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Alzheimer’s Seen on Scans Decades Before Dementia, Study Shows

March 07, 2013

Alzheimer’s Seen on Scans Decades Before Dementia, Study Shows

Doctors at Melbourn's Austin Hospital found it takes about 20 years for the deposits, known as amyloid beta, to lead to dementia. Photographer: Leonard Lessin/Getty Images

Abnormal deposits in the brain thought to trigger Alzheimer’s disease can be detected decades before the memory-robbing illness ensues, a finding that will help guide future treatments, researchers in Australia said.

Doctors at Melbourne’s Austin Hospital followed 200 seniors, including people with Alzheimer’s disease and mild cognitive impairment, for more than three years to chart any decline in cognition and brain size against the deposition of abnormal protein in their brains. They found it takes about 20 years for the deposits, known as amyloid beta, to lead to dementia.

The findings, published today in the medical journal the Lancet Neurology, suggests doctors have a large window of opportunity to potentially slow, or even reverse, the accumulation of amyloid beta to stave off the onset of Alzheimer’s. The disease is the main cause of dementia, which afflicts 35.6 million people globally -- a number the World Health Organization says will double by 2030 and triple by 2050.

“It’s now quite clear that it’s a very slow, gradual process over a couple of decades,” said Christopher Rowe, Austin Hospital’s director of nuclear medicine. For Alzheimer’s to develop, the brain needs to accumulate large amounts of amyloid “and you need it there for a long time,” Rowe, a study co-author, said in a telephone interview from Florence, Italy.

All Alzheimer’s disease patients have amyloid deposits in the brain, though not all people with the deposits have the disease, Rowe said.

Post-Mortem Studies

“We’ve known for a long time from post-mortem studies that apparently normal people can have amyloid in their brain, and it’s been hypothesized that this is representing a slow build up towards Alzheimer’s disease and they just hadn’t developed the dementia by the time that they died,” he said. “It’s very likely that amyloid is the trigger, but the process of Alzheimer’s disease does require other things that happen which we don’t entirely understand.”

Participants underwent a neuropsychological examination, and received magnetic resonance imaging, or MRI, and positron emission tomography, or PET, scans of their heads every 18 months for at least three years. As Alzheimer’s disease progresses, the pace of amyloid deposition slows, the researchers found.

The data indicate that there is a prolonged period in which amyloid beta is forming plaques in the brain without the symptoms of Alzheimer’s disease, the authors said. Even before dementia sets in, shrinkage in the part of the brain linked to memory and attention occurs about four years earlier, and memory is impaired about three years prior.

Early Signs

“We compared when you can first see changes on an MRI scan and on memory testing, and we can pick them up from about seven years before dementia,” Rowe said.

Extrapolating the data suggests beta amyloid deposition can lead to dementia in as few as 10 years, with an average of 19 years, he said. There is also a period in which the early stages of amyloid deposits are occurring though not detectable.

“The entire process is now getting up toward more than 25 years,” Rowe said. “This is much longer than people expected.”

Patients with tertiary education and those with bigger brains prior to the formation of amyloid deposits can tolerate higher levels of the errant protein, he said.

Rowe and colleagues are now studying potential therapies to stymie amyloid plaques before they have had a chance to damage and eventually kill brain cells. If successful, the use of PET scans -- which cost $1,500 to $3,500 apiece -- “will explode,” Rowe said.

‘Great Hope’

“You have a much greater chance of stopping a disease than trying to repair a brain that’s severely damaged,” he said. “This is the great hope now.”

Pfizer Inc. (PFE:US), Roche Holding AG (ROG), Eli Lilly & Co. (LLY:US), GlaxoSmithKline Plc (GSK), Elan Corp. and Prana Biotechnology Ltd. (PBT) are among drugmakers racing to develop treatments for Alzheimer’s. There have been 101 unsuccessful attempts since 1998, according to the Pharmaceutical Research and Manufacturers of America. Current therapies provide some temporary symptomatic improvement.

“The problem with Alzheimer’s disease is that you don’t have an effective therapy, but we can certainly make a better diagnosis with amyloid imaging -- be more precise about what’s going on with the patient and what their prognosis is -- but we can’t change the course of their disease,” Rowe said.

To contact the reporter on this story: Jason Gale in Melbourne at j.gale@bloomberg.net

To contact the editor responsible for this story: Bret Okeson at bokeson@bloomberg.net


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