Kang JH, Cook N, Manson J, Buring JE, Albert CM, Grodstein F. A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. Am J Clin Nutr 88, 1602-1610

Channing Laboratory, Boston, MA 02115, USA.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 01/2009; 88(6):1602-10. DOI: 10.3945/ajcn.2008.26404
Source: PubMed


High homocysteine concentrations may be neurotoxic and contribute to cognitive decline in older persons.
The objective was to examine the effect of supplementation with folic acid, vitamin B-12, and vitamin B-6 on cognitive change in women with cardiovascular disease (CVD) or CVD risk factors.
The Women's Antioxidant and Folic Acid Cardiovascular Study is a randomized placebo-controlled trial designed to test the effect of a combination of B vitamins (2.5 mg folic acid/d, 50 mg vitamin B-6/d, and 1 mg vitamin B-12/d) on secondary prevention of CVD. Female health professionals aged >or=40 y (n = 5442) with CVD or >or=3 coronary risk factors in 1998 (after folic acid fortification began in the United States) were randomly assigned to treatment. Shortly after randomization (mean: 1.2 y), a substudy of cognitive function was initiated among 2009 participants aged >or=65 y. Telephone cognitive function testing was administered up to 4 times over 5.4 y with 5 tests of general cognition, verbal memory, and category fluency. Repeated-measures analyses were conducted, and the primary outcome was a global composite score averaging all test results.
Mean cognitive change from baseline did not differ between the B vitamin and placebo groups (difference in change in global score: 0.03; 95% CI: -0.03, 0.08; P = 0.30). However, supplementation appeared to preserve cognition among women with a low baseline dietary intake of B vitamins.
Combined B vitamin supplementation did not delay cognitive decline among women with CVD or CVD risk factors. The possible cognitive benefits of supplementation among women with a low dietary intake of B vitamins warrant further study.

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Available from: Jae H Kang, Nov 26, 2014
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    • "The authors do not report any data relating to cognitive performance. In one of the longest treatment studies, Kang et al. [39] utilised a placebo-controlled design to investigate the effects of B vitamin supplementation (comprising 2.5 mg B9, 1 mg of B12, and 50 mg of B6) in two thousand and nine elderly (mean age 72 years) women with cardiovascular disease and CVD risk factors (1002 allocated to treatment group) over a five-and-half-year period using a telephone cognitive battery measuring (1) general cognition (Telephone Interview of Cognitive Status (TICS)), (2) verbal memory (delayed recall of the TICS 10-word list and the immediate and delayed recalls of the East Boston Memory Test), and (3) category fluency (asked to name as many animals as possible in 1 minute). Results revealed no effect of treatment. "
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    ABSTRACT: A copious amount of scientific scrutiny has been dedicated to documenting typical and atypical human ageing, with a substantial body of work focusing upon the impact of lifestyle choices. One such lifestyle choice is that of diet and, in particular, micronutrient ingestion. Epidemiological studies have reported positive associations between B vitamin status and cognitive function, including negative associations between biological markers (i.e., homocysteine) of dysregulated one-carbon metabolism and cognitive function. This has led to a surge of randomised control trials (RCTs) investigations into B vitamin therapy. However, results have continuingly failed to show beneficial behavioural effects. Despite this, results reliably show treatment-related increases in B vitamin level and decreases in homocysteine level—both of which have been identified as risk factors for atypical ageing. In this paper we argue that it would be premature to conclude that B vitamin therapy has no potential and that more research is needed to systematically investigate the optimal dose, the therapeutic “window,” and individual differences in therapy responders and nonresponders. We start with a brief look at one-carbon metabolism and then consider the evidence from epidemiological studies and RCTs in relation to three specific B vitamins: folic acid (B9), pyridoxine (B6), and cobamides (B12).
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    • "Previous studies of the effect of the main agents on cognitive change found that neither the antioxidant supplementation (Kang et al., 2009) nor the B vitamin supplementation (Kang et al., 2008) was significantly associated with a slowing down of cognitive change in women with preexisting cardiovascular disease or risk factors. "
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    ABSTRACT: Dietary fat intake may influence the rate of cognitive change among those at high risk due to vascular disease or risk factors. Women's Antioxidant Cardiovascular Study began in 1995-1996 as a randomized trial of antioxidants and B vitamin supplementation for secondary prevention in women with cardiovascular disease or ≥3 coronary risk factors. From 1998-1999, eligible participants aged ≥65 years were administered a telephone cognitive battery including five tests of general cognition, memory and category fluency (n=2551). Tests were administered four times over 5.4 years. The primary outcome was a global composite score averaging z-scores of all tests. Multivariable generalized linear models for repeated measures were used to evaluate the difference in cognitive decline rates across tertiles of total fat and various types of fat. Total fat intake or different types of fat were not related to cognitive decline. However, older age significantly modified the association: among the oldest participants, higher intakes of mono- and polyunsaturated fat were inversely related to cognitive decline (P-interaction: 0.06 and 0.04, respectively), and the rate differences between the highest and lowest tertiles were cognitively equivalent to the rate differences observed with being 4-6 years younger. In women at high risk of cognitive decline due to vascular disease or risk factors, dietary fat intake was not associated with 5-year cognitive change. However, a possible protective relation of unsaturated fats with cognitive decline in the oldest women warrants further study.
    Full-text · Article · Oct 2010 · European journal of clinical nutrition
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    • "The total number of participants varied from 185 to 2009 per study. Patients were mostly selected on elevated serum total homocysteine levels (≥13 or ≥15 mmol/L), apart from the studies by Stott et al42 and Kang et al43 in which homocysteine levels were not specificed and only patients with high risk of cardiovascular disease (ischemic heart disease, TIA/stroke, peripheral arterial disease) were included. In the substudy by Viswanathan and colleagues,44 150 participants from each treatment arm of the original VISP study with the highest plasma homocysteine levels and who did not have a stroke during follow-up were post-hoc included for analysis of cognitive function. "
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    ABSTRACT: Over the last decade, evidence has accumulated that vascular risk factors increase the risk of Alzheimer disease (AD). So far, few randomized controlled trials have focused on lowering the vascular risk profile to prevent or postpone cognitive decline or dementia. To systematically perform a review of randomized controlled trials (RCTs) evaluating drug treatment effects for cardiovascular risk factors on the incidence of dementia or cognitive decline. RCTs studying the effect of treating hypertension, dyslipidemia, hyperhomocysteinemia, obesity, or diabetes mellitus (DM) on cognitive decline or dementia, with a minimum follow-up of 1 year in elderly populations. Cognitive decline or incident dementia. In the identified studies, dementia was never the primary outcome. Statins (2 studies) and intensified control of type II DM (1 study) appear to have no effect on prevention of cognitive decline. Studies on treatment of obesity are lacking, and the results of lowering homocysteine (6 studies) are inconclusive. There is some evidence of a preventive effect of antihypertensive medication (6 studies), but results are inconsistent. The evidence of a preventive treatment effect aimed at vascular risk factors on cognitive decline and dementia in later life is scarce and mostly based on secondary outcome parameters. Several important sources of bias such as differential dropout may importantly affect interpretation of trial results.
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