The Future of Preventing Alzheimer's Moves Closer to Reality

By: Eric Sabo
As researchers scramble to find new treatments for the growing number of Americans with Alzheimer's disease, some of the most dramatic developments are happening in the area of prevention and early detection.
Studies increasingly show how certain lifestyles, such as keeping mentally engaged, eating a heart-healthy diet and staying physically active may protect against Alzheimer's. In addition, new research shows that the first signs of decline may begin years before someone is diagnosed with the memory-robbing disease, offering a chance for doctors to intervene early.

Dr. Ronald Petersen, director of the Alzheimer's Disease Research Center at the Mayo Clinic in Minnesota, discovered a type of pre-dementia stage, known as mild cognitive impairment (MCI). People who develop this early, more severe type of memory problem have a higher chance of progressing to Alzheimer's. Other teams have since found that the signs of Alzheimer's may start even earlier, prompting researchers to search for tests that may help predict who is at risk. Dr. Petersen discusses the latest findings and the steps people can take to prevent the disease.

When do people first begin to show signs that may indicate a greater risk of Alzheimer's?
If you look at the development of Alzheimer's on a continuum, those individuals who are going to develop it start out with normal memory. Then, they go through this transitional phase that we've called mild cognitive impairment, where people are slightly impaired, usually in memory.


And then as things progress even beyond that, they develop the full-blown signs of Alzheimer's disease. A recent study from Sweden indicated that even when people are normal?before the MCI stage?there may be some subtle features of cognitive decline that warn of greater changes in the future. In fact, some of the symptoms of Alzheimer's disease really begin as much as a decade or more before the clinical diagnosis is made.

There are some subtle features, such as memory impairment, trouble with processing multiple pieces of information and difficulty concentrating on what's going around us. These changes may indicate that a person is more likely to develop Alzheimer's disease in the future.

Is there a way to test whether someone is at risk for Alzheimer's?
I think that there are some hints now that we may be able to pick up the very earliest signs of the disease. There may be some measurement of performance?such as memory and thinking?that will indicate a person who might be susceptible to developing Alzheimer's disease. We may need to augment that with brain imaging techniques to measure the size of certain structures in the brain that are critical for learning and remembering.

The most recent work, which is still in its formative stages with regard to imaging, has to do with detection of the actual amyloid protein that is thought to be a major player in the development of Alzheimer's disease. [These proteins, or plaques, gradually clump together in the brains of Alzheimer's patients. It is still unclear if this build up causes the disease or is the result of it.] This is very preliminary, and it's not a diagnostic test by any means at this stage.
But down the road, it may be a combination of measures; perhaps memory, perhaps a structural brain measurement, perhaps measurement of proteins in the brain and perhaps a genetic component. You put all of these together, and we may be able to develop a prediction as to who is more likely to develop Alzheimer's disease in the future.

Can we prevent memory loss if we treat the disease sooner?
That's the presumption. The thought would be that if you identify the disease earlier, hopefully we'll be able to intervene and do something about it; stop it before the damage is done in the brain.

Now, that's a promissory note at this point, since we don't have the preventive treatments, yet. But that's what a lot of people are working on in the basic science laboratory, and I think that we will get there. But before we can use those prevention strategies early, we have to identify people who might be at greater risk for developing this disease.


Your recent study found that patients with mild cognitive impairment could delay more serious memory problems by taking the Alzheimer's treatment, Aricept, but ultimately the drug did not prevent the disease. Is preventing Alzheimer's a matter of finding the disease earlier, a matter of stronger drugs or both?
Both. Our study on mild cognitive impairment indicated that you can intervene at an earlier stage than has previously been recognized. This was the first study demonstrating that you could have any effect at delaying the diagnosis of Alzheimer's. That had not been shown before.

Now, this is not a huge effect, and we didn't stop the disease by any means, but we did indicate that at least this one type of intervention can slow down the progression of Alzheimer's disease by up to 12 months. So, I think if we have better therapeutic interventions and preferably an intervention that would actually have an effect on the underlying disease process, that we can intervene at least at this MCI stage. We'd like to intervene even earlier by getting to those people who have the risk profile of developing Alzheimer's disease before they even become symptomatic.

What other interventions are being tested?
There are several strategies to try to stop the abnormal processing of this amyloid protein in the brain.
You may remember the vaccine therapy of a few years ago. [This was tested on a few patients with Alzheimer's but was found to be too dangerous for practical use.] This approach is still being looked at to see whether we can prevent this amyloid protein from being deposited in the brain or enhance its ability to be cleared from the brain before it does extensive damage. Much of the research is really focusing on delaying or stopping this amyloid protein build up.
What are some of the lifestyle measures people can take to prevent Alzheimer's?
Several studies indicate that staying intellectually active and engaged throughout your lifespan, being physically active, getting out, doing exercise, walking, staying physically fit, as well as possibly some dietary factors, may contribute to the prevention of Alzheimer's disease.

Staying physically active and eating a heart-healthy diet may be good for the heart, but it may also be good for the brain, and in addition, this intellectual activity, staying socially engaged in your various social spheres, might also be helpful in preventing the disease.

Can anyone prevent memory loss by remaining mentally engaged?
Well, I think there's a certain amount of genetic endowment that comes along with this. That is, we're born with a certain genetic deck of cards, and we probably can't change that to a great extent.


But given our own genetic endowment, we can enhance our functional ability by staying intellectually active. People who have been better educated and more intellectually active over their lifespan tend to have a lower risk of developing the disease.

Now, that research is a little bit difficult to interpret at times, because without a so-called biological marker or a black-and-white diagnostic test for Alzheimer's disease, we still must rely on our clinical judgment. Clearly, those individuals who are better educated perform better on tests, so we always have to be concerned that we're not just biasing people with lower education toward performing worse on tests and then concluding that they are in fact at greater risk of developing Alzheimer's disease. But there are some biological measures that indicate that those with higher education may in fact have a lesser chance of Alzheimer's.

Why might exercise help prevent Alzheimer's?
There was a very interesting study reported earlier this year where mice who were genetically predisposed to develop this amyloid protein in the brain were actually encouraged to be more physically active in their cage setting, such as running on wheels and things like that, versus mice who had a less active lifestyle. When the animals ultimately died, and their brains were looked at for the amyloid protein, those mice who had been more physically active over their lifespan had less of this protein in the brain, which is related to Alzheimer's disease.

So, there may be a real connection between physical activity and reduced deposition or development of this protein in the brain. I think this is one of the first hard studies to imply that there may actually be a mechanism of physical exercise and reduced Alzheimer's protein in the brain.

What is your advice for people who are concerned about developing Alzheimer's?
I think that the best, safest measure is to engage in intellectually stimulating activities, physical activity, eating a heart-healthy diet, staying socially involved. I think that these are going to be more promising and probably safer for you than going out and taking a dietary supplement or nutraceuticals [natural food supplements], which have been touted to stimulate the brain and ward off Alzheimer's disease. I think there's very little data for any of those being effective, whereas there's accumulating data that these other lifestyle measures may in fact be important.