Making Our Minds Last a Lifetime

While it may not be possible to completely age-proof our brains, a brave new world of anti-aging research shows that our gray matter may be far more flexible than we thought. So no one, no matter how old, has to lose their mind.

The brain has often been called the three-pound universe. It's our most powerful and mysterious organ, the seat of the self, laced with as many billions of neurons as the galaxy has stars. No wonder the mere notion of an aging, failing brain—and the prospect of memory loss, confusion, and the unraveling of our personality—is so terrifying. About a third of all people age 60 and over have recall problems that are noticeable to them and measurable with testing. At least a quarter of people age 85 and up suffer from dementia—the loss of memory and cognitive function and an inability to understand words, carry out motor activities, and recognize or identify objects. As Mark Williams, M.D., author of The American Geriatrics Society's Complete Guide to Aging and Health, says, "The fear of dementia is stronger than the fear of death itself."

Yet the degeneration of the brain is far from inevitable. "Its design features are such that it should continue to function for a lifetime," says Zaven Khachaturian, Ph.D., director of the Alzheimer's Association's Ronald and Nancy Reagan Research Institute. "There's no reason to expect it to deteriorate with age, even though many of us are living longer lives." In fact, scientists' view of the brain's potential is rapidly changing, according to Stanford University neuroscientist Robert Sapolsky, Ph.D. "Thirty-five years ago we thought Alzheimer's disease was a dramatic version of normal aging. Now we realize it's a disease with a distinct pathology. In fact, some people simply don't experience any mental decline, so we've begun to study them." Antonio Damasio, M.D., Ph.D., head of the Department of Neurology at the University of Iowa and author of Descartes' Error, concurs. "Older people can continue to have extremely rich and healthy mental lives."

Successful Aging

So what's the secret to keeping our brains agile and fit? Activity seems to be in fact, mental and physical challenges are both strongly connected to cerebral fitness. This finding springs in large part from a decade of research sponsored by the MacArthur Foundation Network on Successful Aging. Fifteen scientists across the nation have been studying the genetic, psychological, social, and environmental factors that contribute to mental fitness. In one study, Marilyn Albert, Ph.D., of Harvard Medical School, and colleagues from Yale, Duke, and Brandeis Universities and the Mt. Sinai School of Medicine examined 1,192 healthy and mentally fit individuals between the ages of 70 and 80. Twenty-two different variables were measured. "We looked at them in great detail," Albert says, "measuring everything from their blood pressure and cholesterol levels to psychiatric symptoms and whether they smoked."

The seniors were tested in 1988 and again in 1991. Four factors were found to be related to their mental fitness: levels of education and physical activity, lung function, and feelings of self-efficacy. "Each of these elements alters the way our brain functions," says Albert, who hypothesizes that regular exercise may actually stimulate blood flow to the brain and nerve growth, both of which create more densely branched neurons, rendering the neurons stronger and better able to resist disease. Moderate aerobic exercise, including long brisk walks and frequently climbing stairs, will accomplish this.

Animal studies confirm that both mental and physical activity boost brain fitness. At the Beckman Institute for Advanced Science and Technology in Urbana, Illinois, psychologist William Greenough, Ph.D., let some rats play with a profusion of toys. These rodents developed about 25 percent more connections between their neurons than did rats that didn't get any mentally stimulating recreation. In addition, rats that exercised on a treadmill developed more capillaries in specific parts of their brains than did their sedentary counterparts. This increased the blood flow to their brains.

Education also seems to enhance brain function. People who have challenged themselves with at least a college education may actually stimulate the neurons in their brains. Moreover, native intelligence may protect our brains. It's possible that smart people begin life with a greater number of neurons, and therefore have a greater reserve to fall back on if some begin to fail. "If you have a lot of neurons and keep them busy, you may be able to tolerate more damage to your brain before it shows," says Peter Davies, M.D., of the Albert Einstein College of Medicine in the Bronx, New York. That may explain why the progression of Alzheimer's disease in people who have big heads—craniums with a circumference of more than 24 inches—is slower. These people may simply have more brain tissue and more neurons.

Early linguistic ability also seems to help our brains later in life. A study in the New England Journal of Medicine (1996) looked at 93 elderly nuns and examined the autobiographies they had written 60 years earlier, just as they were joining a convent. The nuns whose essays were complex and dense with ideas remained sharp into their eighties and nineties.

Finally, personality seems to play an important role in protecting our mental prowess. A sense of self-efficacy may protect our brain, buffering it from the harmful effects of stress. According to Albert, there's evidence that elevated levels of stress hormones may harm brain cells and cause the hippocampus—a small seahorse-shaped organ that's a crucial moderator of memory—to atrophy. A sense that we can effectively chart our own course in the world may retard the release of stress hormones and protect us as we age. "It's not a matter of whether you experience stress or not," Albert concludes, "it's your attitude toward it."

Reducing stress by meditating on a regular basis may buffer the brain as well. It also increases the activity of the brain's pineal gland, the source of the antioxidant hormone melatonin, which regulates sleep and may retard the aging process. Studies at the University of Massachusetts Medical Center and the University of Western Ontario found that people who meditated regularly had higher levels of melatonin than those who took 5-milligram supplements. Another study, conducted jointly by Maharishi International University, Harvard University, and the University of Maryland, found that seniors who meditated for three months experienced dramatic improvements in their psychological well-being, compared to their non-meditative peers.

Modern Alchemy and Brain Chemistry

Like professional sleuths, neuroscientists have been hard at work discovering just what happens to brain cells when their power begins to fade. What they've uncovered may eventually lead to an astonishingly wide range of chemical approaches to preserving and enhancing cognitive function. Substances as diverse as nicotine, prednisone, ibuprofen, estrogen, and a whole host of new drugs that seem to fine-tune brain chemistry may have a potent impact on our gray matter. According to James L. McGaugh, Ph.D., who's been working on memory-enhancing drugs for 40 years, there's extensive laboratory evidence that animal recall is improved with drugs as well as hormones. But McGaugh notes that we're still a long way from safely and accurately fine-tuning the brain with chemicals. The first generation of memory-improving drugs may be a breakthrough, yet their effect may be modest.

Here are the most promising chemical substances and their potential impact on cognition:

  • Estrogen may increase cognitive ability, specifically short-term memory and the capacity to learn new tasks. Richard Mayeux, M.D., a professor at Columbia University's School of Public Health, and his colleagues studied over 1,000 women age 70 and up. Those who had taken estrogen for just a year were significantly less likely to develop Alzheimer's disease than women who had never taken the hormone. Dr. Mayeux estimates that women who take estrogen for a decade may reduce their risk for the illness by about 40 percent. Researchers theorize that estrogen may stimulate neurons to grow more branches. The National Institutes of Health (NIH) is launching a study on the impact of estrogen on Alzheimer's disease at 38 medical centers across the country. Eight thousand healthy women who are 65 years old or older and who are already taking estrogen will be studied.
  • Anti-inflammatory drugs may be just as promising as estrogen when it comes to warding off Alzheimer's disease. According to Khachaturian, "our body's reaction to inflammation can cause cells to die." The role of inflammation was first recognized when scientists discovered that arthritis sufferers—who usually take anti-inflammatory drugs—have lower rates of Alzheimer's disease than those who don't take drugs. A review of 17 studies by researchers at the University of British Columbia found that people taking anti-inflammatory drugs reduced their risk of Alzheimer's disease by nearly half. Both steroids and nonsteroidal drugs, like aspirin and ibuprofen, were included in this review. The National Institute on Aging is also studying the effect of the powerful anti-inflammatory drug prednisone on Alzheimer's disease. And two other drugs—the gout medication colchicine and the antimalarial drug chloroquine—are under consideration to be studied, according to neurologist Douglas Galasko, M.D., of the San Diego Veterans Administration Medical Center at the University of California.
  • Nicotine, which mimics some of the effects of acetylcholine, a major neurotransmitter, may enhance brain function. "Acetylcholine is quite important for cognitive function and memory," notes Edward Levin, Ph.D., of the NeuroBehavioral Research Laboratory at Duke University Medical Center in Durham, North Carolina. "Several studies have shown that nicotine will improve cognitive performance in Alzheimer's disease patients," Levin says, adding that it also seems to be effective in treating adults with attention-deficit disorder. Additionally, smokers have lower rates of Alzheimer's disease, though Levin is quick to assert that smoking's health hazards far outweigh its benefits as an antidote to failing memory.
  • Studies looking into the effects of 20 new "cognition enhancing" drugs on humans began in 1995. According to the Dana Alliance for Brain Initiatives, a nonprofit association of neuroscientists, many of these drugs increase the action of acetylcholine or mimic its effect.
  • A class of drugs, called ampakines, may immediately enhance our ability to learn or create new memories. Developed by Gary Lynch, Ph.D., a neuroscientist at the University of California at Irvine, the safety of these drugs has been tested in humans in a small pilot study with no side effects so far. But much research on their safety and efficacy remains to be done.
  • An antibody that enhances learning has been found. "When we put this molecule into the brains of rabbits they learned more quickly," says Jan Leestma, M.D., of the discovery he and his colleagues at the Chicago Institute of Neurosurgery and Neuroresearch made.

At The Corner Store: Vitamins and Nutrients

It's not just scientists who are catching anti-aging fever. Walk into any health food store, and you'll find nutritional formulas—with names like Brainstorm and Smart ALEC—that claim to sharpen mental ability. The book Smart Drugs & Nutrients, by Ward Dean, M.D., and John Morgenthaler, was self-published in 1990 and has sold over 120,000 copies worldwide. It has also spawned an underground network of people tweaking their own brain chemistry with nutrients and drugs—the latter sometimes obtained from Europe and Mexico. Sales of ginkgo—an extract from the leaves of the 200-million-year-old ginkgo tree, which has been shown in published studies to increase oxygen in the brain and ameliorate symptoms of Alzheimer's disease—jumped up by 22 percent within six months in 1996, according to Paddy Spence, president of SPINS, a San Francisco-based market research firm.

Indeed, products that increase and preserve mental performance are a small but emerging segment of the supplements industry, says Linda Gilbert, president of HealthFocus, a company that researches consumer health trends. While neuroscientists like Khachaturian liken the use of these products to the superstition of tossing salt over your shoulder, the public is nevertheless gobbling up nutrients that promise cognitive enhancement. For example:

  • Antioxidants offer a promising approach to safeguarding the brain. They protect cells from attack by free radicals—highly reactive substances that damage cells and contribute to aging. According to Dr. Galasko, small studies in the United States, Canada, and Scandinavia have hinted that two substances with powerful antioxidant properties—vitamin E and deprenyl, a drug used to treat Parkinson's disease—may indeed stem free-radical damage in the brain. Results from a study pairing the two substances, sponsored by the National Institute on Aging, should be available in 1997.
  • Acetyl-L-carnitine, a derivative of the amino acid L-carnitine, protects brain cells in animals. L-carnitine aids the process by which a cell turns fat into energy, but on its own it does not reach the brain. Acetyl-L-carnitine does. It's available by mail order and in some health food stores. However, studies on the impact of this nutrient on Alzheimer's disease patients have not shown promise.
  • Choline is a building block for acetylcholine, a major brain neurotransmitter. Evidence that it actually stimulates acetylcholine production is slim, and choline supplements have not helped Alzheimer's disease patients. But some studies indicate that this may be because damaged brain cells can no longer absorb the choline. If supplements of choline are taken at a younger age, the theory goes, it may help prevent the brain's decline.

Underestimating the Obvious

Despite being a neuroscientist who works with drugs, McGaugh believes that for most people the way to maintain high brain function will not be found in chemicals. "There's growing neurobiological evidence that supports the common sense notion of 'use it or lose it,'" he says. "The brain may be more like a muscle than we ever thought."

Psychiatrist James Gordon, M.D., a professor at the Georgetown University School of Medicine and author of Manifesto for a New Medicine, takes that insight a step further. "I wish people would be more concerned with wisdom and less concerned about cognition," he says. "Why not spend some time meditating, dancing, or performing tai chi every day? These activities will work on your brain chemistry, too." Dr. Gordon recalls a dinner he shared with the then-67-year-old painter Robert Rauschenberg in 1992. "All over his studio there were these huge canvasses. After we finished eating, Rauschenberg said it was time for him to get back to work. My friend asked him if he ever took any time off. 'Honey,' he said, 'I don't want more time off. I want more time on.'"

With an ever-increasing number of anti-aging drugs, nutrients, and hormones available, and new insight into the impact lifestyle has on the brain, we may all have a lot more time to think. However, it will still be up to us to grow wise.

Feed Your Head?

Why wait decades for science to hand us "smart" drugs and nutrients that supposedly enhance brain function when we may already have them at hand? These medications include deprenyl (for Parkinson's disease), vasopressin (used to treat diabetes), piracetam (for learning disabilities), and others that are available only in Mexico and Europe. Also on the list of smart drugs are a host of amino acids that are building blocks for neurotransmitters—such as tryptophan, tyrosine, and choline—as well as dimethylaminoethanol (DMAE) and nicotinamide adenine dinucleotide (NADH), nutrients that seem to enhance cognitive function.

Steven Fowkes, who devised his own smart drug regimen, says it has changed the way he works and sleeps. "I used to be a night owl. But as soon as I began taking piracetam, that changed. I woke up spontaneously at dawn, got a load of work done in the morning, and stopped drinking caffeine. Piracetam gives me all the benefits of caffeine without the feeling of being wired or overstimulated." Piracetam is available by prescription from a few special pharmacies (Apothecure [800-203-2158] and College Pharmacy [800-888-9358]). Fowkes also takes deprenyl, which he imports—and which does not have Federal Drug Administration approval. And he uses a vitamin-and-mineral formula called Extend, which he says has about 40 different nutrients.

Fowkes's colleague John Morgenthaler, co-author of Smart Drugs & Nutrients, the book that may have launched the entire cognitive-enhancement movement, says he's developed his own nutrient regimen, which includes such substances as pregnenolone (a precursor of DHEA), melatonin (an antioxidant hormone), and antioxidants that combat free radicals (highly reactive molecules that damage cells and contribute to aging). "I want to feel good 25 years from now," Morgenthaler says. "You have to think ahead."

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