JUNE 30, 2007
VOLUME 4 NO. 12

PATIENTS & PRACTICE

Alzheimer's surges unchecked

Cases set to quadruple by 2050, but no cure likely: conference


Sometimes the situation with Alzheimer's feels like a runaway train. You can't fix the brakes — but you can always polish the windscreen to get a better view of the oncoming disaster.

Alzheimer's cases are set to quadruple over the next 40 years and there's still not much available by way of treatment. Research presented at the Alzheimer's Association Conference (AAC) in Washington, DC, earlier this month showed again that all of the successful research at the moment is concentrated in the field of diagnosis.

DIRE STRAITS
Researchers from Johns Hopkins University predict that 106 million people will have Alzheimer's by 2050. The study was presented at the AAC and appears in the July issue of Alzheimer's and Dementia. More than 26 million people worldwide have Alzheimer's disease today, with Asia being home to nearly half the world's cases.

"If we can make even modest advances in preventing Alzheimer's disease, or delay its progression, we could have a huge global public health impact," said lead researcher Ron Brookmeyer, PhD. Delaying average onset of disease by just one year would cut the number of cases in 2050 by 12 million, according to the study.

While the figures are alarming, it's worth noting that the predicted global burden of Alzheimer's disease in 2050 — one case per 85 people — is hardly any higher than the current burden in Canada. With its relatively aged population, Canada already has 280,000 full-blown cases of Alzheimer's, and this is expected to rise to a terrifying 750,000 by 2050.

CRYSTAL BALL
It's small consolation, but at least we'll be very good at anticipating these tragedies by then. The diagnosis and prediction of Alzheimer's and milder forms of cognitive impairment is advancing by leaps and bounds.

Three new techniques were unveiled at the AAC. In one, researchers from University of Pennsylvania and the National Institute on Aging combined and analysed MRI images measuring the density and volume of various different tissues and their spatial distribution within the brain. Using a complex algorithm, they were able to distinguish patients diagnosed with mild cognitive impairment from healthy controls with 100% accuracy.

"Our study is the first to show that using MRI techniques to classify tissue patterns in the brain provides very high diagnostic accuracy on an individual basis," said Dr Cristos Davatzikos, of Penn State. Unfortunately it does so at the cost of several thousand dollars per patient.

Perhaps of more immediate application is a "bedside algorithm" developed by Dr Deborah Barnes of the University of California, San Francisco, which effectively sorts patients' dementia risk into low, medium and high risk categories. Six percent of her low risk group will progress to Alzheimer's, she said, compared to 54% of the high risk group. It's good enough to provide reassurance to the low risk group, and may motivate those at high risk to modify their lifestyles, she argues.

A third diagnostic tool was presented by a private Norwegian company, DiaGenic ASA. Using a 1,200-gene DNA micro-array, this method achieved 85% specificity in distinguishing Alzheimer's patients from healthy subjects. But these were patients with advanced disease whom any clinician could have diagnosed from their symptoms. Whether the test will predict earlier-stage disease remains to be seen.

SEARCH FOR ANSWERS
There is sadly not much to be done with these diagnoses in the absence of better treatments. The four drugs currently approved for Alzheimer's — donepezil, memantine, galantamine and rivastigmine tartrate — have achieved modest delays in progression at best, and the drug pipeline is not looking like it contains any sort of radical breakthrough.

At the AAC, it was all about managing expectations on the treatment side of the equation. "I think this is just exactly what we should expect — incremental progress," Dr Sam Gandy, chairman of the Alzheimer's Association's medical and science council, told reporters. He predicted that in the near future, patients are likely to receive a cocktail of drugs, since none stands out from the crowd.

The two drugs closest to market show signs of promise, but any improvement over the current generation is likely to be incremental. A compound called AC-1202 slows disease progression over nine months, at least in patients without the Alzheimer's gene APOE-4.

Another compound called LY450139 that interferes in the formation of amyloid protein was found to reduce this building-block of Alzheimer's plaques by up to 65% in some subjects. But its clinical effects have yet to be measured. The drug has already passed safety tests, though not without revealing some odd side effects, including a tendency to lighten hair colour.

JAB IN THE WORKS
The June 29 issue of the Journal of Biological Chemistry reports on the development of an Alzheimer's "vaccine" based on antibodies to amyloid precursor protein. Wyeth and Irish partner Elan have a vaccine under development, but it hit a major snag in early trials when 6 % of subjects developed encephalitis. The problem is being studied.

The most reliable way we have of avoiding dementia, it seems, is to keep our brains active. This is confirmed yet again in a study in the June 27 issue of Neurology. A longitudinal study of more than 1,200 older people — 90% of whom went on to develop Alzheimer's — found that a cognitively active person in old age was 2.6 times less likely to develop dementia and Alzheimer's disease than a cognitively inactive person.

 

 

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