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Alzheimer's: Few Clues on the Mysteries of Memory

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By Audrey T. Hingley • • May 1, 1998

It happened some years ago but the memory is still firmly implanted in my mind.

One sunny afternoon I heard the sound of a car pulling into our driveway, peered out of my living room window, and saw one of my father's friends, Sam (not his real name), then in his early 80s. Sam got out of his car and walked just a few steps. I watched as he stood for a few moments, gazing at our house with an expressionless face. Then he silently returned to his car, got in, and drove away, without ever knocking on our door or communicating with us in any way.

I thought the incident puzzling, but it wasn't until months later that I learned the reason for it. Sam had Alzheimer's, a progressive disease in which nerve cells in the brain degenerate and brain substance shrinks. A widower living alone, Sam clearly was in a dangerous position. Once he was followed home by a police officer, who told his grown children he had found Sam stopped by the side of the road, not able to remember how to get home by himself.

Sam's story is being played out in the lives of up to 4 million Americans who suffer from Alzheimer's disease. The disease plays no favorites, attacking rich and poor, famous and ordinary. Among its most famous sufferers: former President Ronald Reagan.

Alzheimer's afflicts 1 in 10 people over age 65 and nearly half of all people age 85 and over. People with Alzheimer's live an average of eight years, although some live up to 20 years or more after the first onset of symptoms. With an average lifetime cost of care per patient of $174,000, it is the third most expensive disease in America, following only heart disease and cancer. But perhaps even more staggering than the monetary costs are the emotional and psychological costs borne by both patients and their families.

"People are very frightened of the possibilities because they know it represents a loss of one's self," says Steven T. DeKosky, M.D., director of the Alzheimer's Disease Research Center at the University of Pittsburgh and a practicing neurologist. "It's a very frightening prospect to see a loved one who looks the same but doesn't talk or act the same."

Alzheimer's disease, a progressive, degenerative disease attacking the brain and resulting in impaired thinking, behavior and memory, was first described by Alois Alzheimer, M.D., in 1906. German researchers recently found an important set of notes from Alzheimer's journal of the world's first documented case of the disease. The patient exhibited many of the symptoms seen in Alzheimer's patients today. But perhaps most poignant of all is the patient's own description of the disease: "I have lost myself."

While researchers now have a deeper understanding of the brain and behavioral changes characterizing the disease, Alzheimer's remains shrouded in mystery. Its cause is still unknown, although a number of theories have been proposed, and there is known to be a reduced level of certain brain chemicals in people with Alzheimer's disease. Genetic factors have been linked to Alzheimer's, as have brain damage from strokes, a protein that may accelerate formation of abnormal deposits in the brain, abnormal functioning of mitochondria, the primary energy-producing parts of cells, and even dietary factors, especially a high fat intake. But because so much about what triggers Alzheimer's is still unknown, developing treatment and prevention is an ongoing challenge.

In Alzheimer's, nerve cells in the part of the brain responsible for memory and other thought processes degenerate for still-unknown reasons. Some of the most severely affected cells normally use acetylcholine, a brain chemical, to communicate. Tacrine (brand name Cognex, also called THA), the first drug approved by the Food and Drug Administration specifically to treat Alzheimer's disease, works by slowing the breakdown of acetylcholine. This results in relieving some memory impairment.

Tacrine does not cure Alzheimer's or slow the disease's progression. It has only been studied in those with mild to moderate Alzheimer's disease who were otherwise in generally good health. Because tacrine can increase the blood levels of a liver enzyme that can indicate liver damage, regular monitoring is necessary. Other side effects include nausea, vomiting, diarrhea, abdominal pain, skin rash, and indigestion.

"Many physicians do not use tacrine at first because of the need to monitor for liver function and dose adjustment," DeKosky says. "Relatively few people are now started on it as a preliminary treatment, and it's not given to anyone with a history of liver disease."

Aricept (generic name donepezil hydrochloride, also called E2020), approved by FDA in 1996, is by far the most used drug for Alzheimer's treatment. Like tacrine, Aricept inhibits the breakdown of acetylcholine but does not cause the kind of increase in liver enzymes that tacrine does. It can also cause diarrhea, vomiting, nausea, fatigue, insomnia, and anorexia, but in most cases, such side effects are mild and decline with continued use of the drug. Again, the drug helps only those patients with mild to moderate symptoms of Alzheimer's and does not stop or slow the disease's progression. "There is no way to predict who will respond so you just have to try it," DeKosky says of Aricept. "Symptoms you hope will improve are targeted, and then you try to find a way to assess that improvement."

'Forgetfulness' or Alzheimer's?

While most people understand at least some of the horrifying aspects of Alzheimer's disease, DeKosky says a big challenge is educating people regarding the widely held assumption that people are supposed to have memory impairment as they age. "There's this huge prejudice where we think people should have severe mental impairment as they get older," he says. Memory loss, disorientation, and confusion are not part of the normal aging process, he explains. They are symptoms of dementia, and the most common form of dementia is Alzheimer's. "You need to look at the functional consequences of what someone cannot remember," DeKosky says. "If mom forgets where she put her car in the parking lot at the mall, that's not abnormal. But if she walks home from the mall because she forgot she took her car, that's not normal. Memory is the first and worst change, but you will also see social withdrawal and less willingness to interact with others."

Alzheimer's warning signs include memory loss affecting job skills; difficulty performing familiar tasks; language problems; time and/or place disorientation; poor or decreased judgment; problems with abstract thinking; misplacing things or putting them in inappropriate places; mood, personality or behavior changes; and passivity and loss of initiative. If you notice several of these symptoms in yourself or a loved one, consult a doctor for a complete examination and evaluation.

There are three broad stages to Alzheimer's. In the beginning, the patient may notice his or her own forgetfulness and will solicit others' help or write lists. In the second phase there will be severe memory loss, particularly for recent events. A sufferer may often remember long-ago events while being unable to remember a just-viewed TV show. In this stage, disorientation usually begins, dysphasia (inability to find the right word) may occur, and mood changes happen that can be unpredictable and sudden. By the third stage, people with Alzheimer's experience severe confusion and disorientation, and may suffer hallucinations or delusions. Some may become violent or angry, while others may be docile or helpless. In this stage, sufferers may wander without purpose, experience incontinence, and neglect personal hygiene. Once someone with Alzheimer's becomes bedridden, the complications of bedsores, feeding problems, and infections can make life expectancy very short.

Behavioral symptoms of Alzheimer's result from changes taking place in the brain. The patient neither intends nor can control this behavior. Because families are so often involved in caring for people with Alzheimer's, family education, counseling, and support are vital. Alzheimer's disease can be definitively diagnosed only by examination of the brain after death. But physicians can make a probable diagnosis while the patient is still alive by doing a comprehensive evaluation, including a complete health history and physical exam, mental status assessment and neurological tests, blood and urine analysis, electrocardiogram (EKG), and x-rays. They may conduct additional tests, such as computerized tomography (CT scan), electroencephalography (EEG, or recording of brain wave patterns), and formal psychiatric assessment.

The tests are important to rule out other potential causes of dementia, such as vitamin B12 deficiency, pernicious anemia, hypothyroidism, or tumors. Documenting symptoms over time, in a diary-like fashion, also helps doctors understand the person's illness.

New Studies

Researchers continue to study drugs and other substances as possible treatments for Alzheimer's. Carefully designed and conducted studies are necessary to give a clear picture of safety and effectiveness before any approval can be considered.

A recent report in The New England Journal of Medicine found that mental deterioration from Alzheimer's was slowed by an average of seven months by either selegiline (Eldepryl, Atapryl), a drug normally prescribed for Parkinson's disease, or high doses (2,000 I.U. per day) of vitamin E. In addition to trials with conventional drugs, alternative therapies are also being researched.

"There have been a number of studies on the usefulness of Ginkgo extract [a popular herbal medicine derived from the leaves of Ginkgo trees] in Alzheimer's," says Neil S. Buckholtz, chief of the dementias of aging branch, neuroscience and neuropsychology program, National Institute on Aging, National Institutes of Health. "The bottom line is that this is an interesting compound, but we are still not sure if it works in Alzheimer's disease. We are now funding a small study on Ginkgo. But you have to look at the risks vs. benefits these are not benign compounds." Nevertheless, DeKosky expects to see more studies on "natural" or alternative-type therapies like Ginkgo. "Those studies should be done," he says, "so we know whether it's helpful, patentable, or even to say it does not work."

The Need for Answers

Although no cure for Alzheimer's is available now, planning and medical/social management can help ease the burden on both patient and family members. Physical exercise, good nutrition, and social activities are important. A calm, structured environment may also help the person to continue functioning.

At some point, however, people with Alzheimer's require 24-hour care. The financing of such care, including diagnosis costs, treatment, and paid care, is estimated to be $100 billion annually, according to the Alzheimer's Association. The federal government covers $4.4 billion and the states another $4.1 billion, with much of the remaining costs borne by patients and their families.

"It's a national imperative to find effective means to diagnose, treat and prevent this disease," says David Banks, R.Ph., a public health specialist in FDA's Office of Special Health Issues. "When you look at it demographically, the nearly 80 million baby boomers living in the United States ... now have an average life expectancy of approximately 78 years. One in five Americans could be age 65 or older by 2030, and tens of millions of baby boomers will live into their 80s. The Alzheimer's Association projects that as many as 14 million Americans could have Alzheimer's disease in 2050. When viewed in the context of accelerating Social Security and Medicare cost, the future monetary costs of Alzheimer's disease may be unsustainable. The human costs could be even greater."

"As we learn more about genes and other factors affecting the onset of Alzheimer's, the possibility of delaying the disease becomes more real," says Zaven Khachaturian, Ph.D., director of the Alzheimer's Association Ronald & Nancy Reagan Research Institute. "If we can push back the onset of Alzheimer's for just five years, we can reduce by 50 percent the number of people who get the disease, add years of independent functioning to people's lives, reduce the amount of care they need, and save this country billions of dollars in health-care costs."

Source: FDA Consumer Magazine May-June 1998

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