The Science of Health by Christine Gorman
Christine Gorman is an award-winning
The Heart-Brain Connection
Could exercising regularly and not smoking help to delay dementia?
When the National Institutes of Health convened a panel of
independent experts this past April on how to prevent Alzhei­
mer’s disease, the conclusions were pretty grim. The panel de­
termined that “no evidence of even moderate scientific quality”
links anything—from herbal or nutritional supplements to pre­
scription medications to social, economic or environmental con­
ditions—with the slightest decrease in the risk of developing
Alzheimer’s. Furthermore, the committee argued, there is little
credible evidence that you can do anything to delay the kinds of
memory problems that are often associated with aging. The re­
searchers’ conclusions made headlines around the world and
struck a blow at the many purveyors of “brain boosters,” “mem­
ory enhancers” and “cognitive-training software” that advertise
their wares on the Web and on television. One of the panel ex­
36  Scientific American, December 2010
sad1210Heal3p.indd 36
science journalist who has covered health
and medical topics for more than 20 years.
perts later told reporters in a conference call that
the group wanted to “dissuade folks from spend­
ing extraordinary amounts of money on stuff
that doesn’t work.”
But did the panel overstate its case? Some mem­
ory and cognition researchers privately grumbled
that the conclusions were too negative—particu­
larly with respect to the potential benefits of not
smoking, treating high blood pressure and engag­
ing in physical activity. In late September the Brit-
ish Journal of Sports Medicine published a few of
these criticisms. As a longtime science journalist,
I suspected that this is the kind of instructive con­
troversy—with top-level people taking opposing
positions—that often occurs at the leading edge
of research. As I spoke with various researchers,
I realized that the disagreements signaled newly
emerging views of how the brain ages. Investiga­
tors are exploring whether they need to look be­
yond the brain to the heart to understand what
happens to nerve cells over the course of decades.
In the process, they are uncovering new roles for
the cardiovascular system, including ones that go
beyond supplying the brain with plenty of oxygen-
rich blood. The findings could suggest useful ave­
nues for delaying dementia or less severe memory
problems.
Dementia, of course, is a complex biological
phenomenon. Although Alzheimer’s is the most
common cause of dementia in older adults, it is
not the only cause. Other conditions can contrib­
ute to dementia as well, says Eric B. Larson, exec­
utive director of the Group Health Research Insti­
tute in Seattle. For example, physicians have long
known that suffering a stroke, in which blood flow to the brain
has been interrupted by a clot or a hemorrhage, can lead to de­
mentia. But research over the past few years has documented
the importance of very tiny strokes—strokes so small they can
be detected only under a microscope after death—as another
possible cause for dementia. Studies at autopsy of people who
had dementia have detected many of these so-called microvascu­
lar infarcts either by themselves or along with the plaques and
tangles more typical of Alzheimer’s in the brains of people with
dementia. These findings suggest that most dementias, even those
caused by Alzheimer’s, are triggered by multiple pathological pro­
cesses and will require more than one treatment.
Proving that cardiovascular treatment is one of those ap­
proaches will take some doing. Just because microinfarcts may
Illustration by Ross MacDonald
10/14/10 5:50:51 PM
 The Science of Health
Memory hole: Researchers at Johns Hopkins estimate that by
2050 more than 106 million people worldwide will have Alzhei­
mer’s disease if effective treatments are not found.
Projected number of Alzheimer’s cases worldwide by 2050 (in millions)
120
80
40
0 of physical activity in 170 older adults who had started showing
2010 2020 2030 2040
make dementia worse does not mean that preventing them will
delay the brain’s overall deterioration. Maybe severe dementia
makes people more vulnerable to microinfarcts. And just be-
cause better control of high blood pressure and increased physi-
cal activity seem to decrease a person’s risk of stroke, that does
not necessarily mean they are less likely to suffer microinfarcts.
Correlation, after all, does not necessarily imply causation. That
scientific truism was the problem that kept bothering the panel
of outside experts put together by the NIH. Thus, the expert pan-
el concluded, with one exception, that “all existing evidence sug-
gests that antihypertensive treatment results in no cognitive
benefit.” Data showing the benefits of boosting physical activity
in folks with confirmed memory problems were “preliminary.”
The controversy boils down to semantics, says Martha L. Da-
viglus, chair of the consensus panel and a preventive cardiology
researcher at Northwestern University’s School of Medicine.
“Obviously, smoking and hypertension are risk factors for car-
diovascular disease,” she says. “And they may turn out to be risk
factors for Alzheimer’s disease as well,” she says. But after re-
viewing all the evidence, Daviglus and her fellow panelists con-
cluded that it “failed to provide convincing evidence” of the link,
whereas other researchers see “some evidence” of a link.
Getting better data may be a problem, however. One of the
best ways scientists have to prove cause and effect in medicine
is to conduct a randomized controlled trial, in which study sub-
jects are randomly assigned to two groups. One group—the so-
called control group—receives the usual standard of care. The
other group—the so-called experimental group—gets whichever
intervention is being tested. The simplest way to prove that
treating high blood pressure helps to delay the onset of demen-
tia would be to treat one group for hypertension and leave the
other group deliberately untreated for the sake of the experi-
ment. No ethical physician would participate in such a study.
One way out of this dilemma, Daviglus notes, is to design a
study in which patients suffering from hypertension get treat-
ment, and doctors analyze the results based on how well the pa-
tients’ blood pressure was controlled. If the amount by which
blood pressure dropped closely paralleled the decrease in de-
mentia risk, that would be powerful evidence of a beneficial
link. Such a so-called dose-response study has not been done
38  Scientific American, December 2010
sad1210Heal3p.indd 38
yet—it is a complex and expensive undertaking—but there is
reason to believe it could be worth the investment.
Observational studies, which follow people as they get older
without directly intervening in their treatment, have uncovered
some suggestive trends. Larson and others have shown that peo-
ple who have good control of their blood pressure from age 65 to
80 are less likely to develop dementia. After age 85, controlling
blood pressure does not have much effect on dementia risk. That
doesn’t mean anyone older than 85 should stop taking blood
pressure medication. Lowering high blood pressure still pre-
vents congestive heart failure and promotes kidney health. But
these studies suggest that doctors do not have to take aggressive
measures when treating patients older than 85 for hypertension.
As for physical activity, the best evidence in favor of its bene-
fits for the brain comes from Australia. Two years ago research-
ers there published the results of a randomized controlled trial
2050 greater memory problems than their peers and were thus at in-
creased risk of developing dementia. Study participants aver-
aged an extra 20 minutes a day of physical activity over six
months. The study was so rigorously designed that individuals
undertook the extra exercise by themselves at home to preclude
the possibility that the true benefit had come from socializing
with other people during group activities. The benefits of extra
exercise were obvious and lasted—albeit at a diminishing level—­
for 12 months after the exercise program ended. Not only did
the experimental group score better on tests of their cognition
compared with the control group, but the improvement was
twice as great as the one that had previously been shown for the
antidementia drug donepezil (brand name Aricept). This was
the first time that anyone had proved in a randomized con-
trolled trial that exercise could improve mental functioning in
people with some cognitive problems.
No one understands on a biochemical level why physical ac-
tivity might help the brain. The best explanation so far, says
Henrietta van Praag, a neurobiologist at the National Institute
on Aging, is that exercising the heart somehow stimulates growth
factors to produce new nerve cells in the brain. In 1999 van Praag
showed that more new nerves formed in the hippocampus—­
one of the key centers in the brain for memory and learning—in
physically active mice than in inactive ones. (She was working
at the time as a postdoctoral researcher in Fred Gage’s laborato-
SOURCE: DEPARTMENT OF BIOSTATISTICS, JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH
ry at the Salk Institute.) She has since shown that the new cell
growth is associated with a marked improvement in learning
and memory. The new nerves also show qualitative differences
from their older counterparts. The younger cells are better at es-
tablishing new connections with other cells. The effect is some-
what temporary. After a couple of months, the new cells start act-
ing like the older cells, although they do not die off.
Maybe 10 or 15 years in the future, we will know for sure
whether quitting smoking and exercising regularly help to delay
dementia. That leaves the rest of us—who may have seen the
devastating effects of dementia on older family and friends and
cannot afford to wait for a definitive scientific answer on how
we might avoid a similar fate—in an uncomfortable state of ig-
norance. Even if these steps never end up helping your brain,
however, they will do your heart a world of good. 
for more on alzheimer’s  www.ScientificAmerican.com/dec2010/alzheimers
10/14/10 5:50:56 PM