School of Medicine and Pharmacology, The University of Western Australia, Perth, Western Australia, Australia.
Stroke. 2013 Aug;44(8):2232-9. doi: 10.1161/STROKEAHA.113.001886. Epub 2013 Jun 13.
High plasma total homocysteine (tHcy) has been associated with cognitive impairment but lowering tHcy with B-vitamins has produced equivocal results. We aimed to determine whether B-vitamin supplementation would reduce tHcy and the incidence of new cognitive impairment among individuals with stroke or transient ischemic attack≥6 months previously.
A total of 8164 patients with stroke or transient ischemic attack were randomly allocated to double-blind treatment with one tablet daily of B-vitamins (folic acid, 2 mg; vitamin B6, 25 mg; vitamin B12, 500 μg) or placebo and followed up for 3.4 years (median) in the VITAmins TO Prevent Stroke (VITATOPS) trial. For this prespecified secondary analysis of VITATOPS, the primary outcome was a new diagnosis of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score<24 on ≥2 follow-up visits. Secondary outcomes were cognitive decline, and the mean tHcy and MMSE at final follow-up.
A total of 3089 participants (38%) voluntarily undertook the MMSE>6 months after the qualifying stroke; 2608 participants were cognitively unimpaired (MMSE≥24), of whom 2214 participants (1110 B-vitamins versus 1104 placebo) had follow-up MMSEs during 2.8 years (median). At final follow-up, allocation to B-vitamins, compared with placebo, was associated with a reduction in mean tHcy (10.2 μmol/L versus 14.2 μmol/L; P<0.001) but no change from baseline in the mean MMSE score (-0.22 points versus -0.25 points; difference, 0.03; 95% confidence interval, -0.13 to 0.19; P=0.726) and no difference in the incidence of cognitive impairment (5.51% versus 5.47%; risk ratio, 1.01; 95% confidence interval, 0.69-1.48; P=0.976), cognitive decline (9.1% versus 10.3%; risk ratio, 0.89; 0.67-1.18; P=0.414), or cognitive impairment or decline (11.0% versus 11.3%; risk ratio, 0.98; 0.75-1.27; P=0.855).
Daily supplementation with folic acid, vitamin B6, and vitamin B12 to a self-selected clinical trial cohort of cognitively unimpaired patients with previous stroke or transient ischemic attack lowered mean tHcy but had no effect on the incidence of cognitive impairment or cognitive decline, as measured by the MMSE, during a median of 2.8 years.
URL: http://www.controlled-trials.com. Unique identifier: ISRCTN74743444; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00097669.
血浆总同型半胱氨酸（tHcy）升高与认知障碍有关，但用 B 族维生素降低 tHcy 的效果尚无定论。我们旨在确定 B 族维生素补充是否会降低 tHcy，并降低先前发生过卒中或短暂性脑缺血发作≥6 个月患者新发认知障碍的发生率。
共有 8164 例卒中或短暂性脑缺血发作患者随机分配至每日服用 1 片 B 族维生素（叶酸 2 mg，维生素 B6 25 mg，维生素 B12 500 μg）或安慰剂的双盲治疗，在 VITAmins TO Prevent Stroke（VITATOPS）试验中中位随访 3.4 年。本项 VITATOPS 的预设次要分析中，主要结局是新诊断为认知障碍，定义为 Mini-Mental State Examination（MMSE）评分在≥2 次随访中＜24 分。次要结局为认知衰退以及最终随访时的平均 tHcy 和 MMSE 评分。
共有 3089 例（38%）参与者在符合条件的卒中后≥6 个月自愿接受了 MMSE 检查；2608 例认知未受损（MMSE≥24），其中 2214 例（1110 例 B 族维生素组与 1104 例安慰剂组）在中位 2.8 年的时间内进行了 MMSE 随访。在最终随访时，与安慰剂相比，B 族维生素治疗组的平均 tHcy 降低（10.2 μmol/L 比 14.2 μmol/L；P＜0.001），但 MMSE 基线评分无变化（-0.22 分比-0.25 分；差值 0.03；95%置信区间 0.130.19；P=0.726），认知障碍的发生率也无差异（5.51%比 5.47%；风险比 1.01；95%置信区间 0.691.48；P=0.976）、认知衰退（9.1%比 10.3%；风险比 0.89；95%置信区间 0.671.18；P=0.414）或认知障碍或衰退（11.0%比 11.3%；风险比 0.98；95%置信区间 0.751.27；P=0.855）也无差异。
在认知未受损且先前发生过卒中或短暂性脑缺血发作的自我选择临床试验队列中，每日补充叶酸、维生素 B6 和维生素 B12 可降低平均 tHcy，但在中位 2.8 年的时间内，用 MMSE 测量时，对认知障碍或认知衰退的发生率没有影响。
