Alzheimer's Signs Found In Young Adults, Study Shows 

People Genetically At Risk Show Early Signs

< December 17, 2003 > -- Young adults who are genetically at risk for Alzheimer's disease may show signs of the disease years before the start of memory and thinking problems, a report in the Proceedings of the National Academy of Sciences (PNAS) suggests.

"Patients with Alzheimer's disease have progressive reductions in brain glucose metabolism," says lead researcher Dr. Eric M. Reiman, an associate head of psychiatry at the University of Arizona. "This is an indicator of brain activity in certain parts of the brain."

According to the National Institutes of Health (NIH), nearly 4 million people currently suffer from Alzheimer's disease in the US. The proportion of people with the disease doubles every five years beyond the age of 65.

Experts Look at Signs of Low Glucose Metabolism

Dr. Reiman's research team has been investigating whether people with the apolipoprotein (APOE) episilon4 allele, a gene that is associated with an increased risk for Alzheimer's disease, show this reduction in glucose metabolism. Almost a quarter of the population carries this allele.

In earlier research, Dr. Reiman's group showed people with the APOE episilon4 allele, aged 50 to 65, had reductions in glucose metabolism.

In their current study, the researchers used magnetic resonance imaging (MRI) and positron emission tomography (PET) to measure brain structure and function in 12 APOE epsilon4 carriers and 15 non-carriers, aged 20 to 39.

The researchers found the patients with the APOE epsilon4 allele had abnormally low glucose metabolism in the same brain areas as patients with Alzheimer's disease.

"The earlier you can detect changes in the brain, the better the opportunity to intervene - and the more likely that the treatment would have an effect before the brain is damaged by Alzheimer's," Dr. Reiman says.

Dr. Reiman notes that while there were decreases in glucose metabolism, not all patients with the APOE epsilon4 allele go on to develop Alzheimer's disease.

However, "these early changes are surprising," he adds.

It is possible that decreased glucose metabolism is a very early sign of Alzheimer's disease and may provide a target for preventive treatment, Dr. Reiman says.

"I feel very confident that a prevention therapy of that kind is likely to emerge over time," Dr. Reiman says. "Even if that therapy was only modestly effective, it could have a tremendous public health impact."

According to Dr. Reiman, reduced glucose metabolism might be a cause of Alzheimer's disease or a result of other processes that cause the disease.

"Either way, these changes provide a foothold for changes that result in brain pathology," Dr. Reiman says.

Dr. Reiman goes on to point out that reduced brain glucose metabolism is predictive of Alzheimer's disease, and as the disease progresses this reduction is even more pronounced.

"So it is very relevant to the disease process," he adds.

At this time, Dr. Reiman does not recommend that healthy people be tested for the APOE epsilon4 allele or get a PET scan to predict their risk for developing Alzheimer's disease.

"Neither test tells us with certainty whether someone will develop Alzheimer's disease, nor does it tell us what we might do about it," he says.

Findings May Lead to Prevention for Some

"The findings are consistent with the belief of many Alzheimer's disease experts that Alzheimer changes begin in the brain many years before there are symptoms," says Dr. Stephen P. Salloway, an associate professor of clinical neurosciences at Brown University.

"If [these findings are] confirmed with larger trials, the combination of genetic and imaging techniques could identify people at risk for Alzheimer's disease long before symptoms emerge," Dr. Salloway says. "These patients could be excellent candidates for future preventative treatments."

Dr. Mony J. de Leon, director of the Center for Brain Health at New York University School of Medicine, says, "It's a good clue that something is going on, but not what it is."

Dr. de Leon says whether these early brain abnormalities are predictive, causal, or related to Alzheimer's disease is not proven by the current study in the PNAS.

Always consult your physician for more information.

Online Resources

Alzheimer's Association

Alzheimer's Disease Education and Referral Center

NIH Senior Health

National Institute of Neurological Disorders and Stroke

National Institutes of Health (NIH)

National Institute on Aging

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St. John's Mercy or call our Physician Referral Service at 314-FOR-DOCS.

Stroke May Boost Alzheimer's Risk

A new report in the Archives of Neurology sheds light on important risk factors for Alzheimer's disease and on a possible future therapy for the disease.

Thus far, the only available treatments are those that have a mild effect on symptoms, and nothing that impacts the underlying disease process.

The new study found people who have suffered a stroke are at a higher risk for developing this dementia; that risk is higher still if the person also has cardiovascular disease.

Clinicians traditionally divide dementia patients into two broad categories - vascular dementia (brought on by problems with blood circulation to the brain) and degenerative dementia (usually meaning Alzheimer's).

The problem is that many cases of dementia seem to overlap the two categories, says Dr. Sam Gandy, vice president of the Alzheimer's Association's Medical and Scientific Advisory Council.

"[The new research] begins to revise our thinking because, if this is a continuum of one disease, then they could be thought of that way in designing new therapies," says Dr. Gandy, who also is director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia.

"It is a really solid study to try to revolutionize or revamp the way doctors diagnose, and, more importantly for the patients, eventually develop treatments for dementia," he says.

Columbia University investigators looked at 1,766 Medicare patients aged 65 and older who did not have dementia or Alzheimer's disease at the start of the study. Some of the participants had had a stroke or other cardiovascular risk factors.

Over the course of seven years, the annual incidence of Alzheimer's was 5.2 percent among patients who suffered a stroke and 4 percent among those who did not.

Hypertension, diabetes, and heart disease made the risk even higher. People with a history of stroke also tended to get Alzheimer's earlier.

"The coexistence suggests that one is probably increasing the risk for the other," Dr. Gandy says.

Always consult your physician for a diagnosis.