Delaying Dementia Next Best To A Cure

By Bianca Nogrady, Australian

Australia

August 30, 2008

At this stage of life, Jane and Michael d'Arbon should be looking forward to retirement, long holidays, seeing their four children set off to make their mark on the world, and watching the next stage of their life together take shape.

Instead, they're giving interviews on the devastating impact of Alzheimer's disease. They can't make plans beyond the next 10 years, because Michael is unlikely to survive that long.

D'Arbon used to be a successful criminal barrister in Sydney, crossing swords with the best and worst of them. He loved his job, especially the camaraderie of fellow lawyers. But three years ago, at age 49, "that was shot to pieces". A diagnosis of early-onset Alzheimer's disease ended his courtroom career.

D'Arbon is now at home all day, every day, restoring furniture for friends, helping his former colleagues with the occasional legal brief and running limited errands for his wife.

"I was sort of looking forward to a bit of a break every now and then, but this is a very long one," d'Arbon says. Diagnosed three years ago, the disease is already starting to steal away some of what made him unique.

"He's always been a jolly joker and a laugher, and that part is still the same," his wife says. "What's changed is he always had great stories to tell, and that's really sad because that part of his personality is gone."

If there is any good news in the d'Arbons' story, it is that he was diagnosed early enough to allow him to derive some benefit from drug treatment, even if it is just stabilisation of his symptoms.

Unfortunately for him, and the other 113,000 to 159,000 Australians now estimated to have Alzheimer's disease, no drug is yet available that can halt, or even appreciably slow, the inevitable progression of the disease. And even if one were available, doctors still lack the ability to diagnose Alzheimer's disease early enough for such therapies to make a difference.

It's a shortcoming that researchers such as Professor Christopher Rowe are working hard to address.

"By definition, you can't be given a diagnosis until you're already demented -- that's the clinical criteria for a current diagnosis of Alzheimer's disease," says Rowe, director of nuclear medicine and the Centre for Positron Emission Tomography at Melbourne's Austin Health.

In d'Arbon's case, the symptoms were as benign as headaches and uncharacteristic forgetfulness, but Rowe says things were set in motion long before those symptoms began to manifest. "We know the process probably starts 10 years or more before you get demented."

A neurologist and nuclear medicine specialist, Rowe is using a new scanning technique to try to identify people at risk of developing Alzheimer's disease before they show clinical signs of illness. The first data from that study has just been released, and it's showing promise for early diagnosis of the disease.

A key component of Alzheimer's disease is the build-up of a protein called beta-amyloid, which forms deposits called plaques in parts of the brain. Exactly how these plaques trigger Alzheimer's disease is poorly understood, but they are the most important and well-known pathophysiological sign of the disease, and help distinguish Alzheimer's disease from other forms of dementia.

Rowe and colleagues are using a radioactive tracer called Pittsburgh Compound B, or PiB, that sticks to the amyloid protein in the brain, allowing the plaques to be clearly seen using a positron emission tomography (PET) scan.

By comparing the scans of healthy older patients to those of patients with early memory problems (called mild cognitive impairment) and patients already diagnosed with Alzheimer's disease, the team of researchers has been able to get some clues as to who is more likely to develop Alzheimer's disease.

"Those that have got a positive scan and have mild memory problems have almost all progressed to Alzheimer's disease over that two-year period," says Rowe. However, at this stage, the definition of "positive" scan is still a bit vague, as some patients have small amounts of amyloid while others have a lot.

"But if you have a moderately or strongly positive scan, then you have over an 80 per cent chance you'll develop Alzheimer's disease in the next two years."

Two years' warning might not seem like much, but it's a significant improvement on current diagnostic approaches. Many patients, particularly those with early-onset Alzheimer's, are not diagnosed until symptoms are well advanced, or they are misdiagnosed -- as the d'Arbons experienced.

"The first doctor we went to laughed," Jane recalls. "I said my husband's got memory problems and he just laughed at us, and he was a neurologist."

Rowe's work, part of a larger study called the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing, is still only part-way through. The first milestone, the 18-month follow-up, has just been reached with the first 80 patients in the study. But with around 300 individuals originally recruited to the study back in 2004, there is still plenty of follow-up work to be done.

As the title of the study suggests, imaging is just one component of a much bigger research picture that is examining Alzheimer's disease from a number of different angles. The aim is not only to be able to diagnose the disease earlier, but to identify factors that may increase, or decrease, the likelihood of developing it.

Professor David Ames, chief investigator for the AIBL study, says pre-symptomatic diagnosis and treatment of Alzheimer's disease could have a major impact.

"If we can wind back the age at which an individual gets Alzheimer's disease by five years, we can halve the prevalence in this country," says Ames, director of the National Ageing Research Institute. "That's a massive saving and improvement in quality of life for people."

Alongside the imaging project, researchers are looking for a way to improve early diagnosis of Alzheimer's disease using a blood test, which is considerably cheaper and easier than a scan.

"Because it's never going to be practical to give everybody over the age of 60 a PiB scan at $1000 a pop, we need a less invasive way of picking it up," says Ames.

Every participant in the study also has a blood sample taken, which is then analysed for a range of biochemical and haematological substances, and the findings are tied to the results of their PiB scan. Researchers are looking for any possible correlations between blood markers and risk of developing Alzheimer's disease.

Researchers are also exploring the effects of lifestyle factors such as smoking, exercise and diabetes on disease risk. If the study identified a modifiable risk factor, such as smoking or diabetes, that increased the risk of developing Alzheimer's disease, it would provide a clear strategy for reducing that risk.

"It's probable that within 10 years we will be able to offer a blood test to anybody over a certain age, and those who seem to be at risk, we would be able to offer interventions that would dramatically reduce risk of Alzheimer's disease in the immediate future," Ames says.

It's not a cure, but with a disease that usually manifests in the elderly, delaying the onset is almost as good. "All you need to do with Alzheimer's disease is to push it back to the point at which you're going to die of something else," says Ames.

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