Hard-Working Brains May Be Signs of Early Alzheimer's Disease

From the WebMD Archives

Aug. 16, 2000 -- The brains of people at risk for developing Alzheimer's disease apparently go into overdrive when they are called upon to perform a task involving memory, according to a new study. The researchers hope this finding will someday allow them to help delay or prevent memory problems in people with a genetic risk for the disease.

Their findings suggest that imaging technology showing changes in blood flow within the brain during periods of intense mental activity could be used to help detect people who may be in the earliest stages of Alzheimer's, before symptoms such as extreme memory loss occur.

The technology, called functional magnetic resonance imaging (MRI), shows the brain working in real time. It could also be used to test whether new drugs are effective at slowing or stopping the disease process, writes study author Susan Y. Bookheimer, PhD, in the Aug. 17 issue of The New England Journal of Medicine.

"We looked at people with mild memory complaints, and we had them perform memory tasks during a brain scan. The basic idea is like a heart stress test, but here we're stressing the brain, so we call it a cognitive stress test," Gary W. Small, MD, tells WebMD. Small, a professor of psychiatry and behavioral sciences and director of the Center on Aging at the University of California in Los Angeles, was the senior researcher on the study.

Small and colleagues used the MRI to study 30 people from the ages of 47 to 82 with apparently normal mental abilities, outside of their mild memory complaints. Sixteen of the patients were considered to be at risk for Alzheimer's disease because they carried one or two copies of a gene, called apolipoprotein E-e4 (ApoE e4). The gene has been associated with both an inherited form of Alzheimer's that occurs after age 60 and with so-called "sporadic" forms that occur in people with no known family history of the disease.

The patients were scanned with MRI while at rest and while they were asked to memorize and recall words. The researchers found that in both groups, there were significant increases in blood flow in areas of the brain involved in memory and learning.


But the participants who had the abnormal gene appeared to have much stronger and more active blood flow in the brain, suggesting that they needed to marshal more brain resources to do the same amount of mental gymnastics as people with the normal form of the gene.

Quite simply, although the people with the genetic risk ultimately performed equally as well on the test as those without the genetic risk, Small says "we found that people with a genetic risk for Alzheimer's have to work harder to perform the same memory task."

And in fact, the researchers found that those patients who had the greatest degree of brain activation during the original study tended to have the largest declines in their ability to recall words when given a memory test two years later.

Small tells WebMD that the researchers hope to use the information to develop a program of early detection and prevention of Alzheimer's in patients thought to be at increased risk for developing the disease. They are currently performing a study to determine if current drug treatments can delay the progress of the disease in people with Alzheimer's, and they plan to use this new MRI technology.

But in an editorial accompanying the article, Ingmar Skoog, MD, PhD, from Sahlgrenska University Hospital in Göteborg, Sweden, cautions that just because someone has the specific genetic abnormality mentioned in the study does not mean that he or she will go on to develop Alzheimer's. He writes that longer follow-up is needed before the significance of the findings can be known.

Whether the patients with extra brain activity actually go on to develop Alzheimer's is something that still needs to be studied, says Mike Mullan, MD, PhD, director of the Roskamp Institute at the University of South Florida. But, he says, "I would put money on the fact that that will be the case."

Mullan tells WebMD that this report fits in with a recurrent theme researchers are seeing: Patients develop Alzheimer's disease over a long period of time. But today, doctors don't usually know someone has the disease until there is already damage to the nerves of the brain. The findings of studies like this one could help change that.


Several different studies need to be done to follow up this work, Mullan says. First, researchers should see if they get the same results using a larger number of test subjects, just to be sure their findings weren't simply by chance. Then, they should study whether medications could help preserve mental function.

It is unclear whether currently available Alzheimer's drugs, if given before obvious symptoms develop, could delay the transition to obvious Alzheimer's disease, according to Skoog.

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