Science / Medicine : Alzheimer’s DISEASE : Science Struggles to Ease the Nightmare
The woman loved mirrors and had placed them lavishly around her apartment, where she lived alone.
Normally an easygoing, sociable type, she seemed agitated one day and finally confessed to her visiting sister that her house mates made her angry. They never returned her friendly greetings.
Later, her doctor listened sympathetically and explained to the woman’s family that such delusional beliefs--springing from an inability to recognize people--are common in patients with Alzheimer’s disease, a degenerative brain disorder.
Alzheimer’s disease afflicts 2.5 million to 4 million Americans and is a type of senile dementia, a broad disease category that also includes other types of organic brain disorders.
Although he usually cautions against reinforcing delusions, her physician, Dr. Stephen L. Read, medical director of the John Douglas French Center, a facility for Alzheimer’s patients in Los Alamitos, suggested draping the mirrors.
“I’m almost embarrassed to admit I did this,” he said recently. “But she got better. She believed the people were still there, but she felt a lot better because they weren’t looking at her all the time.”
Read’s anecdote, relayed at a recent medical conference, reflects the challenge facing Alzheimer’s disease researchers and physicians. For them, focusing on science alone--searching for the cause, diagnostic methods and treatments--isn’t enough. They must also create common-sense solutions to help ease the often nightmarish lives of patients and those who care for them. And they must alert care givers about behavior changes, a phenomenon not yet completely understood.
In the last decade, the ranks of Alzheimer’s disease researchers has swelled from a handful to more than 500 nationwide, estimated Zaven Khachaturian of the National Institute on Aging at a recent conference sponsored by the John Douglas French Foundation for Alzheimer’s Disease, Los Angeles. Research funding has increased from $90 million last fiscal year to $130 million in 1989, according to Claire McCullough, an NIA spokeswoman.
Despite that explosion of interest and infusion of funds, scientists are still not certain about what causes the disorder, first described in 1906. At autopsy, the brains of Alzheimer’s patients show two abnormalities: plaques, clusters of degenerating nerve cell ends, and tangles, masses of twisted filaments that accumulate in previously healthy nerve cells. And there is as yet no definitive treatment for the disorder, marked by memory loss and personality changes, communication difficulties and time disorientation.
Still, a number of research avenues may ultimately help unlock the puzzle. While some researchers focus on the origin of the disease, others are investigating better diagnostic methods. And others are zeroing in on psychosocial aspects. Research presented at the recent conference, along with investigations at the Alzheimer’s Disease Research Center at USC, one of 10 NIA research centers nationwide, have shed light on a number of areas.
The long-term debate over the cause of Alzheimer’s disease continues, with scientists suggesting genetic, viral and environmental origins, or a combination. Activation of some genetic factor is probably responsible, Dr. Leslie P. Weiner, USC chair of neurology and professor of microbiology, told conference participants. “There’s no hard evidence for the viral theory,” Weiner claims.
Fewer researchers today espouse the viral theory than in the past, Read believes. The idea that a viral infection causes brain cell death “remains a theoretical possibility, but there is very little experimental evidence,” he said.
In addition, some researchers now believe that there are different forms of the disease. In a study of 100 Alzheimer’s patients, David Freed, psychologist on staff at the USC Alzheimer’s Disease Research Center, identified three subgroups. One subgroup has a loss of nerve cells containing acetylcholine (a type of “messenger” brain chemical called a neurotransmitter) in the basal forebrain. Another group has loss of nerve cells with norepinephrine, another neurotransmitter, in the brain stem, and may also lack acetylcholine. In another subgroup, Freed found movement changes, including tremor and rigidity, and he speculates there may be a loss of nerve cells containing dopamine. This form of the disease is thought to result from long-term exposure to workplace toxins such as metals and solvents, Freed said.
Another USC researcher, Dr. Helena Chui, associate professor of neurology, is studying how the plaques form and has developed two hypotheses. Something may go awry in the nerve cells themselves, or the plaque may originate from the blood vessels. “The capillaries in Alzheimer’s disease patients are very irregular,” she said. In her studies of autopsied brains, she has found some capillary parts in the plaque.
Another researcher, Dr. Carol Miller, USC associate professor of pathology and chief of neuropathology, is using molecular probes to determine exactly which nerve cells are affected in the disease and to track the pattern of progression. Among other questions she’s investigating: Does the disease have identical progression from one patient to another? And how do healthy nerve cells differ on a molecular level from affected ones?
Meanwhile, other researchers are trying to find better diagnostic methods. Definitive diagnosis of Alzheimer’s disease is only possible, experts say, by biopsy, a procedure rarely done for the disease, or by autopsy.
But several less invasive techniques are yielding diagnostic clues as well. An imaging technique called SPECT (single photon emission computerized tomography) is “the best noninvasive procedure we have for making the diagnosis of Alzheimer’s disease,” claims Dr. Ismael Mena, director of the division of nuclear medicine at Harbor/UCLA Medical Center, Torrance, and a UCLA professor of radiological sciences. When memory loss is the presenting symptom, Mena said, SPECT can help determine whether it’s due to stroke, depression or Alzheimer’s.
In the procedure, a radioactive isotope is injected into a vein and an hour later an image is taken of the brain. From the computerized brain picture, the clinician can study the perfusion of blood into the the brain’s temporal and parietal lobes. Reduced blood flow into both temporal and both parietal lobes is “a fingerprint of Alzheimer’s disease,” Mena said, but not of depression or stroke. Since early 1988, Mena has used SPECT on more than 100 Alzheimer’s patients and predicts its use will increase dramatically, partly due to the recent availability of new and better imaging agents.
Also under study as a diagnostic method is the computerized electroencephalogram, a tracing of the brain’s electrical activity.
In healthy people, brain waves in the alpha range predominate and wave frequencies don’t change much with age, explained Dr. Cyrus K. Mody, clinical instructor of neurology, and Dr. Hugh McIntrye, professor of neurology, both at Harbor/UCLA Medical Center. But in Alzheimer’s patients, alpha waves decrease and are replaced with slower delta or theta waves. The computerized EEG technique correctly diagnosed all but one of 50 patients in a recent study at Harbor/UCLA, according to researchers there. The method can also evaluate severity, say the scientists, with greater changes suggesting more advanced disease. Currently, several teaching hospitals and about four Los Angeles area hospitals perform the computerized EEGs for Alzheimer’s detection.
Other researchers are piecing together typical behavior patterns and psychiatric symptoms of Alzheimer’s patients. Delusional beliefs such as those affecting the interior decorator are common, Read finds. “Families often consider the beliefs trivial in talking to doctors,” he said. Patients often believe someone has stolen everyday objects like wallets or purses and accuse the vague “they.” Some patients who no longer recognize a spouse “accuse the care givers of not being there when in fact they are present 24 hours a day.
“Sometimes a delusion is really an unconscious response to an environment that has become very much too complicated for a patient,” he said. In general, Read advises family and friends not to reinforce delusional beliefs, but acknowledges that in the case of the interior decorator, he successfully broke his own rule.
Behavior changes vary greatly, he finds. Besides having delusions, patients might become more out of touch, more listless and dependent, act more childishly or become cruel or mean-spirited. Not all Alzheimer’s disease patients become more agitated as the disease progresses, Read said, although that stereotype flourishes. Some become more passive; some display more self-centered behavior. Agitation is more common in patients who have had the disease longer, Read said.
Another common behavior, wandering, can provoke anxiety and exhaustion in family members and nursing home staff, especially when patients escape from home or facility. But wandering is believed to be a coping mechanism, a way to adjust to altered perceptions of the environment, and perhaps a response to loneliness, said Lynne Morishita, director of the Center for Geriatric Health at Century City Hospital and UCLA assistant clinical professor of nursing who also spoke at the conference. Most likely to wander, she finds, are patients who tended to pace or fidget in their younger days.
As Alzheimer’s disease becomes more well-known by the public, physicians face another dilemma. Aware of the disease, older Americans begin to worry about becoming a victim.
“A lady came to see me recently because she ran a red light,” Read said. “We spend a fair amount of time undiagnosing Alzheimer’s disease these days.” And according to the experts, the patient who says to his doctor, “I think I have Alzheimer’s disease,” almost never does.
