Alzheimer's Disease - Many Lights, Long Tunnel?

Dr Roy Jones, The Research Institute for the Care of the Elderly, St Martin's Hospital, Bath, on 25 January 2002

About 60 people attended on a wet, windy evening to hear Dr Jones. He did not evade the use of technical terms, but explained those it was necessary for the audience to understand. It was clear during the discussion that many of them were familiar with these terms. Alzheimer's disease is one of several dementias; these are defined as acquired decline in memory and other thinking processes, and of behaviour, which is usually progressive. Alzheimer's is usually treated in the UK by psychiatrists and geriatricians although in Europe and Canada treatment is by neurologists.

One in five people over 75 get Alzheimer's; 50% of all nursing home patients have it. Survival is in the range 4 - 20 years, generally 8-10, and because of the demographic changes in the population the numbers over 80 with it are expected to rise from 386,000 to 572,000 by 2011.

Since the disease is diagnosed as a change in behaviour and ability, it is essential that doctors talk to the family of the patient to establish what changes have been observed.

The indications of Alzheimer's (that should have been present for at least six months ) are:

• Loss of short-term memory, initially episodic, although immediate memory is spared

• Loss of orientation (what day is it?)

• Loss of judgement

• Altered behaviour (eg apathy, aggression)

• Disturbance of speech

• Loss of motor skills

• Difficulty in performing complex tasks, like planning and organising

The decline can be estimated at about 10-15% per year, but is not a straight line, and the younger the patient the faster the decline usually is.

An absolute diagnosis cannot be obtained until after death when the brain can be examined, although an EEG can often determine whether CJD is present. Death is rarely due to Alzheimer's directly, but instead through side effects like lack of mobility.

Diagnosis involves

• Taking family history

• Formal tests

• Physical and laboratory tests

• Brain scan

• EEG

Some risk factors are: age, head injury, gender (females more likely than males); educational standard (the more education the lower risk, perhaps because the brain has developed more reserve capacity). Genes on 5 chromosomes have been implicated in Alzheimer's disease, 3 that can cause the rare early onset familial form, and 2 that increase susceptibility for the later onset form. All of these affect the processing of amyloid proteins.

There are no confirmed protective factors, but oestrogens, statins and moderate intake of alcohol may have an effect.

Post-mortem examination of the brain indicates that changes in the hippocampus and loss of neurons, especially in the temporal and frontal lobes, amygdala and nucleus basalis of Meynert, occur.

Treatment with drugs is effective in delaying development for a short time, typically about a year. Current drugs interfere with the action of acetylcholinesterase; newer drugs being tested prevent amyloid accumulation or act on glutamate receptors. The drugs used to reduce inflammation in arthritis may affect Alzheimer's; one trial suggested that exposure for two years reduces onset to 20% of untreated levels. The development is hampered by the difficulty of diagnosing the condition and measuring the responses. Animal models have only recently become available.

An attempt has been made to prevent amyloid being deposited by immunisation against it. Animal results were very promising and studies in humans have started. Unfortunately at present the trials have been suspended after problems with the treatment occurred in France.

Carers of Alzheimer's sufferers are mostly worried by behavioural problems and help for them is a major concern of those treating patients. They often show signs of overall stress, may have financial concerns, feel isolated, and suffer emotional problems related to feelings of guilt, hostility and grief.

Discussion

Dr Jones agreed with a comment that a patient can die with or of Alzheimer's; many are suffering other complaints associated with their age which cause their death.

Behavioural modification is often helpful and works best if the family or staff looking after the patient are enthusiastic to adopt the treatment. It is difficult to prove scientifically that it works.

Placebos often produce short-term improvement, perhaps because the patients receive more attention.

A coronary by-pass operation may sometimes cause memory problems if the oxygen flow to the brain is reduced during the operation, although care is taken to prevent this.

The effect of IQ, race and religious devotion was queried, but only IQ, as a link to education and achievement, may affect the onset of Alzheimer's. People with higher ability may have more strategies to get around the problems, and so delay the onset of symptoms.

Stress has not been shown to increase the risk to patients, but does to carers; depression does affect patients.

Getting informed consent from a patient for drug treatment is sometimes difficult; trials are often confined to patients with slightly impaired memories and their carers are consulted. It is more difficult to involve more severely affected people but necessary if we are to improve treatment for them.

The effect of aluminium as a cause of dementia is still under investigation; it is known to affect dialysis patients producing dialysis dementia although this can now be avoided by controlling the amount of aluminium in the dialysis fluid.

The donations received from the audience on this occasion were given to RICE, which is a registered charity.

Don Lovell