Previous research has shown that raised blood levels of the amino acid homocysteine are associated with increased risk of cognitive impairment and of Alzheimer’s disease. Intake of B12, folic acid and vitamin B6 can lower the levels of homocysteine.
University of Oxford researchers, led by David Smith, Professor Emeritus of Pharmacology, have now found that the subgroup of participants with Mild Cognitive Impairment who had raised blood levels of homocysteine, suffered a rapid rate of shrinkage (atrophy) of particular regions of the brain. This accelerated atrophy was markedly slowed in those who were given the B vitamins and the specific regions protected by the B-vitamin treatment are the same as those that show atrophy in Alzheimer’s disease.
This new analysis was carried out by Dr Gwenaëlle Douaud, in collaboration with Professor Stephen Smith, at the Functional Magnetic Resonance Imaging of the Brain (FMRIB) Centre in Oxford. Dr Douaud showed that the atrophy of these specific regions of the brain was linked to cognitive decline in several different tests on the 156 participants in this study. In order to see if there were causal links between vitamin B treatment and change in cognition, the authors demonstrated how, in those 77 participants with high homocysteine levels, B vitamins (and particularly B12) lowered homocysteine levels, which then slowed the atrophy of the specific brain regions leading to less cognitive decline.
Professor David Smith and his team have previously shown that high levels of homocysteine and low levels of vitamin B12 were both related to a faster shrinkage of the whole brain (global atrophy). An earlier report from the VITACOG trial showed that B vitamin treatment could slow global brain atrophy by up to 50 per cent, but this new report shows that the beneficial effect is largely localised to the Alzheimer-vulnerable areas of the brain. In this latest study, the atrophy rate of these areas of the brain was nearly 90 per cent slower in those with high homocysteine who took B vitamins, compared to the placebo group. The authors also found that those subjects who already had low levels of homocysteine did not benefit from taking the B vitamins as they showed a lower rate of atrophy in the parts of the brain associated with cognitive impairment and Alzheimer’s.
According to Professor David Smith, the new research gives hope that ways will eventually be found to prevent Alzheimer’s disease. He said:
“Our work shows that a key part of the disease process that leads to Alzheimer’s disease, the atrophy of specific brain regions, might be modified by a safe and simple intervention. This needs to be followed up by trials to see if the same intervention can prevent a subgroup (those with high homocysteine) of those with Mild Cognitive Impairment from developing Alzheimer’s disease. We hope that the outcome of this trial will encourage many more studies on the identification of modifiable risk factors for Alzheimer’s disease, now that we have established that in principle a crucial element of the disease, loss of specific brain tissue, might largely be prevented.”
Professor Hugh Perry, Chairman of the MRC’s Neurosciences and Mental Health Board, said:
“We already know that low levels of B vitamins are associated with cognitive impairment. This study adds to that knowledge and shows that high doses of these vitamins – particularly B12 – can lower homocysteine levels and reduce the rate of atrophy of those specific parts of the brain related to Alzheimer’s. The challenge now is to identify the mechanisms by which lower homocysteine influences brain atrophy and to study larger cohorts of patients in trials to confirm that progression to dementia really can be slowed down.”
Dr Eric Karran, Director of Research at Alzheimer’s Research UK, said:
“Very few clinical trials have looked at the effect of B vitamins on people with memory impairments and those that have report mixed results. The VITACOG study was one of the largest studies to look at B vitamins in people with memory problems and so it is good to see as much data being drawn from this study as possible.
“While the VITACOG trial showed that B vitamins slowed brain shrinkage in people with mild cognitive impairment and high homocysteine, it is too early to know whether these effects mean someone is less likely to develop dementia in the long term. It is also not clear from other research in this area whether B vitamins would have any benefit for those who already have dementia. Until further trials have confirmed these findings, we would recommend people think about eating a healthy and balanced diet. Controlling weight and blood pressure, as well as taking exercise, are also ways that we can help to keep our brains healthy as we get older.”
The research is published in Proceedings of the National Academy of Sciences.
Notes to editors
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- Mild Cognitive Impairment (MCI) is found in about 16% of those over the age of 70. About a third of those with MCI develop Alzheimer’s disease within 5 years.
- Douaud G, et al. Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proceedings of the National Academy of Sciences, USA. Early Edition
- The VITACOG trial was part-funded by the MRC Brain Sciences Trial Platform. Other support came from the Charles Wolfson Charitable Trust, Alzheimer’s Research UK, Henry Smith Charity, John Coates Charitable Trust, Thames Valley Dementias and Neurodegenerative Diseases Research Network of the National Institute for Health Research (UK), Sidney and Elizabeth Corob Charitable Trust and Meda AB/Recip (Solna, Sweden).