Vitamin B clue to dementia

“Vitamin B tablets could slow and even halt the devastating march of Alzheimer's disease,” The Daily Telegraph reported. According to the newspaper, large daily doses of vitamin B can halve the rate of brain shrinkage, a process that can precede Alzheimer’s disease and dementia.

This story is based on a well-conducted two-year trial, which compared vitamin B pills with inactive placebo pills in 271 elderly people with mild memory problems. The study found that those given vitamin B experienced brain shrinkage (atrophy) 30% slower than those given inactive tablets. However, slower brain shrinkage may not necessarily lead to any improvement in symptoms.

This research does not show that vitamin B can prevent Alzheimer’s disease or dementia because there is no evidence to confirm that slower brain shrinkage will lead to benefits for people with early dementia symptoms. Nevertheless, these results are promising and clearly warrant more research.

Where did the story come from?

The study was carried out by researchers from the University of Oxford, the Oxford Radcliffe Hospitals NHS Trust and the University of Oslo in Norway.

The study received funding from a number of sources, including the Charles Wolfson Charitable Trust, the Medical Research Council, the Alzheimer’s Research Trust and the National Institute for Health Research. It was published in PLoS One, the peer-reviewed journal of the Public Library of Science.

Newspapers generally covered the research in a balanced way, although the headlines are overly optimistic in proclaiming that vitamin B will delay or beat Alzheimer’s disease. A diagnosis of Alzheimer’s is based on specific, characteristic clinical features and the exclusion of other causes of cognitive impairment. However, this research only assessed an outcome of brain shrinkage, which is not necessarily the same thing. The functional effects of reducing brain shrinkage were not investigated and it is an extrapolation to conclude that B vitamins improved cognitive health or protected against Alzheimer’s disease.

What kind of research was this?

Brain atrophy, which describes the loss of neurones and their connections, can be caused by a number of diseases. Some degree of atrophy and subsequent brain shrinkage is common with old age, even in people who are cognitively healthy. However, this brain shrinkage is accelerated in people with mild cognitive impairment and even faster in those who ultimately progress from mild cognitive impairment to Alzheimer’s disease. A range of factors has been implicated in affecting the rate of brain atrophy, one of which is high levels of an amino acid in the blood called homocysteine (tHcy). Studies have shown that raised levels of tHcy increase the risk of Alzheimer’s disease.

In this randomised controlled trial, the researchers investigated the role of vitamin B in regulating levels of tHcy. They specifically wanted to test whether lowering tHcy through giving high doses of vitamin B for two years could reduce the rate of brain atrophy in people with pre-existing mild cognitive impairment.

What did the research involve?

Volunteers aged 70 and over with concerns about their memory were recruited in the Oxford area, through radio and newspaper advertisements, between April 2004 and November 2006. It was specified that volunteers should have a diagnosis of mild cognitive impairment, defined using specific criteria. These included a concern about memory that did not interfere with activities of daily living and pre-specified scores on some cognitive scales assessing word recall and fluency. The study excluded people with a diagnosis of dementia, who were taking anti-dementia drugs or who had active cancer. People taking folic acid and vitamin B6 or B12 above certain doses were also excluded.

Every six months, the volunteers were randomly assigned to receive either high-dose oral vitamin B tablets (0.8 mg folic acid, 0.5 mg vitamin B12 and 20 mg vitamin B6) or placebo pills during the two-year period. The participants, their partners and all staff directly involved in the study were unaware which pills were being received. The double blind nature of the study was important as it eliminated potential biases associated with the patients’ or researchers’ knowledge of which treatment was being received. MRI scans were performed at the start of the study and again after two years. The researchers used these to calculate the rate of brain atrophy each year.

A total of 271 people were randomly assigned a treatment, although five did not start the study. A similar proportion from each treatment group dropped out along the course of the study. The researchers measured adherence to the study treatments by counting returned tablets. For the main analysis of brain shrinkage, the researchers used data on 168 people (85 receiving active treatment and 83 receiving placebo) who had completed an MRI at both the start and at follow-up. The analyses took into account a variety of factors that may be linked to brain atrophy or use of vitamin B, which the researchers had tested and found to be important. These factors were age, blood pressure, initial brain volume and concentration of tHcy at the start of the study.

What were the basic results?

Treatment with vitamin B tablets had notable effects on the levels of tHcy in the blood, reducing it by 22.5%. Levels of tHcy increased by 7.7% in the placebo group. Overall, treatment with B vitamins for a period of 24 months led to a reduction in the rate of brain atrophy. After the age of the participants was taken into account, the rate of shrinkage in people receiving the vitamins was 30% less than in the placebo group (0.76% shrinkage and 1.08% shrinkage respectively). The effect was greater in people who were more compliant with taking their medication and in those who started with the highest levels of tHcy. The researchers also found that, overall, the safety of vitamins was good with no adverse events.

How did the researchers interpret the results?

The researchers concluded that they have shown that a “simple and safe treatment” can slow down the accelerated rate of brain atrophy in people with mild cognitive impairment.

Conclusion

This is an important but early study in establishing the effects of vitamin B on the stages of brain atrophy that precede Alzheimer’s disease. It assessed the effects of the vitamin on the rate of brain shrinkage, a process that has been linked to old age, mild cognitive impairment and Alzheimer’s disease in other studies. Although other studies have found that the rate of brain atrophy is linked to cognitive decline, this particular study did not assess whether the participants’ brain changes translated into changes of cognitive ability or memory.

This was a well-conducted, albeit small, study. It was a randomised controlled trial, which is the most appropriate way to assess the effects of a new treatment. No study is perfect, though, and the researchers highlighted some shortcomings:

• The treatment was a combination of three B vitamins, so the researchers could not determine whether these have different effects individually.
• The study was not set up to assess the effects of treatment on cognition, but only on the rate of change in brain measurements.

This study will pave the way for future research into the use of vitamin B to prevent Alzheimer’s disease. Based on the evidence gathered so far, it is too early to claim that vitamin B can prevent clinical disease, but these results are promising. More research will undoubtedly follow.