An active and healthy life reduces the risk
In July 2009, the EU Commission launched a raft of proposals for pan-European measures on preventing, diagnosing and treating Alzheimer's disease. The research conducted at Karolinska Institutet is at the cutting edge as regards both diagnostics and prevention. Scientists here are also working diligently to find curative drugs.
Alzheimer's disease is largely attributable to genetic factors, but the risk can be minimised by adopting an active and healthy lifestyle. Scientists hope one day to be able to find ways of offering special preventative treatments for people with a raised genetic propensity.
Why some people develop Alzheimer's disease while others remain healthy is still partly a puzzle, but what scientists do know is that genes have a hand in the process. The average risk of developing the disease is one in ten; for people whose siblings, children or parents have or have had the disease, the risk approximately doubles.
Scientists have so far found one risk gene, APOE, that greatly affects the risk of developing Alzheimer's disease. People with a copy of a certain allele called APOEε4, have a two or four-times higher risk of falling sick at some time in their lives.
According to a common calculation, this allele accounts for about 20 per cent of all Alzheimer's cases. However, the significance of APOEε4 for the individual must not be overstated. Scientists work on the assumption that there are many other unknown genes playing a part, and lifestyle factors are probably just as important.
"Most carriers of the risk genes, such as APOEε4, will never get Alzheimer's, and most of those who do, don't have the risk gene - so we can't predict from a test whether someone will fall ill or not," says Caroline Graff, clinical geneticist and researcher at the Department of Neurobiology, Care Sciences and Society.
Gene testing for APOEε4 is controversial and is offered today by some laboratories and commercial companies, but generally not by the national healthcare services. In her work as clinical geneticist at Karolinska University Hospital's geriatric unit, Dr Graff often encounters people who wonder if they are at particular risk of developing Alzheimer's. She feels that only testing for APOEµ4 can be misleading and causes unnecessary worry. People concerned about their own risk would do better to consult a specialist for genetic guidance, in which other risk and health factors will also be taken into account.
"If it was possible to offer some kind of preventative treatment to people with a higher risk, there'd be a point in also carrying out APOE tests," she say. "Maybe it will be available in the future, but at present it isn't."
Miia Kivipelto, doctor and associate professor at the Department of Neurobiology, Care Sciences and Society, believes that there will one day be stronger reasons for the general testing of risk genes. In a number of much written-about studies, she has shown that middle-age lifestyle and health factors are linked to the risk of developing Alzheimer's disease later on in life. Some of them, such as physical inactivity, high alcohol consumption, smoking and a high intake of saturated fats, are thought to have a particularly adverse effect on people with APOEµ4.
"This needs to be confirmed by further studies, but it seems to be the case that carriers of the vulnerability gene have to be particularly careful about their lifestyles," says Dr Kivipelto. "If it turns out to be true, I think it'll be difficult to explain why people shouldn't find out if theyre carrying the allele."
However, little is still known about how much dementia can actually be prevented through changes in lifestyle. Dr Kivipelto hopes that many questions will be answered by FINGER (the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability), an intervention study currently in progress. One half of the study population is being given specific help living in accordance with the lifestyle that epidemiological studies have shown to be linked to a lower risk of Alzheimer's, the other half is receiving standard care. All participants are tested for APOEε4, which makes it possible to see if the genetic risk of Alzheimer's disease in old-age is affected by changes in lifestyle.
Things are different, however, for familiar early-onset Alzheimer's, a form of the disease that has a much stronger hereditary component and that exists in only a few families. In some cases, the cause is mutations in one of the known genes APP, PSEN1 or PSEN2. The mutation is inherited by half of the family members, and those who carry it will develop the disease with 100 per cent certainty.
When Dr Graff is contacted by families with many sufferers, she can offer what is called "genetic guidance". The first step here is to chart the disease systematically in the family; the more that develop the disease and the earlier its onset, the more genetic its cause.
"Many people are convinced that they'll get sick, and get really surprised when they hear that they actually have a 50 per cent risk."
In some cases, both sick and healthy family members have to be tested for the known mutations. A negative test result can be a great relief; a positive test result can have serious consequences on how people are then to plan their lives, and this includes having children.
"Only a tiny minority get themselves tested, and in only a few of these do we find a mutation," says Dr Graff.
Dr Graff's research focuses on finding new genes involved in Alzheimer's disease, and through large population studies, she is trying to find more risk genes, which, like APOEµ4, contribute to the common, late-onset form of the disease. She also studies seriously affected families to locate new mutations that lie behind the strongly hereditary, early-onset form.
"We're learning a great deal about the disease through the genes," says Dr Graff. "The three most famous Alzheimer's genes to date have opened up the entire field of focus for Alzheimer's research. If we can find more genes behind the disease, maybe it'll turn out that there are completely different mechanisms at work that we were previously aware of."
Text: Ola Danielsson. Published in Medical Science, issue no. 3, 2009.