GAMES, NOT PILLS, FOR ADHD.
When they see restless and agitated children, many doctors are quick to diagnose a disease called attention deficit hyperactivity disorder (ADHD). Many claim that this disorder is genetically determined and should for this reason be treated with pharmacological substances like methylphenidate (Ritalin), which alter the metabolism of a childas brain.
ADHDas estimated worldwide prevalence in people under age 19 is about 5 percent, but there is enormous variability in estimates, and the United States has an especially high rate of ADHD, with 10 percent of males and 4 percent of females diagnosed with it. Thus, according to the statistics, in every cla.s.sroom there are one or two fidgeting kids who need professional help. In recent years, many teachers and parents have arrived at the conclusion that ADHD is an innate disorder affecting the metabolism of the brain. But to this day there is no scientific method of telling the brain of a normal child from the brain of a child who is said to have ADHD.
Only with the aid of arbitrary criteria can a preschool child or young student be given the ADHD label. But the symptoms (aeasily distracted,a adoesnat sit stilla) are so random that they can be seen in a variety of forms among most children. It appears impossible to draw an objective line between a healthy temperament and disturbed behavior.
Methylphenidate was first synthesized in 1944 by a chemist, Leandro Panizzon, with the company Ciba.8 He swallowed the substance in an experiment on himself but did not experience much from it. His wife, Margueritea"known as Ritaa"tried it, too, and felt a quite inspiring effect. From this time on Rita would consume the substance occasionally when she was getting ready for a tennis match, and it was named after her: Ritalin.
At first, Ritalin was given to adults only to treat depression, mental fatigue, and disorientation among elderly people. The disease that would make Ritalin famous, and notorious, had not yet been invented. It was not until the 1960s that research became public showing that methylphenidate, and a similar substance called dexedrine, had a quieting effect on children with learning difficulties. By now, methylphenidate is marketed in specific doses, some lasting 8 to 12 hours. The children who are told to take this drug at breakfast spend the full day under medication.
As the consumption of methylphenidate has exploded in industrialized countries, teens and young adults in the United States take the drug for additional reasons: as an appet.i.te suppressant or to stave off the urge to sleep. They crush the tablets and snort the powder to get high. Youngsters have little difficulty obtaining methylphenidate from cla.s.smates or friends with prescriptions. The U.S. Drug Enforcement Administration has posted a drastic warning: aMethylphenidate, a Schedule II substance, has a high potential for abuse and produces many of the same effects as cocaine or the amphetamines. The abuse of this substance has been doc.u.mented among narcotic addicts who dissolve the tablets in water and inject the mixture. Complications arising from this practice are common due to the insoluble fillers used in the tablets. When injected, these materials block small blood vessels, causing serious damage to the lungs and retina of the eye. Binge use, psychotic episodes, cardiovascular complications, and severe psychological addiction have all been a.s.sociated with methylphenidate abuse.a9 To this day, it is not known what methylphenidate actually does in the still-developing brain of a preschool or kindergarten child. Nora Volkow, now director of the National Inst.i.tute on Drug Abuse in Rockville, Maryland, found that the substance, by blocking certain transporting proteins, increases the level of the neurotransmitter dopamine in the synapses, thus acting much like cocaine.10 However, methylphenidate does not appear to be as addictive, given that it is ingested in pill form. It takes hold much more slowly than cocaine and does not create such a high.
Even when properly prescribed by a doctor, the consumption of the drug comes with a whole range of side effects: agitation, fear, sleeping problems, and paranoia. If the drug is dropped after a long-term treatment, there may be withdrawal symptoms. The drug can spoil a childas appet.i.te.
Yet many parents are relieved when their child is diagnosed with ADHD because it unburdens them: If my childas problems are caused by an innate defect of brain chemistry, the thinking goes, the way we are raising our children is not involved. The label ADHD, however, has serious repercussions for children, who learn to think: I can only be tolerated by my parents and teachers when I take my drugs.
aThe medication with regulating substances might be advisable for correcting some deficits or for starting an integral therapy,a says Christina Hahn at the Inst.i.tute of Sport and Sport Science of the University of Heidelberg, Germany. aAs a child-oriented, long-ranging treatment, however, medication is by no means the only solution of the problem.a11 Among children diagnosed with the syndrome, a familiar pattern appears. More than half of these children not only have problems concentrating but are conspicuously awkward; they are bad at balancing and have difficulties timing their movements. This could mean that exercises in improving coordination might be useful to improve concentration and attention.
Though problems with motor activity are not the main symptoms of ADHD, autism, and dyslexia, it is eye-catching that these problems appear so often along with impaired coordination. Adele Diamond concludes: aMotor development and cognitive development may be much more interrelated than has been previously appreciated. Indeed, they may be fundamentally intertwined.a12 But physical training is nearly never prescribed; the rule instead is to give children medication. On any given day, hundreds of thousands of children are served tablets for breakfast to calm them down and make them attentive. In about 20 minutes the substance takes hold, and the children show a different behavior.
By contrast, prescribing sports programs for children with ADHD appears to be a much gentler and longer-lasting approach. Only a few researchers have developed specific exercise programs for inattentive children, and Gerd Hlter at the University of Dortmund, Germany, is one of them. In one trial, therapists, children, and their parents met once a week for three months in a swimming pool. While educators coached the parents, the children played in the water and tried things like diving for rings. After encouraging results, Hlter plans to expand his program by adding games in a gym. He says: aMore exercise and behavioral therapy and less Ritalina"this is our concept.a13 In the meantime, Hahn has already gathered scientific data doc.u.menting the beneficial influence of exercise on children diagnosed with ADHD. More than 90 children, mostly boys with an average age of eight and a half, partic.i.p.ated in the study. At first, researchers tested motor skills and the ability to concentrate on problems. Some children were actually taking methylphenidate, and their parents were asked not to change the medication during the study so that the results would not be distorted.
The children were randomly a.s.signed to three groups. Members of the first one played ball games most of the time, soccer and field hockey, learning techniques and tactics. That way, the researchers aimed to simulate how children played in the 1950s and 1960s when it was normal for them to spend summer days outside, playing in yards and fields. The partic.i.p.ants of the second group rode mountain bikes, learned in-line skating, and took climbing lessons. Both sports programs lasted 90 minutes and took place twice a week. The third group was used as a control, with 37 ADHD-diagnosed children who did not play any sports at all.
Six months later, Hahn and her colleagues retested the motor skills and concentration abilities of the children. The sedentary children had largely the same results as at the beginning of the study, and there was even further deterioration to be seen, possibly an adverse effect of the methylphenidate some of the children continued to take. The drugs slow down the natural desire to move and thus impair the motor skills all the more.
By contrast, the children in both sports groups did much better. Although their motor skills were markedly subpar at the beginning of the study, they improved dramatically and even reached the lower range of what is considered normal. Their ability to concentrate also improved greatly. These budding athletes solved more cognitive problems than the controls in a given time.14 These results confirm what the findings of the neuroscientists suggest: If we train our motor abilities by exercising, at the same time we strengthen regions of the brain that are important for paying attention and other cognitive capabilities. Playing sports makes us smarter, and all children can benefit from this effecta"whether they are diagnosed with an attention disorder or not.
10.
Lifting the Spirit.
A BLEAK MIND AND A LIFE FULL OF ACTIVITY? THESE TWO THINGS DO not seem to match. Sedentary people tend to have a heavy heart, and sad people are often physically inactive. The correlation is so stable and widespread that it has been demonstrated in many epidemiological trials. Study after study has shown that the more we utilize our muscles, the more positive feelings develop in our heads. This also applies to latecomers to exercise: if a person gets going in advanced age, the risk of developing depression drops to the low levels enjoyed by people who have been active from early on in life. The reverse strategy cannot be recommended. Formerly active people who refrain from using their muscles in middle age have a higher likelihood of developing psychiatric problems.
Although this relationship has been known since the 1980s, psychiatrists and psychologists have just started to use the healing power of exercise in the treatment of mental disorders. In contrast to cardiologists, they largely disregarded the influence of regular exercise on mental well-being.1 Some psychiatrists believe it is high time to alter this att.i.tude: aThe clinical psychiatry of the recent past and present with its focus on psychotherapy and pharmacotherapy regards sports and games rather as simply a fine pastime and doesnat so far attribute any specific therapeutic effectiveness to it.a2 The reservations shown by many psychologists and psychiatrists in this regard are even more astonishing given that there is now a wealth of data indicating specifically that people suffering from depression and anxiety disorders benefit from physical exercise. Multiple studies also show that more than just psychiatric impairments can be successfully treated with training. Neurodegenerative disorders like Alzheimeras disease, characterized by dramatic losses of brain ma.s.s and nerve cells, are being studied in relation to physical activity. These diseases, once they develop, are curable with neither tablets nor training. Yet exercise appears to be one of the best means to prevent them from developing in the first place.
FROM THE COUCH TO THE TREADMILL.
Only a few patients who suffer from depression become healthy again by taking drugs. About 65 to 75 percent of those patients who do so are not cured and have to face recurring depressive episodes: they are sad, easily agitated, and have problems sleeping and concentrating. This is due not only to the fact that drugs have little effect, but it is also because up to 60 percent of patients are believed to stop following their prescriptions after three weeks. Others refuse to take antidepressants in the first place for fear of being stigmatized.
In the face of all these problems, some doctors started to wonder whether there might be a better alternative. Ideally this would be a remedy that is effective, has no adverse side effects, and is socially accepted. Older studies among healthy subjects had indicated that physical exercise is an ideal candidate to fit this description. Endurance training had been found to lighten moods, reduce fears, and increase the capacity to cope with stress. In one study, groups of active and sedentary people were followed for eight years, with the conclusion being that inactive people developed a depression rate twice that of their active counterparts.
Other trials included patients suffering from mild to severe depression. In one study, 40 patients were encouraged either to partic.i.p.ate in a running program for eight weeks or to try strength training for eight weeks. Tests before and after the program revealed improved symptoms in both groups.3 Does that mean exercise beats pharmaceuticals in terms of effectiveness? The research group of James Blumenthal at Duke Medical Center in Durham, North Carolina, set out to answer this question.4 They randomly a.s.signed 156 elderly patients, who suffered from major depression, into three groups: those exercising, those taking antidepressants (in this case sertraline hydrochloride, which is an antidepressant of the selective serotonin reuptake inhibitor cla.s.s), and those trying both. The exercise session lasted for 30 minutes, three days per week.
After 16 weeks, the partic.i.p.ants were reexamined. In all three groups, the patientsa health had significantly improved, and about 60 percent of each group were no longer depressed.
Therefore the program relying solely on physical activity was as effective as state-of-the-art antidepressants.
Over time, the effect of exercise became more p.r.o.nounced. The partic.i.p.ants were examined after six months, and those on exercise regimens had significantly fewer relapses than the drug-takers. The long-lasting effect of activity can be explained by the fact that many of the partic.i.p.ants liked exercising so much that they continued to be active even after the official end of the study. That way, they overcame their depressions. Knowing that they were capable of fighting their illnesses might have further enhanced their success. Blumenthal concludes: aSimply taking a pill is very pa.s.sive. Patients who exercised may have felt a greater sense of mastery over their condition and gained a greater sense of accomplishment. They felt more self-confident and had better self-esteem because they were able to do it themselves, and attributed their improvement to their ability to exercise.a5 As impressive as this result seems, the study could not completely determine if the results were simply a consequence of the social aspect of the workouts because the partic.i.p.ants exercised together. During these sessions, everyday worries seemed to be forgotten, and people made small talk and laughed. Perhaps the new friendships and the collective experience were the main reasons for the improved mood.
In order to exclude this possibility, researchers at the Cooper Inst.i.tuteas Science Research Center in Golden, Colorado, initiated a further study.6 They encouraged 80 men and women who were sedentary, depressive, and not on medication to partic.i.p.ate in a sports program that lasted eight weeks, with three to five sessions per week. They either walked on a treadmill or pedaled on a stationary bike, and were alone (except for gruff a.s.sistants who checked on them to make sure n.o.body was secretly resting).
Half the partic.i.p.ants tried an easy program and in one week burned just three kilocalories per pound of bodyweight. Though their symptoms improved, the effect was small and thus could have been a chance finding.
The members of the second group burned eight kilocalories per pound. This consumption corresponds to moderate exercise, like a brisk 30-minute walk on most days of the week. The symptoms in this group decreased by 47 percent, and in 42 percent of the patients the symptoms disappeared completely. This confirms that physical exercise is as effective as antidepressants and psychotherapy. Interestingly, it did not matter if the patients worked out for three or five days per week. Burning the recommended amount of kilocalories in a week is the main objective.
PLAYING AGAINST PANIC.
Psychiatrists report regularly on patients and cases in which physical training was found to help people suffering from anxiety. Yet only a few trials have been initiated to look into this phenomenon. In one study, 46 individuals with claustrophobia, affective panic disorder, or both partic.i.p.ated in a ten-week program and were asked to jog a distance of 3.1 to 3.7 miles on three or four days of the week. The patients of a second group were inactive and received either standard medication (the antidepressant clomipramine) or a placebo. Compared to the placebo, the medication significantly improved the symptoms. Exercise was also better than placebo, though not as effective as the medication.
In the treatment of alcoholics and drug addicts, moderate training programs are by now quite widespread in Germany, although there are few studies about whether this actually affects the addiction. On the contrary, members of soccer and handball clubs often consume amazing numbers of cigarettes as well as alcoholic beverages like beer and schnapps. It might shock American readers, but in lower-level German soccer leagues, it is not too uncommon for subst.i.tute players to smoke while watching their peers play. After the game, players and their families often gather and open a keg of beer. People with addiction problems might do better to avoid such crowds and pick up healthy ways of exercising like walking and jogging. Andreas Broocks of Helios Kliniken in Schwerin, Germany, is among the leaders in the field of sports therapy in psychiatry, and he concludes: aRegular endurance training substantially improves the self-confidence and self esteem of addicted patients and thus could help them to stay abstinent.a7 Individuals with schizophrenia are also often in a condition for which physical exercise is much needed. Many such patients are heavy smokers, have an unhealthy diet, and hardly move their bodies. A training regimen would not only improve their physical shape but also help work against the psychiatric disorders that can accompany schizophrenia. According to one study, about 50 percent of all schizophrenic people also have symptoms of panic, obsessive-compulsive disorder, and depression. Although the possible benefit of exercise has not been studied until now, some physicians are discovering its potential. Inspired by good experiences with patients, many clinics are now trying to treat patients with schizophrenia with exercise as therapy.8 SOUND BODY FOR A SOUND MIND.
It is thanks to the Roman poet Juvenal that we believe a sound mind (mens sana) resides in a sound body (corpore sano).9 This proverb has spread for centuries, but it was not until recent times that neuroscientists have found enough evidence to rea.s.sure us that the ancient claim can be taken literally. Researchers have now acc.u.mulated evidence showing that exercise can stave off mental decline and the onset of widespread Alzheimeras disease, which leads to the loss of critical brain functions.
Alzheimeras is a disease that strikes with age. Among people aged 70 to 74, it is estimated that fewer than 3 percent are affected; among those older than 90, about one-third are affected. And because people in the United States and other industrialized nations live longer and longer, Alzheimeras is considered one of the most pressing health-care problems of the near future. An estimated 4.5 million Americans have Alzheimeras disease. That number has more than doubled since 1980 and is projected to reach 11.3 to 16 million by the year 2050.
Besides age, there are other risk factors. It may not be a good omen when family members have suffered from Alzheimeras because that suggests a genetic preposition to it. Alzheimeras also relatively frequently afflicts people with low education levels. These factors are hard to change once a person has reached adulthood, but there is another way to postpone the onset of the disease or to prevent it altogether: activities such as brisk walking or bicycle riding.
Results from lab trials indicate that exercise can protect the brain.10 Mice held in cages with treadmills acc.u.mulate fewer harmful molecules in their brains than sedentary animals. These peptides, called amyloid beta, are usually found in demented mice and lead to plaque formation.
Even when this peptide is already spreading in the brain, exercise appears to help stall the progression of dementia. In a study published in the Journal of Neuroscience, researchers at the Inst.i.tute for Brain Aging and Dementia at the University of California, Irvine, took mice that were predisposed to develop Alzheimeras disease and gave them running wheels for exercise. After several months of exercise, the mice showed improved cognitive behaviors and less amyloid-beta plaque. aWhat we found is that levels of the amyloid in these exercising mice went down,a said the princ.i.p.al investigator, Carl Cotman. aInstead of a drug, it was a natural behavior that translated to a reduction of Alzheimeras-like pathology developing in the brain.a11 A similar picture emerges when researchers try to correlate the lifestyles of people and their risk of developing Alzheimeras disease. Chinese researchers studied more than 1,000 elderly inhabitants of Beijing for three years. Those who hardly left their apartments developed dementia more often than was average.
j.a.panese researchers conducted a diligent study in which they monitored 828 citizens older than age 65 for seven years and inspected their brains using CT scans and other methods. More than 200 partic.i.p.ants died in the course of the study, but most of their brains were examined after death. And the result showed again that sedentary seniors were more p.r.o.ne to become ill with Alzheimeras disease.12 Fortunately, there is no need for strenuous activities to stave off this notorious atrophy of the brain. Older men aged 71 to 93 who walk at least two miles every day cut the risk of Alzheimeras in half, compared to people the same age who walk only a quarter of a mile per day.13 The more intense the dose of exercise, the bigger the effect against dementia. This direct correlation was revealed by a five-year trial of elderly women. The most active women had a risk reduction by 50 percent, and a 60 percent reduction specifically for Alzheimeras.
One of the most extensive studies has been carried out by researchers at the Aging Research Center of the Karolinska Inst.i.tute in Stockholm. In 1972 they began studying the leisure-time exercise habits of nearly 1,500 people.14 Those who exercised at least two days per week during midlife lowered their risk of developing Alzheimeras by 50 percent.
For people around age 40, this implies that if they start now on moderate exercise programs, like bicycling and walking, they might be rewarded on some not-too-distant day. The neurologist Miia Kivipelto, senior author of the study, said: aThese findings may have wide implications for preventive healthcare; if an individual adopts an active lifestyle in youth and at midlife, this may increase their probability of enjoying both physically and cognitively vital years later in life.a Apart from these epidemiological findings, brain-imaging studies also indicate that exercise influences the risk for Alzheimeras disease. These images show that physical activity slows down the type of brain atrophy that usually comes with age. Between our 30th and 90th birthdays, approximately 15 to 25 percent of the brainas gray matter is lost, and the areas in charge of learning and memorizing shrink the most.
The psychologist Arthur Kramer of the University of Illinois in Urbana-Champaign was able to demonstrate the presence of this atrophy when he looked at the brains of 55 healthy elderly persons, using magnetic resonance imaging (MRI). But Kramer also had good news, at least for those people who had always been active. They were not only in good shape, but on average their brain atrophy was not as p.r.o.nounced as that in sedentary people. Furthermore, they had specifically retained structures in the lateral and frontal areas of the brain, which are most important for complex cognitive functions.
After this finding, Kramer and his colleagues wanted to check whether moderate exercise might even reverse the usual course of brain atrophy. Healthy but sedentary volunteers aged 60 to 79 partic.i.p.ated in an aerobic training program for six months (consisting of one-hour sessions, three days per week). To provide a comparison, other volunteers of the same age also met three days per week in the gym. But instead of true exercising, they just did some stretching.
The astonishing result has been published in the Journal of Gerontology.15 Parts of the brain actually increased in size for aerobic exercisers! The enlarged areas were primarily located in prefrontal and temporal cortices, the same regions often reported as showing substantial age-related deterioration. Declines in these areas are linked to a broad array of clinical symptoms including Alzheimeras disease. In the group that just did some stretching, such enlargements could not be found.
If this novel and intriguing finding is further confirmed, it will have profound repercussions for the prevention of neurodegenerative diseases. The results suggest that brain volume loss is not an inevitable effect of advancing age and that relatively minor interventions can halt or slow down this loss. Moderate exercise not only helps stave off the onset of cognitive decline, but it might have the potential to halt and even reverse the loss of brain structures in old age! These implications did not escape the attention of the researchers. They conclude that their results adirectly bear on issues of public policy and clinical recommendations in that they suggest a rather simple and inexpensive mechanism to ward off the effects of senescence on human brain tissue.a16 Responsible doctors are prudent enough not to raise hopes that Alzheimeras patients will have effective drugs available to them in the foreseeable future. At the same time, surveys show that more than 40 percent of adults who are 50 or older are afraid of losing control of their minds someday because of Alzheimeras disease. Science has rarely provided us with better arguments to start moving.
TRAINING IS THE BETTER PILL.
As soon as we start sweating, we help our brains. As we saw, growth factors and neurotransmitters start circulating in higher numbers through the brain. Next, the number and length of connections between the nerve cells increase. One could say that the whole brain becomes jazzed up from inside, making it more malleable and more plastic than before. Yet there is an even more astonishing rejuvenator, which we will discuss in the following chapter; exercise appears to promote the growth of new nerve cells in old brains.
11.
A Fountain of Youth in the Brain.
EVERY DAY, THE NEUROSCIENTIST JEFFREY MACKLIS OFFERED HIS MICE A new treat to sniff. One morning, he would blow the smell of chocolate into their cage; the next, he would let them breathe clouds of rosewater.
This way, Macklis introduced the mice to a previously unknown world. The animals were raised in scent-proof habitats and had not experienced a single one of the dozen odors they had been smelling in the course of his experiment. How would their brains respond to novel stimuli?
Macklis and his colleagues at the Center for Nervous System Repair at Ma.s.sachusetts General Hospital and Harvard Medical School in Boston were the first researchers to see what happens in the part of the brain where odors are processed. They achieved this feat by following the fate of new nerve cells that migrate to the olfactory bulb, the brain region enabling us to sense smells. There, new nerve cells appear to originate all the time. But only when animals smell a previously unknown scent do these nascent nerve cells mature into active neurons that integrate themselves into the brainas circuits two to three weeks later. The nerve cells develop long axons and make numerous connectionsa"synapsesa"to other neurons. In contrast to these new arrivals, the older neurons that form the existing network within the olfactory bulb barely get excited by a new odor. aThe new neurons are not replacing the old ones,a says Macklis. aThey have a unique function: learn new smells.a1 New nerve cells for new memories: Elkhonon Goldberg, a clinical psychologist at New York University, believes in this formula, too. Time and again, in his office, two blocks south of Central Park, elderly individuals show up who often misplace their keys, leave the stove burning, or forget what is on the pages of the books they have just read.
To combat their forgetfulness, Goldberg prescribes a program intended to improve several cognitive functions, such as vocabulary retention, mental agility, and spatial perception. To create this program, the psychologist a.n.a.lyzed 200 tests used for the treatment of stroke patients and combined the elements of nearly 60 of them. Two days per week, he requires patients to solve problems presented on a computer screen. A typical task during one such hour-long session is to determine the pattern underlying an arrangement of colored triangles, squares, and circles.
Each individual program usually runs for three months, and at the end Goldberg a.s.sesses whether the sessions have improved his patientsa memories in everyday life. After the first 100 patients who tried this course, says Goldberg, he was apleasantly impressed.a In around 60 percent of the cases, incremental memory loss had been stopped; in 30 percent, the patientsa power to recall things had actually improved.
aOur successes are probably due to the growth of fresh nerve cells in the brain,a says Goldberg. aCognitive activities can trigger the birth of new neurons.a2 NEUROGENESIS: NEW NERVE CELLS IN THE BRAIN.
A fountain of youth in the brain? New mental power thanks to new nerve cells? Until recently, Macklis and Goldberg would have been dismissed as dreamers because they call into question a seemingly irrefutable dogma: our nerve cells lose their power to divide shortly after we are born. If so, the human brain could at best keep its established level of mental capacity, which in most cases would shrink with age.
But these days, neurologists, biochemists, and physicians see more and more data indicating otherwise: new nerve cells do grow in certain parts of the adult brain. With awe and surprise, researchers realize this processa"called neurogenesisa"appears to be essential for the normal functioning of the brain.
aWe are beginning to see the brain from a completely different perspective,a says Gerd Kempermann, a leading expert on neurogenesis now at the Center for Regenerative Therapies in Dresden.3 aThere is a positive tendency: The development of the brains goes on during the whole life.a It is especially encouraging that new nerve cells sprouting in old brains turn out to be particularly malleable and flexible. For that reason, they seem to contribute to the astonishing reserve capacities that allow the brain to master difficult and unexpected challenges. Kempermann says: aThe neurogenesis is probably a fundamental precondition for staying mentally alert up to high age.a The emerging picture of neurogenesis implies that genetics alone do not determine whether people retain mental acuity throughout their lives. Rather, lifestylea"the way we treat the braina"has tremendous repercussions on its ability to renew itself. And, among these ways, itas physical exercise that appears most important because it promotes the production of fresh nerve cells.
The effect of neurogenesis on exercise is apparently due to an ancient mechanism shaped by evolution: the more an animal moves around in its environment, the greater the likelihood that it will encounter novel situations. Thus, the brain of an active creature produces especially high numbers of nerve cells that can be used to process these new stimuli. The new cells mature into fully functioning neurons when they are challenged with new tasks. In the absence of such challenges, it is thought, a big portion of the new nerve cells die before long. And in the absence of physical activity, the production of new nerve cells largely ceases.
Itas not easy to prove that neurogenesis takes place in the adult brains of humans. Nearly all of the relevant data stem from animal studies because, for obvious reasons, scientists cannot perform crucial experiments on humans (such as tracing radioactive bits of DNA in neural networks) to see if nerve cells are new. However, a growing body of indirect evidence leaves no doubt neurogenesis takes place in the human brain. American scientists have published an especially convincing study. They encouraged 11 healthy women and men to train for three months in the gym at Columbia University in New York and thereafter a.n.a.lyzed their brains by magnetic resonance imaging (MRI). In the course of the workouts, a particular area within the hippocampus became increasingly supplied with blood. Parallel studies on mice by the same scientists revealed what this means: new capillaries as well as new nerve cells grow there.4 Fred Gage, of the Salk Inst.i.tute in La Jolla, California, was among the researchers who carried out this study. He and his co-workers Gerd Kempermann and Henriette van Praag first showed that physical exercise can literally act as a fertilizer for the brain. They discovered this by keeping mice in cages with running wheels, so the animals could run as much as they liked. The mobilized mice produced an above-average number of new nerve cells, compared to mice kept without the wheels.5 The effect was actually so big that, ever since Gageas findings were published, researchers studying neurogenesis also keep their mice in environments allowing them to move. Only under these circ.u.mstances do the mice produce fresh neurons in numbers large enough to be studied.
However, does this supply of fresh nerve cells actually make the mice smarter? This is what Henriette van Praag, then a senior researcher in the Gage lab, was able to prove.6 Her experiments actually started when a small biotech company in La Jolla went out of business. The firm had lab mice left over and asked van Praag if she might need some. She happily accepted the offer because these mice were exactly the kind she had been looking for. The animals were 19 months old (equaling a human age of 60), and they had been kept all their lives in small and narrow cages. Thus they were ideal for studying the impact of exercise on old, dulled brains.
Van Praag put half of these mice into cages equipped with running wheels, where the rodents usually ran more than three miles per day. The other half were still kept in cages without the benefit of exercise. After 35 days, van Praag tested the memories of all the mice by putting them into a special water maze. It consisted of a small pool with a shallow platform in the middle, just under the surface. Because mice dislike swimming, they stay on the platform whenever possible, and when repeatedly dropped into the water, will eventually memorize the platformas location and swim to it.
It turned out that the performance of mice in this environment correlated to the amount of exercise they had been granted. aThe aged and sedentary mice just swam around and gave up. Many of them floated and waited for me to take them out of the pool,a Praag recalls. Whereas it took these sedentary animals an average of 30 seconds to find the platform, the physically fit mice needed only 15 seconds to get there.
But was this enhanced learning really due to the production of new nerve cells? To find an answer, the mice were sacrificed and their brains studied 10 days after the test to determine the number of new nerve cells in their brains. Indeed, the mice that had been allowed to run in their cages, and had performed well in the test, had significantly more new neurons in the hippocampus. The brains of these aged runners, who had formerly been kept for so long in narrow cages, had been rejuvenated by exercise.7 Henriette van Praag is convinced that elderly people can benefit greatly from physical exercise. She believes it is worthwhile to abuy your aging relatives a treadmill.a Fred Gage has a similar take on this himself and exercises regularly (he plays squash, runs, and does light weightlifting). The slim and energetic neuroscientist has changed how people see the brain. When I visited him in his lab, he told me: aYour brain is not a computer but a plastic organa"and the way it changes can be controlled by you.a The discovery of neurogenesis not only changes our perception of the healthy brain but also alters our understanding of why and how brains develop certain illnesses. Alzheimeras disease, which leads to the loss of many mental functions, and the movement disorder Parkinsonas disease, were until recently usually ascribed to the loss and death of nerve tissue. Now, physicians are starting to rethink matters and view things from a different perspective. Are these untreatable diseases triggered because the production of new nerve cells is stalling?
Also, for learning disorders, depression, alcoholism, nicotine addiction, and schizophrenia, researchers increasingly discuss whether a lack of neurogenesis might play a rolea"and what sort of activity, including physical exercise, appears to help against precisely these diseases. The scientific exploration of neurogenesis ahas evolved into one of the most interesting and most promising projects of modern neuroscience and in particular of molecular psychiatry,a concludes Amelia Eisch of the University of Texasas Southwestern Medical Center in Dallas.8 Yet some findings remain mysterious. Why is it, for example, that the capability to grow new nerve cells is restricted only to a part of the forebrain and the dentate gyrus of the hippocampus, an area important for learning and memory? This limitation seems even stranger because most other parts of the brain have progenitor cells and stem cells, which have the biological potential of maturing into fully functional neurons. But instead of doing this, they lie dormant, the sleeping beauties of the brain.
To awaken these cells and make them grow is a dream of medicine already pursued by many pharmaceutical companies as well as academic researchers. Brain, the motto goes, heal thyself!
THE MYTH OF THE STATIC BRAIN.
This hope and excitement centers on a phenomenon that was doubted and dismissed by almost all neuroscientists in the last century. They were under the influence of a verdict by the famous Spanish brain researcher and n.o.bel laureate, Santiago Ramn y Cajal. In 1928, he famously declared: aIn adult centers the nerve paths are something fixed, ended, immutable. Everything may die, nothing may regenerate.a A few scientists dared to question this verdict but were not taken seriously and were even ridiculed. One of these skeptics was Joseph Altman, who carried out fascinating experiments at the Ma.s.sachusetts Inst.i.tute of Technology (MIT) in the 1960s. He fed food that contained low-level radioactive chemicals needed to make DNA to rats, cats, and guinea pigs. If the animals produced new nerve cells, they would incorporate the radioactive labeled chemicals into the nuclei of these new cells. And indeed, Altman was able to detect radioactive signals in the brain tissue after he killed the animals and performed autopsies on thema"a sure sign that neurogenesis had occurred. In hindsight, it seems odd, but other researchers simply ignored Altmanas findings. This neglect harmed Altmanas career; he was forced to leave MIT and take a position at a less well-known school.
Ten years later, the researcher Michael Kaplan of the University of New Mexico took pictures with an electron microscope showing newly grown neurons. But he was ignored and ridiculed as well. Kaplan once recounted how the influential neuroscientist Pasko Rakic of Yale University dismissed his results: aThose may look like neurons in New Mexico. But they donat in New Haven.a9 Rakic even came up with a theory why neurons in the adult brain were unable to divide: at one point during evolution, our forebears had traded the capability of producing new nerve cells for the ability to store memories in a constant number of nerve cells. For reasons of stability, Rakic believed, there was simply no s.p.a.ce reserved for new neurons in the human brain.
Eventually, singing canaries greatly contributed to overturning the old, false dogma of the static brain. The male birds sing their songs in the spring, but over the summer lose their repertoire like feathers in the molta"only to impress female birds the next spring with a completely new set of melodies.
One day, as he was taking a shower, it occurred to the biologist Fernando Nottebohm of Rockefeller University in New York how the male canaries accomplish this trick: the areas of the brain containing the memories of the old melodies die off and are replaced by new neurons the next spring. Experiments using radioactive DNA have confirmed Nottebohmas hunch: male canaries indeed produce thousands of new nerve cells per day.
Initially, it was believed that only birds were capable of regrowing brain tissue. But when scientists looked into other species, they found neurogenesis all over the place: frogs, lizards, rodents, and monkeys do it. Why, then, should humans be an exception?
It took quite a while to come up with the ultimate proof. But in 1998, Swedish and American brain researchers realized there was a way to see if neurogenesis takes place in the adult human brain. Physicians routinely inject radioactive, labeled DNA building blocks into severely ill cancer patients. By doing so, they are trying to find out how many new cancer cells grow in a patientas tumors. However, because the labeled DNA is incorporated into any type of dividing cells, new nerve cells should be detectable, too. The researchers were granted permission to study five patients with advanced cancer of the larynx. After their deaths, the patientsa brain tissue was a.n.a.lyzed. The result? Until the last days of their lives, these people had produced new neurons in their brains.
Since this milestone discovery, researchers agree that an adult produces thousands of neurons in the hippocampus every day. In comparison to the roughly 100 billion neurons that comprise the brain, this might appear a small amount. However, the new neurons possess a juvenile excitability lost by the old neurons. The neuroscientist Gerd Kempermann is convinced they have an important impact on our mental capabilities: aApparently a rather small number of newly produced cells is sufficient to profoundly alter the network architecture of our brain.a10 It is evident that freshly produced neurons greatly contribute to a phenomenon called neuroplasticity, the brainas surprising capability to adapt to a constantly changing environment. At least three different mechanisms contribute to the plasticity of the brain. First, existing connections between nerve cells, the synapses, can be strengthened within seconds, allowing us to remember what we just heard, felt, or thought. Second, as new synapses sprout, they create a dynamic neuronal network that can store memories for long periods of time. Finally, the production of new nerve cellsa"a process that takes many daysa"can bring enduring changes upon the brain. Many studies have added weight to the belief that neurogenesis is an aimportant part of plasticity,a says Amelia Eisch of the University of Texas Southwestern Medical Center in Dallas.11 In short: a few extremely versatile neurons are pivotal for the brainas lifelong ability to change itself. Like a muscle that grows when used, the cells of the gray matter thrive when challenged. New neurons in the olfactory bulb develop when they encounter odors, and new neurons in the hippocampus mature when they receive input worth remembering.
BRAIN FITNESS.
The phenomenon of neurogenesis could actually be the long-sought mechanism by which the environment is able to shape and put its imprint upon the brain. Many empirical studies have shown how important physical activity is among these environmental influences. Both physical and cognitive exercises appear to prevent or delay degenerative processes in the aging brain. Researchers at Rush Presbyterian-St. Lukeas Medical Center in Chicago carried out a study of 642 elderly people with varying educational backgrounds. It turned out that with each additional year of formal education, the risk of developing Alzheimeras disease was reduced by 17 percent; several other studies also suggest that a good education can stave off the onset of Alzheimeras.
In the late 1980s Robert Katzman of the University of California in San Diego studied this effect in more detail. In his view, learning and studying increases the density of the synapses in the braina"thereby enhancing something called acognitive reserve.a The bigger the cognitive reserve, reasoned Katzman, the better the brain can cope with the loss of nerve cells due to illness and age.12 This concept was supported by a study of 130 Catholic priests and nuns. During their lives, their cognitive capabilities were a.s.sessed. After their natural deaths, autopsies on their brains were performed. Plaques (protein deposits that interfere with neural networks) typical of Alzheimeras disease were found in all brains with the same frequency, regardless of the level of education each had received. It turned out, however, that these plaques affected the brains in varying degrees. Those people with an extensive education had retained their cognitive capabilities much better than people with less education. The differences were profound: better-educated individuals started to show symptoms of Alzheimeras only when they had five times as many plaques in their brains as people with lower levels of education. The former group possessed a substantial cognitive reserve enabling them to compensate for the effects of Alzheimeras.
Your current occupationa"readinga"as well as playing cards, or doing crafts, can help preserve the cognitive functions, believes the neurologist Robert Friedland at the Case Western Reserve University in Cleveland: aI believe they all involve learning in some way.a13 That would mean an interesting job keeps one healthy, whereas retiring early in life might be a fatal step toward dulling the mind.
In any case, watching television should be avoided. According to Friedlandas research, gawking at the screen increases the risk of being afflicted with Alzheimeras disease. He and his colleagues asked the partners and relatives of 135 Alzheimer patients about their activities before the onset of the disease.14 Subsequently, they compared these data with answers from 331 healthy people. The study results reveal that the Alzheimeras patients spent a much larger part of their lives in front of the television set than healthy people. With each hour of watching television per day, the risk of Alzheimeras increased by a factor of 1.3. That does not necessarily mean the content of television programs dulls the mind (though there is no shortage of stupid shows), but rather frequent television consumption might point toward a lifestyle lacking both physical and mental activity. aTime spent on television viewing may reflect a desire to avoid more stimulating activities and may be indicative of a mentally inactive lifestyle which has been shown to be a.s.sociated with increased risk of cognitive decline with age,a the authors conclude.15 Conversely, an active lifestyle turns out to be an effective remedy against this cognitive decline experienced by so many elderly people. Ulman Lindenberger and Martin Lvdn at the Max Planck Inst.i.tute for Human Development in Berlin have followed 516 persons at ages 70 to 100 and recorded the degree of their asocial partic.i.p.ation.a16 In interviews they asked specific questions about their daily lives: Did they have company the day prior to the interview? Have they recently been involved in hobbies? How often did they dine out, and did they still go to social events like concerts? The data covered a period of eight years and revealed that activity, possibly by triggering beneficial neurological processes, can protect the brain. People who led an active and engaged life showed a significantly smaller cognitive decline than people with limited social partic.i.p.ation. An active lifestyle after retirement can mean many different things: music, sports, strenuous playing with grandchildren, studying a language, political activism, hiking, or writing a book. These and other similar activities can serve to keep the brain young.
Physical exercise further enhances this effect. Lindenberger explains this using the example of crossing a street on foot: usually, this task would be more demanding for the brain of an 80-year-old person than for the brain of a teenager. However, if an old person keeps his body in good shape by regular exercising, the attention needed for the motor task of crossing the street is minimal. aThus, mental energy is saved and can be utilized for other purely cognitive activities,a Lindenberger explains. His example shows how the model of acognitive reservea must be expanded. Not only mental activities, but also physical activities, contribute to the resilience of the brain.
12.
Cancer: A Growing Case for Exercise.
ABOUT 50 EPIDEMIOLOGICAL STUDIES HAVE SHOWN THAT PHYSICAL exercise reduces the risk for colon cancer. In a scientific first, researchers at the Fred Hutchinson Cancer Research Center in Seattle were able to demonstrate this protection on the level of individual cells. Their study included 102 healthy men, who were divided into two groups. Half the partic.i.p.ants were asked to conduct one hour of aerobic activity per day (six days a week); the other half carried on with life as usual. After one year, the doctors took colon tissue samples, biopsies, and examined them under the microscope. That way, they were able to detect how many of the colon cells were about to divide. A jump in cell division can be a warning sign of cancer.
The a.n.a.lysis revealed that there were fewer actively dividing cells in men who exercised diligently for an average of four hours of activity per week. Those with more than five hours of weekly exercise demonstrated an even smaller rate of proliferation. The other half of the men, who hardly exercised at all, did not have the beneficial effect.1 Besides colon cancer, breast cancer can be prevented by physical activity. Even when women become active after entering menopause, they lower their breast cancer risk by 20 percent. To see this effect, it is sufficient to be active for 30 minutes for five days per week, doing things like brisk walking or bicycling. The advantages were biggest for slim and slightly overweight women. Though obese women did not profit, they, too, can reap the benefit by reducing their weight to normal and making themselves more likely to realize the preventive effect.
One large study in Europe has even revealed that ch.o.r.es and housework, such as vacuuming, cooking, washing, ironing, and housecleaning, can help stave off cancer. The researchers a.s.sessed the activity levels and the health status of 218,169 women for more than six years. Active women spent an average of 16 to 17 hours a week on household ch.o.r.esa"and had a reduced breast cancer risk of 20 percent (younger women) to 30 percent (menopausal women) compared to inactive controls. The researchers are not saying that women should be stay-at-home mothers doing all the ch.o.r.es. Rather, the study reiterates a message that is true for both genders: the benefits of exercise kick in at relatively low intensities.2 Finally, the risk for prostate cancer is also reduced by physical exercise. In the United States it is one the most prevalent cancers among men, whereas it is far rarer among men living in Asian countries. However, as men from j.a.pan or China immigrate to the United States and adopt the Western lifestyle, their prostate cancer risk approaches that of American men. Apart from diet, lack of exercise plays a major role influencing the risk for prostate cancer by 10 to 70 percent.
But how can an active life stave off cancer? As with colon cancer, there appears to be a link to digestion. In sedentary bodies the peristalsis of the colon is slowed down. Thus, cancer-causing agents in the food stay for an extended time in the colon. The researchers have also identified numerous other factors that help to prevent tumor growth.3 BODY FAT AND DANGEROUS HORMONE LEVELS.
Physical activity reduces weight and thus the production of female s.e.x hormones, especially estrogens because these are made not only in the ovaries but also in the fat tissue. That is why lack of exercise often leads to both fat deposits and elevated hormone levels, which can promote the growth of tumors in the cervix, endometrium, ovaries, and breast.
The most natural way to reduce the level of these hormones is physical activity. Anne McTiernan of the Fred Hutchinson Cancer Research Center has demonstrated this in a trial of 267 women who did not take artificial hormones.4 Researchers weighed the women, noted their weekly amount of exercise, and a.s.sessed their levels of the hormones estradiol and estrone. These hormones are very active and can promote breast cancer.
The result: women who are heavy and hardly move have hormone levels exceeding those of active and normal-weight women by 50 to 100 percent. So by watching their weight and performing some moderate exercise, women can reduce hormone levels under their own steam to a ahealthy level,a concludes McTiernan.5 According to her study, 30 minutes of moderate training, five days per week, is sufficient. The exercise appears to increase the level of certain proteins that in turn can remove excess hormone levels from the blood.6 Furthermore, it beneficially influences the pathways that are involved in the production of hormones. In physically fit bodies there is a high level of certain intermediate products that cannot be converted into hormones. By comparison, in overweight women there is a high level of products than can be turned into hormones. In addition, exercise seems to be connected with an advantageous composition of the breast tissue. A trial in Norway showed that women who get at least two hours of activity per week have less dense breast tissue than sedentary women. And the higher the tissue density, the higher the breast cancer risk.7 The cancer-causing potential of these hormones is widely known and acknowledged in medical research. All the more odd, then, that pharmaceutical companies manufacture estrogen products and still, despite large studies showing risk, sell them as ahormone replacement therapya (HRT) to menopausal women. In the United States, a large trial of 16,000 women had to be terminated as the emerging data from it revealed that the hormone products do more harm than good: If 10,000 women take the products estrogen and progestogen for one year, eight more of them will develop breast cancer than those who do not take them. Even though these pills were also touted as preventive against heart disease, they were also cardiovascular dangers. What miserable credentials for a product that is claimed to be a remedy.8 Women who take hormone pills face a higher risk of cancer, for two possible reasons. As mentioned, estrogens can trigger the growth of cells in the breast tissue. Moreover, hormone consumption affects behavior and dampens the desire to exercise. Studies with mice suggest a direct link. The more estrogens given to female mice, the less distance they ran on a treadmill.9 Because of the wide publicity given the large trial that had to be stopped, many fewer women are taking pills. Many of the benefits supposedly offered by the replacement hormones, such as a more youthful appearance or a healthier heart, are more easily found on a hike or at a gym.
EXERCISE AS CANCER PREVENTION.
People who exercise also influence their immune system, and thereby their cancer risk. But the effect of exercise can go both ways. An overload can weaken the immune system and even promote the growth of a tumor. On the other hand, the right dose of exercise does strengthen the immune system and can hinder or inhibit tumor growth. Moderate exercise appears to promote the production of certain cells of the immune system. Cytotoxic T cells, natural killer cells, and similar cells patrol the body and are capable of destroying tumor cells. The members of the beneficial platoon of cells have been shown to be produced in bigger numbers by aregular, moderate exercise.a 10 Mice allowed to run as much as they want, on running wheels, boost their production of natural killer cells. They then have significant advantages compared to sedentary mice because their immune systems can fight more cancer cells, and fewer tumors grow.
With age, the immune system becomes weaker, and physicians suspect this decline is one of the reasons cancer risk increases with age. The aging process can be clearly seen in T cells. Their number dwindles in the course of the years, and their ability to detect and fight foreign cells becomes weaker. However, this decline can be halted and reversed: Elderly women and men were shown to improve the function of their T cells by exercise compared with sedentary controls of the same age.11 This finding points to an additional mechanism that underlies the cancer-fighting potential of exercise: it counteracts the age-related decline of the immune system.