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5:31 pm
Wed October 17, 2012

Treatment For Alzheimer's Should Start Years Before Disease Sets In

Originally published on Thu October 18, 2012 10:12 am

Treatment for Alzheimer's probably needs to begin years or even decades before symptoms of the disease start to appear, scientists reported at this week's Society for Neuroscience meeting in New Orleans.

"By the time an Alzheimer's patient is diagnosed even with mild or moderate Alzheimer's there is very, very extensive neuron death," said John Morrison of Mount Sinai Medical School in New York. "And the neurons that die are precisely those neurons that allow you to navigate the world and make sense of the world."

Once those neurons die, he says, critical brain circuits involved in thinking and memory are gone forever, Morrison said. "We need to move way back in time and intervene before there's extensive neuron death."

Morrison and others said it's possible that several recent trials of drugs for Alzheimer's have failed because the drugs were given after symptoms had already started to appear.

"It's possible we've tested things and discarded them prematurely," said Sam Gandy, also at Mount Sinai. "Now that we can see the changes in the brain that underlie Alzheimer's, we really should re-evaluate some of the things we've looked at."

It's still not clear just how early treatment would have to start.

But one study presented at the neuroscience meeting suggested it could be a decade or more.

The study has been following 121 people as they age, said Lori Beason-Held of the National Institute on Aging. Participants have undergone periodic scans that measure the function of certain areas of the brain, she says.

"Our study has discovered changes in the brain that occur up to 11 years before any symptoms occur," Beason-Held said.

But it's likely that the process that leads to Alzheimer's begins even earlier, she said.

"If we need to stop things before they even start, it could be 20 years before somebody develops the symptoms," Beason-Held said. "If it turns out that we can reverse some of the pathology then it might be, say, 10 years."

The new interest in early intervention has some scientists reconsidering experimental drugs that appeared to fail in people. But to retest these drugs, they would have to be administered to younger people who are not experiencing problems with thinking or memory and might never get Alzheimer's.

That raises some tricky ethical issues, Gandy said. "People have to understand the risks and make the decisions for themselves, with their physician, whether it's right for them to begin a drug for which the long-term risks might not be known," he said.

One group that might take part in that kind of experiment is people with a family history of early-onset Alzheimer's, researchers said.

Despite the setbacks in the search for treatments, many scientists at the neuroscience meeting still think they're closing in on drugs that will work.

One reason is the relatively recent discovery that neurons don't die just because someone is getting older. They appear to to remain healthy as long as the connections between them, known as synapses, remain intact, Morrison said.

So it may be possible to prevent Alzheimer's by giving middle-aged people drugs that protect these synaptic connections, he said

"This current thinking that neuron death is not inevitable is a far more optimistic view," Morrison said. "And I think we will get to a point where we push back the average onset of Alzheimer's and may even decrease its prevalence."

But some scientists said they were discouraged by the recent failures with Alzheimer's drugs.

"Twenty years ago when I [began] this work I was hoping by 65 I was going to have a pill for myself," said Fred van Leuven, a researcher from KU Leuven in Belgium. "That's next year and I don't have a pill yet."

But during the neuroscience meeting, Van Leuven also presented a study showing that a new type of drug was able to help mice with an Alzheimer's-like condition.

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Transcript

ROBERT SIEGEL, HOST:

From NPR News, this is ALL THINGS CONSIDERED. I'm Robert Siegel.

MELISSA BLOCK, HOST:

And I'm Melissa Block. Researchers say there is growing evidence that treatments for Alzheimer's disease will need to begin years or even decades before symptoms appear. That news comes as several experimental drugs have failed to help people who've already begun having problems with memory and thinking. NPR's Jon Hamilton reports on why scientists are now leaning toward early intervention.

JON HAMILTON, BYLINE: There has been a lot of talk about Alzheimer's this week at the Society for Neuroscience meeting in New Orleans. At a news conference, Fred Van Leuven, a scientist from Belgium, briefed reporters on a new type of drug that helped mice with an Alzheimer's-like condition. Then Van Leuven described his frustration trying to translate experiments like this one into an effective drug for people.

DR. FRED VAN LEUVEN: Twenty years ago when I started this work, I was hoping by 65, I was going to have a pill for myself. That's next year and I don't have a pill yet. So it's a problem.

HAMILTON: Scientists at the meeting say one reason drugs haven't worked may be that treatment has just started too late. John Morrison from Mount Sinai School of Medicine in New York says that makes sense given recent findings about how Alzheimer's attacks brain cells.

DR. JOHN MORRISON: By the time an Alzheimer's patient is diagnosed even with mild or moderate Alzheimer's, there's very, very extensive neuron death. And the neurons that die are precisely those neurons that allow you to navigate the world and make sense of the world.

HAMILTON: Morrison says there are drugs that can produce new neurons. But he says this approach won't replace the complex circuits that underlie memory and thought.

MORRISON: Trying to bring back dead neurons is not going to be the way to go. We need to move way back in time and intervene before there's extensive neuron death.

HAMILTON: The question is how far back in time? Lori Beason-Held from the National Institute on Aging presented results from a study that could help answer that question. She says previous research found brain changes in people already experiencing the memory and thinking problems that can precede Alzheimer's.

DR. LORI BEASON-HELD: Our study has gone back even further and discovered changes in the brain that occur up to 11 years before any symptoms occur in individuals who eventually become cognitively impaired.

HAMILTON: Beason-Held says it's likely the process that leads to Alzheimer's begins even earlier. But she says it's not clear precisely when a drug would need to interrupt this process.

BEASON-HELD: If we need to stop things before they even start, you know, it could be 20 years before somebody develops the symptoms. If it turns out that we can reverse some of the pathology, then it might be, you know, say, 10 years. But it's really difficult to know at this stage.

HAMILTON: The new interest in early intervention has got some scientists reconsidering experimental drugs that appeared to fail in people. Sam Gandy of Mount Sinai School of Medicine says some of them may be effective drugs that were given too late.

DR. SAM GANDY: It's possible we've tested things and discarded them prematurely. Now that we can see the changes in the brain that underlie Alzheimer's and that we know to look five, 10, 20 years earlier than we have been, we really should re-evaluate things that we've looked at and discarded.

HAMILTON: To do that, researchers would have to give these experimental drugs to younger people who are not experiencing problems with thinking or memory and may never. And Gandy says that raises some ethical issues.

GANDY: People have to understand the risks and make the decisions for themselves with their physicians whether it's right for them to intervene, to begin a trial or begin a drug for which the long-term risks might not be known.

HAMILTON: One group that might take part in that kind of experiment is people with a family history of early onset Alzheimer's. Despite the setbacks and the search for treatments, many scientists at the neuroscience meeting still think they're closing in on drugs that will work. One reason is the relatively recent discovery that neurons don't die just because someone is getting older. Gandy's colleague, John Morrison, says the brain cells seem to remain healthy as long as the connections between them, known as synapses, remain intact. So he says it may be possible to prevent Alzheimer's by giving middle-aged people drugs that protect these synaptic connections.

MORRISON: This current thinking that neuron death is not inevitable, is a far more optimistic view. And I think we will get to a point where we push back the average onset of Alzheimer's and may even decrease its prevalence.

HAMILTON: In people, not just mice. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.