Alzheimer's: The Mysteries of Memory

by Food and Drug Administration (FDA)

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."

'I Have Lost Myself'

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."

About the Author

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