Exercise And the Brain - The New York Times
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Prescribing Exercise to Treat DepressionBy GRETCHEN REYNOLDS
August 31, 2011
Can a stroll help ease depression? That question preoccupied Dr. Madhukar H. Trivedi, a
professor of psychiatry at the University of Texas Southwestern Medical Center in Dallas,
after several of his patients, all suffering from serious depression, mentioned that they felt
happier if they went for a walk. The patients in question were taking the widely
prescribed antidepressants known as S.S.R.I.’s, for selective serotonin reuptake
inhibitors, but not responding fully. They remained, by clinical standards, depressed. Dr.
Trivedi and his colleagues began to wonder if adding a formal “dose” of exercise would
increase their chances of getting better.
Certainly the possibility was worth investigating. Clinical depression, as anyone
who has experienced or watched a loved one struggle with the condition knows, can be
stubbornly intractable. Even if patients have been taking an antidepressant for months,
recovery rates tend to hover below 50 percent.
In order to increase the odds of improvement, doctors frequently add a second
treatment — often another drug, like lithium or an antipsychotic — to the S.S.R.I.
regimen at some point, Dr. Trivedi said. Most patients ultimately require at least two
concurrent treatments to achieve remission of their depression, he said. Studies have
shown that these secondary drug treatments help an additional 20 to 30 percent of
depressed patients to improve, but the medications can be expensive and have unpleasant
side effects.
Which prompted Dr. Trivedi to look to exercise. His investigation joins a growing
movement among some physiologists and doctors to consider and study exercise as a
formal medicine, with patients given a prescription and their progress monitored, as it
would be if they were prescribed a pill.
In this case, Dr. Trivedi and his collaborators, who included researchers at the
Cooper Institute in Dallas, the Pennington Biomedical Research Center in Louisiana and
other institutions, recruited 126 people with depression who had been using S.S.R.I.’s for
a minimum of two months, without achieving remission. None of the patients exercised.
Dr. Trivedi and his colleagues divided these volunteers into two groups. One began
a gentle aerobic exercise routine, under the tutelage of Cooper Institute researchers,
which required them to burn a certain amount of calories per session, depending on their
weight. How the subjects expended the energy was up to them. Some walked for about 10
minutes a day, on a treadmill or by strolling around the block, at a pace of three miles an
hour. Others chose an equivalent easy cycling workout.
The second group was more energetic, walking briskly for about 30 minutes a day at
a pace of four miles an hour, or the cycling equivalent, a regimen that meets the current
exercise recommendations from the American College of Sports Medicine.
Each volunteer exercised for four months, while continuing to take an
antidepressant. At the end of that time, according to the study published recently in The
Journal of Clinical Psychiatry, 29.5 percent had achieved remission, “which is a very
robust result,” Dr. Trivedi said, equal to or better than the remission rates achieved using
drugs as a back-up treatment. “I think that our results indicate that exercise is a very valid
treatment option” for people whose depression hasn’t yielded to S.S.R.I.’s, he said.
As with most scientific findings, though, there are caveats.
One is practical. More patients improved in the group that completed the longer,
brisker workouts than in the group assigned the easier exercise, but more of them also
dropped out of the study. “We need to find ways to support people’s efforts to exercise,”
Dr. Trivedi said. “It’s not going to be enough to casually say, ‘Go for a walk.’” Exercise,
if it’s to be medicinal in depression treatments, will have to be monitored, he said, so it
can’t be shrugged off.
Even then, many people will not respond. Almost 70 percent of the volunteers in
this study did not achieve full remission. Failure rates were particularly high for women
with a family history of depression, perhaps as a result of some as yet unknown genetic
quirk. And women in that group who did recover were more likely to succeed using the
lighter exercise program than the more strenuous routine.
Then there is the issue of a control group, whose members would have continued
with their S.S.R.I.’s but not exercised. This study did not have one, making interpreting
the results tricky, said James A. Blumenthal, a professor of psychology and neuroscience
at Duke University who was not involved with this study but who has written extensively
about exercise and depression. Perhaps four additional months of S.S.R.I. treatment
raised people’s moods, and the exercise was incidental. “Evidence is accumulating that
exercise may be an effective treatment for depressed patients who are receptive to
exercise as a possible treatment and who are able to safely engage in exercise,” he said.
But the evidence is by no means definitive.
Still, Dr. Trivedi said, although additional studies certainly are needed, there’s no
reason for people with unyielding depression not to talk now with their doctors about
exercise as a treatment option. “Side effects are almost nonexistent,” he said, “while you
get additional benefits, in terms of improvements in cardiovascular health and reductions
in other disease risks,” things antidepressant drugs do not provide. “Plus,” he pointed out,
“the cost profile is very favorable.” Exercise, as medicines go, is cheap.
How Exercise Can Strengthen the BrainBy GRETCHEN REYNOLDS
September 28, 2011
Can exercise make the brain more fit? That absorbing question inspired a new study at
the University of South Carolina during which scientists assembled mice and assigned
half to run for an hour a day on little treadmills, while the rest lounged in their cages
without exercising.
Earlier studies have shown that exercise sparks neurogenesis, or the creation of
entirely new brain cells. But the South Carolina scientists were not looking for new cells.
They were looking inside existing ones to see if exercise was whipping those cells into
shape, similar to the way that exercise strengthens muscle.
For centuries, people have known that exercise remodels muscles, rendering them
more durable and fatigue-resistant. In part, that process involves an increase in the
number of muscle mitochondria, the tiny organelles that float around a cell’s nucleus and
act as biological powerhouses, helping to create the energy that fuels almost all cellular
activity. The greater the mitochondrial density in a cell, the greater its vitality.
Past experiments have shown persuasively that exercise spurs the birth of new
mitochondria in muscle cells and improves the vigor of the existing organelles. This
upsurge in mitochondria, in turn, has been linked not only to improvements in exercise
endurance but to increased longevity in animals and reduced risk for obesity, diabetes and
heart disease in people. It is a very potent cellular reaction.
Brain cells are also fueled by mitochondria. But until now, no one has known if a
similar response to exercise occurs in the brain.
Like muscles, many parts of the brain get a robust physiological workout during
exercise. “The brain has to work hard to keep the muscles moving” and all of the bodily
systems in sync, says J. Mark Davis, a professor of exercise science at the Arnold School
of Public Health at the University of South Carolina and senior author of the new mouse
study, which was published last month in The Journal of Applied Physiology. Scans have
shown that metabolic activity in many parts of the brain surges during workouts, but it
was unknown whether those active brain cells were actually adapting and changing.
To see, the South Carolina scientists exercised their mice for eight weeks. The
sedentary control animals were housed in the same laboratory as the runners to ensure
that, except for the treadmill sessions, the two groups shared the same environment and
routine.
At the end of the two months, the researchers had both groups complete a run to
exhaustion on the treadmill. Not surprisingly, the running mice displayed much greater
endurance than the loungers. They lasted on the treadmills for an average of 126 minutes,
versus 74 minutes for the unexercised animals.
More interesting, though, was what was happening inside their brain cells. When the
scientists examined tissue samples from different portions of the exercised animals’
brains, they found markers of upwelling mitochondrial development in all of the tissues.
Some parts of their brains showed more activity than others, but in each of the samples,
the brain cells held newborn mitochondria.
There was no comparable activity in brain cells from the sedentary mice.
This is the first report to show that, in mice at least, two months of exercise training
“is sufficient stimulus to increase mitochondrial biogenesis,” Dr. Davis and his co-
authors write in the study.
The finding is an important “piece in the puzzle implying that exercise can lead to
mitochondrial biogenesis in tissues other than muscle,” says Dr. Mark Tarnopolsky, a
professor of medicine at McMaster Children’s Hospital, who was not involved with this
experiment but has conducted many exercise studies.
The mitochondrial proliferation in the animals’ brains has implications that are
wide-ranging and heartening. “There is evidence” from other studies “that mitochondrial
deficits in the brain may play a role in the development of neurodegenerative diseases,”
including Alzheimer’s and Parkinson’s diseases, Dr. Davis says. Having a larger reservoir
of mitochondria in your brain cells could provide some buffer against those conditions, he
says.
Dr. Tarnopolsky agrees. “Epidemiological studies show that long-term runners have
a lower risk of neurological disease,” he points out.
More immediately, Dr. Davis speculates, re-energized brain cells could behave like
mitochondrial-drenched muscle cells, becoming more resistant to fatigue and, since
bodily fatigue is partly mediated by signals from the brain, allowing you to withstand
more exercise. In effect, exercising the body may train the brain to allow you to exercise
more, amplifying the benefits.
Revitalized brain cells also, at least potentially, could reduce mental fatigue and
sharpen your thinking “even when you’re not exercising,” Dr. Davis says.
Of course, this experiment was conducted with animals, and “mouse brains are not
human brains,” Dr. Davis says. “But,” he continues, “since mitochondrial biogenesis has
been shown to occur in human muscles, just as it does in animal muscles, it is a
reasonable supposition that it occurs in human brains.”
Best of all, the effort required to round your brain cells into shape is not daunting. A
30-minute jog, Dr. Davis says, is probably a good human equivalent of the workout that
the mice completed.
How Exercise Benefits the BrainBy GRETCHEN REYNOLDS
November 30, 2011
To learn more about how exercise affects the brain, scientists in Ireland recently asked a
group of sedentary male college students to take part in a memory test followed by
strenuous exercise.
First, the young men watched a rapid-fire lineup of photos with the faces and names
of strangers. After a break, they tried to recall the names they had just seen as the photos
again zipped across a computer screen.
Afterward, half of the students rode a stationary bicycle, at an increasingly strenuous
pace, until they were exhausted. The others sat quietly for 30 minutes. Then both groups
took the brain-teaser test again.
Notably, the exercised volunteers performed significantly better on the memory test
than they had on their first try, while the volunteers who had rested did not improve.
Meanwhile, blood samples taken throughout the experiment offered a biological
explanation for the boost in memory among the exercisers. Immediately after the
strenuous activity, the cyclists had significantly higher levels of a protein known as brain-
derived neurotrophic factor, or BDNF, which is known to promote the health of nerve
cells. The men who had sat quietly showed no comparable change in BDNF levels.
For some time, scientists have believed that BDNF helps explain why mental
functioning appears to improve with exercise. However, they haven’t fully understood
which parts of the brain are affected or how those effects influence thinking. The Irish
study suggests that the increases in BDNF prompted by exercise may play a particular
role in improving memory and recall.
Other new studies have reached similar conclusions, among both people and
animals, young and old. In one interesting experiment published last month, Brazilian
scientists found that after sedentary elderly rats ran for a mere five minutes or so several
days a week for five weeks, a cascade of biochemical processes ignited in the memory
center of their brains, culminating in increased production of BDNF molecules there. The
old, exercised animals then performed almost as well as much younger rats on rodent
memory tests.
Another animal study, this one performed by researchers in the Brain Injury
Research Center at the University of California, Los Angeles, and published in September
in the journal Neuroscience, showed that if adult rats were allowed to run at will for a
week, the memory center of their brains afterward contained more BDNF molecules than
in sedentary rats, and teemed with a new population of precursor molecules that
presumably would soon develop into fully functioning BDNF molecules.
Perhaps the most inspiring of the recent experiments is one involving aging human
pilots. For the experiment, published last month in the journal Translational Psychiatry,
scientists at Stanford University School of Medicine asked 144 experienced pilots ages 40
to 65 to operate a cockpit simulator three separate times over the course of two years.
For all of the pilots, performance declined somewhat as the years passed. A similar
decline with age is common in all of us.
Many people find it more difficult to perform skilled tasks — driving an
automobile, for instance — as they grow older, says Dr. Ahmad Salehi, an associate
professor of psychiatry and behavioral sciences at Stanford and lead author of the study.
But in this case, the decline was especially striking among one particular group of
men. These aging pilots carried a common genetic variation that is believed to reduce
BDNF activity in their brains. The men with a genetic tendency toward lower BDNF
levels seemed to lose their ability to perform complicated tasks at almost double the rate
of the men without the variation.
While the pilot experiment wasn’t an exercise study, it does raise the question of
whether strenuous exercise could slow such declines by raising BDNF levels, thereby
salvaging our ability to perform skilled manual tasks well past middle age.
“So many studies have shown that exercise increases levels of BDNF,” says Dr.
Salehi. While he notes that other growth factors and body chemicals are “upregulated” by
exercise, he believes BDNF holds the most promise.
“The one factor that shows the fastest, most consistent and greatest response is
BDNF,” he says. “It seems to be key to maintaining not just memory but skilled task
performance.”
Dr. Salehi plans next to examine the exercise histories of the pilots, to see whether
those with the gene variant, which is common among people of European or Asian
backgrounds, respond differently to workouts.
In people who have the variant and less BDNF activity, “exercise is probably even
more important,” he says. “But for everyone, the evidence is very, very strong that
physical activity will increase BDNF levels and improve cognitive health.”
Exercising an Aging BrainBy DENISE GRADY
March 7, 2012
More and more retired people are heading back to the nearest classroom — as students
and, in some cases, teachers — and they are finding out that school can be lovelier the
second time around. Some may be thinking of second careers, but most just want to keep
their minds stimulated, learn something new or catch up with a subject they were always
curious about but never had time for.
For many, at least part of the motivation is based on widespread reports that
exercising the brain may preserve it, forestalling mental decline and maybe even
Alzheimer’s disease and other types of dementia.
Is there any truth to it? And if there is, what type of learning is best suited to the
older brain?
Many studies do find that being mentally active is associated with a lower risk of
Alzheimer’s disease. But the standard caveat applies: association does not prove cause
and effect, and there is always the chance that the mentally active people who never got
Alzheimer’s simply had healthier brains to begin with.
Even, so, researchers say, there is no harm in telling people to try to stay engaged.
“When you and I are having this conversation, you’re taking notes, thinking,
remembering pieces of it, trying to relate it to other things,” said Arthur Toga, a professor
of neurology and director of the laboratory of neuroimaging at the University of
California, Los Angeles. “You’re changing the circuitry in your brain. That is because
you have changed something in your brain to retain that memory.”
Dr. Toga elaborated: “The conversation requires nerve cells in the brain to fire, and
when they fire they are using energy. More oxygen and sugar must be delivered, by
increased blood flow to those regions.
“Why would that be good? If you are vasodilating, delivering more blood to certain
regions of the brain, that is important. It increases the longevity and the health of those
circuits. In adults, if I ask you to perform tasks you’ve never done before, the amount of
brain it takes for you to try and do it is far greater than the amount of brain it takes for
you to do something you’re already good at. So yes, exercising the brain is good.”
Playing video games probably qualifies as a type of brain exercise, he said, though older
people might not sharpen their skills as fast as younger ones do.
But Dr. Toga warned that while using the brain might help avert some of the mental
slowing that normally comes with aging, it had its limits. “I do not believe that it
forestalls degenerative disease, however,” he said. “That’s a different process.” There is a
“little bit of snake oil,” he added, in the various products and programs that are being
marketed with the implied promise that they will ward off Alzheimer’s disease.
But research continues. Dr. William Jagust, a professor of public health and
neuroscience at the University of California, Berkeley, said there were two main theories
that tried to explain why exercising the brain might make it more resistant to disease.
One is the “cognitive reserve” theory, which says that if the brain is in the best
possible shape with extensive neuronal connections from being used a lot, it may be able
to withstand the onset of Alzheimer’s disease for a while and symptoms may take longer
to develop.
A hallmark of Alzheimer’s is deposits in the brain of an abnormal form of a protein
called amyloid.
“A paper we published showed that people who were more cognitively active over
their whole life span had less amyloid,” Dr. Jagust said.
Animal research, he said, shows that neural activity actually releases amyloid into
the brain. How, then, could mentally active people have less amyloid?
“My interpretation is that people who are more cognitively active have more
efficient brains,” Dr. Jagust said. “What seems to happen in aging is that older people
seem to have less efficient brains.” A scan of brain activity on a 20-year-old being asked
to remember something will show less activity needed than in an 80-year-old asked to
perform the same task.
“Older people seem to activate or bring on line brain areas that young people don’t
use,” Dr. Jagust said. “They have to work their brains harder. So people who stay
cognitively active may use their brains more efficiently.”
That way, they may generate fewer amyloid deposits. But he emphasized that being
mentally active throughout life — not just in old age — was what mattered.
“It has to do with lifelong patterns of behavior,” Dr. Jagust said. “We tend to focus
on what people do at 75 in terms of dementia. But there is more evidence that what you
do in your life, at 40 or 50, is probably more important.”
Nonetheless, Dr. Jagust acknowledged, “this is all theoretical.”
As to what kinds of things older people tend to be best at learning, the researchers
said there were no hard and fast rules. Memory usually does diminish, even in people
who do not have dementia, and reaction time slows.
“You’re not going to learn to hit a fastball,” Dr. Jagust said.
Over time, he said, the best-preserved abilities seem to involve vocabulary and
knowledge about the world, what researchers call “crystallized intelligence.” Problem-
solving and math ability, part of “fluid intelligence,” do not seem to stick as well.
The slippage in memory may make it tough to learn a new language. But people
who already know more than one language may be more adept than others, because the
process of learning different rules of syntax and grammar, especially early in life, seems
to program extra skills into the brain, ones that people appear to retain.
Dr. Toga said that the sensorimotor parts of the brain that control the senses and
muscle movement did not tend to shrink later in life the way the cognitive centers did. So
in theory, learning physical skills like dancing ought to come easily. But nature can be
cruel: where the brain is strong, the flesh may be weak. Failing eyesight and hearing,
weakened muscles and stiff joints may all sabotage the signals the brain needs to
choreograph smooth moves on the dance floor.
“Everything is sliding downward, unfortunately,” he said, laughing.
But it is still a good idea to try something new.
“A variety of things is important,” Dr. Toga said. “We try to encourage people to do
certain things because it couldn’t hurt and may be good. Retaining lots of social
interaction is really important. It involves so much of the brain. You have to interpret
facial expressions and understand new concepts. If you want to learn to ride a monocycle
or do acrobatics at 75, it’s probably not a good idea. But exercising more geography in
the brain, I think that’s important.”
Columbia University has had a program for “lifelong learners” since 1986. About
200 participants take regular Columbia courses. They are expected to keep up with the
reading, but there are no term papers, homework, exams or grades.
The older students tend toward history courses, renowned professors and language
classes that they hope will help in their travels.
“A lot of the time, when seniors are in history classes, specially if it’s relevant to the
topic, they are often used by professors as sort of experts to give testimony to events that
actually occurred during a certain period,” said Kristine Billmyer, the dean and a
professor at Columbia’s school of continuing education. “That’s pretty cool, and I think
it’s something that’s highly valued by the students as well as the faculty.”
Programs geared to older people also exist at many other colleges and universities.
An organization based in California, the Bernard Osher Foundation, supports lifelong
learning programs at 117 colleges and universities, at least one in every state, based on
the idea that many older students go back to school for the joy of learning.
One of the largest programs for retirees is at the University of Wisconsin, Green
Bay (it is not associated with Osher). Called Learning in Retirement, it is sponsored by
the university, with more than 1,000 members and more than 240 courses a year. Classes
— mostly short, a few two-hour sessions — include painting, jazz, travel, eBay,
osteoarthritis, Zumba, the periodic table, the history of the earth, building with straw
bales and “motorcycling and aging awareness.” Most require no outside reading,
homework or exams. Some are taught by college faculty, some by members of the group
or others in the community.
Michael W. Murphy, who spent more than 30 years as an English professor, said
this program had brought him some of the greatest joy he had experienced in the
classroom. Since 2001, when he stepped down from his post as acting dean at the
university, he has been teaching poetry and other subjects to Learning in Retirement
members. It is an unpaid position.
“I’ve always enjoyed teaching, and the idea of teaching without having to read
papers, correct tests and worst of all, give out grades, was really appealing,” Dr. Murphy
said.
To his delight, the students actually want to be there. They take the time to tell him
how much they appreciate him and sometimes even break into applause after his lectures.
One of his courses filled a hall with seats for 120 and had 130 more people on the waiting
list. The students include doctors, lawyers, professors and high-school dropouts, who
have all been around the block a few times, and every so often someone challenges him
— a kind of mental jousting he enjoys.
“The biggest problem I had teaching 18-year-olds was a kind of general apathy,” Dr.
Murphy said. “They were looking forward to a career in high finance and I was trying to
teach them to appreciate Tennyson. The fact that these people show up, and toddle in or
waddle in, some with their walkers or wheelchairs, it’s heartwarming.”
How Exercise Could Lead to a BetterBrainBy GRETCHEN REYNOLDS
April 18, 2012
The value of mental-training games may be speculative, as Dan Hurley writes in his
article on the quest to make ourselves smarter, but there is another, easy-to-achieve,
scientifically proven way to make yourself smarter. Go for a walk or a swim. For more
than a decade, neuroscientists and physiologists have been gathering evidence of the
beneficial relationship between exercise and brainpower. But the newest findings make it
clear that this isn’t just a relationship; it is the relationship. Using sophisticated
technologies to examine the workings of individual neurons — and the makeup of brain
matter itself — scientists in just the past few months have discovered that exercise
appears to build a brain that resists physical shrinkage and enhance cognitive flexibility.
Exercise, the latest neuroscience suggests, does more to bolster thinking than thinking
does.
The most persuasive evidence comes from several new studies of lab animals living
in busy, exciting cages. It has long been known that so-called “enriched” environments
— homes filled with toys and engaging, novel tasks — lead to improvements in the
brainpower of lab animals. In most instances, such environmental enrichment also
includes a running wheel, because mice and rats generally enjoy running. Until recently,
there was little research done to tease out the particular effects of running versus those of
playing with new toys or engaging the mind in other ways that don’t increase the heart
rate.
So, last year a team of researchers led by Justin S. Rhodes, a psychology professor
at the Beckman Institute for Advanced Science and Technology at the University of
Illinois, gathered four groups of mice and set them into four distinct living arrangements.
One group lived in a world of sensual and gustatory plenty, dining on nuts, fruits and
cheeses, their food occasionally dusted with cinnamon, all of it washed down with
variously flavored waters. Their “beds” were colorful plastic igloos occupying one corner
of the cage. Neon-hued balls, plastic tunnels, nibble-able blocks, mirrors and seesaws
filled other parts of the cage. Group 2 had access to all of these pleasures, plus they had
small disc-shaped running wheels in their cages. A third group’s cages held no
embellishments, and they received standard, dull kibble. And the fourth group’s homes
contained the running wheels but no other toys or treats.
All the animals completed a series of cognitive tests at the start of the study and
were injected with a substance that allows scientists to track changes in their brain
structures. Then they ran, played or, if their environment was unenriched, lolled about in
their cages for several months.
Afterward, Rhodes’s team put the mice through the same cognitive tests and
examined brain tissues. It turned out that the toys and tastes, no matter how stimulating,
had not improved the animals’ brains.
“Only one thing had mattered,” Rhodes says, “and that’s whether they had a running
wheel.” Animals that exercised, whether or not they had any other enrichments in their
cages, had healthier brains and performed significantly better on cognitive tests than the
other mice. Animals that didn’t run, no matter how enriched their world was otherwise,
did not improve their brainpower in the complex, lasting ways that Rhodes’s team was
studying. “They loved the toys,” Rhodes says, and the mice rarely ventured into the
empty, quieter portions of their cages. But unless they also exercised, they did not
become smarter.
Why would exercise build brainpower in ways that thinking might not? The brain,
like all muscles and organs, is a tissue, and its function declines with underuse and age.
Beginning in our late 20s, most of us will lose about 1 percent annually of the volume of
the hippocampus, a key portion of the brain related to memory and certain types of
learning.
Exercise though seems to slow or reverse the brain’s physical decay, much as it does
with muscles. Although scientists thought until recently that humans were born with a
certain number of brain cells and would never generate more, they now know better. In
the 1990s, using a technique that marks newborn cells, researchers determined during
autopsies that adult human brains contained quite a few new neurons. Fresh cells were
especially prevalent in the hippocampus, indicating that neurogenesis — or the creation
of new brain cells — was primarily occurring there. Even more heartening, scientists
found that exercise jump-starts neurogenesis. Mice and rats that ran for a few weeks
generally had about twice as many new neurons in their hippocampi as sedentary animals.
Their brains, like other muscles, were bulking up.
But it was the ineffable effect that exercise had on the functioning of the newly
formed neurons that was most startling. Brain cells can improve intellect only if they join
the existing neural network, and many do not, instead rattling aimlessly around in the
brain for a while before dying.
One way to pull neurons into the network, however, is to learn something. In a 2007
study, new brain cells in mice became looped into the animals’ neural networks if the
mice learned to navigate a water maze, a task that is cognitively but not physically taxing.
But these brain cells were very limited in what they could do. When the researchers
studied brain activity afterward, they found that the newly wired cells fired only when the
animals navigated the maze again, not when they practiced other cognitive tasks. The
learning encoded in those cells did not transfer to other types of rodent thinking.
Exercise, on the other hand, seems to make neurons nimble. When researchers in a
separate study had mice run, the animals’ brains readily wired many new neurons into the
neural network. But those neurons didn’t fire later only during running. They also lighted
up when the animals practiced cognitive skills, like exploring unfamiliar environments. In
the mice, running, unlike learning, had created brain cells that could multitask.
Just how exercise remakes minds on a molecular level is not yet fully understood,
but research suggests that exercise prompts increases in something called brain-derived
neurotropic factor, or B.D.N.F., a substance that strengthens cells and axons, fortifies the
connections among neurons and sparks neurogenesis. Scientists can’t directly study
similar effects in human brains, but they have found that after workouts, most people
display higher B.D.N.F. levels in their bloodstreams.
Few if any researchers think that more B.D.N.F. explains all of the brain changes
associated with exercise. The full process almost certainly involves multiple complex
biochemical and genetic cascades. A recent study of the brains of elderly mice, for
instance, found 117 genes that were expressed differently in the brains of animals that
began a program of running, compared with those that remained sedentary, and the
scientists were looking at only a small portion of the many genes that might be expressed
differently in the brain by exercise.
Whether any type of exercise will produce these desirable effects is another
unanswered and intriguing issue. “It’s not clear if the activity has to be endurance
exercise,” says the psychologist and neuroscientist Arthur F. Kramer, director of the
Beckman Institute at the University of Illinois and a pre-eminent expert on exercise and
the brain. A limited number of studies in the past several years have found cognitive
benefits among older people who lifted weights for a year and did not otherwise exercise.
But most studies to date, and all animal experiments, have involved running or other
aerobic activities.
Whatever the activity, though, an emerging message from the most recent science is
that exercise needn’t be exhausting to be effective for the brain. When a group of 120
older men and women were assigned to walking or stretching programs for a major 2011
study, the walkers wound up with larger hippocampi after a year. Meanwhile, the
stretchers lost volume to normal atrophy. The walkers also displayed higher levels of
B.D.N.F. in their bloodstreams than the stretching group and performed better on
cognitive tests.
In effect, the researchers concluded, the walkers had regained two years or more of
hippocampal youth. Sixty-five-year-olds had achieved the brains of 63-year-olds simply
by walking, which is encouraging news for anyone worried that what we’re all facing as
we move into our later years is a life of slow (or not so slow) mental decline.
How Working the Muscles May BoostBrainpowerBy GRETCHEN REYNOLDS
May 9, 2012
Upending the cliché of muscleheads, scientists at the Laboratory of Neuroscience at the
National Institute on Aging recently set out to examine whether changes in muscles
prompted by exercise might subsequently affect and improve the brain’s ability to think.
Lab animals and people generally perform better on tests of cognition after several
weeks of exercise training, and studies have shown that over time, running and other
types of endurance exercise increase the number of neurons in portions of the brain
devoted to memory and learning. But the mechanisms that underlie this process remain
fairly mysterious. Do they start within the brain itself? Or do messages arrive from
elsewhere in the body to jump-start the process?
The researchers were especially interested in the possibility that the action starts
outside the brain — and specifically in the muscles. “We wondered whether peripheral
triggers might be activating the cellular and molecular cascades in the brain that led to
improvements in cognition,” says Henriette van Praag, the investigator at the National
Institute on Aging who led the study.
Muscles are, of course, greatly influenced by exercise. Muscle cells respond to
exercise by pumping out a variety of substances that result in larger, stronger muscles.
Some of those compounds might be entering the bloodstream and traveling to the brain,
Dr. van Praag says.
The problem is that exercise is such a complicated physiological stimulus that it’s
very difficult to isolate which compounds are involved and what their effects might be.
So she and her colleagues decided to study “fake” exercise instead, using two specialized
drugs that had been tested several years ago by scientists at the Salk Institute in San
Diego. The drugs had been shown to induce the same kinds of changes in sedentary
animals’ muscles that exercise would cause, so that even though the mice didn’t exercise,
they physiologically responded as if they had.
One of the drugs that they used, known as Aicar, increases the muscles’ output of
AMPK, an enzyme that affects cellular energy and metabolism. Regular endurance
exercise, like running or cycling, increases the muscles’ production of this enzyme. In the
Salk experiments, Aicar enabled untrained mice to run 44 percent farther during treadmill
tests than other, sedentary animals that hadn’t received the drug.
The second compound, GW1516, a cholesterol drug, also stimulates biochemical
changes in muscle cells like those caused by endurance exercise. But in the Salk studies,
it had amplified endurance primarily in animals that also ran, allowing them to run farther
than another set of running mice that didn’t get the drug. But it hadn’t done much muscle-
wise for animals that remained sedentary.
By using these drugs in unexercised animals under well-controlled conditions, the
scientists from the National Institute on Aging sought to determine whether changes in
muscles then initiated changes in the brain.
And as it turned out, muscles did affect the mind. After a week of receiving either of
the two drugs (and not exercising), the mice performed significantly better on tests of
memory and learning than control animals that had simply remained quiet in their cages.
The effects were especially pronounced for the animals taking Aicar.
The results, published in the journal Learning and Memory, showed that the
drugged animals’ brains also contained far more new neurons in brain areas central to
learning and memory than the brains of the control mice, an effect found by microscopic
examination.
Because the two drugs “don’t cross the blood-brain barrier much, if at all,” Dr. van
Praag says, “we could be fairly confident that the changes we were seeing were related to
an exercise-type reaction in the muscles” and not to brain responses to the drugs.
The message of this finding, she continues, is that “improvements in cognition” that
follow exercise “would seem to involve changes throughout the body and not just in the
brain.”
Although the exact process isn’t clear, Dr. van Praag speculates that some of the
AMPK enzyme created during exercise enters the bloodstream and travels to the brain,
setting off a series of new reactions there.
The implication, she continues, is that exercise may need to be aerobic if it’s going
to substantially affect the brain. “You probably need to increase blood flow, which
mostly occurs during endurance training,” she says. Also, in animal studies, AMPK
production has been found to increase principally after running. Of course, “it’s very hard
for us to study weight lifting in mice,” Dr. van Praag says, so it’s possible that other types
of exercise might improve AMPK production and cognition too, she says.
Interestingly, when the scientists continued injecting mice with Aicar for an
additional week, the animals’ brains stopped responding. They actually began losing their
augmented ability to learn, compared with the control animals, a finding that suggests,
Dr. van Praag says, that drugs may be an unsatisfactory — and potentially detrimental —
way to emulate the effects of exercise.
Exercise, on the other hand, is generally safe. “And the scientific evidence,
including ours,” she says, “is strong and growing that it is very good for the muscles —
and for the brain.”
How Exercise Can Jog the MemoryBy GRETCHEN REYNOLDS
May 30, 2012
It’s well established that exercise substantially changes the human brain, affecting both
thinking and emotions. But a sophisticated, multifaceted new study suggests that the
effects may be more nuanced than many scientists previously believed. Whether you gain
all of the potential cognitive and mood benefits from exercise may depend on when and
how often you work out, as well as on the genetic makeup of your brain.
For the experiment, published last month in Neuroscience, researchers in the
department of psychology and neuroscience at Dartmouth College in Hanover, N.H.,
recruited 54 adults, ages 18 to 36, from the college and the surrounding community. The
volunteers were healthy but generally sedentary; none exercised regularly.
During their first visit to the lab, they completed a series of questionnaires about
their health and mood, including how anxious they were both at that moment and in
general.
They also gave blood for genetic testing. Earlier studies had shown that exercise can
increase levels of a protein called brain-derived neurotropic factor, or BDNF, which is
thought to play a role in the positive effects of exercise on thinking. But some people
produce less BDNF after exercise than others because they have a variation in the gene
that controls BDNF production, though it’s unknown whether they derive less cognitive
benefit from exercise as a result. So the scientists wanted to determine each volunteer’s
BDNF gene status.
Then the group submitted to a memory test, consisting of pictures of objects flashed
across a computer screen. Soon after, another set of pictures appeared, and the volunteers
were asked to note, with keystrokes, whether they’d seen each particular image before.
This task involves a different part of the brain from the one most often focused on in
studies of exercise and memory, says David Bucci, an associate professor of psychology
and brain science at Dartmouth, who oversaw the study. Other experiments typically
examine the effect of exercise on the hippocampus, the brain’s primary memory center,
he says, but the object-recognition task involves activity in the perirhinal cortex, a portion
of the brain essential to remembering particular things or objects and whether they
happen to be new in your experience. Without a healthy perirhinal cortex, you might
recall where you’ve put your car keys (a hippocampal memory task), but not what car
keys are.
Finally, after completing the tests, the volunteers were randomly assigned to
exercise or not during the next four weeks. Half began a supervised program of walking
or jogging four times a week for at least 30 minutes. The other half remained sedentary.
After a month, the volunteers returned to the lab for retesting. But first, some
exercised. Half of the exercising group walked or jogged before the testing; half did not.
Ditto for the sedentary group: Half exercised that day for the first time since the start of
the study; the rest did not.
The earlier tests of memory and mood were repeated.
The results were, in certain aspects, a surprise. As expected, many of the volunteers
who’d been exercising for the past month significantly improved their scores on the
memory and mood tests. But not all of them did. In general, those volunteers who had
exercised for the past month and who worked out on the day of retesting performed the
best on the memory exam. They also tended to report less anxiety than other volunteers.
Those who had exercised during the preceding month but not on the day of testing
generally did better on the memory test than those who had been sedentary, but did not
perform nearly as well as those who had worked out that morning.
Interestingly, while exercising before the test didn’t improve the memory scores of
those who’d remained sedentary for the past month, it did increase their self-reported
anxiety levels. They were more jittery than they had been on the first lab visit.
Perhaps most intriguing, though, was what the researchers discovered when they
compared the volunteers’ BDNF gene variants and their scores on the memory test. They
found that those with the variant that blunts BDNF production after exercise — a fairly
common variation, existing in about 30 percent of people of European Caucasian heritage
— did not improve their memories, even if they exercised regularly. (No consumer test
exists to check for the variant.)
What all of this means for people who are hoping that exercise will improve their
minds is unclear, Dr. Bucci says, but it does suggest that the interplay of physical activity
and brainpower is more complex than we have perhaps yet acknowledged.
Some people’s ability to recall objects, for instance, “may respond less robustly” to
exercise than other people’s, he says, if their genetic makeup doesn’t promote the release
of BDNF.
But the overall message of this study and of ongoing research in his lab, Dr. Bucci
adds, is that exercise generally enhances the ability to remember. The people who did
improve their memory test scores, he points out, were invariably those who’d exercised
throughout the previous month and again the morning of the testing, suggesting a
powerful cumulative effect from the exercise sessions, he says.
More generally, Dr. Bucci says, there are many types of memory involving many
different areas within the brain, and few seem unaffected by regular, moderate exercise,
although the effects may be inconsistent from person to person.
“The current data strongly suggests that people should be physically active” if they
wish to enjoy a sturdy, unporous memory in the long term, Dr. Bucci says. Walk or jog
regularly, in other words, and most of us can expect to continue recognizing our keys as
keys.
Exercise May Ease Depression in HeartFailure PatientsBy ANAHAD O’CONNOR
July 31, 2012
Heart failure can take a heavy psychological toll, with many patients developing
symptoms of depression. But a new study suggests that an exercise plan can ease the
melancholy, creating improvements in mood that are comparable to the effects seen with
medication.
For roughly a year, researchers followed more than 2,000 people treated for
congestive heart failure at 82 medical centers in the United States, France and Canada.
Those who were assigned to a moderate aerobic exercise program — about 90 to 120
minutes a week — saw greater reductions in symptoms of depression than those who
were not enrolled in such a program.
“I think this shows that for patients who have heart failure, exercise is certainly an
excellent treatment,” said Dr. James A. Blumenthal, a professor of medical psychology at
Duke University Medical Center and the lead author of the study, which was published in
the Journal of the American Medical Association. “It’s something that most patients can
engage in. It results in improved cardiorespiratory fitness, they have more stamina, and
now we see that not only do they derive these physical benefits, but they also derive
psychological benefits as well.”
An estimated five million Americans are living with heart failure, with more than
half a million new cases diagnosed each year. Patients often experience a drastic decline
in their physical abilities, and with it a blow to their mental health. Up to 75 percent of
patients develop some symptoms of depression, with about 40 percent suffering from
full-blown clinical depression, which can worsen their overall prognosis.
Building on a growing body of research suggesting that aerobic exercise can elevate
mood surprisingly well in people who have depression, Dr. Blumenthal and his
colleagues set out to determine whether regular activity might have similar benefits in
depressed heart failure patients. They began by assessing their subjects, whose average
age was about 60, with a standard questionnaire called the Beck Depression Inventory II
that rates depressive symptoms on a scale from 0 to 59. Higher scores indicate greater
severity of depression, with a score of 14 or more generally considered to represent
clinically significant depression.
At the beginning of the study, the median score of the participants was about 8,
though about a third had a score of 14 or more.
The researchers then randomly assigned patients to one of two groups. Those in the
first group completed three supervised exercise sessions a week for three months,
typically at a cardiac rehab center, followed by 120 minutes a week of home exercise for
another nine months. The patients primarily used treadmills and stationary bikes.
Those in the second group, meanwhile, received what the researchers called “usual
care.” They did not receive any formal exercise instructions, only traditional
recommendations to get about 30 minutes of activity most days of the week, in line with
American Heart Association guidelines. Like those in the exercise group, they were also
given detailed educational materials with information on things like medication and
sodium intake.
As the researchers checked in at regular intervals, they found that the depression
scores in the exercise group were consistently lower than in the control group — by about
a point, which was a modest reduction. Patients who reported greater adherence to the
exercise program had the most significant reductions in depressive symptoms.
For those who made up the subset of patients with the most severe symptoms — a
depression score of 14 or greater — the difference between the exercise group and the
control group was greater, with a reduction of about two points. Dr. Blumenthal said this
magnitude of difference was similar to what has been shown in studies that have
compared antidepressant use with placebo.
At the start of the study, one of the questions for the research team was whether
heart failure patients could even exercise without hazard, which is why the first three
months of exercise were supervised.
“I think historically, physicians have been very cautious about recommending
exercise for these patients because it wasn’t clear that it was safe or that they would even
derive the same benefits that other people derive,” said Dr. Blumenthal.
But it’s now clear that they do benefit in terms of aerobic capacity, he said, and that
a moderate exercise program can be safe.
As for why exercise would provide psychological benefits, Dr. Blumenthal said he
could only speculate.
“When you have a debilitating condition like this, there’s a tendency to feel you
don’t have a lot of control over your health,” he said. “But I think for a lot of patients in
this study, they felt like they were doing something positive for themselves, and they had
an enhanced sense of self confidence. They could do more, they increased their strength
and stamina, and I think that really served to improve their moods.”
Changing Our Tune on ExerciseBy JANE E. BRODY
August 27, 2012
What would it take to persuade you to exercise?
A desire to lose weight or improve your figure? To keep heart disease, cancer or
diabetes at bay? To lower your blood pressure or cholesterol? To protect your bones? To
live to a healthy old age?
You’d think any of those reasons would be sufficient to get Americans exercising,
but scores of studies have shown otherwise. It seems that public health experts, doctors
and exercise devotees in the media — like me — have been using ineffective tactics to
entice sedentary people to become, and remain, physically active.
For decades, people have been bombarded with messages that regular exercise is
necessary to lose weight, prevent serious disease and foster healthy aging. And yes, most
people say they value these goals. Yet a vast majority of Americans — two-thirds of
whom are overweight or obese — have thus far failed to swallow the “exercise pill.”
Now research by psychologists strongly suggests it’s time to stop thinking of future
health, weight loss and body image as motivators for exercise. Instead, these experts
recommend a strategy marketers use to sell products: portray physical activity as a way to
enhance current well-being and happiness.
“We need to make exercise relevant to people’s daily lives,” Michelle L. Segar, a
research investigator at the Institute for Research on Women and Gender at the University
of Michigan, said in an interview. “Everyone’s schedule is packed with nonstop to-do’s.
We can only fit in what’s essential.”
Dr. Segar is among the experts who believe that people will not commit to exercise
if they see its benefits as distant or theoretical.
“It has to be portrayed as a compelling behavior that can benefit us today,” she said.
“People who say they exercise for its benefits to quality of life exercise more over the
course of a year than those who say they value exercise for its health benefits.”
Her idea for a public service advertisement to promote exercise for working women
with families: A woman is shown walking around the block after dinner with her children
and says, “This is great. I can fit in fitness, spend quality time with my kids, and at the
same time teach them how important exercise is.”
Based on studies of what motivates people to adopt and sustain physical activity, Dr.
Segar is urging that experts stop framing moderate exercise as a medical prescription that
requires 150 minutes of aerobic effort each week. Instead, public health officials must
begin to address “the emotional hooks that make it essential for people to fit it into their
hectic lives.”
“Immediate rewards are more motivating than distant ones,” she added. “Feeling
happy and less stressed is more motivating than not getting heart disease or cancer,
maybe, someday in the future.”
In a study of 252 office workers, David K. Ingledew and David Markland,
psychologists at the University of Wales, found that while many began to exercise as way
to lose weight and improve their appearance, these motivations did not keep them
exercising in the long term. “The well-being and enjoyment benefits of exercise should be
emphasized,” the researchers concluded.
Dr. Segar put it this way: “Physical activity is an elixir of life, but we’re not
teaching people that. We’re telling them it’s a pill to take or a punishment for bad
numbers on the scale. Sustaining physical activity is a motivational and emotional issue,
not a medical one.”
Other studies have shown that what gets people off their duffs and keeps them
moving depends on age, gender, life circumstances and even ethnicity. For those of
college age, for example, physical attractiveness typically heads the list of reasons to
begin exercising, although what keeps them going seems to be the stress relief that a
regular exercise program provides.
The elderly, on the other hand, may get started because of health concerns. But often
what keeps them exercising are the friendships, sense of community and camaraderie that
may otherwise be missing from their lives — easily seen among the gray-haired women
who faithfully attend water exercise classes at my local YMCA.
In a recent study of 1,690 overweight or obese middle-aged men and women, Dr.
Segar found that enhancing daily well-being was the most influential factor for the
women in the study. Men indicated they were motivated by more distant health benefits,
although Dr. Segar suspects this may be because men feel less comfortable discussing
their mental health needs.
“What sustains us, we sustain,” Dr. Segar said. “We need to promote what
marketers call ‘customer loyalty.’ We need to help people stay engaged with movement
by teaching them how it can help sustain them in their lives.”
Many, if not most, people start exercising because they want to lose weight. But
very often they abandon exercise when the expected pounds fail to fall off. Study after
study has found that, without major changes in eating habits, increasing physical activity
is only somewhat effective for losing weight, though it helps people maintain weight loss
and shedding even a few pounds, especially around one’s middle, can improve health.
For example, researchers in Brisbane, Australia, and in Leeds, England, studied 58
sedentary overweight or obese men and women who participated in a closely monitored
12-week aerobic exercise program. Weight loss was minimal, but nonetheless the
participants’ waistlines shrunk, their blood pressure and resting heart rate dropped, and
their aerobic capacity and mood improved.
“Exercise should be encouraged and the emphasis on weight loss reduced,” the
researchers concluded. “Disappointment and low self-esteem associated with poor weight
loss could lead to low exercise adherence and a general perception that exercise is futile
and not beneficial.”
I walk three miles daily, or bike ten miles and swim three-quarters of a mile. If you
ask me why, weight control may be my first answer, followed by a desire to live long and
well. But that’s not what gets me out of bed before dawn to join friends on a morning
walk and then bike to the Y for my swim.
It’s how these activities make me feel: more energized, less stressed, more
productive, more engaged and, yes, happier — better able to smell the roses and cope
with the inevitable frustrations of daily life.
How Testosterone May Alter the BrainAfter ExerciseBy GRETCHEN REYNOLDS
September 12, 2012
It’s widely accepted among scientists that regular exercise transforms the brain,
improving the ability to remember and think. And a growing and very appealing body of
science has established that exercise spurs the creation of new brain cells, a process
known as neurogenesis. But just how jogging or other workouts affect the structure of the
brain has remained enigmatic, with many steps in the process unexplained.
A new study published last month in Proceedings of the National Academy of
Sciences may fill in one piece of the puzzle, by showing that male sex hormones surge in
the brain after exercise and could be helping to remodel the mind. The research was
conducted on young, healthy and exclusively male rats — but scientists believe it applies
to female rats, too, as well as other mammals, including humans.
The decision to use only males was carefully considered. “We’ve known for a while
that estrogen,” the female sex hormone, “is produced in the brain” not just of female
animals but also, to some degree, in males, says Bruce S. McEwen, the director of the
Laboratory of Neuroendocrinology at Rockefeller University in New York and an author
of the study, which also involved scientists from the University of Tsukuba in Japan and
other institutions. Estrogen has been well studied and has many effects, he said,
including, scientists suspect, new brain cell growth.
But far less has been known about the role of male sex hormones in mammalian
brains, particularly after exercise.
While both sexes produce male sex hormones, males produce far more of it —
mostly in the gonads but, the researchers suspected, also in the brain.
The only way to know for sure if the hormones were being synthesized in the brain
would be to shut off production in the testes, to guarantee that hormones from that site
wouldn’t migrate to the brain. So some of the rats in the experiment were surgically
castrated. The rest underwent a sham operation, in which nothing was removed. That
procedure ensures that stress from the operation won’t skew results; all animals will have
had the same unpleasant experience.
Separately, some of the animals also were injected with a drug that blocks the ability
of male sex hormones to bind to receptors in the brain. Those animals might be able to
produce the hormones, but they wouldn’t have any effects on the brain.
After recovery, most of the rats ran for two weeks on treadmills set at a leisurely
jogging pace. Some remained sedentary.
Then the scientists examined all of the animals’ brains. They found that, compared
with the sedentary animals, the running rats had significantly more of a potent
testosterone derivative called dihydrotestosterone, or DHT, in their brains. Even the
brains of rats that had been castrated sloshed with DHT.
So the exercise had prompted increased production of the hormone.
Most of the animals also had a plethora of new neurons in the hippocampus, a
portion of the brain associated with learning and memory. Unexpectedly, however, the
animals in this experiment that could not use the DHT in their brains did not experience
enhanced neurogenesis. They exercised just as the other animals did, but their brains did
not benefit in the same way.
This tells us that the uptake of DHT in the brain after exercise “appears to be a
necessary step in achieving adult hippocampal neurogenesis,” Dr. McEwen says.
In essence, exercise prompts the production of more DHT. And more DHT helps to
create more new brain cells.
But while those findings may be salutary for men who are active and fit, or planning
to become so, they seem potentially troubling for those of us without testes. If DHT is
necessary for neurogenesis after exercise and women produce far less of it than men, do
women gain less brain benefit from exercise than men?
“It’s unlikely,” Dr. McEwen says. One reason that early experiments into exercise
and neurogenesis tended to be performed in female rats was that “in rats, females exercise
more than the males,” he said. “They’ll run for hours and keep running, even when
they’re old.” Elderly males, in contrast, willingly quit working out. In those experiments,
neurogenesis was plentiful in the female brains.
“It’s very probable that estrogen plays a role” like that of DHT in the female brain
after exercise, Dr. McEwen says. Meanwhile, female brains also produce varying
amounts of male hormones. So there may be some as-yet-undiscovered interactions
between the male and female hormones in the brain that mesh after jogging to increase
brain cell numbers and improve the ability to think.
But for the moment, the full effects of exercise and sex hormones on the brain are
still being teased out.
But one aspect of the new experiment is already resoundingly clear and reassuring,
Dr. McEwen points out. “The exercise in this experiment was quite mild,” he says — the
equivalent of jogging at a pace at which someone could speak (or squeak) to a
companion. “That’s achievable for most people,” he concludes, “and the evidence
suggests that it will improve brain health.”
How Exercise Can Help You MasterNew SkillsBy GRETCHEN REYNOLDS
September 26, 2012
Can you improve your body’s ability to remember by making it move? That rather odd-
seeming question stimulated researchers at the University of Copenhagen to undertake a
reverberant new examination of just how the body creates specific muscle memories and
what role, if any, exercise plays in the process.
To do so, they first asked a group of young, healthy right-handed men to master a
complicated tracking skill on a computer. Sitting before the screen with their right arm on
an armrest and a controller similar to a joystick in their right hand, the men watched a red
line squiggle across the screen and had to use the controller to trace the same line with a
white cursor. Their aim was to remain as close to the red squiggle as possible, a task that
required input from both the muscles and the mind.
The men repeated the task multiple times, until the motion necessary to track the red
line became ingrained, almost automatic. They were creating a short-term muscle
memory.
The term “muscle memory” is, of course, something of a misnomer. Muscles don’t
make or store memories. They respond to signals from the brain, where the actual
memories of any particular movement are formed and filed away.
But muscle memory — or “motor memory,” as it is more correctly referred to
among scientists — exists and can be quite potent. Learn to ride a bicycle as a youngster,
abandon the pastime and, 20 years later, you’ll be able to hop on a bicycle and pedal off.
To date, most studies of the effect of exercise on memory have looked at more
intellectual tasks, like memorizing lists of words. In those cases, regular exercise appears
to improve the brain’s general ability to remember.
But the Copenhagen scientists wanted to see how exercise influences the
development and consolidation of physical memories. So before having their volunteers
master the squiggle test, they first had a third of the group ride a bicycle at an intense but
not exhausting pace for 15 minutes. The other two-thirds of the group rested quietly
during this time.
Then, after the computer motor-skill testing, a third of those who’d previously rested
completed the same strenuous 15-minute bike ride. The others rested.
All of the volunteers then repeated the follow-that-squiggle test after an hour, a day
and a week, to see how well they’d learned and remembered that particular skill.
Their scores for speed and accuracy of squiggle shadowing were almost identical at
the one-hour point, although the group that had ridden the bicycle after the first computer
practice session was a bit less accurate.
After a week, though, things looked different. The men who had exercised just after
first learning the motor skill were noticeably better at remembering the task, with their
tracing of the red line on the computer more agile and accurate. The men who’d exercised
before learning the new skill were not quite as adept now, although they were better than
those in the group that hadn’t exercised at all.
What this result suggests, says Marc Roig, a postdoctoral researcher at the
University of Copenhagen who led the study with his colleague Kasper Skriver, is that
physical exercise may help the brain to consolidate and store physical or motor memories.
Consolidating a memory is not instantaneous, after all, or even inevitable. Every
memory must be encoded and moved from short-term to long-term storage. Some of
those memories are, for whatever reason, more vividly imprinted than others.
It may be that physical, aerobic exercise performed right after a memory has been
formed intensifies the imprinting, Dr. Roig says. It makes the memory stronger.
In the short term, though, exercise may leave the brain overstimulated, he continues,
making it less able to pinpoint and access new memories. That may be why men who had
exercised after learning the new skill performed worst during the first motor-memory
recall test.
But they performed better in the long term, because their memory of the new skill
was, it would seem, sturdier.
How a single workout can strengthen a particular memory is uncertain, Dr. Roig
acknowledges, but he suspects biochemistry. “There is evidence that aerobic exercise
produces substances” in the brain, like brain-derived neurotropic factor and
noradrenaline, that drive memory consolidation and learning, he says.
Ultimately, how exercise operates in this context may be less significant for most of
us than when. The “timing of the exercise is critical,” Dr. Roig says. To be maximally
effective, it needs to be performed “right after exposure to the information to be
remembered.”
Want to remember how to ride that bike, in other words? Then ride it as soon as you
have managed to stop wobbling. The exercise seems able then to cement the memory of
how to ride. Ditto if you’ve just perfected the snap of your tennis serve or the spin on
your soccer kick. Go for a run immediately afterward, and your body may later better
remember.
Whether that same run will strengthen the creation and storage of more intellectual
memories remains to be seen, although Dr. Roig is optimistic. He and his colleagues are
working with schoolchildren in Copenhagen to determine whether having the youngsters
run about or otherwise exercise immediately after being taught a new concept improves
their later test scores in that subject. Early results are promising, and could make the
mastering of algebra almost invigorating.
Exercise May Protect Against BrainShrinkageBy ANAHAD O’CONNOR
October 26, 2012
Remaining physically active as you age, a new study shows, may help protect parts of
your brain from shrinking, a process that has been linked to declines in thinking and
memory skills. Physical exercise not only protected against such age-related brain
changes, but also had more of an effect than mentally and socially stimulating activities.
In the new report, published in the journal Neurology, a team at the University of
Edinburgh followed more than 600 people, starting at age 70. The subjects provided
details on their daily physical, mental and social activities.
Three years later, using imaging scans, the scientists found that the subjects who
engaged in the most physical exercise, including walking several times a week, had less
shrinkage and damage in the brain’s white matter, which is considered the “wiring” of the
brain’s communication system. The relationship remained even after the researchers
controlled for things like age, health status, social class and I.Q.
As far as mental exercise, “we can only say we found no benefit in our sample,” said
Dr. Alan J. Gow, an author of the study and a senior research fellow at Edinburgh. He
added: “There might be associations earlier in the life course. Such activities also have
important associations with well-being and quality of life, so we would certainly agree it
is important for older adults to continue to pursue them.”
Because the findings showed only an association, not a causal relationship, the
authors could not rule out the possibility that people with less deterioration in their brains
were simply more likely to be physically active. But they said that based on their
findings, they would advise that people take up physical exercise “whatever their age.”
Can Exercise Protect the Brain FromFatty Foods?By GRETCHEN REYNOLDS
November 7, 2012
In recent years, some research has suggested that a high-fat diet may be bad for the brain,
at least in lab animals. Can exercise protect against such damage? That question may
have particular relevance now, with the butter-and cream-laden holidays fast
approaching. And it has prompted several new and important studies.
The most captivating of these, presented last month at the annual meeting of the
Society for Neuroscience in New Orleans, began with scientists at the University of
Minnesota teaching a group of rats to scamper from one chamber to another when they
heard a musical tone, an accepted measure of the animals’ ability to learn and remember.
For the next four months, half of the rats ate normal chow. The others happily
consumed a much greasier diet, consisting of at least 40 percent fat. Total calories were
the same in both diets.
After four months, the animals repeated the memory test. Those on a normal diet
performed about the same as they had before; their cognitive ability was the same. The
high-fat eaters, though, did much worse.
Then, half of the animals in each group were given access to running wheels. Their
diets didn’t change. So, some of the rats on the high-fat diet were now exercising. Some
were not. Ditto for the animals eating the normal diet.
For the next seven weeks, the memory test was repeated weekly in all of the groups.
During that time, the performance of the rats eating a high-fat diet continued to decline so
long as they didn’t exercise.
But those animals that were running, even if they were eating lots of fat, showed
notable improvements in their ability to think and remember.
After seven weeks, the animals on the high-fat diet that exercised were scoring as
well on the memory test as they had at the start of the experiment.
Exercise, in other words, had “reversed the high-fat diet-induced cognitive decline,”
the study’s authors concluded.
That finding echoes those of another study presented last month at the Society for
Neuroscience meeting. In it, researchers at Kyoto University in Japan gathered a group of
mice bred to have a predisposition to developing a rodent version of Alzheimer’s disease
and its profound memory loss.
Earlier studies by the same scientists had shown that a high-fat diet exacerbated the
animals’ progression to full-blown dementia, and that both a low-fat diet and exercise
slowed the animals’ mental decline.
But it hadn’t been clear in these earlier experiments which was more effective at
halting the loss of memory, a leaner diet or regular rodent workouts.
So the scientists set out now to tease out the effects of each intervention by first
feeding all of their mice a high-fat diet for 10 weeks, then switching some of them to low-
fat kibble, while moving others to cages equipped with running wheels.
A third group began both a low-fat diet and an exercise routine, while the remainder
of the mice continued to eat the high-fat diet and didn’t exercise.
After an additional 10 weeks, this last group, the animals that ate lots of fat and
lounged around their cages, had developed far more deposits of the particular brain
plaques associated with Alzheimer’s disease than the other mice. They also performed
much more poorly on memory tests.
The mice that had been switched to a low-fat diet had fewer plaques and better
memories than the control group.
But the mice that were exercising had even healthier brains and better memory
scores than the low-fat group — even if they had remained on a high-fat diet. In other
words, exercise was “more effective than diet control in preventing high-fat diet-induced
Alzheimer’s disease development,” the authors write.
Just why high-fat diets might affect the brain and how exercise undoes the damage
is not yet clear. “Our research suggests that free fatty acids” from high-fat foods may
actually infiltrate the brain, says Vijayakumar Mavanji, a research scientist at the
Minnesota VA Medical Center at the University of Minnesota, who, with his colleagues
Catherine M. Kotz, Dr. Charles J. Billington, and Dr. Chuan Feng Wang, conducted the
rat study. The fatty acids may then jump-start a process that leads to cellular damage in
portions of the brain that control memory and learning, he says.
Exercise, on the other hand, seems to stimulate the production of specific
biochemical substances in the brain that fight that process, he says.
In the Japanese study, for instance, the brains of the exercised animals teemed with
high levels of an enzyme that is known to degrade the plaques associated with
Alzheimer’s disease.
Of course, lab animals are not people, Dr. Mavanji cautions, and it’s not known if
exercise might protect our brains in the same manner as it does in mice and rats.
Still, he says, there’s enough accumulating evidence about the potential cognitive
risks of high-fat foods and the countervailing benefits from physical activity to
recommend that “people exercise moderately,” he says, particularly during periods of
repeated exposure to alluring, fatty holiday buffets.
The amount of exercise required to potentially protect our brains from the possible
depredations of marbled beef and cheesecake isn’t excessive, after all, he continues. His
rats were running for the human equivalent of about a daily 30-minute jog. So if you
can’t walk away from the buffet table, be sure to at least take a walk afterward.
Exercise and the Ever-Smarter HumanBrainBy GRETCHEN REYNOLDS
December 26, 2012
Anyone whose resolve to exercise in 2013 is a bit shaky might want to consider an
emerging scientific view of human evolution. It suggests that we are clever today in part
because a million years ago, we could outrun and outwalk most other mammals over long
distances. Our brains were shaped and sharpened by movement, the idea goes, and we
continue to require regular physical activity in order for our brains to function optimally.
The role of physical endurance in shaping humankind has intrigued anthropologists
and gripped the popular imagination for some time. In 2004, the evolutionary biologists
Daniel E. Lieberman of Harvard and Dennis M. Bramble of the University of Utah
published a seminal article in the journal Nature titled “Endurance Running and the
Evolution of Homo,” in which they posited that our bipedal ancestors survived by
becoming endurance athletes, able to bring down swifter prey through sheer doggedness,
jogging and plodding along behind them until the animals dropped.
Endurance produced meals, which provided energy for mating, which meant that
adept early joggers passed along their genes. In this way, natural selection drove early
humans to become even more athletic, Dr. Lieberman and other scientists have written,
their bodies developing longer legs, shorter toes, less hair and complicated inner-ear
mechanisms to maintain balance and stability during upright ambulation. Movement
shaped the human body.
But simultaneously, in a development that until recently many scientists viewed as
unrelated, humans were becoming smarter. Their brains were increasing rapidly in size.
Today, humans have a brain that is about three times the size that would be
expected, anthropologists say, given our species’ body size in comparison with that of
other mammals.
To explain those outsized brains, evolutionary scientists have pointed to such
occurrences as meat eating and, perhaps most determinatively, our early ancestors’ need
for social interaction. Early humans had to plan and execute hunts as a group, which
required complicated thinking patterns and, it’s been thought, rewarded the social and
brainy with evolutionary success. According to that hypothesis, the evolution of the brain
was driven by the need to think.
But now some scientists are suggesting that physical activity also played a critical
role in making our brains larger.
To reach that conclusion, anthropologists began by looking at existing data about
brain size and endurance capacity in a variety of mammals, including dogs, guinea pigs,
foxes, mice, wolves, rats, civet cats, antelope, mongooses, goats, sheep and elands. They
found a notable pattern. Species like dogs and rats that had a high innate endurance
capacity, which presumably had evolved over millenniums, also had large brain volumes
relative to their body size.
The researchers also looked at recent experiments in which mice and rats were
systematically bred to be marathon runners. Lab animals that willingly put in the most
miles on running wheels were interbred, resulting in the creation of a line of lab animals
that excelled at running.
Interestingly, after multiple generations, these animals began to develop innately
high levels of substances that promote tissue growth and health, including a protein called
brain-derived neurotrophic factor, or BDNF. These substances are important for
endurance performance. They also are known to drive brain growth.
What all of this means, says David A. Raichlen, an anthropologist at the University
of Arizona and an author of a new article about the evolution of human brains appearing
in the January issue of Proceedings of the Royal Society B, is that physical activity may
have helped to make early humans smarter.
“We think that what happened” in our early hunter-gatherer ancestors, he says, is
that the more athletic and active survived and, as with the lab mice, passed along
physiological characteristics that improved their endurance, including elevated levels of
BDNF. Eventually, these early athletes had enough BDNF coursing through their bodies
that some could migrate from the muscles to the brain, where it nudged the growth of
brain tissue.
Those particular early humans then applied their growing ability to think and reason
toward better tracking prey, becoming the best-fed and most successful from an
evolutionary standpoint. Being in motion made them smarter, and being smarter now
allowed them to move more efficiently.
And out of all of this came, eventually, an ability to understand higher math and
invent iPads. But that was some time later.
The broad point of this new notion is that if physical activity helped to mold the
structure of our brains, then it most likely remains essential to brain health today, says
John D. Polk, an associate professor of anthropology at the University of Illinois at
Urbana-Champaign, and co-author, with Dr. Raichlen, of the new article.
And there is scientific support for that idea. Recent studies have shown, he says, that
“regular exercise, even walking,” leads to more robust mental abilities, “beginning in
childhood and continuing into old age.”
Of course, the hypothesis that jogging after prey helped to drive human brain
evolution is just a hypothesis, Dr. Raichlen says, and almost unprovable.
But it is compelling, says Harvard’s Dr. Lieberman, who has worked with the
authors of the new article. “I fundamentally agree that there is a deep evolutionary basis
for the relationship between a healthy body and a healthy mind,” he says, a relationship
that makes the term “jogging your memory” more literal than most of us might have
expected and provides a powerful incentive to be active in 2013.
Do the Brain Benefits of Exercise Last?By GRETCHEN REYNOLDS
January 9, 2013
It is well established that exercise bolsters the structure and function of the brain.
Multiple animal and human studies have shown that a few months of moderate exercise
can create new neurons, lift mood and hone memory and thinking.
But few studies have gone on to examine what happens next. Are these desirable
brain changes permanent? Or, if someone begins exercising but then stops, does the brain
revert to its former state, much like unused muscles slacken?
The question may be particularly relevant at this time of year, when so many people
start new exercise programs. Helpfully, two recent animal studies that were presented at
the 2012 annual meeting of the Society for Neuroscience in New Orleans have taken on
the issue and may have relevance for people, though the results are disquieting.
Of the two experiments, the more dramatic looked at what happens to the brain’s
memory center when exercise is stopped.
Researchers from the University of Sao Paulo in Brazil began by allowing half of a
group of healthy, adult rats to run at will on running wheels. Rats enjoy that activity and,
for a week, they enthusiastically skittered on their wheels. The animals were also injected
with a substance that marks newborn neurons in the hippocampus, or memory center of
the brain, so that the scientists would be able to track how many cells had been created.
Inactive animals, including people, create new brain cells, but exercise is known to spark
the creation of two or three times as many new hippocampal neurons.
A separate control group was housed in cages with locked wheels, so that they
remained sedentary. They were also monitored for new brain cell growth.
After a week, the runners’ wheels were locked and they, too, became inactive.
A week later, some of the exercised and control rats completed memory testing that
required them to find, then remember, the location of a platform placed along the wall of
a small swimming pool. (Rats aren’t fond of being in the water, and the platform allowed
them to clamber out.) Those with better memories remembered and paddled to the
platform more quickly.
The remaining animals completed the same memory test after either three weeks or
six weeks of inactivity.
Afterward, the researchers compared the animals’ performance on the memory test,
as well as the number of new brain cells in the hippocampus of each group of rats.
They found that, after only a week of inactivity, the rats that had run were much
faster on the water maze test than the control animals. They also had at least twice as
many newborn neurons in the hippocampus.
But those advantages faded after several more weeks of not running. The brains of
the animals that had been inactive for three weeks contained far fewer newborn neurons
than the brains of the animals that had rested for only one week. The brains of the animals
that had been inactive for six weeks had fewer still.
The animals inactive for three or six weeks also performed far worse on the water
maze test than the animals that had been inactive for only a single week. In fact, their
memories were about as porous of those of the control animals, “indicating,” the authors
write, “that the exercise-induced benefits may be transient.”
The other new study of exercise-induced brain changes found that they were
similarly fragile, although this study explored the impacts of exercise on mood.
In earlier experiments by the same group of scientists, from McMaster University in
Hamilton, Ontario, rats given access to a running wheel, toys and other types of
environmental enrichment were able to use serotonin, a neurotransmitter involved in
anxiety and other moods, more efficiently. After several months of exercise, the exercised
animals became noticeably less anxious and more resilient to stress during behavioral
testing. But that savoir-faire dissipated rapidly if they were removed from the cages with
running wheels and toys.
In their latest experiment, also presented at the Society for Neuroscience meeting,
the researchers reported that after 10 weeks of running, followed by three weeks of
inactivity, the running rats’ brains were almost indistinguishable from those of animals
that had never exercised. They had almost comparable levels of an enzyme in the brain
that affects the synthesis and uptake of serotonin. It was as if they had never run.
In other words, the brain benefits “wear off quickly,” said Dr. Michael Mazurek, a
professor of neurology at McMaster, who oversaw the study. “This is analogous to what
happens to muscle bulk or heart rate following exercise withdrawal.”
Gilberto Xavier, a professor of psychology at the University of Sao Paulo and senior
author of the study of hippocampal neurons, agrees. “Brain changes are not maintained
when regular physical exercise is interrupted,” he said, adding that, “though our
observations are restricted to rats, indirect evidence suggests that the same phenomenon
occurs in human beings.”
Meaning that the lessons of both studies point in the same direction. For the ongoing
health of our minds, as well as for the plentiful other health benefits of exercise, it might
be wise to stick to those New Year’s exercise resolutions.
How Exercise May Keep Alzheimer's atBayBy GRETCHEN REYNOLDS
January 18, 2012
Alzheimer’s disease, with its inexorable loss of memory and self, understandably alarms
most of us. This is especially so since, at the moment, there are no cures for the condition
and few promising drug treatments. But a cautiously encouraging new study from The
Archives of Neurology suggests that for some people, a daily walk or jog could alter the
risk of developing Alzheimer’s or change the course of the disease if it begins.
For the experiment, researchers at Washington University in St. Louis recruited 201
adults, ages 45 to 88, who were part of a continuing study at the university’s Knight
Alzheimer’s Disease Research Center. Some of the participants had a family history of
Alzheimer’s, but none, as the study began, showed clinical symptoms of the disease.
They performed well on tests of memory and thinking. “They were, as far as we could
determine, cognitively normal,” says Denise Head, an associate professor of psychology
at Washington University who led the study.
The volunteers had not had their brains scanned, however, so the Washington
University scientists began their experiment by using positron emission tomography, an
advanced scanning technique, to look inside the volunteers’ brains for signs of amyloid
plaques, the deposits that are a hallmark of Alzheimer’s. People with a lot of plaque tend
to have more memory loss, though the relation is complex.
Next they genetically typed their volunteers for APOE, a gene involved in
cholesterol metabolism. Everyone carries the APOE gene, but scientists have determined
that those who have a particular variation of the gene known as e4 are at 15 times the risk
of developing Alzheimer’s compared with those who do not carry the variant. The report
also noted that carriers tend to show symptoms of dementia at a younger age, beginning
in their late 60s, on average, instead of in their early 80s for people without the variant.
Fifty-six of the volunteers, of various ages and both sexes, turned out to be positive
for APOE-e4. (A family history of Alzheimer’s may suggest that someone is a carrier for
the e4 variant, Dr. Head says, but it also may not; there are probably many other, still-
unknown genetic causes of the disease, she says.)
Finally, the scientists asked the volunteers to fill out detailed questionnaires about
their exercise habits during the past 10 years. Recently, many studies have looked at
whether being active can lessen someone’s risk for Alzheimer’s, but the results have been
inconsistent, with some studies, in both animals and people, suggesting that regular
exercise has a protective effect and others finding little discernible benefit.
One reason for the inconsistency, Dr. Head suspected, might be that many earlier
studies did not differentiate between people with the e4 variant and those without, and
each group, at least potentially, could respond differently to exercise.
And that certainly proved to be the case in this study. For the group as a whole,
exercise provided marginal benefits. The volunteers who reported walking or jogging
often — meeting (or, in rare instances, exceeding) the American Heart Association’s
exercise recommendation of 30 minutes of moderate or vigorous activity five times a
week — had fewer amyloid plaques than the volunteers who reported almost never
exercising. But the preventive value of the exercise was small, barely reaching the level
of statistical significance.
That situation changed, however, when the scientists examined the results for people
with the e4 gene variant. Most of those who carried the APOE-e4 gene displayed much
larger accumulations of amyloid plaques than those without it.
Unless they exercised. The carriers of the gene who reported walking or jogging for
at least 30 minutes five times a week had plaque accumulation similar to that of
volunteers who were e4-negative. In essence, the APOE-e4 gene carriers mitigated their
inherited risk for developing Alzheimer’s by working out. Or, as the study authors wrote,
a “physically active lifestyle may allow e4 carriers to experience brain amyloid levels
equivalent to e4-negative individuals.”
“The good news is that we found that activity levels, which are potentially
modifiable, could have an impact” on plaque accumulation — and presumably on the
course of Alzheimer’s — in people with a genetic predisposition to the condition, Dr.
Head says.
But the findings came with a downside, too. An overwhelming majority of the
people in the study were sedentary, and for them, an inactive lifestyle seemed to be
accelerating the accumulation of amyloid plaques. Those with the e4 variant who rarely
or never exercised had the most plaques, putting them at heightened risk for the memory
loss of Alzheimer’s in the years to come.
At the moment, it’s not known whether beginning to exercise after plaques have
started to build up might alter that outcome, Dr. Head says. But, she continues,
experiments in mice bred to develop memory loss “have shown that elderly animals that
began a running program benefited.” They experienced less dementia than mice that
didn’t run.
Still, countless questions remain about the interactions of exercise, genetics and
Alzheimer’s, including why the protective benefits of exercise in this study seemed
substantial only for those with the gene variant. “It is looking as if there is some still-
unexplained biochemical interplay between being e4-positive and inactive,” Dr. Head
says, “which heightens risk” for the disease.
“But that doesn’t mean that everyone shouldn’t exercise,” she continues, regardless
of whether they suspect they have a genetic risk for dementia. “There are so many
benefits to exercise,” she says, “and one may be that it helps the brain” to defend itself
against the slow leaking away of memory.
Fitness May Lower Dementia RiskBy NICHOLAS BAKALAR
February 11, 2013
Being physically fit in midlife is associated with a lower risk of dementia in old age, a
new study reports.
Between 1971 and 2009, 19,458 healthy adults younger than age 65 took a treadmill
fitness test as part of a broader health examination. Researchers followed the subjects
through their Medicare records for an average of 24 years.
After adjusting for age, smoking, diabetes, cholesterol and other health factors, the
researchers found that compared with those in the lowest 20 percent for fitness in midlife,
those in the highest 20 percent had a 36 percent reduced risk of dementia.
The reason for the association is unclear, but it was independent of cardiovascular
and cerebrovascular risk factors for dementia, suggesting that both vascular and
nonvascular mechanisms may be involved.
“Dementia is a disease with no cure and no good therapies,” said the lead author, Dr.
Laura F. DeFina, the interim chief scientific officer at the Cooper Institute in Dallas.
Physical activity may be “a preventive way to address dementia instead of addressing the
costs of a disabled elder.”
The study population was largely white and highly educated, and the researchers
acknowledge that their findings, published last week in The Annals of Internal Medicine,
cannot be generalized to other populations. They emphasize that the study is
observational and does not prove causation.
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