What causes dementia and Alzheimer’s?
AD is a complex disease without a single cause, but with many contributors. Many researchers are now converging on the idea that it is a degenerative inflammatory disease that damages a particular part of the brain called the Medial Temporal Lobe. This may be largely due to the long-term consequence of faulty nutrition plus certain negative lifestyle factors, much like cardiovascular disease, and that any long-term solution must involve fundamental changes to a person’s diet. The contributory factors may include:

• Lack of antioxidant nutrients
• Lack of omega 3 Fatty Acids
• Excessive stress and the stress hormone cortisol
• Raised homocysteine and a lack of B vitamins
• Excess aluminium and/or mercury
• Acetylcholine and precursor deficiency
• A genetic predisposition
• A lack of physical and mental exercise – use it or lose it

You can find out which of these factors is likely to affect you be completing the FREE Mental Health Check.

To find out more about these factors read on, or click on our  Action Plan to Overcome Memory Decline

DIET & NUTRITION – WHAT WORKS

UP YOUR ANTIOXIDANTS
Inflammatory reactions invariably mean increased production of oxidants, and hence an increased need for antioxidants such as vitamin A, beta-carotene, and vitamins C and E, all of which have been shown to be low in those with AD. Other antioxidants, including cysteine, glutathione, lipoic acid, anthocyanidins, and co-enzyme Q10, possibly other quinones, and melatonin may also prove important. In simple terms this means eating a lot more fresh fruit and vegetables – at least six portions a day – and oily fish and seeds.

Vitamin E appears to have a protective effect. A study published in the Journal of the American Medical Association found that the risk of developing AD was 67 per cent lower in those with a high dietary intake of vitamin E, versus those with a low intake¹.

 A US study gave 633 disease-free 65-year-olds large amounts of either vitamin E or vitamin C. A small number in each group would have been expected to show the signs of AD five years later. None did².  Vitamin E appears to not only plays a key role in early prevention in this way, but also in slowing down the progression of the disease. In a study reported in the New England Journal of Medicine in 1997, AD patients received either 2,000ius of vitamin E, the drug Selegiline, or a placebo³.  Vitamin E was shown to reduce progression most significantly.

Where’s the evidence? Enter ‘dementia’ and ‘antioxidants’ into the search field for a summary of studies on antioxidants and Alzheimers/dementia.

Side effects? None known, however some studies indicate that high intakes from vitamin E supplements (above 300mg) may increase cardiovascular risk. We recommend supplementing vitamin E with Co-enzyme Q10, and ideally in an all-round antioxidant supplement.

Contraindications with medication? Vitamin E, in large amounts above 300mg may thin the blood. This is a benefit however if you are already on blood thinning medication you should discuss this with your doctor first. Statin drugs interfere with the body’s ability to use vitamin E. If you are on a statin drug and wish to take vitamin E also supplement 90mg or more of Coenzyme Q10.

See action plan for our recommendations.

OMEGA 3 FATTY ACIDS
Omega-3 fats are most prevalent in carnivorous, cold water fish such as salmon, tuna, herring and mackerel. According to recent a study by Dr. Martha Morris and colleagues at Chicago’s Rush Institute for Healthy Aging, eating fish once a week reduces your risk of developing AD by 60 percent.

The researchers followed 815 people, aged 65 to 94 years, for seven years and found that dietary intake of fish was strongly linked to AD risk. They found that the strongest link was the amount of DHA, a form of omega 3-fat found in fish. The higher a person’s DHA, the lower their risk of developing AD. The lowest amount of DHA per day that offered some protection was 100 mg. While intake of EPA (another omega-3 fat) did not reach significance, the highest intake of EPA consumed was 30 mg a day.  

But why exactly might fish have this protective effect? One theory is that it helps to ease brain inflammation, which, in turn damages brain cells. Omega-3 fatty acids are also a vital component of brain cell membranes and help control calcium flow in and out of cells. This is important because too much calcium inside brain cells is known to contribute to the production of the toxic beta-amyloid protein, which is found in excessive levels in most people who develop Alzheimer’s.

Where’s the evidence? Enter ‘omegas’ and ‘dementia' into the search field for a summary of studies on omega 3 and Alzheimers/dementia.

Side effects? None reported.

Contraindications with medication? Omega 3 oils, in large amounts, can thin the blood. This is a benefit however if you are already on blood thinning medication you should discuss this with your doctor first.

See action plan for our recommendations.

STRESS, CORTISOL AND MEMORY LOSS
Under prolonged stress, the body produces the adrenal hormone cortisol. The research of Professor Robert Sapolsky at Stanford University has shown that although cortisol is a powerful anti-inflammatory hormone, raised cortisol can damage the brain. In studies with rats he found that two weeks of induced stress causing raised cortisol levels causes dendrites, those connections between brain cells, to shrivel up . He believes that brain cell loss in ageing and AD may be, in part, due to high levels of cortisol and recommends that corticosteroid drugs should not be used in AD patients for other medical problems like asthma or arthritis. 

Using a brain imaging technique, Douglas Bremner of Yale University has shown that the part of the brain responsible for learning and memory is smaller in patients with post-traumatic stress disorder, and that this correlates with poorer memory.    Researchers at the La Sapienza University have shown that cortisol levels are significantly higher in AD patients than in controls, and correlate with the severity of the disease.  Linda Carlson and colleagues at McGill University in Montreal have confirmed that in AD patients, the higher the cortisol, the worse their memory. They also found that the higher the levels of DHEA the better their memory. 

Adrenal exhaustion can also lead to a lack of cortisol, which increases inflammation. It’s a question of balance. All this research implies that the ability to create a lifestyle that minimises prolonged stress is also important for reducing AD risk.

Where’s the evidence? Enter ‘stress’ and ‘dementia’ into the search field for a summary of studies on stress and Alzheimers/dementia.

See action plan for our recommendations.

UP YOUR B VITAMINS TO LOWER HOMOCYSTEINE
The single, hottest nutritional discovery is that your risk of developing Alzheimer’s disease (AD) is strongly linked to your level of the toxic amino acid homocysteine, which can be measured from a pinprick of blood on a home test kit. The lower your level throughout life the smaller your chances of developing serious memory decline.  Homocysteine is a neurotoxin, capable of directly damaging the medial temporal lobe, which is the area of the brain that rapidly degenerates in AD.  Homocysteine is easily lowered with inexpensive B vitamins. 

A study in the New England Journal of Medicine, published in 2002 charted the health of 1,092 elderly people without dementia, and measured their homocysteine levels. Eight years later, 111 were diagnosed with dementia, 83 of whom were given the diagnosis of AD. Those with high blood homocysteine levels (above 14 units) had nearly double the risk of Alzheimer’s.   There’s also evidence that even before a decline in mental function starts to show up in so-called “healthy” elderly individuals, high homocysteine predicts physical degeneration in certain parts of the brain. 

In Scotland, researchers have found that reduced mental performance in old age is strongly associated with high homocysteine and low levels of vitamins B12 and folic acid. Following up participants in the Scottish Mental Surveys of 1932 and 1947, which surveyed childhood intelligence, they found that the most mentally agile had the highest levels of B vitamins and lowest levels of homocysteine; high homocysteine was linked with a 7 to 8 percent decline in mental performance. 

A similar Californian study, asked 579 men and women aged 60 and over to keep track of their diet and the supplements they took. After nine years, 57 of them developed Alzheimer's. Those with the highest folate intake reduced their risk of developing Alzheimer's by 55 percent .

A research group led by Dr. Teodoro Bottiglieri at the Baylor University Metabolic Disease Center in Dallas, Texas, suggests that low levels of folic acid (which leads to raised homocysteine) may cause brain damage that triggers dementia and Alzheimer’s. Their research has found that one-third of those with both dementia and homocysteine levels above 14 units were deficient in folic acid. 

So there is a lot of research that points to a link between high homocysteine, low B vitamin intake and a raised risk of brain degeneration. The link between brain deterioration – memory loss, cognitive deficits, depression, and personality breakdown – and B vitamin deficiency is well established. But why? What is the link between B vitamins and damaged brain cells. The reason for this link may be that the body needs B vitamins to convert the toxic and brain damaging homocysteine into two very useful chemicals called glutathione – an antioxidant – and the amino acid called SAMe. SAMe is vital for ‘methylation’, which is a key chemical process happening millions of times every second, which keeps the brain’s chemistry in balance.

So the theory makes sense but does supplementing with vitamins prevent, or actually reverse memory loss? In truth, it’s early days but large amounts to seem to be effective. There are trials going on right now giving B vitamins to people with age-related cognitive decline and AD; a Dutch one involving 818 people aged between 50 and 75 was completed last year. They either got a vitamin containing 800mcg of folic acid a day - almost three times the RDA and the equivalent of 2.5 pounds of strawberries - or a dummy pill.  After three years supplement users had scores on memory tests comparable to people 5.5 years younger. On tests of cognitive speed, the folic acid helped users perform as well as people 1.9 years younger.

Mega-doses are also being used in a trial currently being run by Professor David Smith of the Optima Project at the University of Oxford. He’s giving people with age-related memory decline 1,000mcg of folic acid, 20mg of B6 and 500mcg of B12, which is 250 times the RDA; a far cry from the amount you could get by ‘eating a well balanced diet’.

Such high amounts are being used for the simple reason that they work. ‘The lowest dose of oral cyanocobalamin (B12) required to normalize mild vitamin B12 deficiency older people is more than 200 times the recommended dietary allowance,’ concludes a paper by scientist at the University of Wageningen in Holland, one of the top B12 research centres in the world.

Although more needs to be done to find out both how early supplementation has to begin in order to halt or even reverse memory loss, and what is the most effect combination of diet and supplements, it certainly makes sense to ensure an optimal intake of B6, B12 and folic acid along with an amino acid N-Acetyl Cysteine (NAC) which is used to make the valuable brain antioxidant glutathione.
Nutritional supplements aimed at lowering homocysteine not only produce reduction in symptoms, but also potentially stop the disease progression. Although this has not yet been proven in double-blind controlled studies, case studies do show this type of improvement.

Where’s the evidence? Enter ‘vitamins’ or ‘homocysteine’ and ‘dementia’ into the search field for a summary of studies on homocysteine, B vitamins and Alzheimer’s/dementia.

Side effects? None known. However, supplementing folic acid on its own can mask the symptoms of B12 deficiency. Hence we recommend only supplementing extra folic acid if you also supplement extra vitamin B12.

Contraindications with medication? Certain drugs such as methyltraxate are anti-folate. If you are on an anti-folate drug you should discuss with your doctor before taking large amounts of folic acid.

See action plan for our recommendations.

TOXIC MINERALS – ALUMINIUM AND MERCURY
Another brain toxin sometimes found in the plaques of dementia and Alzheimer’s sufferers is aluminium. While some studies have shown this increased accumulation of aluminium, what isn’t clear is whether this is a cause or a consequence of the disease. The likelihood is that it’s a bit of both and may be a significant contributor to memory problems. Numerous epidemiological surveys have linked aluminium intake in water to increased risk of AD. Other sources (food, medicines, toiletries and cosmetics) are less well investigated. In a study in the 1980s of 647 Canadian gold miners who had routinely inhaled aluminium since the 1940s (this used to be a common practice, thought to prevent silica poisoning), all tested in the ‘impaired’ range for cognitive function, suggesting a clear link between aluminium and memory loss.  A number of recent review papers have kept aluminium firmly on the map of potential contributors to dementia and AD.    While the mechanism for action of aluminium in brain degeneration is far from clear, alumunium does exert a pro-oxidant effect in combination with copper, but not an inflammatory effect. 

Beta-amyloid is a metaloprotein that contains zinc, copper, and iron. One hypothetical cause of its build-up and neurotoxic effect is that it mops up surplus metals and that these metals make beta-amyloid produce more hydrogen peroxide, a toxic free radical linked to its neurotoxic effect. Copper encourages this effect, while zinc appears to render beta-amyloid less harmful. This hypothesis, proposed by Dr Ashley Bush from Harvard Medical School, and colleagues from the University of Melbourne, Australia, has only been put to the test in a small randomized trial, giving AD patients clioquinol, a drug that prevents copper and zinc binding to beta-amyloid, thereby potentially promoting its dissolution and diminishing its toxic properties. This resulted in a reduction in deterioration of AD patients versus those receiving placebos.  This line of investigation is likely to encourage further research into the possible toxic effects of copper and protective effects of zinc.

Mercury is another potential cause for concern. Autopsies of brains from AD patients, compared to control patients of the same age, have shown raised levels of mercury.  Researchers from the University of Basel, Switzerland, have also found high blood mercury levels, more than double those of the control groups, in AD patients, with early-onset AD patients having the highest mercury levels of all.  Trace amounts of mercury can cause the type of damage to nerves that is characteristic of AD, according to recent research at the University of Calgary Faculty of Medicine, strongly suggesting that the small amounts we are exposed to, for example from amalgam fillings, may be contributing to memory loss.  Although the research on the link of mercury to AD is in its infancy, it is certainly logical to reduce exposure to this highly toxic metal. It is possible that a small amount of cases of dementia may be due to mercury toxicity, although it is unlikely to be a major contributor to the epidemic of Alzheimer’s disease.

Where’s the evidence? Enter ‘metals’ or ‘toxins’ and ‘dementia’ into the search field for a summary of studies on aluminium, mercury and dementia.

See action plan for our recommendations.

ACETYLCHOLINE ENHANCERS AND MEMORY
Whatever the contributory causes to the brain damage seen in AD, once the brain damage occurs, there is memory loss. Understanding how that occurs opens up avenues for treatment.

A memory is not held in one, but in several brain cells joined together in a network. The memory itself is thought to be put into storage by the neurotransmitter acetylcholine, and stored by altering the structure of a molecule called RNA within brain cells. The limbic system, which is the 'doughnut' on top of the brain stem, then has to decide if the memory is worth keeping. The amygdala, part of the limbic system, decides about more emotional memories, while the hippocampus decides about others. In AD the hippocampus loses its ability to file memories, resulting in an inability to create new ones. People with AD also show marked deficiencies in acetylcholine, no doubt largely because these acetylcholine-producing brain cells have been damaged or destroyed. Even if a memory is intact, without sufficient acetylcholine one cannot connect one part of the memory with others. For example, you know the face but can’t remember the name.

Most currently prescribed medication for dementia and AD block the breakdown or re-uptake of acetylcholine. An alternative approach would be to supplement the nutrients the brain uses to make acetylcholine in the first place. The primary precursor nutrient is phosphatidyl choline, the conversion of which is dependent on pantothenic acid (vitamin B5). However, phosphatidyl choline is synthesized from phosphatidyl dimethylaminoethanol (DMAE), itself synthesized from phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS), reactions dependent on good methylation. That’s where B vitamins, zinc and and magnesium are needed. While each of these nutrients has demonstrated mild memory promoting effects  the combined therapeutic effect of these ‘acetylcholine friendly’ nutrients has yet to be adequately explored in the prevention or treatment of AD patients.

Also of interest in the amino acid pyroglutamate, from which the drug Piracetam (and various other nootropic drugs) is derived. Early animal research indicated a potential to increase acetylcholine reception.   A recent meta-analysis of studies demonstrates a difference between those individuals treated with piracetam and those given placebo.  

Where’s the evidence? Enter ‘acetylcholine’ and ‘dementia’ into the search field for a summary of studies on acetylcholine enhancers and dementia/Alzheimers.

Side effects? None known in reasonable amounts.

Contraindications with medication? None known.

See action plan for our recommendations.

HERBS - GINKGO BILOBA AND VINPOCETINE
The herbs Ginkgo Biloba and the herbal extract Vinpocetine, have also demonstrated potential memory enhancing effects in the elderly. While a systematic review of all research up to 2002 concluded ‘promising evidence of improvement in cognition and function with Ginkgo’  three recent randomized trials on Gingko have failed to confirm earlier positive results for those with cognitive impairment  , however one  showed mild improvement for those who werenot diagnosed with dementia. Ginkgo may therefore have a role to play in prevention. Research on Vinpocetine, an extract of the Periwinkle plant, is also promising, but in its infancy.

Where’s the evidence? Enter ‘herbs’ and ‘dementia’ into the search field for a summary of studies on Ginkgo Biloba, Vinpocetine and Alzheimer’s/dementia.

Side effects? These herbs, in large quantities can reduce blood clotting. On rare occasions nose bleeds have been reported.

Contraindications with medication? Ginkgo biloba and possible Vinpocetine can thin the blood. If you are already on blood thinning medication you should discuss this with your doctor first.

See action plan for our recommendations.

References :

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 2. M. Morris et al., ‘Vitamin E and vitamin C supplement use and risk incident Alzheimer disease’, Alzheimer Dis and Assoc Disorders, Vol 12, 1998, pp. 121-6
 3. M. Sano et al., ‘A controlled trial of selegiline, alpha tocopherol or both as treatment of AD’, New Eng J Med, Vol 336, 1997, pp. 1216-22
 4. M. Morris, et al.. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol, vol 60, pp. 940-946 (2003)
 5. R. M. Sapolsky, ‘Why stress is bad for your brain’, Science, Vol 273(5276), 1996, pp. 749-50
 6.  R. M. Sapolsky and B. S. McEwen, ‘Stress, glucocorticoids, and their role in the aging hippocampus’, in Treatment Development Strategies for AD, Mark Powley Associates (1986), pp. 151-71
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11.  S. Seshadri et al.. Plasma homocysteine as a risk factor for dementia and AD. N Engl J Med, vol 346(7), pp. 476-483. (2002)
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