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| CSIRO | SOLVE | Issue 9 | NOV 06 | |
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ARTICLE
PREVENTATIVE HEALTH:
Early Warnings Examined By Bianca Nogrady
A research 'cluster' will study 1000 Australians in a bid to identify the early warning signs of Alzheimer's diseaseAlzheimer's disease is a devastating condition; still largely unexplained and becoming more common. As the population ages, more Australians will be affected by this degenerative condition and so far medical science has been unable to prevent or cure it. Alzheimer's disease costs the Australian health system $3.2 billion a year in direct costs, a figure expected to reach $6 billion within five years. Indirect costs are also considerable. However, positively, if lifestyle or other interventions can delay the onset of the disease by even five months, there would be a five per cent reduction in the cost of Alzheimer's disease to the economy.
This has prompted CSIRO researchers to turn their attention to the disease's early detection and prevention. The Preventative Health Flagship has established a research 'cluster' for Alzheimer's, which brings together some of Australia's leading specialists in psychiatry, neuroscience, nuclear medicine, pathology, epidemiology and nutrition. Their focus will be a three-year study of 1000 Australians in Melbourne and Perth, with the hope of identifying reliable early warning signs. The next step will be to see whether diet and lifestyle interventions can be brought to bear on the disease. The $10 million cluster, which will undertake the Australian Imaging Biomarker and Lifestyle (AIBL) Flagship Study of Ageing, was created under the auspices of the Preventative Health Flagship in partnership with NeuroSciences Australia (NSA), a national consortium of neuroscience research bodies. The study is led by Professor David Ames, Professor of Psychiatry of Old Age at the University of Melbourne, and comprises researchers drawn from NSA members, including the University of Melbourne, the Mental Health Research Institute, Edith Cowan University and the University of Western Australia. The director of the Preventative Health Flagship, Dr Richard Head, says Alzheimer's disease was identified as an area of national need because of Australia's changing demographics. "With an aging population you want people to have healthier years with their longevity," he says. "You need to give people the ability to participate in community life in whatever way they want – volunteer work, continued employment – but you'll only get that if you've got healthy years, and you'll only have healthy years if you can reduce the burden of these chronic disorders." Professor Ashley Bush, a well-respected senior researcher at the Mental Health Research Institute of Victoria, says the cluster approach means no stone will be left unturned. "We've got a piece of everything, and that's very important," Professor Bush says. "We might be able to find that there is a lifestyle issue that stands out if you have a certain biochemical profile." In 2003, 162,000 people in Australia were diagnosed with Alzheimer's disease, representing 0.8 per cent of the population. By the time they turn 85, one in five Australians could have the disease. What begins as occasional forgetfulness slowly degenerates into a state where a person no longer recognises close friends and family, and requires constant, attentive care. Unfortunately, by the time any symptoms are noticed, the disease process in the brain is well advanced. Alzheimer's disease is characterised by the build-up in the brain of plaques of a protein called amyloid, and when disease is diagnosed these plaques are rife. A key research leader in the cluster will be Professor Colin Masters, whose co-discovery of the structure of amyloid in Alzheimer's disease plaques has enabled many advances understanding the disease over the past 20 years.
One approach to early diagnosis of the disease may be to look for the first signs of these plaques. Nuclear medicine physician and neurologist Associate Professor Christopher Rowe, who heads the neuroimaging arm of the cluster, is evaluating a new imaging agent called Pittsburgh Compound-B (PIB) for brain scans. "It's derived from a chemical dye that pathologists have been using for decades to stain amyloid in post-mortem brains," says Professor Rowe, director of Nuclear Medicine and the Centre for PET at Melbourne's Austin Health. The AIBL study will be the world's largest of its type using PIB. Increasing evidence suggests these scans will enable the researchers to detect the very early signs of amyloid accumulation in the brain. "That will enable us to relate diet and lifestyle factors to amyloid accumulation, which may turn out to be more sensitive than waiting for people to show Alzheimer's disease symptoms," Professor Rowe says. "Obviously if you can treat something before it has done irreversible brain damage then you've got a much greater chance of success." Taking the same approach but from a different angle, another group of researchers in the cluster are looking for a blood test for early diagnosis. Diagnosis currently relies on psychometric tests such as the Mini Mental State Examination, which assesses cognitive mental state, but by the time clinical symptoms are advanced enough to be picked up by psychometric testing, much of the damage has already been done. Monitoring levels of Alzheimer's biomarkers in the blood will also allow researchers to continuously evaluate the impact of diet and lifestyle interventions on progression of the disease. Professor Ashley Bush in Melbourne and Professor Ralph Martins in Perth are leading the research on biomarkers for Alzheimer's disease. An obvious first candidate for a biomarker is the plaque-forming ß-amyloid protein, which forms plaques in the brains of people with Alzheimer's, Professor Martins, Foundation Professor of Ageing and Alzheimer’s at Edith Cowan University, says. "Its levels definitely build up in the brain and levels have also been shown to rise in the blood," he says. Current blood tests for amyloid protein are not sensitive enough, and the situation is complicated by the fact that in the blood, ß-amyloid binds to a whole range of other proteins, making it much harder to detect. "There is a hint that there is a large pool of amyloid bound to other proteins, much larger proteins such as albumin, but that has been very poorly investigated." In this study, researchers will take blood samples from participants every 18 months and screen the blood for biochemical and haematological parameters. The study design means they can then compare the changing levels of amyloid and other biomarkers in patients over time. Of the 1000 people involved in the study, 20 per cent will already have been diagnosed with Alzheimer's disease and another 20 per cent will have clinically defined mild cognitive impairment but not diagnosed with Alzheimer's; this group is believed to be at high risk of developing Alzheimer's disease.
Another 20 per cent of participants will have less specific memory problems, 20 per cent will be mentally healthy but have a genetic mutation that predisposes them to Alzheimer's disease, and the last 20 per cent will be completely healthy. This selection of participants will allow the researchers to correlate the biomarker data with data from the neuroimaging and psychometric arms of the study. "Once it's clear which individuals definitely have Alzheimer's disease according to the neuroimaging, we can then look into screening for other markers that might be more sensitive," Professor Martins says. Once researchers are better able to monitor progression of Alzheimer's disease, they can evaluate the effectiveness of dietary and lifestyle interventions. Little is known about what causes Alzheimer's disease, according to Professor Bush. "Age is the number-one risk factor but Alzheimer's is a disease, it's not simply a variant of normal aging," he says. "We know there's a protein (amyloid) involved, but we're born with that protein, so there's no reason why production of that alone should cause the disease." One theory the cluster is examining is that Alzheimer's could be triggered by abnormalities in regulation of metals such as copper, zinc and iron in the brain, with evidence suggesting these metals interact with amyloid in the brain and cause plaques to form. One approach to prevention may be to use a drug called chloroquinol, which binds to the metals and deactivates them, preventing the formation of plaques. The cluster is also focusing on non-pharmaceutical interventions. Research suggests that Alzheimer's shares many risk factors in common with heart disease, such as high cholesterol, smoking, high blood pressure and lack of exercise – all of which can be modified with changes to diet and lifestyle. Dr Head says CSIRO has particular strengths in the area of nutritional research. "What has really occurred over recent decades as a generality is an understanding that some foods go beyond sustenance, that they actually have a protective role," he says. "CSIRO has the capacity to understand the constituents within food and has the ability to actually fractionate or separate those components." This will allow a new depth of understanding of the health potential of foods in a whole range of chronic conditions. It will be several years before the first results emerge from the study, but it is already sparking interest from overseas, according to Professor Martins, who says the multifactorial, preventative approach is an important first for Alzheimer's research. "I think we are probably leading the world with the level we're looking at this". For further information contact: |
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