Americans spend more than $40 billion a year caring for an estimated 2.5 million Alzheimer's patients. Although it is the fourth-leading cause of adult deaths in the U.S., killing an estimated 120,000 annually, Alzheimer's is sometimes the silent epidemic because so little is known about it. A leading authority on AD is Dr. Dennis Selkoe, 43, research neurologist and associate professor at Harvard Medical School and also co-director of the Center for Neurologic Diseases at Boston's Brigham and Women's Hospital. Recently he discussed advances in the war on Alzheimer's with correspondent Gayle Verner.
When and how does Alzheimer's strike?
It's a very common degeneration of the brain that most often strikes people over 50, particularly those over 70. By and large it is a memory and intellectual dysfunction. As the disease progresses, the brain becomes less able to transmit signals properly. AD is the most common cause of senility, accounting for 60 percent of the cases. Senility is a general term which means loss of mental function with age.
What are the symptoms?
First and foremost some memory loss—especially of recent events, such as why you went shopping. As time goes on, victims lose more and more memory. Eventually they forget important things like the names of their own children. They will lose the ability to balance a checkbook, to find their way from one town to the next, to remember the location of the bathroom in their own home. Language is also affected. They'll mix up words, substituting, for instance, "book" for "cook." Over time, they won't be able to use complicated words or to form complicated thoughts or sentences.
How does it affect people physically?
Some patients in the early stage of Alzheimer's are still playing tennis, but they can't remember the score. In the late stages, three to sometimes 10 years after onset, victims' ability to walk deteriorates. They almost look like Parkinson's patients. They may not have bladder control. Some will have a blank stare. Ultimately AD sufferers will fall victim to a host of infectious diseases.
Is Alzheimer's hereditary?
Yes. About 25 to 50 percent of all patients have a history of one or more relatives with the disease. In some of these families there is a one-out-of-two chance that you will inherit the disease from a parent who has had it. It's really a flip of the coin though.
Does heredity always play a role?
No. It can happen with no history of a relative having the disease before. We don't know what percentage of sporadic cases is really sporadic. But I think in many cases the disease is hereditary. Often there are no good records or case histories kept, so there's no way to trace a family's patterns. For example if the mother died of cancer at age 63, she might have developed Alzheimer's at age 81 had she lived that long.
What causes Alzheimer's?
We don't know yet, but we're closer than ever to learning the causes. Victims exhibit certain abnormal brain structures. They have an accumulation of plaques [protein deposits] and abnormal fibers—known as neurofibrillary tangles—in the brain. These deposits seem to bring about a loss of nerve cells. Normally nerve cells make several different message molecules, such as acetylcholine. These message molecules are usually released from the endings of nerve cells and travel across the synapse [the area between nerve cells] to transmit information to the next nerve cell. Alzheimer's victims are unable to transmit and store information properly.
In what areas are scientists looking for clues?
Among the possible causes being investigated are a slow virus, genetic predisposition and environmental toxins. In my opinion there is no good evidence that aluminum is either a cause or an exacerbator of Alzheimer's disease. But there have been a lot of exciting breakthroughs. Several laboratories here and around the world, including ours, are investigating abnormal protein deposits called amyloid. Our research shows that it is a central feature of the disease. If it's not the cause, it's closely linked to it.
Why is the protein amyloid significant?
The gene that makes amyloid protein has been cloned and studied in the test tube. It's found to be located on chromosome 21. We think the amyloid gene on chromosome 21 is a real clue to the cause of Alzheimer's. A group of scientists at Massachusetts General Hospital has shown that a genetic marker on chromosome 21 is directly linked to whatever causes Alzheimer's in certain families—and the amyloid gene is close by. This genetic marker, which is a piece of DNA localized to a specific region of a chromosome, could eventually be used to identify family members at risk of the disease. These discoveries are far more exciting than anything we have seen in the last 10 years of research.
How do these discoveries help?
They don't yet help patients who have the disease. But they are a powerful tool for scientists to decipher the causes of the disease, and ultimately could lead to an accurate blood test and specific treatment. For example there may be a specific mutation of the sequence of DNA molecules in the region of chromosome 21 containing the amyloid gene. This might cause either too much production of amyloid protein or an abnormal breakdown of the protein. Patients with Down Syndrome, who have an extra set of chromosome 21, almost always develop the amyloid plaques of Alzheimer's disease at an early age.
How does the amyloid protein affect the brain?
We don't know for sure what harm it does to the nerve cells. We just know it's present right in the middle of a bunch of degenerating nerve cells. So we assume it must damage those cells, but it's not proven.
How are doctors treating Alzheimer's?
We really don't have anything that influences or slows the course of the disease. There are almost no proven drugs that really help. There are only straws in the wind regarding possible treatment.
What are they?
The drug THA [tetrahydroaminoacridine] appears to alleviate mild symptoms at certain stages. It helps a little with some of the memory problems, some of the confusion. There are two other antidotes that have effects similar to THA: the drug physostigmine and the food additive lecithin. These given together helped a few with their memory for a short period of time. But the majority of Alzheimer's patients don't improve.
Are we close to finding the cause?
At most we're a few years away from understanding Alzheimer's. When we know the cause, we have to learn the co-factors that precipitate the cause. When we get both pinpointed, we can develop rational therapies. We don't need to know all the details about amyloid, for example, to try to devise ways to inactivate it.
Rita Hayworth is one of the most famous victims of Alzheimer's disease, a relentless ailment that slowly erodes the brain with devastating and heartbreaking results. First identified in Germany by Alois Alzheimer in 1906, its symptoms can at onset seem harmless—a forgotten word, a sudden mood change. But in its final stages it reduces victims to emotional and physical helplessness, placing enormous burdens on their families. The average annual cost to a family caring for an AD victim at home is $22,000; at a nursing home the average cost is $25,000.