Prednisone Could Be Part of Alzheimer's Treatment By Gary Payinda Researchers at Johns Hopkins and 11 other national cites are beginning a 15-month study to determine whether the body's natural response to trauma--inflammation--is somehow connected to the onset and progression of Alzheimer's disease. The study is based on research begun in Sweden, which tested the effects of aspirin, a mild anti-inflammatory drug, on arthritis. In the course of the investigation, scientists discovered that aspirin not only slowed the progression of arthritis, but also had an effect on Alzheimer's disease. The study remained inconclusive, however, because of the limited number of Alzheimer's patients involved. The current national clinical trials will refine the work done in Sweden. Prednisone, the strongest anti-inflammatory drug available, will be used on a large cohort of test subjects (8 to 12 at Hopkins, 150 nationally) and for a longer trial period. The trials also will focus on the behavioral neuropsychiatric symptoms of Alzheimer's disease, like forgetfulness and dementia. "Previous treatments have largely focused on replacing what the disease destroyed, like neurotransmitters," said Constantine Lyketsos, professor of psychiatry and behavioral sciences and director of the Hopkins portion of the National Alzheimer's Disease Collaborative Study. "This experiment represents an attempt to keep the brain healthy and to prevent the damage before it begins." Immediately after an injury, immune system proteins come out of the lymph fluid and blood and congregate around the wound. These proteins, called acute phase reactants, initiate the cascade of events known as inflammation. APRs call immune cells to the site of the injury where they remove dead and damaged tissue and clean the area, priming the tissues for healing. By the time the cleanup is under way, APRs have usually stopped their migration to the site of the wound and the inflammation recedes. In some cases, however, the inflammation does not subside. When this occurs on the skin, for example, we get a rash. When it occurs in the joints, we get arthritis. Researchers believe that for some reason, this occurs in the brain, and Alzheimer's disease may either result from or become exacerbated by the body's wayward defense system. Treatment with prednisone will suppress inflammation, preventing buildup of APRs. Scientists believe that this accumulation of APRs in the brain chokes neurons, interfering with their ability to successfully conduct the currents necessary for normal brain activity. As these neurons eventually die, the disease progresses irreversibly. Researchers hope that prednisone will prevent the initial influx of APRs and keep the neurons alive longer. Dr. Lyketsos, while enthusiastic about the new direction of Alzheimer's research, is cautious about expected findings, because, he said, there are many aspects to Alzheimer's disease besides the immune system, such as the environment and the patient's genetic makeup. "Even if the prednisone is effective and can reduce inflammation in the brain, anti-inflammatory therapy would probably constitute only one aspect of a complete treatment for [a patient with] Alzheimer's disease," he said. Dr. Lyketsos hopes the drug treatment will be able to retard the spread of the disease in its earliest stages, which in itself would be a therapeutic breakthrough. "Though we might not achieve an outright reversal of the disease, you've got to keep in mind that the majority of these patients are elderly," he said. "The ability to significantly slow a disease like Alzheimer's, one with a time course of up to 15 years, could--for many--prove to be tantamount to a cure." Alzheimer's disease affects about 5 million people in the United States, about one in 50 Americans. Dr. Lyketsos is seeking additional volunteers for the study. For information, contact Elizabeth Galik, of the Neuropsychiatry and Memory Group at Copper Ridge in Sykesville, Md., at (410) 795-8808, ext. 108.
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