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Holub Daily Gazette 2008

Shortly after Dr. Richard Holub started working with people with Alzheimer’s disease in 1985, magnetic resonance imaging became available, allowing doctors to see the brain in a detailed image.

In recent years, Holub, director of Neurological Associates in Albany, said Positron Emission Tomography (PET) scanning has been able to measure the metabolism of the brain or show where brain tissues are working normally.

“Traditionally, PET scanning shows changes in Alzheimer’s disease after the damage to the metabolism has already occurred,” Holub explained. “But this isn’t early enough . The earlier we can diagnose Alzheimer’s disease, the sooner we can start the patient on medication to help slow it down.”

Now Holub is involved in a national trial that is studying a new molecular imaging compound made by Avid radiopharmaceuticals, called F-AV-45.

The compound, which is injected into the patient, is used with PET scanning to allow visualization of the amyloid plaque deposits  in the brain that are characteristic of Alzheimer’s disease.

Amyloid plaque is thought to slowly accumulate in patients over years, eventually causing the death of brain cells and dementia.

In the United States, the Phase II clinical trial of F-AV-45 will enroll approximately 200 patients of varying degrees of memory loss at more than 30 centers across the country.

The trial involves a single administration of F-AV-45 and a PET imaging procedure that is completed in less than 1 hour. The study is designed to show how F-AV-45 imaging of amyloid plaque compares between healthy volunteers, patients with mild cognitive impairment and patients with Alzheimer’s disease.

“We all collect some amyloid in the brain,” said Holub. “Some more than others. If amyloid can be imaged in the brain before there is any evidence of dementia, then that would give us an opportunity to treat Alzheimer’s disease before it ever appears.”

Ideally, Holub said patients with mild memory loss would have a baseline scan, be treated with the drugs approved to treat Alzheimer’s disease, then be rescanned to follow the patients’ progress.

“The F-AV-45 radiopharmaceutical targets the amyloid deposits specifically,” Holub explained. ” so after it is injected at the time of the scan, it goes directly to the amyloid in the brain, and makes it easily identifiable. It tells us how much amyloid there is, and it documents the location of the amyloid within the brain.”


If the compound becomes approved in the future, Holub said it will help doctors identify patients who have a true problem with Alzheimer’s disease, versus a patient who may be concerned about memory loss but actually doesn’t have a problem.

“It will help us to identify patients with Alzheimer’s earlier and people who are destined to get the disease, but who do net yet have it today,” he said. “Then later, it will help us identify how well people are responding to therapy.”

Holub said one of the reasons that this study is important is that the population is aging and baby boomers are reaching retirement age, they are also beginning to reach the age where they will begin to have Alzheimer’s disease.

Scientists think that as many as 4.5 million Americans suffer from Alzheimer’s.

The disease usually begins after 60 and the risk goes up with age. About 5 percent of men and women ages 65 to 74 have the disease, and nearly half of those age 85 and older may have it.

“We have to do something now to identify it early, prevent it if we can, and control it, so that the cost and burden on society won’t become excessive,” said Holub.

“In addition to the cost, Alzheimer’s disease robs people in their golden years of a useful and enjoyable life. By being able to prevent or control these symptoms, we can certainly improve the quality of life for the patients, their families, their children and their grandchildren.”

Holub said the study will end in September, and the results should be published by the end of the year. If the results look good, then the compound will be put before the Food and Drug Administration for their consideration for approval.

“We’ve been waiting for a long time in neurology to have a way to identify and quantify Alzheimer’s disease, and this seems very promising,” said Holub. “So I am very excited.”


David Martin of Slingerlands, 67, a retired neuroscientist for the Wadsworth Center for the state health department, recently decided to take part in the study when he heard about it. “I thought it sounded interesting,” said Martin who has no memory problems. “It would be a real advantage from a diagnostic point of view if there was a way to determine how much of this amyloid plaque is present in the tissue,” Martin continued. “It would give doctors a better understanding of what stage the disease is, and how to treat it. It’s really a diagnostic tool that could [be] used to help improve the diagnosis of memory problems.”

Anyone interested in the study should contact Neurological Associates, 760 Madison Ave., Albany.

The Daily Gazette, August 5, 2008 /  Article by Kathy Ricketts, Gazette Reporter /  Photo by Barry Sloan for The Daily Gazette