Exercise
helps maintain brain structure and function with aging and may
delay onset of Alzheimer's disease and other dementias, according
to a review presented at the 114th annual convention of the
American Psychological Association (APA).
"There
is a diverse body of evidence from retrospective and prospective
clinical studies, as well as from animal research, all of which
suggests that exercise has beneficial effects from middle age
to old age,"Arthur F. Kramer, a faculty member in neuroscience
and psychology at the University of Illinois at Urbana in Champaign,
told Medscape.
"Exercise
has neuroprotective effects enabling higher levels of cognition
and delaying the onset of various forms of dementia such as
Alzheimer's disease in prospective epidemiological studies.
It also has positive effects on brain structure and function,
both from human research with magnetic resonance imaging (MRI),
functional MRI, and event-related potentials, and especially
from the animal literature showing proliferation of active capillary
beds, new dendritic connections, and even new neurons in selective
areas such as the hippocampus."
Along
with co-authors Kirk I. Erickson and Stanley J. Colcombe, Dr.
Kramer reviewed research evidence accumulated during the past
four decades, including epidemiologic studies of the relationship
between exercise and physical activity at various ages with
cognitive ability and subsequent probability of developing Alzheimer's
disease or other age-related neurological diseases. They also
reviewed longitudinal randomized trials studying the effect
of specific fitness training on cognition and brain function
in older adults, as well as animal studies of the molecular
and cellular basis of exercise effects on brain structure and
function.
"Clinical
data show that people who exercise several times per week show
a reduced rate of cognitive decline with age compared with those
who have low levels of activity," Carl Cotman, director
of the Institute for Brain Aging at the University of California,
Irvine, told Medscape. Dr. Cotman was not involved
with Dr. Kramer's presentation but reviewed it for Medscape
as an independent expert. "The best evidence, though, comes
from animal studies, where it has been established that voluntary
running increases neuroprotective molecules in the brain, such
as brain-derived neurotrophic factor (BDNF), and also reduces
the accumulation of molecules associated with Alzheimer's disease,
such as beta-amyloid."
In
the review by Dr. Kramer and colleagues, the epidemiologic literature
showed a significant protective effect of physical activity
on cognitive function and on decreased incidence of dementia,
with the benefits lasting up to several decades. A few studies
of human subjects older than 65 years showed that exercise lasting
at least 15 to 30 minutes, three times weekly, reduced the probability
of developing Alzheimer's disease, even in subjects who were
genetically predisposed.
Clinical
trials also suggest a relationship between fitness training
and improved cognition, more efficient brain function, and prevention
of brain atrophy in the elderly. A 4-year study of the relationship
between physical activity and cognition and brain function in
subjects aged 62 to 70 years showed that those who were still
employed and retirees who exercised regularly had sustained
levels of cerebral blood flow and superior performance on general
measures of cognition compared with inactive retirees. In a
6-month study, elderly subjects who participated in aerobic
exercise had a significant increase in gray matter volume in
regions of the frontal and superior temporal lobe compared with
controls.
NO
DOWNSIDE TO RECOMMENDING EXERCISE
"With
the human data, there have been enough meta-analyses over the
last ten years suggesting that exercise does have neuroprotective
effects and also does tend to decrease depression ratings,"
Dr. Kramer said. "I don't see any downside to recommending
exercise, even if the effects aren't as large or as robust as
we think they are, because we already know that exercise tends
to reduce mortality and decrease the incidence of cardiovascular
disease, type 2 diabetes, and osteoporosis. I think there is
no reason not to come up with a set of recommendations based
upon both the disease literature and the animal literature."
Aerobic
exercise appears to confer more positive effects on brain function
with aging than do other forms of exercise. In a study of older
adults, those who were randomized to a walking group for six
months performed better on a distractibility task than did those
randomized to a stretching and toning control group. Furthermore,
the aerobically trained group had increased neural activities
in frontal and parietal brain regions mediating attention, and
reduced activity in the dorsal region of the anterior cingulate
cortex, which is thought to be sensitive to behavioral conflict,
or the need for increased cognitive control. Aerobic exercise
also appears to help the brain maintain its plasticity.
"Physical
activities that have a fairly strong aerobic component appear
to be associated with spared cognition and delayed onset of
dementia," Dr. Kramer said. "Other forms of exercise
that have to do with toning and stretching, that lead to increased
flexibility and decreased falls in older adults, are also beneficial,
but they don't seem to be implicated in the cognitive-sparing
effects. The animal literature suggests that learning new psychomotor
skills can be beneficial in increasing new dendritic connections."
Animal
studies offer additional insight into the neuroprotective effects
of physical activity because they allow direct observation of
morphologic, neurochemical and neurophysiologic changes associated
with exercise. In studies using voluntary wheel running as a
measure of aerobic activity, animals with increased wheel running
performed better on spatial learning tasks mediated by the hippocampus.
In other studies, aged rodents that exercised in a water maze
learned and retained information about a hidden platform better
than did age-matched controls. Both young and aged animals benefited
from exercise, as reflected in increases in nerve growth factor
levels that can offset or prevent certain age-related diseases.
QUESTIONS
REMAIN
In
terms of clinical implications of these findings, certain questions
remain unanswered.
"There
are certainly unknowns, such as dose-response relationship in
humans: how much exercise leads to how much cognitive benefit
or decrease in odds ratios for Alzheimer's disease or vascular
dementias," Dr. Kramer pointed out. "We also need
studies that combine various lifestyle choices or interventions
that research suggests are neuroprotective for humans, such
as intellectual engagement, nutritional choices, use of antioxidants
and other supplements, to determine the way these various interventions
are additive or multiplicative."
Dr.
Cotman agreed that clinical trials are needed to answer these
questions. He recommended that exercise should have some type
of aerobic component, but that the exact type is probably not
as critical.
"The
current data support that levels of activity will help but they
do not provide an exact prescription," he concluded. "Based
on epidemiological data and animal data, however, it is likely
that exercise for three or more times per week is beneficial
. . . Walking three or more times per week for 30 to 45 minutes
also is beneficial."
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