Alzheimer’s and Dementia – Time for ‘A Novel Therapeutic Programme’?

The announcement recently that “NHS bosses say family doctors in England are to be paid £55 for each patient they diagnose with dementia” provoked a good deal of controversy and strong opinions, both within the medical profession, the media and general public.

Alzheimer’s and Dementia have certainly been in the news frequently in recent months. This included the announcement last year by prime minster David Cameron of a welcomed increase in funding for Alzheimer’s and Dementia research as the UK hosted the first G8 dementia summit to lead international action on tackling the condition.

One criticism of the GP payment scheme was that there is currently no effective treatment or cure for the disease. The comment in the Guardian was “There’s no effective treatment yet for dementia. So rather than paying doctors to spot new cases, we should spend the £55 where it will make a difference”. And with the prediction that there will be around 850,000 people in the UK with dementia in 2015 one can see why there is an increased urgency to help diagnose and improve the lives of sufferers.

Early identification will clearly be a benefit in terms of seeking to manage the symptoms, however many health professionals suggest that current identification methods are limited too. Although opinions are divided regarding the £55 payment scheme many people argue that surely a focus on identifying this terrible disease is better than not?

Naturally the race to find some form of treatment has focussed on the pharmaceutical industry. However what is emerging more recently is the need for a proactive programme of multiple non drug related ‘activities’ to hopefully reduce the severity of the symptoms if unfortunately you are a sufferer. In addition such a ‘lifestyle therapeutic’ approach would seem logically recommended for anyone who wishes to decrease the risks of dementia and Alzheimer’s as they age.

Such activities in this type of programme may include regular gentle physical exercise, a good diet rich in fruit and vegetables, relaxation techniques (such as mindful meditation), avoidance of alcohol and tobacco, the use of select food supplements, and keeping the brain ‘active’ (‘exercised’, whatever term you wish to use) etc.

B Vitamins & Omega 3

In terms of diet the two nutritional groups most commonly associated with seeking to support cognitive health, and the ones particularly cited in dementia and Alzheimer’s research, are certain B vitamins and Omega 3. Both have a range of permitted health claims in relation to normal brain function, psychological function and the nervous system.

In addition a number of B vitamins have permitted health claims in relation to maintaining normal homocysteine metabolism. Managing homocysteine levels have been frequently cited as important not just for good health but especially in relation to reducing dementia and Alzheimer’s risks. Interestingly the same factors that improve elevated homocysteine also improve outcomes in Alzheimer’s patients.

We have recently written articles of some depth on the topics of dementia and Alzheimer’s research, the potential role of B vitamins in reducing the risks of these diseases, plus the role of homocysteine in the body and in relation to cognitive health. Links to these specific articles are to be found further below.

When it comes to food supplements such as B vitamins and Omega 3 (e.g. fish and flaxseed oils) it is often hard to get suitable levels from diet alone, especially if you are on a restricted diet (e.g. vegan or vegetarian). In addition there are common genetic issues relating to bodily absorption and unfortunately as we age our ability to uptake many nutrient levels decreases. Hence the suitability of enhancing the diet with certain supplements to ensure good nutrient levels and also to negate uptake and absorption issues. A good specific example here is sublingual vitamin B12.

‘Cognitive Decline; A Novel Therapeutic Program?’

The ‘multi-factorial’ approach toward managing dementia and Alzheimer’s has been highlighted by the study “Reversal of cognitive decline; A novel therapeutic program”, published in the journal Aging. The program has been developed by Dale Bredesen, Professor of Neurology and Director of the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA. The link to this study online is provided further below. Do please note the different patient studies as they make for interesting reading. The abstract describing the research contains the following:

“This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer’s disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer’s disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD.

Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted.

The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.”

It is fascinating to see both the personalised approach in this study plus the use of a variety of herbs, vitamin and mineral supplements. However, despite the apparent success of this research, the next step in testing the effectiveness of this program on a much wider scale may be substantially hindered by the fact that it is not pharmaceutical led research with the absence of drugs as part of the program.

The thought provoking website ‘HealthInsightUK’ reviewed the study and their article (link to the full story further below) is worth a read. They commented on the study and the absence of drugs in the trial:

“Alzheimer’s is a complex disease affected by sleep, diet, even exercise,’ he says (Dale Bredesen). That’s why he developed a protocol called MEND – Metabolic Enhancement for NeuroDegeneration – which is a ‘novel, comprehensive and personal approach to treating memory loss’.

Everyone agrees that what is needed now is a large scale, randomised, blinded trial to confirm the benefits. However the shocking truth is that it’s perfectly possible that such a trial will never happen. The big randomised trial showing dramatic benefit from high dose B vitamins has never been followed up.

The problem is that the compounds used weren’t drugs but diet, supplements, herbs and exercise – so little in the way of profit. And to complicate things further different patients got different combinations depending on their problems.

Running a “gold standard” randomised controlled trial of that package was described by other doctors as ‘a major challenge’. But given the scale and seriousness of the problem wouldn’t a more useful response be to say if our current method of testing treatments can’t handle this lets develop another one? The situation, as everyone also agrees, is desperate.”

Curcumin

One of the supplements used as part of the Dale Bredesen program comprises curcumin a compound which comes from the popular Asian spice Turmeric, well know in foods such as many curries. Curcumin is a powerful polyphenolic compound, a natural chemical found in many fruits, vegetables, and other plants.

Dried turmeric stem has been used historically as a natural treatment for a wide range of conditions including use as a topical anti-inflammatory. There is also a good volume of research which provides evidence for the systemic anti-inflammatory activity of this ingredient. Curcumin as part of a food supplement is popularly used as a powerful anti-inflammatory for wide ranging inflammatory conditions.

It is due to these properties and mechanisms of action that curcumin has been researched in relation to Alzheimer’s and related cognitive health issues. We must stress that currently however there are no permitted health claims for curcumin (or turmeric) from EFSA, the European Food Safety Authority.

In research curcumin has been reported to diminish inflammatory cytokine production and to have been demonstrated to suppress cox-2 expression. Both inflammatory cytokine production and cox-2 expression are implicated in Alzheimer’s disease. There has also been research on the effect of curcumin on the stability of Aβ dimmers (which are peptides of amino acids). Amyloid-β (Aβ) pathology is a major component in the mechanisms behind Alzheimer’s disease.

For health professionals who are interested in finding more information on this topic we have included a list of research studies specifically on curcumin and Alzheimer’s; this list is further below.

GP’s and Dementia Diagnosis

Back to the debate on dementia and GP’s. Below is the opening excerpt from the BBC report on this news; the link to their full story is to be found further below.

“Family doctors in England are to be paid £55 for each patient they diagnose with dementia, NHS bosses say. NHS England said the aim of the six-month £5m scheme was to increase the number of sufferers who receive treatment for the condition, which causes a decline in brain function.

It is estimated up to 90,000 patients are living with undiagnosed dementia.But the Patients Association called it “a step too far” that would mean a “bounty on the head” of some patients.

  • It is predicted there will be around 850,000 people in the UK with dementia in 2015
  • It mainly affects people over the age of 65
  • Approximately one in 14 people over the age of 65 have dementia
  • There are more than 40,000 people in the UK under the age of 65 who have dementia

 

Summary

A personalised approach seems essential in seeking to support sufferers of dementia and Alzheimer’s. Yes, the NHS has a finite budget but surely such an approach will be the most cost effective in the long-term too. First and foremost though dementia and Alzheimer’s are terrible diseases for both the sufferers and their families and they all deserve the best care and support.

There is now sound evidence that a combination of health engendering ‘activities’ as highlighted in the Dale Bredesen programme can help in all aspects of prevention and improvement in those who have the disease. A summary of the totality of factors that are seen to be influential in preventing dementia and Alzheimer’s are:

  • Sleep
  • Exercise
  • A good diet
  • Mental stimulation
  • Emotional nourishment (e.g. friends and family)
  • Relaxation techniques (e.g. yoga or mindful meditation)
  • The appropriate vitamins & minerals
  • Omega 3 fats
  • Curcumin
  • Good gut health
  • Avoidance of alcohol and tobacco

For the diet it needs to be one that avoids ‘inflammatory foods’ and is low in processed foods, gluten, carbohydrates, alcohol and high in wholefoods, fruit and vegetables. The ‘Paleo Diet’ would be ideal and is a dietary regime we have advocated at Cytoplan for some years. More information can be found by following the link further below.

Exercise is an important part of the programme, as noted before this doesn’t need to be overly strenuous, but certainly regular. Ideally in combination with friends for example for additional emotional nourishment.

When it comes to supplements for specific nutrients ‘form’ is, as far as we at Cytoplan are concerned, all important. Not all supplements are the same and this greatly affects how your body reacts and uses the supplements that you ingest – these actions can be termed as ‘Bioavailability’ and ‘Bioefficacy’.

Bioavailability and Bioefficacy are two words close to the heart of Cytoplan and our philosophy in respect of health and nutrition. They are particularly relevant for our ‘uniqueness’ in terms of our range of vitamin and mineral supplements – which are either in a ‘Food State™’ or ‘Wholefood’ base.

These are supplements that present vitamins and minerals in a format as close as possible to the foods where those micronutrients naturally occur. This means they work in the body like food, and hence the body knows how to use them to nourish whichever part of the body is in need.

Thus nutrients in such a supplement form seek to maximise their ‘availability’ (bioavailability) to our body once ingested, whilst also maximising the nutrient ‘efficacy’ (or efficiency or bioefficacy) within the body. One might term this a ‘natural’ nutrient approach. Or an additional analogy is one where the body sees such food bound supplements as ‘friendly’ and seeks to utilise the nutrients within to good effect, just as it would when ingesting healthy foods.

When it comes to supplements a personalised approach is always best, and none more so than with issues such as dementia and Alzheimer’s. The individual needs suitable levels of nutrients particularly based on a range of factors including their age, gender and existing medical conditions. And for cognitive health we need specific nutrients for every aspect of brain health and correct signalling.

As we mentioned earlier, even for those of us in good health, adopting the types of activities advocated in the ‘therapeutic program’ should act as ‘best practice’ for good health and ailment prevention, and this includes cognitive health.

We can only hope, and encourage, that a much fuller scale study is carried out in the near future on this approach to tackling dementia and Alzheimer’s risks and symptoms.

If you have any questions regarding this article, any of the health topics raised, or any other health matters please do contact me (Amanda) by phone or email at any time.

Amanda Williams, Cytoplan Ltd
[email protected], 01684 310099


Relevant Links

AGING (High-Impact Journal on Aging Research) – Reversal of cognitive decline: A novel therapeutic program
HealthInsightUK – Alzheimer’s: the new radical life-style program that can reverse it
BBC News – GPs to be paid £55 for each dementia diagnosis
Cytoplan Blog – B-Vitamins & Alzheimer’s The Debate Intensifies
Cytoplan Blog – Can B-Vitamins Help Deter Alzheimer’s & Dementia?
Cytoplan Blog – Vitamins for the Brain?
Food For The Brain
Gov UK – Global Dementia Legacy Event: David Cameron’s speech
The Guardian – Why pay GPs to identify people with dementia if we can’t help them?
Cytoplan Blog – The Paleo Diet

Curcumin Research Links

1. Curcumin suppresses soluble tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice. Ma QL, Zuo X, Yang F, Ubeda OJ, Gant DJ, Alaverdyan M, Teng E, Hu S, Chen PP, Maiti P, Teter B, Cole GM, Frautschy SA. J Biol Chem. 2013 Feb 8;288(6):4056-65.

2. Oral curcumin for Alzheimer’s disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Ringman JM, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, Gylys KH, Badmaev V, Heath DD, Apostolova LG, Porter V, Vanek Z, Marshall GA, Hellemann G, Sugar C, Masterman DL, Montine TJ, Cummings JL, Cole GM. Alzheimers Res Ther. 2012 Oct 29;4(5):43.

3. Improvement of neuropathology and transcriptional deficits in CAG 140 knock-in mice supports a beneficial effect of dietary curcumin in Huntington’s disease. Hickey MA, Zhu C, Medvedeva V, Lerner RP, Patassini S, Franich NR, Maiti P, Frautschy SA, Zeitlin S, Levine MS, Chesselet MF. Mol Neurodegener. 2012 Apr 4;7:12. doi: 10.1186/1750-1326-7-12.

4. Why pleiotropic interventions are needed for Alzheimer’s disease. Frautschy SA, Cole GM. Mol Neurobiol. 2010 Jun;41(2-3):392-409. doi: 10.1007/s12035-010-8137-1.

5.Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. Ma QL, Yang F, Rosario ER, Ubeda OJ, Beech W, Gant DJ, Chen PP, Hudspeth B, Chen C, Zhao Y, Vinters HV, Frautschy SA, Cole GM. J Neurosci. 2009

6. Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer’s disease. Begum AN, Jones MR, Lim GP, Morihara T, Kim P, Heath DD, Rock CL, Pruitt MA, Yang F, Hudspeth B, Hu S, Faull KF, Teter B, Cole GM, Frautschy SA. J Pharmacol Exp Ther. 2008 Jul;326(1):196-208. doi: 10.1124/jpet.108.137455.

7. Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL. A potential role of the curry spice curcumin in Alzheimer’s disease.Curr Alzheimer Res. 2005 Apr;2(2):131-6.PMID: 15974909 [PubMed – in process]

8. Cole GM, Morihara T, Lim GP, Yang F, Begum A, Frautschy SA. NSAID and Antioxidant Prevention of Alzheimer’s Disease: Lessons from In Vitro and Animal Models.Ann N Y Acad Sci. 2004 Dec;1035:68-84.PMID: 15681801 [PubMed – in process]

9. Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo.
J Biol Chem. 2005 Feb 18;280(7):5892-901. Epub 2004 Dec 7.PMID: 15590663 [PubMed – indexed for MEDLINE]

10. Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging. 2001 Nov-Dec;22(6):993-1005. PMID: 11755008 [PubMed – indexed for MEDLINE]

11. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. Related Articles The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse.J Neurosci. 2001 Nov 1;21(21):8370-7.PMID: 11606625 [PubMed – indexed for MEDLINE


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7 thoughts on “Alzheimer’s and Dementia – Time for ‘A Novel Therapeutic Programme’?

  1. This is a great article that once more raises the important issue that chronic disease should be looked at more holistically – that drugs are often not the solution. An important study mentioned above is No 4. Why Pleiotropic interventions are needed for Alzheimer’s, because it emphasises levels of therapy that drugs cannot mimic, specifically because phytonutrients are a group of compounds that has pleiotropic and hormetic effects not yet fully understood in conventional (drug-based) paradigms of evaluation.

    Another study, in 2012, “Pleiotrophic protective effects of phytochemicals and Alzheimer’s Disease”, discusses the complex and multiple causes of Alzheimer’s and how “therapeutic agents acting on multiple levels of the pathology are needed”. The researchers examined curcumin, catechins and resveratrol. They found that curcumin is able to clear amyloid plaques through several mechanisms and has additional activity; that ECGC (catechins) has a wide array of biological effects, that includes a synergistic effect with fish oil, in its ability to improve memory; and, resveratrol (in combination with glucose and malate) is under Phase III clinical trials to determine the effects in mild to moderate Alzheimer’s.

    Hormesis is another factor that drugs cannot mimic. It’s defined as, “a process in which exposure to a low dose of a chemical agent or environmental factor that is damaging at higher doses induces an adaptive beneficial effect on the cell or organism”. This is like the principles of homeopathy. It means that the impact of phytonutrients, whilst weak compared with drugs, has a much wider (bigger?) impact than we are currently able to evaluate.

    All food for thought!

    This sudden epidemic of Alzheimer’s is a big concern and must be based on the modern lifestyle – don’t you think?

    Thank you, Amanda – I hope this becomes a topic of discussion.

  2. I enjoyed reading your blog Amanda. Sadly, two members of my family have dementia. My brother(66) and my aunty(89). Both are in the later stage. The things you suggest have been mentioned to both of their families over the years but due to the negative comments from their doctors when mentioned to them – supplements especially – the families did not want to know any more from me about my ideas for dementia.

    The lowering of homocysteine, inflammation and oxidative stress, whilst also increasing circulation, are key areas to target. The product called Souvenaid, by Nutricia, is an interesting formula for helping cognitive function in the early stages and may be more effective when combined with the supplements you mention and for a longer time. ie these measures may actually slow down the disease process.

    Given that lowering hcy and taking fish oil first came to light as a way of combating cardiovascular disease, I am now wondering that as we now know that what is good for the heart is also good for the brain, whether or not dementia is a form of cardiovascular disease process, like stroke is say. Perhaps Vascular dementia would fit the description more so than the other forms maybe.

    However, what is true I feel, is that finding a nutritional intervention for this dreadful disease is rather similar to that remarkable film, Lorenzo’s Oil, don’t you think? The medical profession and even the Alzheimer’s society shun any suggestion that help can be gained from synergistically targeted nutrients…

    Good work

    Kind regards

    Ray

    1. Dear Ray,

      Thank you so much for your comment. I am sorry to hear of your family ailments and you are brave to air them in public for many more people to benefit. Well done too for the research you have carried out into Alzheimer’s and your knowledgeable conclusions.

      I don’t know if you have seen it but Dr Alyssa Burns-Hill has posted a comment on the same blog saying that the best evidence is that dementia can most certainly be prevented and modified by a set of protocols which include nutrition. So do read her comments if you haven’t already.

      Some of us are more susceptible to dementia and Alzheimer’s than others, and the factors that predispose to high homocysteine seem to be the same as predispose to Alzheimer’s but are modifiable, and most particularly so if remedial protocols start early on before the symptoms are really apparent.

      The same predisposition that gives susceptibility to homocysteinaemia and Alzheimer’s is impaired methylation, which is discussed in other Cytoplan blog articles. It is modifiable via diet but bearers of the polymorphisms that give rise to impaired methylation have to be much more careful with diet than others, in particular to ingest a high level of methyl donor nutrients.

      Very best wishes and thanks again for your comment. Amanda x

    1. Hi Bruce,

      There are many natural supplements to help with high homocysteine. The most common ones are: trimethyl glycine, Vitamin B12 and folate as all of these products are “methyl donors”. As elevated homocysteine is a result of dysfunctional methylation these are usually the best support nutrients as they enable the methylation cycle. But as much as low levels of these nutrients can predispose to high homocysteine, other factors also need to be considered when implementing programmes for sustainable reduction, such as genetic errors and medication.

      Our product Methyl Factors contains all of the above nutrients (TMG, b12 and folate) so please let me know if you would like me to send you a pot.

      All the best,
      Amanda

  3. I live in Ontario, Canada. Are you aware of a clinic or facility near Toronto that would have knowledge of the Bredesen protocol?

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