Aisen Paul S, Schneider Lon S, Sano Mary, Diaz-Arrastia Ramon, van Dyck Christopher H, Weiner Myron F, Bottiglieri Teodoro, Jin Shelia, Stokes Karen T, Thomas Ronald G, Thal Leon J
Department of Neurosciences, University of California, San Diego, 9500 Gilman Dr, M/C 0949, La Jolla, CA 92093, USA.
JAMA. 2008 Oct 15;300(15):1774-83. doi: 10.1001/jama.300.15.1774.
Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B(6) and B(12). Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline.
To determine the efficacy and safety of B vitamin supplementation in the treatment of AD.
DESIGN, SETTING, AND PATIENTS: A multicenter, randomized, double-blind controlled clinical trial of high-dose folate, vitamin B(6), and vitamin B(12) supplementation in 409 (of 601 screened) individuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B(12), and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States.
Participants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B(6), 1 mg/d of vitamin B(12)] and 40% treated with identical placebo); duration of treatment was 18 months.
Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog).
A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], -2.42 [3.35] in active treatment group vs -0.86 [2.59] in placebo group; P < .001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-cog score during 18 months (0.372 points per month for placebo group vs 0.401 points per month for active treatment group, P = .52; 95% confidence interval of rate difference, -0.06 to 0.12; based on the intention-to-treat generalized estimating equations model), or on any secondary measures. A higher quantity of adverse events involving depression was observed in the group treated with vitamin supplements.
This regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD.
clinicaltrials.gov Identifier: NCT00056225.
阿尔茨海默病（AD）患者的血液同型半胱氨酸水平可能升高，高同型半胱氨酸血症可能通过血管和直接神经毒性机制导致疾病病理生理改变。即使在没有维生素缺乏的情况下，服用高剂量的叶酸、维生素B6和维生素B12补充剂也可降低同型半胱氨酸水平。既往关于B族维生素降低AD患者同型半胱氨酸水平的研究规模或持续时间均不足以评估其对认知功能减退的影响。
确定补充B族维生素治疗AD的疗效和安全性。
设计、地点和患者：一项多中心、随机、双盲对照临床试验，纳入601名经筛查的患者中的409名患有轻度至中度AD（简易精神状态检查表评分在14至26分之间，包括14分和26分）且叶酸、维生素B12和同型半胱氨酸水平正常的个体。该研究于2003年2月20日至2006年12月15日在美国各地的阿尔茨海默病协作研究临床研究点进行。
参与者被随机分配到两组，两组人数不等以增加入组人数（60%接受高剂量补充剂治疗[5毫克/天叶酸、25毫克/天维生素B6、1毫克/天维生素B12]，40%接受相同安慰剂治疗）；治疗持续时间为18个月。
阿尔茨海默病评估量表认知分量表（ADAS-cog）的变化。
共有340名参与者（活性治疗组202名，安慰剂组138名）在服用研究药物期间完成了试验。尽管维生素补充方案有效地降低了同型半胱氨酸水平（活性治疗组平均[标准差]为-2.42[3.35]，安慰剂组为-0.86[2.59]；P<0.001），但对主要认知指标、18个月期间ADAS-cog评分的变化率（安慰剂组每月0.372分，活性治疗组每月0.401分，P = 0.52；率差的95%置信区间为-0.06至0.12；基于意向性治疗广义估计方程模型）或任何次要指标均无有益影响。在接受维生素补充剂治疗的组中观察到更多涉及抑郁的不良事件。
这种高剂量B族维生素补充方案并不能减缓轻度至中度AD患者的认知功能减退。
clinicaltrials.gov标识符：NCT00056225。
