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US Government, Private Sector to Speed Up Alzheimer's Research - 2004-10-14

Among the most important tools for understanding the brain are imaging technologies that take pictures inside the skull by scanning the head. A new U.S. government collaboration with the private sector is aimed at making brain imaging a definitive tool for diagnosing and tracking Alzheimer's disease, the degenerative brain disorder that is becoming more widespread as the world's population ages.

In the last few decades, researchers have made great strides in understanding the biology of Alzheimer's disease, which the World Health Organization says affects about five percent of the global population. We now know, for example, that the patient's brain shrinks significantly because of the loss of nerve cells, causing dementia.

Yet despite the biological progress, there are no cures for Alzheimer's or treatments to delay its onset. Some drugs reduce the symptoms, but an expert on the imaging of degenerating brains, Dr. Michael Weiner of the University of California at San Francisco, says they are only short-term solutions.

"These drugs temporarily improve memory function, but they do not affect the progression of the disease at all," Dr. Weiner says. "They are kind of like morphine for the pain of cancer. They reduce the symptoms, but they do not slow the progression of the disease. What we want are disease modifying agents."

To speed progress in Alzheimer's research, U.S. government health agencies have teamed with private drug companies and Alzheimer's interest groups to develop biological standards to measure the disease's progression and determine its severity.

Currently, researchers focus on behavioral measures of dementia, such as memory changes and the ability to perform daily tasks. But the director of the U.S. government's National Institute on Aging, Dr. Richard Hodes, says scientists need additional, more objective, physical markers. Therefore, the project will focus on measuring the brain's deterioration through modern imaging techniques.

Dr. Hodes says this will provide data about the nature of Alzheimer's and possibly identify targets for drug intervention.

"If we can follow and track the progression of disease and can as sensitively as possible then determine the effective interventions to alter the course of disease, we have the real potential to accelerate and make much more efficient and effective our ability to design drugs and other interventions," Dr. Hodes says.

Laboratories follow different procedures to image the brain. Some use a technique called magnetic resonance imaging that looks at brain structure. Others use a so-called PET scan, which looks at brain chemistry and function. One goal of the new project is to determine what the standard should be to determine the state of an Alzheimer's brain accurately. It will also seek other biological markers to measure the state of dementia, such as conditions in the blood and brain-spinal fluid.

Project researchers will take various types of brain scans and blood and urine samples of 800 elderly people for five years - some of them normal men and women, others with mild cognitive disorder who are considered at high risk for developing Alzheimer's, and the rest who have been diagnosed with Alzheimer's. The participants will also take standard clinical tests of memory and problem solving.

The University of California's Michael Weiner says the physical images of each person's brain will be compared to his or her mental test results to determine if brain shrinkage or other biological indicators are accurate markers for disease progression.

"That is what we call the validation process - to determine the extent to which the rate of change on the imaging and the biomarker data correlates to clinical progression," Dr. Weiner says. "Hopefully we will find that it will because we have a lot of preliminary data that suggests that we will, but we need to do it on a large scale."

The quest for physical markers to measure Alzheimer's is like the search for one for HIV. Researchers learned that the virus destroys disease-fighting immune cells called CD4 and that the number of CD4 cells a patient has determines the severity of HIV. The CD4 measure is a standard for treatment and AIDS research.

National Institute on Aging director Richard Hodes says doing the same for Alzheimer's might help reduce the number of people who get the dementia, now expected to triple to perhaps 90 to 100 million worldwide by 2050.

"The toll that would involve in terms of human suffering above all, but also the stress upon the medical system, the economy, and society at large is intolerable," Dr. Hodes says. "Hence the urgency in carrying through the studies that we are talking about."