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June 9, 2004

Alzheimer’s Disease—When Will We Conquer It?

Dr. Peter Zandi

Dr. Peter Zandi

The recent death of President Ronald Reagan from Alzheimer's disease reminds us that many are at risk of this modern scourge. When German physician Alois Alzheimer first described the disease in 1907, it was considered rare; today, Alzheimer's disease (AD) is the most common cause of dementia, affecting 10 percent of people 65 years old, and nearly 50 percent of those age 85 or older. And as the baby boomers age over the next 30-50 years, we are going to experience a public health emergency of immense proportions unless we can find some means of preventing the disease. The Office of Communications and Public Affairs talked about Alzheimer's with Peter Zandi, PhD, an assistant professor of Mental Health at the School.

Office of Communications and Public Affairs: What is Alzheimer's disease?
Peter Zandi: Alzheimer's is a progressive, neurodegenerative disease caused by unknown factors that leads to loss of neurons in the brain and manifests as dementia among the elderly. Individuals who suffer from Alzheimer’s experience cognitive problems and eventually have increasing trouble carrying out their activities of daily living until death.

OC&PA: Are there other types of dementia besides Alzheimer's?
PZ: Yes, but AD accounts for 60 to 90 percent of all cases of dementia.

OC&PA: How does Alzheimer’s cause the loss of neurons in the brain?
PZ: How Alzheimer's causes neuronal shrinking and loss is not entirely known, but there are two hallmark features to the disease. The first are amyloid plaques, which are composed of protein fragments that gravitate to and clump within the extracellular spaces between the neurons in the brain. The second hallmark are neurofibrillary tangles, altered proteins that build up within the brain's neurons themselves. We're not sure how the plaques or the neurofibrillary tangles injure the brain.

OC&PA: How is Alzheimer's diagnosed?
PZ: A definitive diagnosis for Alzheimer's can only be made at autopsy, after the person dies.

OC&PA: Then how can a person tell if they're getting Alzheimer's?
PZ: The main symptom is memory impairment. Alzheimer's affects other important cognitive skills—such as language, concentration, attention, problem-solving—but memory is affected first and over time this forgetfulness gets worse and worse.

OC&PA: So if you happen to forget your keys. . . ?
PZ: Everybody does that, and as we age we forget things like that more and more. But if you put your keys in the car but forget how to get home by the same route you've traveled for 10 years, and you suddenly don't know where you are, then something more significant may be happening.

OC&PA: What are the risk factors for Alzheimer's?
PZ: There are two main risk factors, age and genetics, or family history. Simply put, the older you are, the greater your risk of getting Alzheimer's. After age 65, the risk of Alzheimer's doubles every 5 years.

OC&PA: Does this huge increase in risk continue right up until a person dies?
PZ: There is some debate about whether everyone would get Alzheimer’s if they lived forever. Some researchers believe that the incidence of Alzheimer's levels off in the 90s; others believe that even at more advanced ages the incidence keeps rising.

OC&PA: What about the genetic risk factor?
PZ: If you have a first-degree relative with Alzheimer's, your own risk of contracting the disease is four times greater than normal.

OC&PA: Can a person do anything to lessen those odds?
PZ: There are no known proven preventions, but we are feverishly trying to identify factors that may help prevent the disease, and there are many lines of research aimed at discovering effective strategies. While none of these lines of study have yielded conclusive results, researchers are getting closer in finding out what causes Alzheimer's and what can prevent it.

OC&PA: What are some possible preventives?
PZ: One line of research suggests nonsteroidal anti-inflammatory drugs, or NSAIDs, such as ibuprofen. Aspirin is also an NSAID but the evidence for a protective effect for aspirin is not as robust as for other NSAIDs. Population-based studies that have followed cohorts of elderly people for long periods of time have yielded data showing that regular users of NSAIDS may lower their risk of Alzheimer's by 40 percent. However, formal proof of their efficacy can only come from randomized, prevention trials measuring the effects of an NSAID against those of a placebo. In fact, such a trial involving multiple sites is currently underway.

OC&PA: Why just one study of a single NSAID?
PZ: Because large-scale prevention trials, especially those involving great numbers of participants over long periods of time, as is necessary in Alzheimer's studies, are very expensive. And in addition to the cost, NSAIDS can have serious side effects in elderly people, such as silent and sometimes fatal gastrointestinal bleeds.

OC&PA: So you aren't recommending that people go out and start taking NSAIDS to head off Alzheimer's.
PZ: No. There are certainly risks involved.

OC&PA: Are there any other, safer options?
PZ: Epidemiologic data do indicate that some antioxidants may have a protective effect. Several of these observational studies have shown that, in particular,high doses of vitamins E and C can reduce the risk of Alzheimer's in the elderly.

OC&PA: What are those dosages?
PZ: In our study, daily doses of from 400 IUs to  2,000 IUs of vitamin E and at least 500 mg of vitamin C, when taken together, had the best preventive effect.

OC&PA: There've been some studies indicating that elderly people who keep mentally active might be able to stave off Alzheimer's.
PZ: Yes, that's another whole line of study related to the “cognitive reserve” hypothesis. This hypothesis says that people who have large “cognitive reserves”—brainpower to spare—either from natural endowment or from high levels of education or cognitive activity, may not show the effects of Alzheimer's as quickly as those who have less reserve. That is, it's thought that the pathology must do more damage over a longer period of time before the clinical symptoms of dementia manifest themselves.

OC&PA: How can people preserve or increase their “cognitive reserve”?
PZ: By keeping mentally active. Think of it as exercise for the brain. For example, a recent study found that ballroom dancing may be helpful in this respect, possibly because this activity involves keeping time with a partner and being continuously aware of your spatial orientation.

OC&PA: Do you see a cure for Alzheimer's any time soon?
PZ: I don’t know if we will have a cure any time soon, but we are making great advances in our understanding of Alzheimer’s. I believe that in the next five maybe ten years we will be able to leverage this knowledge to develop strategies for delaying the onset of Alzheimer’s among the elderly and for more effectively treating those who eventually succumb the disease. --Rod Graham
