With new funding from the National Institutes of Health, the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas will be a key player in what researchers are calling the "A4 Trial," the study of a drug designed to clear the brain of amyloid protein plaques, foreboding deposits that are a major feature of Alzheimer's disease.
The funding, made available this week to a national consortium of research centers set up by the NIH to collaborate on the development of Alzheimer's treatments and diagnostic tools, could total as much as $55 million over five years.
It also allows studies to be done on medication to reduce agitation in people with the disease, the effect of exercise intervention in people in early stages of the disease, and methods to increase the speed of drug development.
"The A4 Trial is so important because we are trying to prevent the onset of Alzheimer's," said Dr. Jeffrey Cummings, medical director of the Ruvo Center. "That is so important and powerful, both in terms of lives and financial stress. In terms of scientific urgency, it's a great study."
Alzheimer's disease, which causes dramatic problems with memory, thinking and behavior, is the sixth-leading cause of death in the United States and the only one of the top 10 without an identified way to cure, prevent or even slow its progression.
Researchers say that without medical advances, the number of Americans living with the disease is expected to jump from 5.4 million to 16 million in less than 40 years ---- with costs of care projected to rise from $200 billion today to $1.1 trillion in 2050.
The A4 Trial will study people who are normal cognitively but who have been found - through positron emission tomography brain imaging - to have shown the abnormal levels of amyloid accumulation that are generally a precursor to Alzheimer's disease, Cummings said.
Amyloid plaques and tau protein tangles are what caught the eye of German physician Alois Alzheimer when he first described the disorder more than a century ago during a post-mortem examination of a patient's brain.
Cummings, who is on the compound selection committee for the national consortium of research centers, said the drug to be studied has yet to be chosen.
Several have been developed by pharmaceutical companies. Many researchers, including Cummings, think that the major problem with amyloid clearing drugs to date is that researchers haven't been able to get them to patients soon enough: Too much harm has been done to the brain before the drugs have been given.
"I think with our new imaging machines we can identify people much earlier," Cummings said.
About 1,000 symptom-free older volunteers from across the country will be studied - structural and functional brain changes will be tracked - over three years as part of the A4 Trial.
Like Cummings, Dr. Richard Hodes - head of the National Institute on Aging, the lead institute within NIH for Alzheimer's research - is optimistic about the new studies.
"I am particularly excited that this round of studies will use what we have learned by testing interventions pre-symptomatically, as early as we can in the development of the disease, where we now think the best hope lies for keeping Alzheimer's at bay," Hodes said.
Although as many as 70 centers are part of the consortium, Cummings said about 25 centers usually participate in all the trials.
Cummings said the Ruvo Center also will participate in the exercise trial and the study of a drug to reduce agitation in Alzheimer's patients. He said the center will not participate in efforts to speed testing of drugs in clinical trials because a hospital is needed at the research site.
The exercise trial seeks to find out whether controlled aerobic exercise can influence cognitive decline, slowing brain atrophy and Alzheimer's symptoms in older adults with mild cognitive impairment, a condition that often leads to Alzheimer's. Older sedentary adults with mild cognitive impairment will participate in a yearlong program in which one group will do high-intensity exercise and the other stretching.
Cerebrospinal fluid biomarkers, magnetic imaging testing results and cognitive testing will provide data on the usefulness of exercise in improving cognition and Alzheimer's-related pathology.
"We have general information on the benefits of exercise but not precise, well-conducted research," Cummings noted.
The Ruvo Center also will test the generic drug prazosin as a treatment for agitation, a chronic problem for Alzheimer's patients, Cummings said. Often, agitation increases distress to both patients and caregivers, frequently resulting in long-term care outside the home.
Current drugs are largely ineffective and may even cause harm in older people, such as increased risk for stroke or excessive sedation.
"In a small trial, prazosin was very effective," Cummings said. "Now we have to see if it holds up in a larger trial."
As many as 300 more volunteers will be needed at the Ruvo Center for the new research studies. To learn more about these trials and others that are scheduled, call 702-659-0850.
Contact reporter Paul Harasim at pharasim@ reviewjournal.com or 702-387-2908.