的影响。方法多领域阿尔茨海默病预防试验是一项为期3年的多中心、随机、安慰剂对照的优势试验，在法国和摩纳哥的13个记忆中心有4个平行小组。参与者是非痴呆的，年龄在70岁或以上，居住在社区，他们要么向医生传达了自发的记忆抱怨，要么是日常生活中一种工具性活动的限制，要么是步态缓慢。他们被随机分配(1：1：1：1)接受多领域干预(43次结合认知训练、体力活动和营养的小组会议，以及3次预防性会诊)加omega 3多不饱和脂肪酸(即每天两粒胶囊，每天总剂量为800毫克二十二碳六烯酸和225毫克二十碳五烯酸)，多领域干预+安慰剂，单独使用omega 3多不饱和脂肪酸，或仅使用安慰剂。计算机生成的随机程序被用来按中心对患者进行分层。所有参与者和研究人员对多不饱和脂肪酸或安慰剂的分配是盲目的，但对多域干预成分是非盲目的。对认知结果的评估是由独立的神经心理学家完成的，他们对小组分配视而不见。主要结果是在改良的意向治疗人群中，结合四项认知测试(自由和线索选择性提醒测试的自由和全面回忆、十个简易精神状态检查定向项目、数字符号替代测试和类别命名测试)的综合Z分从基线改变到36个月。该试验在ClinicalTrials.gov(NCT00672685)上注册。结果在2008年5月30日至2011年2月24日期间随机分配了1680名参与者。在修改的意向治疗人群(n=1525)中，三个干预组中的任何一个组与安慰剂组之间的3年认知下降没有显著差异。与安慰剂相比，联合干预组的组间差异为0.093(95%可信区间为0.001至0.184；调整后的p=0.142)，多域干预加安慰剂组为0.079(-0.012至0.170；0.179)，omega 3多不饱和脂肪酸组为0.011(-0.081至0.103；0.812)。多域加多不饱和脂肪酸组146人(36%)，多域加安慰剂组142人(34%)，多不饱和脂肪酸组134人(33%)，安慰剂组133人(32%)至少有一次严重的新出现的不良事件。记录了4例与治疗相关的死亡(2例在多领域加安慰剂组，2例在安慰剂组)。这些干预措施没有引起任何安全问题，在严重或其他不良事件中，两组之间也没有差异。解释说，多领域干预和多不饱和脂肪酸单独或联合使用，在3年内对有记忆障碍的老年人的认知能力下降没有显著影响。预防或延缓认知障碍和目标人群的有效多领域干预策略仍有待确定，特别是在现实世界的环境中。
Background No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline.Methods The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1: 1: 1: 1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685).Findings 1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0.093 (95% CI 0.001 to 0.184; adjusted p=0.142) for the combined intervention group, 0.079 (-0.012 to 0.170; 0.179) for the multidomain intervention plus placebo group, and 0.011 (-0.081 to 0.103; 0.812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events.Interpretation The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings.