Treating Alzheimer's disease

• Introduction - treating Alzheimer's disease

• Current drug treatments

• Drug treatments for cognitive problems

• Drug treatments for co-existing conditions

• Talking therapies and support

• Alternative therapies

• The future

Introduction - treating Alzheimer's disease

Alzheimer's disease is a progressive illness - with symptoms such as memory loss and impaired thinking that gradually get worse. This is followed by loss of ability to do everyday things, behavioural difficulties and gradual loss of interaction with what happening So far there is no cure, and no treatment that will stop the condition developing. However, certain drugs can slow down the progress of the disease and improve a person's thinking and functioning. Three of these cholinergic drugs (listed below) are now recommended treatments in the UK. See "NICE delivers good news to Alzheimer's disease patients"

While physical treatment may be limited, there is much that can be done for the psychological health of people with Alzheimer's disease and their carers. Seeking early diagnosis and receiving information about the condition early in the illness helps patients and carers prepare for what lies ahead, rather than discover things alone by default. Support groups, specialist dementia services and talking treatments can be of immense benefit for people learning to live with the condition. It is important for carers to get support and to look after their own physical and mental health.

People with Alzheimer's disease may have other problems alongside it, such as psychosis, depression or a physical illness such as pneumonia. If these are treated effectively, the quality of life for people with Alzheimer's and their carers can be greatly improved.

Researchers are working to find new, more effective ways to treat Alzheimer's Disease, see below

Current drug treatments

Drug treatments for cognitive problems

Cholinergic drugs are the most common drugs for cognitive problems in Alzheimer's disease. They aim to preserve the chemical neurotransmitter acetylcholine (decreased in Alzheimer's), by stopping an enzyme called acetylcholinesterase, (the enzyme that normally breaks it down) from working. Three drugs in this category are recommended for mild to moderate Alzheimer's by the National Institute of Clinical Excellence ¹ (the body responsible for offering guidance on treatment for the National Health Service in the UK):

Donepezil or Aricept® - Probably the most widely used medication. People with mild to moderate Alzheimer's disease can usually tolerate it; but not all people respond to it. If it does work it can improve thinking and reduce behavioural problems. ^{2 3}

Rivastigmine tartrate, ENA 713 or Exelon® - This drug can significantly improve cognitive function in people with mild to moderate Alzheimer's disease ⁴ and is particularly useful in the treatment of sufferers with other medical conditions for example those with vascular risk factors. ⁵ This is because there seems to be very little interaction with other common tablets prescribed to the elderly.

Galanthamine or Reminyl® - has recently gained approval for use in Europe. It has a slightly different action to the other cholinergic drugs, but whether this makes it more effective is unclear. ⁶ The dual action is being studied, but this drug has extensive evidence to show its effect in all domains of Alzheimer's disease, and a significant effect on caregiver burden as well.

Problems with cholinergic drugs

• THEY MAY HAVE SIDE-EFFECTS: such as nausea, diarrhoea and abdominal pain in some people. ⁷
• THEY DO NOT WORK FOREVER: Their effects usually wear off in the short to mid term. The progress of the disease may be slowed down for several months (especially in people with mild Alzheimer's disease) but is not stopped.
• THEY MAY INTERACT WITH OTHER DRUGS: It is important to check that all drugs taken (prescription and over-the-counter) are compatible. ⁸
• THEY MAY INHIBIT THE RELEASE OF ACETYLCHOLINE IN THE LONG RUN: Cholinergic drugs work to increase amounts of acetylcholine in the brain. There's a danger that the brain will adapt to these increases, and will consequently produce less acetylcholine. ⁹ In these cases, an effect could be worsening cognitive problems, especially if the drug is stopped too precipitously.

Drug treatments for co-existing conditions

People with Alzheimer's disease often experience physical and mental health problems alongside it, including depression, sleep disturbances, behavioural problems and psychosis. Once physical causes are eliminated, and if behavioural methods and support do not help these problems, then drug treatment may be given.

Antipsychotics - preferably atypical, such as risperidone:

These drugs may be given to people with Alzheimer's disease who are aggressive or agitated. They are also given for psychotic symptoms such as delusions or paranoia. There is not a lot of published evidence in this area. What there is, is almost all for risperidone. ¹⁰

Typical antipsychotics are best not used as there is evidence they worsen the disease and little evidence that they are that effective. ^{11 12} Before any drugs are used, a thorough assessment is made of the person's social and environmental situation, and a physical examination carried out to check they are not in pain. This would usually be carried out by a doctor, in collaboration with experienced community staff. Any drugs used should be reviewed to ensure they are having the desired effect, and because these behavioural problems wax and wane in Alzheimer's disease, reviewed again after about four months to ensure they are still needed.

Find out more - see Treatment of schizophrenia

Anticonvulsants such as carbamazepine:

The use of mood stabilisers has increased in recent years, in spite of little published proof of their benefit. A series of small number trials using both carbamazepine and valproate are encouraging - but a definitive study has not occurred.

It would be appropriate to use these drugs where agitation or distress was not directly caused by psychotic phenomena (where an antipsychotic would be a better option), and this seems to be where anecdotal reports claim they do well, on their own or to supplement other therapies.

Find out more - see Treatment of bipolar disorder

Anti-depressants, such as paroxetine, fluoxetine:

Many people with Alzheimer's disease experience an episode of depression. This is happens at any stage of the illness, not just early - and the reason is not fully understood. The only published study of an antidepressant is using moclobemide. ¹⁴ This is a rarely used drug and most people choose a selective serotonin reuptake inhibitor (paroxetine, fluoxetine) or a mixed noradrenergic and serotonergic drug (mirtazapine,venlafaxine).

Older drugs, especially tricyclics (amitryptilline, prothiaden) have a high number of side effects and adverse events in patients with Alzheimer's disease. Cognitive problems such as memory loss can be a sign of depression as well as Alzheimer's, and anti-depressants can improve these problems. But older people can be more susceptible to side-effects of anti depressants than younger people and care taken accordingly.

Sleeping tablets:

These are often given for night time disturbance, or day/night reversal that is sometimes seen. Old valium-like drugs can accumulate in older people and cause confusion. Lorazepam is metabolised normally, so is safer to use.

It is probably better to use newer drugs like zopiclone, zolpidem or zalepton for sleep induction, or one older antidepressant in common use is trazodone, which is quite sleep inducing. Antipsychotics and sedative old tricyclics are often inappropriate - but still frequently used.

Talking therapies and support

Emotional and practical support, understanding and advice is essential to both the person with Alzheimer's and their carer(s). People respond to their condition in very different ways and so treatment should be geared to the individual.

• Talking therapies such as counselling can help people cope with the demands of caring for someone with Alzheimer's disease. It can also help people with Alzheimer's, especially in the early stages of the disease.
• Specialist dementia services and groups can improve the quality of life of sufferers and carers by providing information, support, understanding and respite care (link to Alz Disease Society). Groups and services helpful for people with dementia may include:

Reminiscence therapy encourages people to talk about past events, often assisted by photos, music, objects and videos of the past. There has been very little research in this area ¹⁵ but it can temporarily improve the mood and cognitive skills of people with Alzheimer's.

Creative therapies such as music, dance, crafts, art and gardening are stimulating and can help people express themselves and make sense of their environment.

Behaviour therapies usually offered by psychologists working in the memory assessment services, but also from occupational therapy and occasionally physiotherapy services. Behavioural therapies may be useful in offering guidance on dealing with (and preventing) difficult behaviours. Find out more from Alzheimer's Society leaflet.

Carers themselves constantly come up with ingenious solutions to everyday problems, hence the value of meeting in carers groups. Some people respond to dementia by becoming angry and argumentative, whereas other people will be passive and depressed. Most people are affected by their environment. Simple behavioural techniques can identify contributing factors that may help to stop problem behaviour or allow the carer to cope with it. A study of carer training in New York showed a delay in the sufferer going into a nursing home of almost a year, when the carer was better able to understand what was happening. ¹⁸

Alternative therapies

Nutritional supplements can be useful in Alzheimer's Disease:

• Vitamin E: Found in foods such as eggs, vegetables, vegetable oils, fruits and nuts. It is possible that Vitamin E might slow functional decline in people with moderate Alzheimer's disease. ¹⁹ A study from the USA showed a delay in entering nursing homes in people taking Vitamin E. This has convinced many professionals to take Vitamin E themselves, but the dose in the study was very high and most take less. The study needs to be repeated, but antioxidants like Vitamin E are good for the body in general, so it is a worthwhile strategy to ensure an adequate intake. Find out more…
• Ginkgo biloba extract: Sometimes called Egb 761, ginkgo can cause a moderate improvement in people suffering memory loss, cognitive impairment and Alzheimer's-type dementia. ^{20 21 22 23} No one is exactly clear how it works, possibly a combination of antioxidant and an increase in blood flow through the brain. In studies in the general population the drug seems to have a protective effect and it is widely taken. ²⁴ It is not available on prescription in the UK. Find out more…

These treatments can be easily obtained from health food shops, but medical advice should be sought beforehand because:

• They may interfere with other, prescribed therapies.
• They may produce adverse effects under certain conditions e.g., vitamin E may be associated with blood clotting problems in vitamin K deficient people. ²⁵

Aromatherapy massage and other complementary therapies: some people with Alzheimers Disease (and their carers) find these therapies useful for agitation, anxiety and sleep disturbances. They can also relieve physical discomfort. A guide to complementary therapy is available from the Alzheimer's Society

The future

A vaccine has shown promising results in specially bred mice, and trials are underway in humans in the UK and USA - and it is early days yet to predict how successful this will be. Methods to prevent Alzheimer's are still a long way off,. find out more, link to vaccine story but researchers are working on a number of different approaches to treating Alzheimer's disease, as interest in the area increases.

Investigations are presently underway to test new anticholinesterase cholinergic drugs.

A build-up of reactive molecules called free radicals may play a major role in Alzheimer's disease. Antioxidants neutralise free radicals and may help prevent or treat Alzheimer's.Oestrogen was first linked to Alzheimer's disease when it was noticed that post menopausal women undergoing hormone replacement therapy seemed less likely to develop the disorder. This is an observation rather than definitive proof, and treatment studies to date have been disappointing. It is an interesting and plausible treatment option, but longer term studies and further research in to understanding the interaction between oestrogen and the brain are needed - and ongoing. It is not recommended that oestrogen be used as a treatment in Alzheimer's disease, but it is another factor to weigh up if considering HRT for other reasons.

Nimodipine is used in some areas to treat dementia-type illnesses, and it may be of some use in Alzheimer's disease.

Anti-inflammatory drugs (such as Ibuprofen) have also been associated with a reduction in the frequency of Alzheimer's disease in patients with longstanding arthritis, which has sparked interest in their potential to treat Alzheimer's.

Adrian Burton

with input from Dr Roger Bullock, Clinical Director and Consultant at the Department of Old Age Psychiatry, Victoria Hospital in Swindon