Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: A randomized controlled trial

OPTIMA, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
International Journal of Geriatric Psychiatry (Impact Factor: 2.87). 06/2012; 27(6):592-600. DOI: 10.1002/gps.2758
Source: PubMed


Homocysteine is a risk factor for Alzheimer's disease. In the first report on the VITACOG trial, we showed that homocysteine-lowering treatment with B vitamins slows the rate of brain atrophy in mild cognitive impairment (MCI). Here we report the effect of B vitamins on cognitive and clinical decline (secondary outcomes) in the same study.
This was a double-blind, single-centre study, which included participants with MCI, aged ≥ 70 y, randomly assigned to receive a daily dose of 0.8 mg folic acid, 0.5 mg vitamin B(12) and 20 mg vitamin B(6) (133 participants) or placebo (133 participants) for 2 y. Changes in cognitive or clinical function were analysed by generalized linear models or mixed-effects models.
The mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo. B vitamins stabilized executive function (CLOX) relative to placebo (P = 0.015). There was significant benefit of B-vitamin treatment among participants with baseline homocysteine above the median (11.3 µmol/L) in global cognition (Mini Mental State Examination, P < 0.001), episodic memory (Hopkins Verbal Learning Test-delayed recall, P = 0.001) and semantic memory (category fluency, P = 0.037). Clinical benefit occurred in the B-vitamin group for those in the upper quartile of homocysteine at baseline in global clinical dementia rating score (P = 0.02) and IQCODE score (P = 0.01).
In this small intervention trial, B vitamins appear to slow cognitive and clinical decline in people with MCI, in particular in those with elevated homocysteine. Further trials are needed to see if this treatment will slow or prevent conversion from MCI to dementia.

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    • "A recent clinical cohort trial found that plasma homocysteine levels are inversely related to cognitive performance, but no evidence of a significant protection of high plasma folate against dementia was found (Morris et al., 2012). However, B12- and B6-vitamin treatment has been demonstrated to stabilize performance on the CLOX test (Royall et al., 1998) as well as on executive and planning function (De Jager et al., 2012). Kado et al. (2005) and colleagues demonstrated that folate, but not cobalamin levels, are independently predictive of cognitive decline over a 7-year period in high functioning old people. "
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    • "To describe this critical level of brain shrinkage on cognitive performance, novel data analysis comparing the measures of brain shrinkage at the end of the VITACOG trial with certain cognitive scores collected at a number of time points over the 2 years has been performed. The rate of brain volume change was measured as described previously (Smith et al., 2010), and the cognitive measures (Telephone Inventory for Cognitive StatusdModified [TICS- M] and Hopkins Verbal Learning TestdDelayed Recall [HVLT-DR]) are described in de Jager et al. (2012) (supplementary appendix). When these measures were analyzed by quartiles for rate of brain shrinkage for all the trial participants with 2 magnetic resonance imaging scans (n ¼ 168), it was found that those who had the fastest brain shrinkage showed the most cognitive decline (Fig. 2A and B). "
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    • "). Nonetheless, the efficacy of B-vitamins is not yet settled; in an Oxford University study of older individuals with elevated homocysteine levels and mild cognitive impairment, supplementation with these 3 vitamins maintained memory performance and reduced the rate of brain atrophy (de Jager et al., 2012; Douaud et al., 2013; Smith, 2010). Healthful sources of folate include leafy green vegetables, such as broccoli, kale, and spinach, beans, peas, citrus fruits, and cantaloupe . "
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