by Patrick Holford
Have you had one of those nasty moments recently when it is clear that your memory is failing? Confidently rushing up stairs to get something then realising you have no idea what it was; meeting someone you know perfectly well and being unable to remember their name. A few of these moments and a name that none of us forgets comes all too easily to mind: Alzheimer’s.
Very scary since, as everybody knows there is no cure and nothing really to be done to prevent this horrible disorder. The Alzheimer’s Society website, for instance, advocates a “healthy balanced diet” (low in fat high in carbohydrates) which is also recommended for the prevention of obesity and diabetes and we know how successful that has been.
And there are other myths that you are probably aware of. Just give the drug companies a bit more time and money (they have already had twenty years and spent in the region of £25 billion) and they will come up with a cure. Another is that the two villains responsible, which can be targeted, blocked or destroyed, are a couple of damaged proteins found in sufferers brains – amyloid plaque and tau tangles.
Drugs don’t regenerate dead cells
However it is extremely unlikely there will ever be a drug “cure” because once brain cells are destroyed, no drug is going to bring them back. Drugs block things, they don’t regenerate brain cells. But surely some people are genetically doomed to develop the disease, so what about targeting genes? Another blind alley unfortunately (although possibly profitable one day) since genes only account for fewer than 1% of cases of Alzheimer’s.
However there is reason to believe that at those moments when the word ‘Alzheimer’s’ pops up, the next thought shouldn’t be ‘despair’ but ‘prevention’. Despite the defeatist attitude of the charities and the understandable lack of interest by the drug companies, there are actually a number of sensible and plausible steps to take that have a chance of cutting your risk. This was the powerful message set out in a statement by 112 leading dementia experts, delivered to the G8 summit on dementia in London last December.
It claimed that half of the risk of developing the disease is attributable to known risk factors and recommended that: ‘Health authorities should aim to identify high risk individuals at an early stage, when intervention is likely to help.’ Adding that: “There is already sufficient evidence to justify immediate action.’
Steps to cut your risk
The steps they mentioned included controlling blood sugar and blood pressure, taking exercise, cognitive training, social activities, and supplementing with omega 3 fatty acids and B vitamins. This statement has since been published in the Journal of Alzheimer’s Disease.
Unfortunately the health authorities, even when they are officially committed to “public health”, have so far proved pretty inept at changing nation’s diet and lifestyle, not least because they prefer to rely on funding and collaboration from commercial organisations that are part of the problem in the first place
The response of UK health minister Jeremy Hunt to the looming crisis, for example, has not been to announce funding for a national prevention programme on a scale that matches the 50 per cent that life style contributes to the risk but instead to pledge to speed up the diagnosis of dementia from 6 months to 6 weeks. Far too little and far too late. With nothing else on offer those at risk must be identified much earlier and helped to make changes that could reduce it. The reality is that serious action to address the leading cause is effectively non-existent. How demented is that?
So given that you are unlikely to get any support from drug companies, charities or health ministers to reduce your risk along the lines suggested by those 100+ experts, what can you do? The first course of action is to check out a third marker for Alzheimer’s, along with plaques and tangles, that is almost never mentioned– a high level of a potentially toxic amino acid called homocysteine, which is one of the best early predictors of risk.
Prevention needs public investment
It is simply a statement of fact to say that billions have been spent targeting amyloid and tau because that way lies patents and profits. The only way to lower homocysteine, by contrast, is with high doses of B vitamins which are not going to make anyone a fortune. That’s why this approach needs public investment. Already it has far more evidence for effectiveness than anything the drug research has come up with. A dozen phase three trials of amyloid protein drugs have failed, some with quite disastrous side-effects. Tau protein drugs have also failed, but there are more in the pipeline.
However there have so far been five randomised controlled trials (the sort champions of evidence based medicine demand) of homocysteine lowering and each one has been extremely promising. Three came from the OPTIMA project at Oxford University treating patients with Mild Cognitive Impairment, a precursor to Alzheimer’s.
Memory decline almost stopped, shrinkage of the whole brain dropped by half, and shrinkage in areas that are specifically affected by Alzheimer’s was cut by an astonishing 88%.  A Chinese study found a drop in cognitive decline in patients with mild Alzheimer’s who had high homocysteine, while US researchers reported that memory decline virtually stopped in response to the vitamins among mild Alzheimer’s patients, but they didn’t measure homocysteine levels.
What all this suggests is that raised homocysteine is almost certainly causing memory problems and isn’t just a marker for raised risk. It makes sense that raised homocysteine would lead to brain shrinkage, because we know it leads to the formation of amyloid plaques and tau tangles. 
Older people often low in B vitamins
These results are hugely encouraging in their own right but they are even more important in light of what we know about levels of homocysteine and B vitamins in older people, the ones who develop Alzheimer’s. To begin with approximately half of people over 65 have raised levels homocysteine and we know that their risk of accelerated brain shrinkage and Alzheimer’s is about four times higher than those with normal levels..
We also know that having a raised level of homocysteine is linked with more amyloid and tau and that low levels of B vitamins probably causes high homocysteine. And which group of people is most likely to have low B vitamins? Older people.
Partly because we simply get worse at extracting it from food as we get older but also because a largely ignored side-effect of common prescription drugs, such as the proton pump inhibitors that block stomach acid and the diabetes drug metformin, is to reduce the ability of the gut to absorb vitamin B12. Insufficient B12 levels in more than a third of people over the age of 61 are linked to accelerated brain shrinkage.
So what you have here is a story that deserves serious investigation linking old people, high homocysteine, low levels of B vitamins and Alzheimer’s. It is not nailed down in every detail because the bodies you might think would fund it – charities, NHS and government funded research councils – consistently ignore it. But it makes sense and if a drug were involved you could be sure millions would be being poured into researching it.
Evidence ignored or distorted
Instead this non-drug approach is consistently side-lined or denied. For example, a recent review of all evidence by Alzheimer’s Disease International describes all these B vitamin RCTs as “effective” then falsely states in their conclusion that: ‘RCTs targeting elevated homocysteine levels…[have no] significant effect on cognitive function.’
And there are plenty of other ways to distort the results. One is to lump together well designed positive studies with ones that were done for too short a time to be able to measure a cognitive change or were done on people who didn’t have high homocysteine (and so couldn’t be expected to benefit). The result is that the total effect of B vitamins shows up as zero.
But we all deserve something better than this sort of playing fast and loose with clinical trials. Perhaps we shouldn’t be surprised it happens since it is well established that drug companies are equally adept at manipulating trials to produce positive results.
The B vitamin results suggest not only the kind of steps that would be involved in a sane public health policy but they also offer everyone the chance to do something for themselves
What to do for yourself
The first step would be to take a memory and cognitive test to find out if you actually were at risk. If you are, then you need to find out if have high homocysteine – if you don’t the vitamins won’t have any benefit. You may be able to do this through your GP but it is unlikely at the moment because they are not being educated about the extremely positive evidence that does exist, and there is virtually no funding for further research into dementia/Alzheimer’s prevention. Of the £272 million spent to date by all health research councils and charities only 1.7% has been spent on prevention, a dreadful skewing of priorities given that half the identified risk is due to preventable nutrition and lifestyle factors.
So you may have to have the test done privately. If you aren’t likely to benefit from the vitamins, there are the other preventative steps recommended in the statement signed by the experts at the G8 – eat fish for omega 3s, minimize sugar and follow a low GL diet, up your intake of antioxidant rich foods, keep physically, mentally and socially active.
I’m committed to trying to make this happen through the charity Food for the Brain Foundation. We have tested and validated a free online Cognitive Function Test in a pilot study against the best paper and pencil tests used in memory clinics and to date, over 160,000 people have taken it. It is free and available to all at Food for the Brain [www.foodforthebrain.org]
In an ideal world GPs could contact all their patients over 50, encourage them to do such self-screening online and then support them in taking the various prevention steps. The charity publishes a free guide on all the evidence-based prevention steps anyone can take on the website and keeps it up to date as we learn more.
You can check if it is working
Mike is an example of how this pro-active approach can benefit. He had started having difficulties with recall and felt his thoughts weren’t as clear as they once were. He did the Cognitive Function Test and, due to a poor score, it advised him to test his homocysteine level. He scored 24µmol/l, well above the level of 10 than indicates increased Alzheimer’s risk.
He saw a nutritional therapist at the charity’s clinic, the Brain Bio Centre, who devised a nutrition programme including diet changes and supplementing specific B vitamins, plus other brain-friendly nutrients such as omega 3, antioxidants and vitamin D. Six months on Mike says “I followed the advice given and as a consequence my homocysteine level rapidly reduced and presently stands at 6.7 units. My memory is much improved and I can think clearly again.”
But until the public health authorities start getting serious about prevention you are also going to have to take responsibility for doing it yourself. Instead of dreading the ‘A’ word, it is reassuring to know that there are things you can do right now, including keeping your homocysteine low – and you can tell if they are making a difference by simply doing the test again.
We recommend an annual check up and are tracking thousands of people to see who improves and who doesn’t and why. This kind of practical grassroots research needs funding but, guess what? There’s virtually none available. It’s almost all being spent on finding a drug ‘cure’!
Conflicts of interest: Patrick Holford is CEO of the Food for the Brain Foundation. He also receives royalties on a homocysteine lowering nutritional supplement, marketed under his name, and also on his book The Alzheimer’s Prevention Plan.
 Bekris, L et al., ‘Genetics of Alzheimer disease’ Journal of Geriatric Psychiatry and Neurology 2010, 23(4) 213-227). [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044597/]
 Smith,D., Jaffe,K. ‘Dementia (Including Alzheimer’s Disease)can be Prevented: Statement Supported by International Experts’ Journal of Alzheimer’s Disease 38 (2014) 699–703 [http://www.ncbi.nlm.nih.gov/pubmed/24326609]
 Castello MA, Soriano S. ‘On the origin of Alzheimer’s disease. Trials and tribulations of the amyloid hypothesis.‘Ageing Res Rev. 2014 Jan;13:10-2 [http://www.ncbi.nlm.nih.gov/pubmed/24252390]
 De Jager, C. et al., ‘Cognitive and clinical outcomes of homocysteine lowering B
vitamin treatment in mild cognitive impairment: a randomized controlled trial’, Int J
Geriatr Psychiatry (2012) Jun;27(6):592-600 [http://www.ncbi.nlm.nih.gov/pubmed/21780182]
 Smith, A.D. et al., ‘Homocysteine-lowering by B vitamins slows the rate of
accelerated brain atrophy in mild cognitive impairment: a randomized controlled
trial’, Public Library of Science ONE, 5(9) (2010) [http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012244]
 Douaud, G., et al. (2013) Preventing Alzheimer’s disease-related gray matter atrophy by B vitamin treatment. Proceedings National Academy Sciences, USA 2013 Jun 4;110(23):9523-8 [http://www.pnas.org/content/110/23/9523.long]
 Kwok, T., et al. (2011) A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people. Clinical Nutrition, 30: 297-302. [http://www.ncbi.nlm.nih.gov/pubmed/23754255]
 Aisen P. et al., ‘High-dose B vitamin supplementation and cognitive decline in
Alzheimer disease’, JAMA, 300(15):1774–83 (2008). [http://www.ncbi.nlm.nih.gov/pubmed/18854539]
 Zhuo JM1, Wang H, Praticò D. ‘Is hyperhomocysteinemia an Alzheimer’s disease (AD) risk factor, an AD marker, or neither?’ Trends Pharmacol Sci. 2011 Sep;32(9):562-71 [http://www.ncbi.nlm.nih.gov/pubmed/21684021]
 Vogiatzoglou A et al, ‘Vitamin B12 status and rate of brain
volume loss in community-dwelling elderly’ Neurology. 2008 Sep 9;71(11):826-32 [http://www.ncbi.nlm.nih.gov/pubmed/18779510] [