Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia
Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia
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DOI：
10.1046/j.1365-2796.2003.01154.x
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发表时间：
2003-07-01
影响因子：
11.1
通讯作者：
Richards, S
中科院分区：
文献类型：
--
作者：
Clarke, R;Harrison, G;Richards, S
目标.研究认知功能障碍与血小板活化、活性氧和总同型半胱氨酸水平的关系;评估阿司匹林和维生素补充剂治疗痴呆高危人群的生化疗效。患有痴呆症或轻度认知障碍的人。设计和干预。在一项2 × 2 × 2析因设计试验中，149名痴呆症高危人群随机接受低剂量阿司匹林（81 mg）或安慰剂;叶酸（2 mg）加维生素B12（1 mg）或安慰剂;维生素E（500 mg）加C（200 mg）或安慰剂。参与者在治疗前接受两次就诊，12周后接受一次就诊。主要结果指标。在每次访视时，对参与者的认知功能进行评估，并采集血液进行同型半胱氨酸、叶酸和维生素B12测定，采集尿液进行血小板活化标志物（11-脱氢血栓烷B-2）和活性氧（8-epi-PGF（2 α））测定。治疗前，认知功能与同型半胱氨酸、尿血栓素和异前列腺素呈负相关，且与年龄无关。阿司匹林与11-脱氢血栓烷B-2的中位数降低73%相关（P < 0.001）。B族维生素降低血浆同型半胱氨酸浓度30%（P < 0.0001），抗氧化维生素降低异前列腺素排泄26%（P < 0.1）。治疗对认知功能无影响。阿司匹林和B族维生素可有效减少与痴呆症风险人群认知障碍相关的生化因素。现在需要进行大规模的试验来评估阿司匹林和B族维生素对维持痴呆症风险人群认知功能的相关性。
Objectives. To examine the association of cognitive impairment with platelet activation and reactive oxygen species and total homocysteine levels; and to assess the biochemical efficacy of treatment with aspirin and vitamin supplements in people at high risk of dementia.Subjects. People with dementia or mild cognitive impairment.Design and intervention. In a 2 X 2 X 2 factorial design trial, 149 people at high-risk of dementia were randomized to receive either low-dose aspirin (81 mg) or placebo; and folic acid (2 mg) plus vitamin B12 (1 mg) or placebo; and vitamins E (500 mg) plus C (200 mg) or placebo. Participants were seen twice before and once after 12 weeks of treatment.Main outcome measures. At each visit, participants had their cognitive function assessed and had blood collected for homocysteine, folate and vitamin B12 determination and urine collected for markers of platelet activation (11-dehydro-thromboxane B-2) and reactive oxygen species (8-epi-PGF(2alpha)).Results. Prior to treatment, cognitive function was inversely related with homocysteine and with urinary thromboxane and isoprostane, and these associations were independent of age. Aspirin was associated with a median reduction in 11-dehydrothromboxane B-2 of 73% (P < 0.001). B-vitamins lowered plasma homocysteine concentration by 30% (P < 0.0001) and antioxidant vitamins lowered isoprostane excretion by 26% (P < 0.1). No effect of treatment on cognitive function was detected.Conclusions. Aspirin and B-vitamins were effective in reducing biochemical factors associated with cognitive impairment in people at risk of dementia. Large-scale trials are now required to assess the relevance of aspirin and B-vitamins for the maintenance of cognitive function in people at risk of dementia.