By Jerome Burne
We all agree that Alzheimer’s is a dreadful disease and something has to be done about it because there’s no treatment and it’s costing billions. So prevention would be a good idea, wouldn’t it, especially since if it works it would both cut your risk and save vast amounts of money.
However a severe case of cognitive dissonance (believing in two contradictory ideas simultaneously) is gripping Alzheimer’s charities and experts as to the best way to tackle this epidemic. They declare their allegiance to prevention and extol the benefits of the likes of exercise and healthy eating (without specifying exactly what that involves) along with stopping smoking and keeping your brain busy.
But it seems largely for public show, like the obligatory affirmations of religious faith by American politicians on the campaign trail. The amount spent studying prevention is a few percent of the research budget which is heavily drug based. Not content with outsourcing the search for treatments to drug companies the charities and Department of Health actively seek to discredit and disprove any plausible and serious non-drug lifestyle therapy.
Anger at what the Alzheimer’s charities are doing
A few people who have experienced the hostility to an active engagement in the lifestyle approach fume at this hypocrisy. Most of those for whom Alzheimer’s is a daily reality, however, aren’t even aware of it. They should be.
So I make no apology for writing again about what happened to the Oxford professor of Pharmacology who ran a very proper trial showing that high dose B vitamins could reduce shrinkage in areas of the brain specifically involved in Alzheimer’s by 90%. Was there excitement, congratulations, funding for a follow up? Absolutely not. Instead the result was greeted with a studied lack of interest and the cold shoulder.
Two new developments have strengthened the B vitamins case. One is a review of Alzheimer’s research last month which concluded that we have already poured too much money in to the drug approach and that what needs funding are: ‘preventative strategies throughout life to reduce dementia risk rather than the overemphasis on pharmaceutical interventions.’ Lancet Neurology (behind paywall).
The other is a fascinating and important finding that increases our understanding of what is needed to make the high dose B vitamin supplementation much more targeted and effective.
Non-drug strategies top prevention chart
The Lancet article on why it is time to get serious about dementia prevention set out the percentage benefit the UK population overall would gain from engaging in lifestyle factors known to lower the risk of Alzheimer’s.
- Taking exercise 32%
- Stopping smoking 31%
- Getting some adult education 24%
- Supplementing B vitamins to slow brain shrinkage 22%
- Eating more fatty fish or taking omega 3 supplements 22%
- Dropping your cholesterol 14%
- Lowering your blood pressure 10%)
What jumps out from this small chart is hat behavioural changes are the most effective, followed by providing supplements where there is a deficiency while the fewest bang for your bucks come from lowering biomarkers with drugs. But evidence like this which points to the sensible targets for tackling this public health crisis has been ignored.
Not only has there been no funding to follow up the original B vitamin trial but the response of the NHS and several large charities has been to support trials which seem designed to show that vitamin B doesn’t benefit memory or cognitive decline in any way at all. (For details, see below)
A remarkable result with B vitamins
The B vitamin research was led by David Smith, Emeritus Professor of Pharmacology at Oxford University and published in 2010. The original trial involved 250 people with a condition known as Mild Cognitive Impairment – when your memory and thinking is getting a bit worse, but isn’t yet serious.
It was a randomised controlled trial (RCT); the volunteers were divided randomly into two groups, one of which got high dose B vitamins the other a placebo. The aim was to lower the blood levels of an amino acid – homocysteine – associated with Alzheimer’s. Brain scans on some patients were done at beginning and end.
The remarkable result was that those getting the vitamins had a 90% reduction in brain shrinkage in precisely the brain regions the disease normally affects. Two details are important for what happened later – that those treated had all been diagnosed with MCI and that only those with a high level of homocysteine benefitted from the B vitamins. Any follow up that didn’t treat people with MCI or didn’t check patients’ starting homocysteine levels wouldn’t provide useful information about the validity of Smith’s trial.
From the moment it was published it was clear Smith’s work wasn’t going to get a dispassionate scientific evaluation. Responses ranged from hostile to indifferent; only patients were desperate to know more. One charity warned that B vitamins had failed before and it was important not to raise false hope, a professor jeered that the ‘fraudulent supplement industry’ would be delighted, bloggers wrongly claimed there was no proven link between brain shrinkage and cognitive or memory problems.
Drug with lowest predicted benefit gets £2 million funding
Over the next five years no funding was available to repeat the study. Further trials are regularly ordered within months for drugs reporting results a fraction as impressive.
Interestingly £2 million was made available 3years later to investigate the possible benefits of a drug previously used to lower blood pressure to see if it could reduce brain shrinkage. The press release said it was known that brain shrinkage “strongly linked with memory function”.
The advantages of trialling this drug were said to be that it would be cheap, already available and was known to be fairly safe. The fact a cheap, safe and available B vitamins had already been shown to dramatically cut brain shrinkage was ignored. The Lancet paper rated lowering blood pressure as the least effective prevention strategy.
The way the supposedly scientific, evidence-based Alzheimer’s establishment has lined up against Smith doesn’t inspire hope that it will develop an informed and effective approach to prevention anytime soon. Challenging findings is a vital part of science; but these trials were done in a way that was either ignorant or designed to fail.
B vitamin trials designed to fail
The first one published in the Annals of Internal medicine set the tone, declaring that ‘antioxidants, folic acid, and B vitamins are harmful or ineffective for chronic disease prevention’. As far as B vitamins were concerned it didn’t show anything of the sort. It gave healthy people very low OTC doses of B vitamins and made no attempt to measure homocysteine levels. This was one of the trials the New Scientist magazine relied on to declare authoritatively that B vitamins didn’t help people with cognitive and memory problems.
The next one looked at first sight more damning – a meta-analysis involving 22,000 people run by an Oxford professor. It also claimed to be definitive: ‘Our study draws a line under the debate: B vitamins don’t reduce cognitive decline as we age’. Again this was hot air. It also used healthy subjects, in fact it excluded anyone with MCI, mixed up trials that gave high and low doses of B vitamins and paid no attention to homocysteine.
What makes the situation even worse is that it’s funding came from the large charities for heart disease, cancer and Alzheimer’s but apparently none of these chronic disorder experts spotted the glaring flaws. A clue that might have alerted them was that the cognitive ability of those in the placebo group and those in the treatment group was very similar at the beginning and end.
This doesn’t mean the B vitamins didn’t work, as is sometimes assumed, it means those in both groups didn’t have a problem with their thinking skills so there was nothing for the vitamins to improve.
Meanwhile B vitamin strategy gets more precise
The poor science used to discredit B vitamins looks even feebler in light of Smith’s latest paper published last month. which took his original study further. It showed that having high homocysteine wasn’t sufficient to benefit from B vitamins; you also had to have healthy levels of omega 3 from fish oil. This is important since it would allow nutritional clinicians to target treatment even more precisely.
Even so the odds that will be followed up any time soon are very long, The big money is still firmly on drugs. The latest in a long line of plaque clearing drug is called solanezumab. It is still the best hope for an Alzheimer’s treatment, according to a senior geneticist quoted in a (paywalled) BMJ news story last month.
Others have pointed out that the improvement in cognition in the trials run so far have been pretty marginal. Media reports describe Solanezumab as the ‘first to provide evidence that it could slow the rate at which the disease damages patients’ brains’. Sounds familiar? The geneticist warned it would be “hugely expensive”, adding that if it doesn’t work there is always a drug for “altering brain cholesterol”. Another low-gain strategy. And this is where the cognitive dissonance must surely begin to cause serious mental strain. If either of the drugs is found to work, it will be given to older patients, who are likely already to be on half a dozen or more pills for prevention – polypharmacy as it is called. And polypharmacy greatly increases your chance of nasty side-effects.
Combining non-drug therapies doesn’t raise risks
This however is not a problem that happens with non-drug prevention approaches – exercise, diet, B vitamins and omega 3 and the like. In fact a combination is highly likely to be more effective than any single change. Better diet and more exercise combined do not generate side effects.
But we are not going to find out what improvements such combinations could produce while the charities and the government refuse to fund them and instead subject them to biased trials apparently designed to produce negative results.
Changing this commercially driven bias is obviously a huge challenge and the topic for another blog but it will involve doctors becoming much more informed about nutrition and making lifestyle treatments for chronic disease a public health issue and so less vulnerable to being side-lined by commercial values.
A starting place for such a change could be with the patients and carers themselves. It’s already happening in other specialities; diabetes patients are increasingly questioning the benefits of a low fat diet and reporting much greater benefits by going low carb.
So what about a donation strike by those who give time and money to Alzheimer’s charities until prevention becomes a guiding principle rather than a broken promise?