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Getting Lost in Alzheimer's By Liz Kumru
The retired three-star Air Force general was in New York City for a visit with friends. He stepped out to take a walk and stepped instead into a new world of disorientation. Although Colladay never ventured more than a few blocks away, it took him two hours to find his way back. "I had no idea this could be Alzheimer’s," he said. Looking back, he now sees that it was an early warning that the disease was invading his brain. About 80 percent of the people with Alzheimer’s disease do not recognize they have a problem, said William Burke, M.D., director of research for the UNMC Department of Psychiatry. "It’s an unusual illness in that the person has very little insight that he or she has the disease," he said. It was actually Colladay’s wife, Danny, who began noticing his memory trouble and arranged for him to see Dr. Burke and enroll him in a clinical trial to test a new treatment for Alzheimer’s. "At first, I thought it was just normal memory loss for this age. But then, it began to affect his reading," she said.
An active reader, Colladay loved staying current with national and international events. After all, he lived in the throes of world events while serving at NATO Headquarters in Brussels, Belgium, at the Pentagon in Washington, D.C., and as Chief of Staff at SAC Headquarters in Bellevue, Neb. During his 31-year military career, he had helped place Minuteman missiles throughout the country and kept records for all military generals. He was a trusted officer. After retiring in 1978, he entered the corporate world in another trusted position as vice president of public affairs at ConAgra. His legislative lobbying efforts won ConAgra considerable incentives to stay in Nebraska. After retiring from ConAgra in 1992, Colladay continued to read newsmagazines cover to cover and enjoyed examining the morning and evening papers. But, over these past four years, the gradual eroding of neurotransmitters critical to learning and memory has robbed him of even those small pleasures. Now at 73, he gets lost reading, speaking and writing. His words are being stolen. He can still decipher banner newspaper headlines, but he’ll stop in the middle of a sentence to ask directions, "Now, where was I?" Writing his name takes minutes, rather than seconds. The memory center is often the first area to be affected by the insidious onset of the disease, Dr. Burke said. "This happens anytime the brain is damaged and doesn’t work in a coordinated fashion," he said. The ability to plan, sequence and control emotions are localized to the front part of the brain. When affected, people have mood swings, are impulsive and they engage in uncharacteristic behaviors.
One of the major traumas family members endure is watching a person with whom they’ve lived disappear by degrees, he said. "It’s frightening." Dr. Burke has helped build UNMC’s geriatric psychiatry program into one of the best in the nation. It includes an inpatient and outpatient psychiatric service, a Memory Disorders program, and consultation to the geriatric assessment center and a large number of area nursing homes. As director of the department’s division of geriatric psychiatry and the sychopharmacology Research Center, he also is co-director and chief of clinical affairs for the Center for Neurovirology and Neurodegenerative Disorders (CNND). Delaying the onset of Alzheimer’s disease or controlling the physical change in the brain that cause dementia is one of the goals of the collaborative basic and clinical research conducted through the CNND. As part of the CNND, it is Dr. Burke’s goal to provide patients the opportunity to enroll in national clinical trials to test new therapies. CNND’s first clinical trial is evaluating thalidomide, a drug known for causing severe birth defects in the 1960s, as a novel treatment for Alzheimer’s. "It’s a potent modifier of the immune system. It turns off the cells in the brain that produce nasty chemicals which rip up nerve cells. The hope is that it will have some impact on the rate of progression of the disease," Dr. Burke said. Researchers at UNMC believe Alzheimer’s begins when plaques, formed by a protein called beta amyloid, "gum up" neurons, Dr. Burke said. When the brain produces an excess of beta amyloid, the body’s immune system perceives it as foreign and mounts an attack. Inflammation gets out of control, damaging normal nerve cells, including nerve cells that make acetylcholine. Acetylcholine is a neurotransmitting chemical essential to learning and memory. Neither of the drugs used most widely for Alzheimer’s, Cognex and Aricept, slow the death of those cells. Instead, the drugs slow the deterioration by inhibiting the action of acetylcholinesterase, an enzyme that breaks acetylcholine down. Colladay is one of 10 patients in the six-month study that will test the safety, effectiveness and tolerability of thalidomide. Patients in this trial have mild to moderate Alzheimer’s disease, are living at home and need little or moderate assistance with daily activities. Some patients may have serious memory problems – short-term memory is particularly impaired – but other mental abilities are more intact. There may be problems with language, judgment, and keeping track of finances, but the patient can still accomplish personal care. Patients in the study are randomly assigned to receive either 100 or 200 milligrams of thalidomide a day. Two of the 10 patients are receiving a placebo. Neither patients nor medical staff knows the dosage each participant is taking.
Upon entering the trial, the patient completes a clinical evaluation, nerve testing, magnetic spectroscopy, and blood tests to measure chemicals that indicate inflammation. After six weeks, the initial tests are repeated. Researchers are hoping that results from the novel use of proton magnetic resonance spectroscopy (MRS) will compare to results from the blood work. If the MRS provides accurate results, the non-invasive test may be useful as a clinical test. The blood tests also are being conducted in hopes of developing ways to measure the progression of Alzheimer’s. Robin Cotter, a graduate student in the CNND laboratory, is attempting to recreate the process that leads to dementia. She and other CNND graduate students, Lisa Ryan and Eric Benner, are trying to correlate the amount of inflammatory factors found in the blood with the level of damaged neurons in the brain. The experiments may lead to a blood test that physicians can use to measure the progression of disease or prevent the neurodegenerative process. "Inflammation is one of the pathways of neuronal injury in Alzheimer’s. The immune system goes from being a protector to a destroyer," Cotter said. Six weeks into the study, Colladay and his wife have yet to see any changes in his memory, but remain hopeful. "I guess I expected a miracle drug," Danny Colladay said. At the end of the study, they will learn the outcome. If it is determined that thalidomide made a difference, patients will be given the option to continue. Additional participants are needed for the thalidomide study. For more information about this clinical trial, call (402) 559-5028. |
