The Alzheimer's Puzzle

A US study shows that better educated sufferers of dementia are able to stave off the affliction's most debilitating effects longer.

Ronald Reagan, the 40th president of the United States, suffered from Alzheimer's disease and died at the age of 93, 14 years after leaving office.

Despite ongoing discoveries regarding some of the mechanisms of Alzheimer's disease, effective treatments remain as elusive as the true nature of the disease. First described in the early 20th century by Alois Alzheimer, a German clinician, the illness tends to affect people aged 65 and over. The risk of developing the disease roughly doubles every five years after age 65. While everyone from paupers to presidents - most notably the former US president Ronald Reagan - is at risk, the degree to which people can cope with the condition varies. For example, latest research shows that a victim's level of education may play an important role.

A study published in the Archives of Neurology said that well-educated Alzheimer's victims performed better in problem solving and memory tests than less-educated patients. Among people who did not have the condition, or who had few of the brain plaques - accumulations of a protein fragment - that develop in sufferers, the test performance was not influenced by educational level. The research, which was led by Catherine Roe of Washington University School of Medicine in St Louis, Missouri, did not produce surprising results, according to Sir John Grimley Evans, professor emeritus of clinical geratology at Green College at the University of Oxford. Previous studies, he says, have made similar findings.

One suggestion, according to Sir John, is that better educated or more intelligent people can more easily "cover up" their condition and compensate for its effects. "Most people think it's reasonable that if your brain starts to go, you find ways round it if you've had a good education and can find a number of ways of dealing with problems," he says. Population studies appear to support this explanation. For example, in the United States, Sir John says disabilities in old age related to dementia are becoming less common even though the population is ageing.

"In the case of the black population, this has been correlated with the improvement in their education," he says. Another hypothesis to explain the better performance of educated Alzheimer's patients is that people with lower education levels have spent their careers in more hazardous jobs. "They have been exposed to other things that damage their brain. They may smoke more, drink more and may have been exposed to industrial chemicals," he says.

"These things have got to be thought of, but most people think the idea that the brain can compensate longer [in more educated people] is the most likely explanation." If education can help compensate for Alzheimer's, Sir John says it means people should stay mentally active to stave off the condition. Indeed, patients with Alzheimer's are encouraged to keep their minds exercised by, for example, setting themselves tests.

However, Sir John says by the time someone is diagnosed, their ability to learn new things is impaired. "These ways round your difficulties have got to be there before you have the difficulties," he says. Just as individuals vary in the extent to which they can compensate for the brain damage caused by Alzheimer's, so the speed at which deterioration occurs shows "enormous variation". The time between a patient first presenting with symptoms and being unable to look after themselves varies, as "a very crude measure", from two to 10 years in Sir John's experience.

"I've known patients who've deteriorated and become static and then deteriorated again," he says. The huge variation could stem from the possibility that more than one disease is affecting the patient. Since diagnoses are nearly always made on the basis of symptoms, rather than brain biopsies - once in vogue but generally not performed now - it is possible several conditions are being lumped together.

Doctors certainly believe that early-onset Alzheimer's, which affects people prior to their 50s, represents a distinct form of the disease. It is usually more aggressive and is thought to have a genetic component since it is heritable. Unfortunately, Sir John says research into possible environmental factors behind Alzheimer's has not yet yielded significant results. "My own field was looking at the epidemiology and causes in diet and lifestyle, but we came up with nothing very definite," he says.

Laboratory studies have attempted to discern the biochemistry of the condition and there are several lines of inquiry. One looks at the neurotransmitter acetylcholine, which is depleted in brains affected by Alzheimer's. Doctors have prescribed sufferers with acetylcholinesterase inhibitors, which are drugs that interfere with the enzymes that break down acetylcholine, a major neurotransmitter in the brain. "There has been a big row over whether they could be prescribed on the NHS [Britain's state funded National Health Service]," says Sir John.

"About a third of people show some benefit. Sometimes it's a slowing up, sometimes it's a small improvement. They don't make enormous difference but they sometimes do buy a little more time. "My view is that they're worth a try. I used to run a memory clinic and I saw some promising results in some people." Scientists have also focused on amyloid beta, a protein fragment that makes up the brain plaques of people with Alzheimer's.

Mutations in a gene that codes for a precursor protein to amyloid beta are thought to cause early-onset Alzheimer's. Other evidence pointing to the involvement of amyloid beta in Alzheimer's comes from looking at people with Down's syndrome. Such individuals have three copies - instead of the normal two - of chromosome 21, which contains the gene that appears to regulate plaque development in the brain. Duplicate copies of chromosome 21 appear to make those with Down's syndrome more susceptible to Alzheimer's, as most individuals with Down's syndrome develop the brain disease by the time they are 40.

Vitamin supplements have also been experimented with to inhibit plaque formation, although Sir John says "the jury is still out" on their effectiveness. "The necessary trials have not yet been done. People hope there's something in it, but as we don't know what causes the problems, we're probably not doing the right experiments," he says. @Email:[e-mail]