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Time Magazine September 13, 1999

Elixirs For Your Memory

The blitz is on for ginkgo and other herbal products, but are they panaceas or placebos? BY TAMMERLIN DRUMMOND Tired of frantically searching for your keys? Or of rushing into a room only to forget what you were looking for? If you're worried about memory lapses, just flick on the TV. There are Annie Potts, former star of Designing Women, and Hector Elizondo of Chicago Hope hawking dueling versions of the herbal supplement ginkgo biloba. Or click on the website , where you can read about a "delicious" supplement derived from the compound phosphatidyl serine. All offer hope for improving memory and brain function. The graying of America has created a whole new industry aimed at people worried about remembering and concentrating. In health-food stores, you'll find dozens of products that claim to do wonders for your brain. They range from vitamins to exotic herbal concoctions. But at the head of the pack is the enormously popular ginkgo biloba--a derivative of a leafy ornamental tree originating in eastern China that racked up $240 million in sales in 1997. Countless people swear that ginkgo has changed their lives. So effective has the advertising blitz been that ginkgo products seem to be leaping off the shelves. Even old-line pharmaceutical houses are offering their versions of brain boosters. In their first year on the market, Bayer Consumer Care's new vitamin pills, spiked with ginkgo--and sold under the label Memory and Concentration Formula--took in a cool $8 million. The no-brain question: Does any of this stuff actually work? Traditional healers have no doubts about ginkgo, a staple of Chinese medicine. Nor do manufacturers of so-called nutriceuticals--the unregulated natural "medications" found in health-food stores and supermarkets. They say it somehow improves memory by increasing the flow of blood to the brain. Leading memory experts, however, are skeptical about ginkgo and other brain boosters. "Most of these products have not been investigated to any significant extent that would warrant the claims that are being made,'' says Dr. Ronald Petersen, a neuroscientist at the Mayo Clinic in Rochester, Minn. Other geriatricians are more blunt. All the hoopla, they say, is merely a case of the placebo effect run amuck: people want their memories to get better, so they do. Give them a sugar pill, and they probably wouldn't know the difference. Government researchers are understandably concerned that millions of people are gulping supplements without any idea what their effects are, positive or negative. The National Institutes of

Health is undertaking a study of the effects of ginkgo on elderly people with mild memory impairment. But it could be years before results are in. Meanwhile, what are healthy souls in search of a quick boost to do? Consumers have little to go on other than manufacturers' claims and inconclusive research. Moreover, since ginkgo and other supplements are not regulated by the Food and Drug Administration, potency and purity vary from brand to brand. Most troubling, however, is that few people read labels. The list of don'ts for ginkgo biloba include the warning that those taking aspirin or other blood thinners should first consult their physician. Why? Because ginkgo, which has anticlotting characteristics, when taken in combination with a blood thinner can cause internal bleeding. The one thing generally agreed on is that too little is known about most memory supplements to assess their risks. So far, the research has focused on humans with Alzheimer's and lab animals like Princeton's Doogie mice. Scientists are only now beginning to examine what happens to memory in normal people during the aging process. "People jump to the conclusion that if it helps my grandfather, it must help me," says Dr. Jerry Cott, a neuropharmacologist at the National Institutes of Health. But it's a lot more complicated than that. Much of how memory works remains murky. We know, though, that memory involves chemicals called neurotransmitters--one of which is acetylcholine--and the signals they carry through the brain. As people learn, the synapses--interconnections between brain cells--are reinforced, creating a complex network of associations. But with age, the synapses somehow falter--about 25% of them between ages 25 and 55--and so does the ability to effectively retrieve memories. One day it may be possible to delay or even reverse the course of Alzheimer's with medication. Two FDA-approved drugs are currently available for treating the symptoms of Alzheimer's disease--donepezil, marketed under the brand name Aricept, and tacrine (Cognex). Both block an enzyme that destroys acetylcholine, and have been shown to sometimes slow the progress of the disease. Animal tests suggest that the drugs might also make a difference in less serious memory disorders. But the side effects are no picnic. Cognex builds up an enzyme that can lead to liver damage. And though many patients can better tolerate Aricept, the newer of the two drugs, it can cause diarrhea and vomiting. The National Institute on Aging is embarking on a study to determine if Aricept can help people with mild cognitive impairment. If you suffer from MCI, you might consistently come out of the mall and not remember where you parked your car (with dementia, you'd forget that you even owned one in the first place). Fifty percent of people over age 65 with MCI will develop Alzheimer's within five years. An estimated 4 million Americans are afflicted with Alzheimer's, which is characterized by an accumulation of protein that gums up the brain so the neurons can't fire. Eventually, what began as problems remembering names or telephone numbers ends in full-scale dementia. Memory-loss experts around the country are testing an array of treatments in the hope of finding that one universal brain tonic that will arrest those changes. Scientists speculate that megadoses of 2

antioxidants such as vitamins E and C may reduce the cell damage associated with severe memory loss. The theory is that antioxidants soak up tissue-damaging chemicals called free radicals. But as with so much of what makes memory tick, no one knows for sure. In some studies, high doses of vitamin E slowed the progress of Alzheimer's for up to seven months. That may not sound like a big deal, but if you have a parent suffering from Alzheimer's, it's a godsend. Many geriatricians recommend vitamin E for mild cognitive decline. "There is nothing absolutely known," says Dr. Barry Gordon, director of the memory clinic at Johns Hopkins Medical Institutes and author of the self-help book Memory (MasterMedia Limited; $14.95). "But physicians feel this has enough evidence in its favor and few enough known side effects." Physicians also recommend prescription doses of anti-inflammatory agents such as Naprosyn and ibuprofen to reduce Alzheimer's-related inflammation. Meanwhile, a dozen brain-boosting therapies ranging from estrogen replacement (which may promote the growth of some neurons) to entirely new drugs are at various stages of development. In the near future, two new cholinesterase inhibitors, ENA 713 (Exelon) and metrifonate, are expected to become available. Memory researchers have also been looking at the NMDA receptor, target of the Princeton experiment. But tests of possible drugs to enhance memory have been inconclusive. Says Bill Thies, vice president for medical and scientific affairs at the Alzheimer's Association: "I think in a 10-year window we'll see some revolutionary stuff to prevent the disease." What can you do while waiting? To fend off normal age-related memory loss, follow the adage Use it or lose it, the experts say. Simply reading a book or working a crossword puzzle on a regular basis can do wonders, even if it's not clear why. "The most solid piece of advice is to stay active," says Patricia Tun, associate director of the memory and cognition lab at Brandeis University. In the long run, a common-sense diet and healthy lifestyle may be the best memory boosters of all.

Time Magazine February 28, 2000

Speak, Memory
As we age, remembering often is harder work than it once was. Here are some ways to improve your sense of recall
BY EMILY MITCHELL Memory makes us who we are. And because it is our identity, we worry about it, fretting if we can't remember the name of someone we just met--or know well--getting upset when we can't recall where we put our keys or left the car in the parking lot or whether we mailed the phone bill. We walk into a room and halt in midstride, the purpose forgotten. These annoying things happen to most of us eventually, and for a simple reason. Just as the body changes over time, so does the brain. "On any intelligence or memory test," says University of Chicago gerontologist Michael Roizen, "we lose, on average, 5% of our capability for every decade after 30." As scientists discover more about the mysterious workings of the brain, it is encouraging to learn that many age-related changes can be slowed, including the decline of memory. The first step is to understand how memory works. Our head doesn't have a separate, identifiable system for remembering. A single memory is made of tiny pieces of information accumulated and stored over time. Those bits are held in a complex network of some 100 billion neurons, or nerve cells, that can make thousands of connections with other cells in the brain. Subsystems within the cortex handle specific things like names, sounds, textures, faces and smells. Say the word dog, and the busy brain fires up a host of images, sensory impressions and emotions, then reconstructs a specific, unique memory. The connections between neurons--the synapses--are formed on branchlike structures called dendrites. In a normal, healthy person, these can gradually shrink over time, slowing the process of recalling information and leading to those familiar lapses called "senior moments." Memory gridlock is bothersome, but, says Johns Hopkins neurologist Barry Gordon, "what most people complain about is not that serious at all. They're probably not going to get Alzheimer's; they just care more about forgetfulness as they get older.'' Attention Must Be Paid When adults concerned about their memory come to the Pisgah Institute for Psychiatry and Education in Asheville, N.C., psychologist Ed Hamlin gives them standard tests for visual and verbal memory, delayed recall and delay in attention and concentration. For most, the results are reassuring: their memory is not only good, it exceeds the average for their age. 1

But what about those times when they experience a total blank? Says Hamlin: "A number of problems are not problems with memory at all. They are really problems with your attention." There are three basic steps in memory: registration, retention and retrieval. They occur sequentially; if new information isn't taken in (registered), it can't be stored. Focusing on incoming material, whether heard, seen or read, helps implant it in memory. Psychologist Cynthia Green advises students in her memory classes at New York City's Mount Sinai Medical Center that "often what we think we forgot we really didn't 'get' in the beginning." Sorting and storing the multitude of information available in the modern world takes work. Just look at a teenager listening to music and chatting on a cell phone while simultaneously tapping out commands on a computer. For many older men and women, such sensory overload makes focusing more difficult. Eliminating unnecessary sounds and other distractions, experts suggest, makes it easier to concentrate on exactly what you want to remember. Attention can be reinforced by repeating new information or making associations to link it to other memories. When introduced to someone new, for example, repeat the person's name, ask how it's spelled or make some other comment that will help fix it in your mind. Professor Arthur Wingfield, director of Brandeis University's Memory and Cognition Laboratory, explains: "What you are trying to do is get yourself to pay attention and encode it. Younger people can do this faster; older people have to work harder." The Harder You Try If there's a golden rule for remembering, it's this: the best way is not to try. In a memory-enhancement course Hamlin teaches at the University of North Carolina's College for Seniors, he emphasizes that when something previously known is truly forgotten, the struggle to recall it defeats the purpose. "Anxiety about your memory," he maintains, "is actually harming it." People sometimes stew for hours trying to dredge up the name of a movie star from a past era. It seems right on the tip of the tongue. The face floats up before the eyes, co-stars' names and titles of past movies spring to mind, but the name, ah, remains elusive until you awake in the middle of the night, saying "Mona Freeman" or "Louis Jourdan" with satisfaction. Why this frustrating delay? In the view of some scientists, the brain is working on recall, but the other names are interfering. Don't try to think about the names that are blocking it. Brandeis' Wingfield says, "They will dissipate, and you will be able to retrieve it." Or divert the mind by thinking about something else, and the name will frequently pop up. Older people simply have more to remember. Says Professor Albert Rizzo of the University of Southern California's School of Gerontology: "After you have lived a rich, full life, you have a larger amount of 'books' in your brain, thousands of them, as opposed to the hundred when you were younger. You have to sift through more, like a librarian." Re-creating the original stimulus can often prompt recall. If the reason for entering a room seems to have temporarily vanished, retrace your

footsteps. Rizzo explains, "This re-energizes the brain and brings it back to where you were 'mentally' beforehand, and--bong!--you remember." Get Sharp with Strategies One key to sharpening memory skills, Rizzo tells students in his eight-week memory seminars, is to become "your own personal scientist." You have to figure out where the fault lines are and then apply various strategies and techniques. Organization won't necessarily improve memory, but it will help reduce the number of things you have to remember. Deciding on a specific place for everyday items is a good way to avoid having to play hide-and-seek with them. Making lists, keeping track of appointments in a calendar or daily diary or using sticky notes as quick reminders help free the mind. Billie Stewart, 64, of Asheville keeps a sticky pad in her car, and when she thinks of an errand that needs to be done, she jots it down. "If I write down bakery," she says, "I can let go of it and don't have to clog up my memory." Written reminders aren't cheating. Far from it. They make it easier for the brain to handle a larger quantity of information. Technology gives us an increasing number of things to remember--pin numbers, passwords, all those pesky dotcom names--but at the same time provides excellent aids to jog the memory. Some people leave daily reminders on their own answering machines or send themselves e-mail messages. Try memorizing the country code, city code and phone number for someone outside the U.S. as one string of digits and see how difficult it is. Breaking unwieldy pieces of information into smaller pieces makes them easier to remember. The process is called "chunking," and that's why we can remember Social Security and telephone numbers. Large unbroken sets of numbers, such as driver's licenses, can be artificially divided into chunks for easier recall. "Clustering" is another effective technique. Seven, according to experts, is the magic number for short-term, or working, memory. That's roughly how many things we can consciously hold in the mind at one time. But we can trick it into holding more by inventing seven or so main categories and then grouping several things under each. Wake Up, Brain! Until a few years ago, it was thought that everyone was born with a finite number of brain cells. Then in the 1990s--designated by Congress as the Decade of the Brain--scientists raised the possibility that the miraculous organ inside our head is capable of creating new cells. Just as important, they found it can grow additional dendrites, those spiky branches on each cell that help communication with other cells. The brain never stops learning, and forcing it to absorb new information or figure out a different way of doing a routine task stimulates it to make new dendritic connections that help offset some of the normal, age-related loss. The brain is essentially lazy, and when asked to do something over and over, it invariably finds the easiest way. Doing things differently challenges the brain. Brush your 3

teeth with the nondominant hand or take a shower with your eyes closed, and suddenly you're not on automatic pilot. The more robust the brain, the better the chance that memory can be improved. Says Duke University neurobiologist Lawrence Katz: "Anything that uses all your senses to do something forms associations that make the brain more fit and agile." Katz and co-author Manning Rubin came up with 83 "neurobic" exercises for their book Keep Your Brain Alive. Sample different food, they suggest, reposition your furniture, travel by a different route, learn a language--try anything that will alter the brain's neural pathways. Certain activities, like gardening and fishing, are beneficial because they involve so many senses. Your lifestyle shapes how your brain will be as you get older. Everyday life can excel as a brain gym where you are your own personal trainer. At 72, Harold Gallay of Clearwater, Fla., has a memory as keen as that of a man half his age, rattling off sports statistics and regularly besting his four grown children at Trivial Pursuit. For years, he and his wife Leona, 71, have played bridge, done daily crossword puzzles, read newspapers cover to cover and discussed current news. Value the Mature Mind Though everyone hopes for a long life, most fear old age and the decline of body and brain. "The mind does change," says Hamlin, "but it is not inferior. It is different." Each of us needs to appreciate our mind as it is instead of as it once was. Teens who can talk, listen to music and surf the Web at the same time are admirably adept at taking in many bits of information, but they may not connect them in meaningful ways. Speed, after all, isn't everything. Though less swift, the older person continues to absorb new material, comparing it with knowledge and insights gleaned over a lifetime. The process becomes less reflexive and more reflective. And the word for that is wisdom.