Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of certain B vitamins -- folic acid, vitamin B6 and vitamin B12.
The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. which are cofactors or substrates for enzymes involved in homocysteine metabolism
Sixteen percent of people over the age of 70 have mild cognitive impairment, experiencing problems with memory, language, or other mental functions, but not to a degree that interferes with daily life. And half of these develop Alzheimer's disease within five years of diagnosis.
In elderly, the brain shows significant progressive atrophy. The atrophy occurs even in cognitively healthy subjects but is much accelerated in patients suffering from Alzheimer's disease. An intermediate rate of atrophy is found in people with mild cognitive impairment (MCI).
Since the rate of brain atrophy is more rapid in subjects with MCI who convert to Alzheimer's disease, it is important to identify factors that determine the rate of atrophy since reducing the rate of atrophy is likely to slow the conversion to Alzheimer's disease.
One factor that determine the rate of atrophy appears to be raised concentrations of plasma total homocysteine (tHcy). Moderately elevated concentrations of tHcy have been associated with an increased risk of dementia, notably Alzheimer's disease, in many cross-sectional and prospective studies. Raised tHcy is also associated with both regional and whole brain atrophy, not only in Alzheimer's disease but also in healthy elderly.
Certain B vitamins -- folic acid, vitamin B6 and vitamin B12 -- are known to control levels of homocysteine in the blood by acting as cofactors or substrates for enzymes involved in metabolism of this amino acid.
So the Oxford Project to Investigate Memory and Ageing (OPTIMA) team set out to determine whether supplementation with B vitamins can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial.
The study followed 168 volunteers aged 70 or over with mild memory problems, half of whom took high dose B vitamin tablets and the other half a placebo tablet. The researchers assessed disease progression in this group by using MRI scans to measure the brain atrophy rate over a two-year period.
The team found that on average the rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001), People with the highest levels of homocysteine benefited most, showing atrophy rates on treatment that were half of those on placebo. Cognitive test scores also revealed that those with the slowest rate of shrinkage scored more strongly.
Conclusions and Significance
The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. No safety issues were found, so it can be concluded that high doses of B vitamins can be used to reduce the rate of atrophy of the brain in elderly people with MCI.
Journal Reference:
Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, et al. (2010) Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS ONE 5(9) FULL TEXT
Homocysteine is an amino acid in the blood. Epidemiological studies have shown that too much homocysteine in the blood (plasma) is related to a higher risk of coronary heart disease, stroke and peripheral vascular disease.
Other evidence suggests that homocysteine may have an effect on atherosclerosis by damaging the inner lining of arteries and promoting blood clots. However, a direct causal link hasn’t been established.
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