Rivals line up in battle on Alzheimer’s
The race is on to cure the growing worldwide burden of the most common form of dementia. Kellie Bisset reports
IT started with forgetting to close the front door. Then there was confusion over how to operate a washing machine, and simple television drama plots suddenly became hard to follow. Aged just 54, and worried for her health, Marie Valenta took herself off and had an MRI scan.
It returned an unbelievable Alzheimer’s disease.
There was no family history, no clue at all in fact, that such a seemingly healthy person would be robbed of her memory so swiftly and so easily. Just four years later, Valenta doesn’t know her husband and needs 24-hour care.
She can’t dress, eat, or go to the toilet unaided. She has developed depression and psychotic paranoia, and is dangerously underweight. Doctors don’t think she’ll live for much more than a year.
She has not been my wife — or the person I knew as my wife — for the best part of two years now,’’ her husband, Tom, says. ‘‘ It has been a pretty long and torturous nightmare.’’
Marie Valenta is one of more than 200,000 Australians enduring the torment of Alzheimer’s disease, a figure experts say will jump to 750,000 by the year 2050.
There is currently no cure, although those in the field are upbeat about a wide range of research currently under way.
Director of the Mental Health Research Institute at the University of Melbourne and world expert in the field, professor Colin Masters, says the race is on for an effective treatment, with each of the big pharma companies running their own research programs — and this represents an exciting new era for patients.
‘‘ The competition is very, very stiff at the moment,’’ he says. ‘‘ Results [from drug trials] are expected in the next 12 to 24 months.’’
Professor Masters believes the answer to the Alzheimer’s riddle will come in the next five years. But in the meantime, researchers are investigating several avenues, one of which is the link between high cholesterol and brain function.
New research just published in the journal Neurology (2007; 69:878-885) suggests that widely prescribed cholesterol-lowering drugs, known as statins, may cut the risk of developing Alzheimer’s.
The researchers, from the University of Washington, studied 110 people who had donated their brains for research, and found
‘‘diagnosis: significant differences in the brains of those Alzheimer’s patients who had taken a statin and those who had not.
Important markers of Alzheimer’s are clusters of protein between and around the brain cells called beta-amyloid plaques, and groups of twisted fibres inside the cells called neurofibrillary tangles.
These lead to a breakdown in the cells’ ability to communicate with each other, causing the cells to eventually die.
The Neurology study showed significantly fewer neurofibrillary tangles in the brains of statin users. If statins are proved to have an effect on Alzheimer’s, the implications would be huge.
Used to lower cholesterol and prevent heart attacks and strokes, they are among the most commonly prescribed drugs in Australia.
Atorvastatin and simvastatin alone are the biggest drain on the Pharmaceutical Benefits Scheme — they cost the Government nearly $800 million in the year to June 30 2006.
While there is increasing evidence of an association between cardiovascular risk factors such as high blood pressure and high cholesterol and risk of Alzheimer’s, it’s still unclear exactly what role cholesterol might play.
The authors of the Neurology study are cautious about applying their results to a living population. And they acknowledge that while some research suggests a decreased Alzheimer’s risk in statin users, there are other studies that have found no overall reduction in risk.
is involved in one study that may shed some more light on the issue. The director of the memory unit at Queen Elizabeth Hospital says the results of the trial, which is looking at whether statins slow the progression of Alzheimer’s, are not yet published.
But she’s confident there is ‘‘ certainly something’’ in the cholesterol hypothesis.
‘‘ We know cholesterol does interact with amyloid,’’ she says. ‘‘ I think we are a fair way away from broadening the [PBS statin eligibility] for people at risk of Alzheimer’s disease, but if people do qualify for lipid treatment under PBS criteria and they do have risk factors for dementia, then they should be discussing with their doctor whether taking a statin is appropriate.’’
Boundy agrees that while statins may prove to be an extra piece of armour in the battle against Alzheimer’s rather than a cure, if they have a role in delaying the onset of symptoms the consequences would be significant.
‘‘ There have been epidemiological studies that have suggested if you can delay the onset of symptoms by a couple of years, you might half the actual prevalence of the disease.’’
According to Colin Masters though, the statin connection remains elusive. ‘‘ What we are after is a drug that actually alters the course of the illness,’’ he says. ‘‘ The question is, do the statins do this or not? The trials to date have not been very convincing.’’
Another avenue of inquiry is a class of drugs called gamma-secretase inhibitors, which could stop beta amyloid plaques from forming.
Masters and his Mental Health Research Institute colleague professor Ashley Bush, are working with company Prana Biotechnology on the theory that plaques are formed by an abnormal reaction with the brain’s own chemistry.
By removing copper and zinc ions, which bind amyloid together, the beta-amyloid falls apart and the plaques can be cleared away.
Bush is focusing on a drug called PBT2, which has shown ‘‘ spectacular results’’ in mice and human trials are about to begin.
‘‘ We are cautiously optimistic,’’ he says. ‘‘ It’s the most potent result that has ever been seen at the mouse stage. But it is still another two to three years off — all things being well.’’
Another exciting development in the pipeline is positron emission tomography (PET), where the brain is scanned for beta-amyloid protein. A chemical tracer is injected into patients and binds to the plaques in the brain, allowing the PET scan to detect them.
Bush says this can pick up brain changes associated with Alzheimer’s well before symptoms appear.
And if new drugs become available to break down plaques, the disease could then be knocked on the head.
Measuring markers found in the cerebrospinal fluid (CSF) and the blood will also become more and more important in detecting Alzheimer’s early, Masters says.
And hopes for a vaccine are also on the horizon. Patients in an early trial however, suffered the serious side effect of brain inflammation and while that trial was halted, more research is continuing.
At the moment, patients treatment options.
Cholinesterase inhibitors have been around for about 15 years, and a recent Cochrane Review found they caused only modest improvements in cognitive function.
Newer drugs, called NMDA receptor antagonists, prevent too much calcium moving into the brain cells causing damage, but Bush says while they offer a slight benefit, they don’t change the pathology of the disease.
For those concerned about here and now prevention rather than long-term cure, Alzheimer’s Australia says while it’s no guarantee, adopting a ‘‘ brain-healthy’’ lifestyle is associated with a reduced risk of dementia.
Its ‘‘ mind your mind’’ program recommends several strategies, including keeping the brain active through mind games and hobbies, physical exercise, eating a diet low in saturated fats and high in omega-3 fatty acids, antioxidants and folate, and watching your cholesterol, body weight, blood pressure and blood sugar levels.
For Marie Valenta though, who ‘‘ did everything right’’, none of this worked.
Husband Tom, who has recently published a book about his experiences, describes his cynicism about potential cures but he’s hopeful enough to have donated all his royalties to research.
In the meantime, he is coping day-to-day with the gradual disappearance of his ‘‘ extraordinarily brave’’ wife. ‘‘ We had a good 12-18 months of good times when Marie was first diagnosed,’’ he says. ‘‘ We squeezed every drop out of every day.’’
Treatment: Marie Valenta prepares to undergo MRI