A progressive, inexorable loss of cognitive function associated with an excessive number of senile plaques in the cerebral cortex and subcortical grey matter, which also contains b -amyloid and neurofibrillary tangles consisting of tau protein ¹.

Alzheimer’s is a progressive degenerative disease of the neurons in the brain associated with the neurotransmitter Acetylcholine, where it may show up as senile plaques or lesions. It is the most common cause of dementia, with widespread cerebral damage that manifests in a variety of symptoms, including memory loss, disorientation, restlessness, impaired judgment, and irritability.

In 1906 German neurologist Alois Alzheimer happened to perform an autopsy on the brain of a 56-year-old woman, who had died after several years of progressive mental deterioration marked by increasing confusion and memory loss. Using new (at the time) staining techniques he noticed an odd disorganisation of the nerve cells in her cerebral cortex. The cells were bunched up like ropes tied in knots. He called these bunches "neurofibrillary tangles". He also saw an unexpected accumulation of cellular debris around the affected nerves, which her called senile plaques. He speculated in a journal article that the tangles and plaques might have been responsible for the women’s condition. Over the next few years autopsies revealed similar findings.

Alzheimer’s is believed to affect between 5 – 10% of people over the age of 65 years² and up to 47% of people over the age of 85 years of age³.

In Australia, AD is the most common cause of dementia accounting for 50 to 60% of cases. It has been estimated that the number of Australians over 80 years of age will increase approximately 65% over the next 20 years⁴.

Women are more susceptible to Alzheimer’s Disease than men. By the age of 90 they are 13% more likely to develop the condition⁵. In addition, women who develop the condition decline more rapidly than men⁶.

A definite cause of AD is unknown. Current wisdom suggests that there may be a number of factors that must occur in sequence or combination to bring about the condition. The following list presents many of the prevalent theories on cause today.

Fat consumption with high total caloric consumption – a compelling meta-analysis has shown that there is a very strong correlation between a high fat/caloric diet and the incidence of AD⁷. Significant clinical studies, which are still in progress, support this hypothesis⁸.

Oxidation and free radicals – oxidative damage is shown to contribute to development of AD. Brain tissue is especially susceptive to free radical damage and does not have many of its own natural antioxidents⁹.

High LDL Levels – LDLs favour the deposition of b -amyloid the major component of senile plaques found in AD¹⁰.

Deficiencies of acetylcholine (ACh) – it is widely held that a decrease in the production of the neurotransmitter acetylcholine is responsible for most of the signs and symptoms of AD. In AD, cholinergic nerve terminals in the brain are specifically attacked. The resultant decrease in ACh may be due to either a decrease in the activity of the enzyme responsible for producing ACh (choline acetyl transferase), or an increase in the enzyme that destroys ACh (acetylcholinesterase)¹¹.

Nitric Oxide Hypothesis – NO is an important component of brain function; however, increased amounts can cause brain cell death. Increased NO is released in response to various stresses, and toxins released by infective agents. Repeated bouts of systemic illness could lead to excess release of NO and subsequent cell death¹².

Low B9, B12 and high Homocysteine levels – an increased level of homocysteine has been implicated in much pathology including AD. Both Folic Acid and B12 are involved with the metabolism of homocysteine and disruptions in the metabolism of homocysteine have been linked with the incidence of AD¹³.

Biochemical changes in growth factors – decrease in neural growth promoting factor (nerve growth factor, NGF) causes nerve cell death, and may be related to AD¹⁴.

Toxic chemical excess – aluminium is often related to AD; however, it is still a matter of debate as to whether it causal or subsequent to the disease. It is known that Aluminium can cause progression of AD once established¹⁵.

Genetic factors – It was noted that individuals with Down’s Syndrome that survived to 50 years of age almost always developed dementia. Subsequently it has been found that certain genetic defects result in a higher prevalence of AD.

Autoimmune theory – anti-brain antibodies have been found in AD & non-AD patients. The significance is unknown; however, it is known that b -amyloid peptides evoke an immune response from the brain’s immune system that can result in damage to brain tissue².

Slow virus theory – similarities between AD and other diseases, which are known to be caused by a virus, have led to this hypothesis. At this point in time there is not enough evidence to either confirm or deny this theory¹⁶.

Blood-brain barrier damage – damage to the blood brain barrier is suspected owing to a prevalence of the development of AD in patients with head trauma earlier in life. It is suspected that damage to the barrier permits entry of toxins and other agents that may be responsible for AD¹⁷.

Diminished oestrogen – the prevalence of AD is high in post-menopausal women that are not using HRT. It has been found the oestrogen has many preventative effects on the development of AD¹⁸.

High Blood Pressure – research has shown a relationship between high blood pressure and reduced cognitive function¹⁹.

In Alzheimer’s there is a marked gradual deterioration of all mental processes – this can be viewed to occur in clinical stages. It should be noted that there is great variation amongst patient signs and symptoms and naturally progression of the condition does not follow the same pattern in all cases.

The early stage¹:

• Loss of recent memory
• Inability to learn and retain new information
• Language problems (particularly word finding)
• Mood swings
• Personality changes
• Progressive decrease in ability to perform activities of daily living (balancing chequebooks, reading maps)
• May not result in anti-social behaviour but family will note "strange" behaviour (like getting lost on the way to the local shops)

The intermediate stage:

• Unable to learn and recall new information
• Memory of distant events is affected but not totally lost
• Assistance with bathing, eating, dressing, and toileting may be required
• There may be wandering, agitation, hostility, uncooperativeness, or physical aggressiveness
• Loss of all time and place as normal cues are used ineffectively
• Sufferers often get lost, sometimes to the point of not being able to find the bathroom, bedroom etc
• Risk of falls and other accidents is increased due to confusion

The severe stage:

• Sufferers are unable to walk or perform any activity of daily living
• Usually totally incontinent
• Memory is completely lost
• May be unable to eat and swallow – the risk of malnutrition, pneumonia (from aspiration) and pressure sores is high
• Owing to the level of care required patients are often placed in institutions
• Eventually patients become mute
• Because patients cannot speak and there is often no febrile or leucocytic response to infection in the elderly people can only guess as to when a patient is ill

The end stage is usually coma and death, usually from infection.

Currently AD cannot be diagnosed with 100 percent certainty until a brain autopsy is conducted. An accurate diagnosis of the type of dementia is essential, as many forms of dementia are in fact reversible if treatment is applied early enough.

Diagnosis of AD rests largely on the judgment of doctors experienced in dealing with dementing illnesses. However, the ability of such physicians is quite sophisticated – it is estimated that diagnostic accuracy sits at around 85 - 90%.

Diagnosis is based on history, physical examination, laboratory tests and the exclusion of other causes of dementia. A formal mental status exam is usually performed, the Folstein Mini-Mental Status Examination being the most common.

The following criteria are used to establish a diagnosis of AD¹:

• Dementia established by a clinical examination and documented by a formal test of mental status
• Deficits in two or more areas of cognition
• Progressive worsening of memory and other cognitive functions
• No disturbances of consciousness
• Onset between the ages of 40 and 90
• No systemic or brain disorders that could account for the progressive deficiency in memory and cognition

A MRI, PET, or CT scan is used to eliminate other forms of dementia or brain disease. A recent report suggests that a MRI may be used to diagnose AD before onset of condition-related symptoms²⁰.

Metabolic screening tests are also used to provide differential diagnosis including tests for B12 deficiency, thyroid problems, and electrolyte imbalance²¹.

Research is currently focused on developing a practical reliable early diagnostic technique for AD.

Owing to the essential need to accurately diagnose AD and differentiate it from other, reversible forms of dementia, naturopathic investigations should never be used without the patient being diagnosed by an expert in the field. The trauma caused by an incorrect diagnosis of AD would obviously be extreme.

The following investigations may give rise to suspicion of Alzheimer’s.

• Fingerprint patterns²²
• Aluminium, cadmium and lead – hair analysis for these and other toxic metals²³
• Vitamin B12 deficiency
• Food sensitivities – especially wheat and milk²

As AD is irreversible most treatments are used to slow the progression of the condition or to treat the accompanying symptoms (depression, anxiety, sleeplessness etc). Naturally the chief concern of all caregivers is the quality of life they can provide for the patient. Given the nature of the condition compliance with any treatment is difficult and supervision is required to insure medication is actually taken.

Cholinesterase Inhibitors – It is suspected that drugs that either boost ACh production or decrease cholinesterase activity may improve the patient’s condition. Two drugs currently used are tacrine and donepezil. They are both cholinesterase inhibitors. Tacrine (Cognex) is costly and shows limited effectiveness in the clinical environment, it also has significant side effects including nausea vomiting and possible liver damage. Donepezil (Aricept) has lesser side effects and is more cost effective but like tacrine does not work for all users.

Eptastigmine – is the latest drug to be tested against Tacrine and Donepezil it apparently slows cognitive deterioration as well as the other two drugs but provides the additional benefit in helping people carry out the tasks of daily living.

Acetylcholine boosters – these drugs are still in development and include xanomeline, milameline, SB-202026, AF-102B, and ABT-418.

Antioxidant therapy – The antioxidant drug Selegiline has been shown to have mild improvement on memory in a Czech study. The same drug has been shown to enhance the benefits of Tacrine¹⁸.

Estrogen – can be used with female patients. Several studies have shown that women taking estrogen post-menopause have an unexpectedly low incidence of AD. Estrogen has the effect of boosting acetylcholine production, and inhibits the deposition of b -amyloid.

NSAIDS – ibuprofen, naproxen, indomethacin, and meclofenamate have all been shown to delay the progression of AD when used long term; however, the severe side effects of long-term NSAID use are acknowledged.

Nerve Growth Factor (NGF) – is being tested, the biggest problem with its use is overcoming the blood-brain barrier.

Vaccination – a recent report has shown evidence for a vaccine that prevents the formation of b -amyloid plaques in mice. The blood protein apoE has been shown to prevent deposition of amyloid plaques in mice.

There is no treatment that can reverse AD, but it seems likely that diet can play a role in the prevention of AD. Evidence suggests that some supplements can slow the progression of AD to some extent.

Naturally, compliance is one of the biggest problems with AD patients. Depending on the stage of progression, a caregiver will probably have to prepare most meals. A further consideration, given the age of the typical AD patient, is deterioration of the GIT and consequential absorption issues.

The ability to provide quality of life for both patient and carer is a big issue in the management of an AD case.

In general the following factors should be considered when developing a diet for someone suffering from or attempting to prevent the onset of AD.

A diet with the following objectives should be devised:

• High in antioxidants – to reduce oxidative damage.
• High in the specific nutrients, B6, Folic Acid and B12 – to metabolise homocysteine.
• High in phytoestrogens – especially for women due to relationship to estrogen levels.
• High in EFAs particularly fish oils (EPA) balance with Omega 6 – to help manage inflammatory responses in neural tissue.
• Low in goitrogens – due to potential thyroid involvement.
• Lower cholesterol – due to suspected LDL involvement in pathogenesis.
• Lower blood pressure – due to suspected involvement in pathogenesis.
• Generate a balance of alkalising/acid forming foods⁷ – due to suspected involvement in pathogenesis.
• Low in total calories – due to suspected involvement in pathogenesis.

Table 1 lists some suggestions to meet these criteria.

Table 1: Foods to consider in diet.

• Drink filtered water in order to avoid toxic metals - especially aluminium and lead – possible involvement in pathogenesis.
• Provide adequate hydration to avoid "secondary" dementia from dehydration.

• Reduce alcohol intake (2 glasses red wine/night for antioxidants) – impact on neural tissue.
• Avoid allergenic foods – suspected involvement with pathogenesis.

In addition to using supplementation of the nutrients outlined above the following should be considered:

Multivitamin Supplements – several studies have shown over the years that vitamin supplements improve memory and mental functioning²⁴. This will also provide a source of B vitamins involved with homocysteine metabolism as well as a source of Vitamin C for serine synthesis (see below).

Carnitine – is composed of lysine and methionine. Two studies show that it supports certain AD patients, by slowing mental deterioration^{25, 26}. It has been shown to aid in the synthesis of AcetylCholine.

Provide adequate material to aid the manufacture of acetylcholine? Given that one of the results of AD is a disruption in the enzymes that either create or destroy ACh it is not surprising to find that simply supplementing with choline has proved unsuccessful.

Phosphatidyl serine – is the major phospholipid in the brain that plays a major role in determining the integrity and fluidity of cell membranes. However, it is extremely expensive and the body can make it from the basic constituents EPA, B9, B12 and Vitamin C²³.

Ginkgo biloba extract – Studies have shown it to be a powerful agent in the treatment of AD²⁷. It has been shown to improve cerebral blood flow.

Avoid aluminium – the basis for concern over aluminium and its impact on Alzheimer’s patients was a study that appeared in The Lancet in 1989. The study linked an increased risk of Alzheimer’s to drinking water with more than 11 micrograms of aluminium per litre²⁸. There is still much controversy over Aluminium and it being a cause or a result of Alzheimer’s – at this point in time it cannot hurt to exercise caution. The following everyday sources should be considered: Cookware, anti-diarrhoeal preparations, douches buffered aspirin, food additives, antacids, shampoos, deodorants, and containers (cans).

Avoid High Levels of Zinc – Australian researchers showed that unusually high levels of Zinc promote brain changes similar to those found in Alzheimer’s. However, low levels of Zinc caused no such problem²⁹. It is advised that Zinc supplementation be kept to under 30mg/day according to the Editor of The Townsend Letter for Doctors and Patients.

• Do not smoke – along with everything else it feeds carbon monoxide to brain cells.
• Stay mentally active – studies have linked education to a reduced risk of mental impairment in the elderly.
• Get enough sleep – reduced sleep impairs many mental functions.
• Reduce Stress – adrenaline can damage the hippocampus.
• Beware indoor air pollutants – a woman was diagnosed with AD but it turned out to be the result of living in a poorly ventilated brand new unit exuding toluene. The family had booked a nursing home and everything!
• Enjoy complex music – tests have shown that short bursts of complex (non-repetitive music) boost intelligence.
• Have hearing checked – could be a person is not forgetting but not hearing in the first place!
• Beware of lead – an obvious factor in cognitive impairment.
• Exercise!! – multiple benefits are derived from exercise in terms of mental alertness.

The following herbs may be useful in the treatment of AD.

• Ginkgo biloba (Ginkgo)
• Rosmarinus officinalis (Rosemary)
• Salvia officinalis (Sage)
• Melissa officinalis (Lemon Balm)
• Bacopa moniera (Brahmi)

Aromatherapy massage has been found to minimise disruptive behaviour in people with AD. As little as two six-minute massages per day have been shown to be beneficial³⁰.

Alzheimer’s Association has a national office based in Canberra and produces a national newsletter, ‘Dementia Today’.

Alzheimer’s Association (Australia)

PO Box 191 Deakin West ACT 2600

Tel: (06) 285 3684 Fax: (06) 285 3711

Alzheimer’s Association NSW

PO Box 42 North Ryde 2113

Tel:(02) 805 0100 Fax: (02) 805 1665