Thursday January 2 2014
Dementia is associated with loss of brain tissue
Research suggests that a daily dose of vitamin E could help people with dementia, BBC News reports.
However, high doses of vitamin E are not safe or suitable for everybody and should not be taken without medical advice.
The BBC reports on a US trial with a group of 613 people with mild to moderate Alzheimer’s disease who were already receiving treatment with widely used medication – acetylcholinesterase inhibitors (AchE inhibitors).
Researchers looked at whether adding daily treatment with either a vitamin E supplement, another Alzheimer’s drug called memantine, or a combination of the two, improved the person’s ability to perform activities of daily living.
In comparison with a placebo, they found that during the average two-year study period people taking vitamin E alone showed slower decline on the activities scale than those taking the placebo. They were able to carry out everyday tasks such as washing and their caregivers reported spending less time looking after them.
There was no significant difference between the memantine and combination groups and the placebo groups.
However, the trial had a large drop-out rate, which might have affected the results.
It’s important to note that people in the trial took vitamin E in very large doses, which may be unsafe for some people and can lead to adverse interaction with other medications.
Further research is required on both the effectiveness and safety of vitamin E before it can be recommended as a treatment for dementia.
Do not take high doses of vitamin E without checking with your GP that it is safe to do so.
Where did the story come from?
The study was carried out by researchers from a number of academic institutions in the US involved in the care of US veterans. It was funded by the US Department of Veterans Affairs Cooperative Studies Program.
The study was published in the peer-reviewed Journal of the American Medical Association.
The study was covered fairly and responsibly by most of the media, with many stories including comments from independent experts in the UK warning about the indiscriminate use of high-dose vitamin E supplements.
But the claim in the Daily Express that “a daily vitamin E pill or a diet rich in nuts and oils could be a cheap and effective way of keeping the mind healthy for years after a diagnosis of dementia” was misleading. The study did not look at the effects of dietary vitamin E on dementia. In this trial, the supplements were taken by a specific group of people already receiving dementia treatment; the supplement doses were far higher than the limits advised by experts here.
Also of note, the treatment had no effect on “the mind” in terms of cognitive function, only on functional ability, such as the ability for participants to wash themselves or go to the toilet.
What kind of research was this?
This was a randomised controlled trial (RCT).
The RCT set out to look at whether vitamin E, a drug called memantine or a combination of both could slow the rate of progression in people with mild or moderate Alzheimer’s disease who were already taking another class of drug for dementia (AchE inhibitors).
In the UK, three AchE inhibitors (donepezil, galantamine and rivastigmine) are recommended for people with mild to moderate Alzheimer's disease who fulfill specific criteria.
Memantine is a different drug that is recommended as an option for people with severe Alzheimer's disease, and for some people with moderate Alzheimer's who cannot take AchE inhibitors.
Combination treatment of memantine with an AchE inhibitor (as used in this trial), is not currently recommended in the UK.
The researchers say that although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer's disease (AD), evidence of their effect in mild to moderate AD is limited.
An RCT is the best way to examine the effect of a particular intervention or treatment on health outcomes. This study was also double blinded, which means neither researchers nor patients knew which treatment “arm” they were allocated to – this reduces the possibility of bias (either conscious or unconscious) in the results.
What did the research involve?
The patients in the trial were recruited from 14 Veterans Affairs medical centres between August 2007 and March 2012. They had all been diagnosed with possible or probable Alzheimer’s disease (AD) of mild to moderate severity, using an internationally accepted assessment of their mental ability. All were taking an AchE inhibitor.
Of the 706 first approached for inclusion, 93 were excluded, either because they did not meet eligibility criteria or refused to take part. The 613 remaining participants were randomly assigned to one of four treatment groups, each with a matching placebo group:
- One group was given a vitamin E supplement (known as alpha tocopherol), taken as an oral dose of 1,000 international units (IU) twice a day.
- One group was given 10mg of memantine twice a day.
- One group was given both vitamin E and memantine, at the same doses as above.
- One group was given an inactive placebo.
Researchers were permitted to adjust doses of both vitamin E and memantine as the trial proceeded, based on how well the treatments were tolerated.
All participants were scheduled for an assessment every six months, for a period ranging from six months to four years.
The main outcome of interest was the effect on functional ability. Using an established tool called the Alzheimer’s Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory, researchers examined the effects of the different treatments on the ability of patients to carry out daily living tasks such as dressing and bathing, independently.
The ADCS-ADL’s total score ranges from 0 to 78, with lower scores indicating worse function. A difference of two points is regarded by clinicians as meaningful because it potentially represents, for example, a loss of the ability to dress or wash independently.
Other outcomes of interest were participants’ cognitive function (such as their memory), the severity of their dementia and the severity of their behavioural problems. These were assessed using a number of widely accepted tools.
The study also used a recognised caregiver activity survey to measure the time caregivers spent assisting the person in six major areas of daily activity, and also a dependence scale which assesses six levels of dependence.
Researchers also recorded any adverse events (AEs) and serious adverse events (SAEs) among each group. They asked caregivers and patients about adverse experiences at each contact. In particular they asked about patients falling, loss of consciousness and symptoms of heart failure. Their questions were based on concerns raised by previous studies of high-dose vitamin E treatment.
Participants had an annual assessment, which included a physical examination, a review of other medications, and a blood test to measure levels of vitamin E and memantine. This last was used to see if patients in the active treatment groups were taking their treatments as prescribed.
The researchers used validated statistical methods to assess the effects of the different treatments.
Their analysis was designed to detect an average difference in four points in the ADCS-ADL inventory, which they say represents an approximate 20% reduction in the annual rate of decline.
This they say, equates to slowing the rate of progression of the disease by nearly six months over the follow-up period.
Because a number of participants either dropped out of the trial or died, the original enrolment period was extended from 3 to 4.5 years and the average follow-up extended from 2.5 to 3 years. This was needed to maintain the power of the study to detect differences in the effects of treatment.
What were the basic results?
People in the study were followed up for an average of 2.27 years. Of the 613 original participants, 256 (42%) did not complete the trial. The most common reasons for non-completion were death and withdrawal of consent.
Over the follow-up period:
- People receiving vitamin E alone declined more slowly in their ability to perform daily tasks than those in the placebo group. The average difference in rate of decline was 3.15 units (95% confidence interval (CI), 0.92 to 5.39). The researchers say this translates into a delay in clinical progression of the disease of 19% per year, or 6.2 months, compared with placebo.
- There was no significant difference between the memantine and combination groups and the placebo group in ability to perform daily tasks.
- Caregivers of those taking vitamin E showed least increase in the time spent caring for these people compared to all other groups.
- There were more serious adverse events in people taking memantine (31 events in 23 participants) or combined memantine and vitamin E (13 events in 11 participants).
- There were no other significant differences in the groups receiving memantine alone or memantine plus vitamin E, compared to placebo.
- None of the treatments had any effect upon rate of decline in cognitive function.
How did the researchers interpret the results?
They say that among people with mild to moderate AD, 2,000 IU of vitamin E a day resulted in a slower functional decline than a placebo treatment. The slower rate of increase in caregiver’s time in the vitamin E group could also have a major effect on informal and direct medical cost, they say.
This was a well-conducted randomised controlled trial with a relatively long follow-up period (average two years). The aim was to see whether adding treatment with either a vitamin E supplement, memantine, or the combination, improved functional ability in people with mild to moderate Alzheimer’s disease. And who were also already receiving treatment with licensed acetylcholinesterase inhibitor drugs.
The study found a small though statistically significant difference in the decline of ability to carry out daily tasks in people taking vitamin E compared to placebo. There was also a corresponding small difference in the time caregivers said they spent helping patients.
Oddly, no significant effect was seen in the group taking vitamin E plus memantine, compared with placebo – a result that researchers were unable to explain. There was also no effect with memantine alone.
However, as the researchers point out, the study had a high drop-out rate, which may have affected the results. A second limitation was the small number of women who took part. It is also worth noting that despite the media’s references to “healthy mind” none of the treatments had any effect on the rate of cognitive decline.
Overall the research suggests that the addition of vitamin E may have modest benefits in terms of functional ability and caregiver burden for people with mild to moderate dementia who are already receiving treatment with AchE inhibitors.
However, further research is required into both the safety and effectiveness of this treatment in people with dementia. It is important to know that the vitamin E used in the trial was a high dose, and previous research has suggested safety risks from using a high dose of vitamin E, such as an increased risk of mortality.
High doses of vitamin E can be harmful and can interact with other medications in ways that could be harmful. It is advisable to talk to your doctor before taking supplements; especially if you are planning to take a high dosage.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.