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.
"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. "
[Show abstract][Hide abstract] ABSTRACT: Several chemical substances belonging to classes of natural dietary origin display protective properties against some age-related diseases including neurodegenerative ones, particularly Alzheimer's disease (AD). These compounds, known as nutraceuticals, differ structurally, act therefore at different biochemical and metabolic levels and have shown different types of neuroprotective properties. The aim of this review is to summarize data from observational studies, clinical trials, and randomized clinical trials (RCTs) in humans on the effects of selected nutraceuticals against age-related cognitive impairment and dementia. We report results from studies on flavonoids, some vitamins and other natural substances that have been studied in AD and that might be beneficial for the maintenance of a good cognitive performance. Due to the substantial lack of high-level evidence studies there is no possibility for recommendation of nutraceuticals in dementia-related therapeutic guidelines. Nevertheless, the strong potential for their neuroprotective action warrants further studies in the field.
Frontiers in Pharmacology 06/2014; 5:147. DOI:10.3389/fphar.2014.00147 · 3.80 Impact Factor
"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). "
[Show abstract][Hide abstract] ABSTRACT: Few B-vitamin trials to lower homocysteine (Hcy) have reported evidence of beneficial effects on cognition in older adults with cognitive impairment or Alzheimer's disease. This article reviews the role of Hcy in cognitive decline. It also considers some reasons why meta-analyses have failed to find effects of B-vitamin treatment. Findings from the successful VITACOG trial are examined from a new perspective of critical levels of Hcy and brain atrophy that may impact on the efficacy of B-vitamin treatment. It appears that there is a critical level of brain shrinkage, possibly mediated by elevated Hcy, which when reached, results in cognitive decline, especially in episodic memory performance. Supplements, food sources, and effects of folic acid fortification are discussed in relation to B12 deficiency.
Neurobiology of Aging 05/2014; 35. DOI:10.1016/j.neurobiolaging.2014.03.040 · 5.01 Impact Factor
"). 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 . "
[Show abstract][Hide abstract] ABSTRACT: Risk of developing Alzheimer's disease is increased by older age, genetic factors, and several medical risk factors. Studies have also suggested that dietary and lifestyle factors may influence risk, raising the possibility that preventive strategies may be effective. This body of research is incomplete. However, because the most scientifically supported lifestyle factors for Alzheimer's disease are known factors for cardiovascular diseases and diabetes, it is reasonable to provide preliminary guidance to help individuals who wish to reduce their risk. At the International Conference on Nutrition and the Brain, Washington, DC, July 19-20, 2013, speakers were asked to comment on possible guidelines for Alzheimer's disease prevention, with an aim of developing a set of practical, albeit preliminary, steps to be recommended to members of the public. From this discussion, 7 guidelines emerged related to healthful diet and exercise habits.
Neurobiology of Aging 05/2014; 35. DOI:10.1016/j.neurobiolaging.2014.03.033 · 5.01 Impact Factor
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