Myths and Facts about Alzheimer’s

Very scary since, as everybody knows there is no cure and nothing really to be done to prevent this horrible disorder. And there are other myths that you are probably aware of. Just give the drug companies a bit more time and money 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.

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 since genes only account for 1% of cases of Alzheimer’s. ¹

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 by half.

This was the powerful message set out in a statement by 112 leading dementia experts, delivered to the G8 summit on dementia in London in December 2013. 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.’

The steps they mentioned included controlling blood sugar and blood pressure, taking exercise, cognitive training, social activities, and supplementing with omega-3 fatty acidsOmega-3 fatty acids are considered essential fatty acids – they cannot be made within the body so must be obtained from the diet. EPA and… and B vitamins. This statement has since been published in the Journal of Alzheimer’s Disease. ²

Unfortunately the health authorities, even when they are officially committed to “public health”, have so far proved pretty inept at changing the nation’s diet and lifestyle. 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 diet and 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. Since 2006 the total spend on prevention research by UK health councils has been £156,000 – 0.1% of dementia research funding. 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?

Homocysteine and B vitamins

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 homocysteineHomocysteine is an amino acid found in the blood. Elevated levels of homocysteine have been associated with narrowing and hardening of the arteries, an increased…, which is one of the best early predictors of risk

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 proteinProteins are large molecules consisting of chains of amino acids. Proteins are essential nutrients for the human body – they are a building block of… drugs have failed, some with quite disastrous side-effects. ³ Tau protein drugs have also failed, but there are more in the pipeline.

However there have so far been five randomised controlled trials 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 ⁴, shrinkage of the whole brain dropped by half ⁵, and shrinkage in areas that are specifically affected by Alzheimer’s was cut by an astonishing 88%. ⁶ A Chinese study found a drop in cognitive decline in patients with mild Alzheimer’s who had high homocysteine ⁷, 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. A number of highly plausible mechanisms have been identified that explain why raised homocysteine would lead to brain shrinkage, such as the fact that high homocysteine leads to the formation of amyloid plaques and tau tangles. ⁹

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 of 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.¹⁰

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.

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.’ ¹¹

But there are plenty of 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.

In fact, a major review in July 2014 of 247 studies, working out how much each risk factor, if dealt with, could reduce Alzheimer’s incidence, concludes that

“The strongest evidence thus far is an increased risk of elevated plasma homocysteine or lower educational attainment and a lowered risk with increased physical activity.” The authors estimate that “on average, one in five to one in three cases of Alzheimer’s disease can potentially be averted if those risk factors were eliminated from populations.”.

Their analysis finds that having a high homocysteine level, compared to a lower level almost doubles the risk of developing Alzheimer’s and accounted for 22% of Alzheimer’s disease in the population; that low fish intake versus high fish consumption accounted for 22%; having a high intake of omega-3 fats significantly lowered risk; smoking in mid-life accounted for 31%; low physical activity versus high accounted for 32%, while low educational attainment accounted for 24% of Alzheimer’s disease. These risk factors can be reduced by testing and lowering high homocysteine (above 10mcmol/L) with B vitamins, increasing intake of omega-3 with fish oil supplements and eating more fish, not smoking and exercising. A combination of these factors could, they estimate, eliminate one third of Alzheimer’s cases.

Recently, the Oxford researchers found that those participants given B vitamins who had a high omega-3 status at the start of the study¹³, further reduced their total rate of brain shrinkage by 73% compared to placebo – while those with low omega-3 status didn’t have any benefit from the B vitamins. This study shows how vital combined prevention steps really are. One EU estimate of the likely cost saving from preventing these two factors alone is in excess of €50 billion over the next 5 years.

First step – take a memory and cognitive test

The first step in prevention 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 you 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% is spent on prevention. 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, minimise sugar and follow a low GL diet, up your intake of antioxidantAntioxidants are substances that protect cells within the body from damage caused by free radicals. They help to strengthen the body’s ability to fight infection… 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 ¹² and to date, over 200,000 people have taken it. It is free and available here. In an ideal world GPs could contact all their patients over 50, encourage them to do such self-screening online, then support them in taking the various prevention steps. Food for the Brain 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.

References

1. Bekris, L et al., ‘Genetics of Alzheimer disease’ Journal of Geriatric Psychiatry and Neurology 2010, 23(4) 213-227).
2. 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
3. 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
4. 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
5. 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)
6. 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
7. 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.
8. Aisen P. et al., ‘High-dose B vitamin supplementation and cognitive decline in Alzheimer disease’, JAMA, 300(15):1774–83 (2008).
9. 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
10. 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
11. Nutrition and Dementia, a review of available research, Alzheimer’s Disease International
12. Trustram-Eve, C., de Jager C. A. (2013) Piloting and validation of a novel self-administered online cognitive screening tool in normal older persons: the Cognitive Function Test. Int J Geriatr Psychiatry. 2013 Jun 11. doi: 10.1002/gps.3993
13. Jernerén F, Elshorbagy AK, Oulhaj A, Smith SM, Refsum H, Smith AD (2015). Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr. 2015 Jul;102(1):215-21