Several drugs can improve thinking, memory, and alertness in people with Alzheimer's disease and other diseases that affect the mind. So can these drugs help healthy people, too?
By Martin Downs
Reviewed By Brunilda Nazario
The drive to self-improvement is one of the defining aspects of our culture. We are willing to go to great lengths to match our ideals; and if you're not an Adonis or Venus, a mental equal to Einstein, or the spiritual equivalent of a saint, you may have felt a twinge of shame and pressure to whip yourself into shape.
So it's no surprise that as soon as medical science develops a treatment for a disease, we often ask if it couldn't perhaps make a healthy person even healthier. Take Viagra, for example: developed to help men who couldn't get erections, it's now used by many who function perfectly well without a pill but who hope it will make them exceptionally virile.
The same thing is happening with psychopharmaceuticals -- drugs that work on the mind. Ritalin, the first drug to treat attention deficit hyperactivity disorder, has been widely used by normal students hoping to be extra sharp while taking SATs or cramming for college exams.
Several new medications are on the market and in development for Alzheimer's disease, a progressive neurological disease leading to memory loss, language deterioration, and confusion that afflicts about 4.5 million Americans and is expected to strike millions more as the baby boom generation ages. Yet the burning question for those who aren't staring directly into the face of Alzheimer's is whether these medications might make us smarter.
'Flogging Your Nerves'
Memory loss, as well as dementia, is a key feature of Alzheimer's disease. If medications to treat Alzheimer's can improve memory, why shouldn't they help healthy people, too?
In theory, it's possible, says Marvin Hausman, MD, CEO of Axonyx Inc., a company whose Alzheimer's drug Phenserine is undergoing clinical trials in Europe. Phenserine is not available in the U.S.
Phenserine, as well as the drugs Aricept and Exelon, which are already on the market, work by increasing the level of acetylcholine, a neurotransmitter that is deficient in people with the disease. A neurotransmitter is a chemical that allows communication between nerve cells in the brain. In people with Alzheimer's disease, many brain cells have died, so the hope is to get the most out of those that remain by flooding the brain with acetylcholine.
"If you start flogging your nerves in an indiscriminate fashion, you're going to increase both short-term and long-term memory," Hausman says.
Yet there is no proof that an Alzheimer's drug could improve brain function in healthy people, although the results of one tantalizing study conducted by Stanford University researchers showed that a small group of middle-aged pilots given Aricept did better on flight simulation tests compared with those given a placebo.
Hausman hastens to add that his company has no interest in developing Phenserine as a "smart drug," for use in normal people. "I don't know if the FDA would ever allow a normal memory drug," he says.
Once a drug is FDA-approved, however, doctors can prescribe the drug for "off-label" uses other than those for which it was approved. But Hausman says, "I will never recommend off-label use."
Pending approval for Phenserine in Alzheimer's patients, he says Axonyx does intend to study the drug further as a treatment for mild cognitive impairment (MCI). People with MCI have some memory loss, but they don't yet have full-blown dementia. Many, however, go on to develop Alzheimer's disease.
In addition to increasing the levels of acetylcholine, Phenserine also seems to block the gene that makes beta amyloid, a toxic protein that builds up and causes plaques in the brains of people with Alzheimer's disease. Scientists believe this protein is responsible for killing brain cells in people with Alzheimer's disease.
A New Pathway
Less far along in the development pipeline is Memory Pharmaceuticals' experimental drug, MEM 1414. It's currently in phase I trials, which are designed to test safety in people.
MEM 1414 works by blocking phosphodiesterase, an enzyme that breaks down an important brain chemical, cyclic AMP. It appears to work in the area of the brain where new memories are formed. "It's very important for facts and events," says Axel Unterbeck, PhD, president and chief scientific officer of Memory Pharmaceuticals.
"In order to be able to form new long-term memories -- which are memories lasting for more than three hours, by definition ... the [brain] also processes that information for facts and events to be stored long term, he says. "If you enhance this pathway, you get, potentially, enhancement of this very function."
A drug that blocks phosphodiesterase has potential for treating Alzheimer's and MCI, as well as age-related memory decline, which is the forgetfulness that often comes with older age but is not necessarily a sign of impending Alzheimer's disease.
Unterbeck says that while age-related memory loss is common, "it's not a necessary consequence of aging" because it doesn't affect everyone. He says he thinks it should be looked at as a medical problem that might be treated with a memory-enhancing drug.
As for whether MEM 1414 could be used to improve memory in young, healthy people, "that would be pure speculation," he says. "It is clearly not a target for us as a company."
The possibility that memory-enhancing drugs may be as commonly prescribed in the future as Prozac and Ritalin are today raises some social and ethical questions, which Martha Farah, PhD, a professor of psychology at the University of Pennsylvania, addressed in a paper published in the May 2004 issue of Nature Reviews Neuroscience.
American employers are already squeezing more productivity out of fewer workers, so one wonders whether we might feel pressure to enhance our brainpower pharmaceutically, should the state of the art develop so far. Already, workers may be tempted to seek prescriptions for Provigil, a drug that treats daytime sleepiness. Provigil was originally approved as a treatment for narcolepsy and was subsequently approved for use by people who work swing shifts and suffer from excessive daytime sleepiness.
Could smart drugs, rather than being another tool in our self-improvement kit, turn us into worker drones?
"I think that you have to be careful when you jump from somebody enhancing their attention to get ahead at work to Brave New World," Farah says. "In some ways it's not a different problem from all the other ways that Americans are encouraged to be workaholics."
What Is Intelligence?
The question remains, also, whether drugs that improve memory or concentration can really be called smart drugs. The idea that a "smart pill" might come to exist took root with "nootropic" drugs, such as Piracetam and Hydergine, which were studied for decades as potential cognitive enhancers and treatments for Alzheimer's.
"These compounds were supposed to have some effect on global brain function, very similar to what people believe is the case for ginkgo biloba," Unterbeck says.
They still have a cult following, but the scientific evidence for their effectiveness is "very anecdotal and poorly documented," he says.
"I certainly don't think that there will be a smart pill," Howard Gardner, PhD, Hobbs Professor of Cognition and Education at Harvard University and a co-author on the Nature Reviews article, tells WebMD in an email.
Gardner is famous for his theory that the human mind has not one, but many distinct intelligences that work together to make up what we broadly call intelligence. "Any pill will and should have much more targeted effects," he says.
Nevertheless, a drug that improved your memory could be said to have made you smarter. We tend to view rote memory, the ability to memorize facts and repeat them, as a dumber kind of intelligence than creativity, strategy, or interpersonal skills. "But it is also true that certain abilities that we view as intelligence turn out to be in fact a very good memory being put to work," Farah says.
Pills cannot impart wisdom or make everyone capable of brilliant leaps of imagination, but they may tune up the machinery and give you more raw material to work with.
Published July 13, 2004.
SOURCES: Marvin Hausman, MD, CEO, Axonyx Inc. Axel Unterbeck, PhD, president, chief scientific officer, Memory Pharmaceuticals. Martha Farah, PhD, professor, department of psychiatry, University of Pennsylvania. Howard Gardner, PhD, Hobbs Professor of Education and Cognition, Harvard Graduate School of Education. Nature Reviews Neuroscience, May 2004. Neurology, July 2002. Alzheimer's Association.