"This study not only tells us that there is a benefit to being
highly fit, it pinpoints where in the brain it matters for
postmenopausal women who have been using the two strategies," said
lead author Kirk I. Erickson, a postdoctoral researcher at the
Beckman Institute for
Advanced Science and Technology at the University of Illinois.
The study appeared online in January in advance of regular
publication in the journal Neurobiology of Aging. By using magnetic
resonance imaging and voxel-based morphometry, researchers
documented the combined effects on specific areas of the brain,
based on fitness of short- and long-term users of hormone therapy.
Researchers also looked at how well 54 postmenopausal women
performed on a computerized version of the Wisconsin Card Sort Test,
in which constantly changing rules challenge memory, inhibition and
task-switching abilities known as executive functions. The women
were divided into groups based on use or non-use and duration of
hormone therapy and existing fitness levels.
"We found that higher fitness levels enhance the effects of
shorter durations of hormone treatment and offset the declines
associated with long-term use," said Arthur F. Kramer, a Beckman
psychology professor. "It may be that a combination of HRT and
exercise boosts both cognition and brain structure of older women."
Participants ranged in age from 58 to 80, with a mean age of 70.
Hormone status and duration of use were assessed based on their
self-reports, and aerobic fitness was measured by monitoring
respiration, heart rate and blood pressure during a treadmill test.
Magnetic resonance images of the participants' brains were taken,
segmented into 3-D maps and analyzed by voxel-based morphometry,
which allows for high spatial resolution of the volume of gray and
white matter. The women also were screened for duration of hormone
use, aerobic fitness levels, age, education, socioeconomic status,
age at menopause and for dementia.
Voxel-based morphometry analysis revealed that four regions of
gray matter -- left and right prefrontal cortex, left
parahippocampal gyrus, and left subgenual cortex -- varied with
duration of hormone treatment. Longer hormone usage resulted in
significantly less tissue volume in these areas. However, higher
fitness scores were tied to greater tissue volume.
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While there were no significant effects of the interaction of
hormone duration and fitness on white matter in general, higher
fitness levels were tied to greater prefrontal white matter regions
and in the genu of the corpus callosum, a key area that
interconnects frontal areas of the brain.
"Critically, the tissue volume measures in all four gray matter
regions revealed that high fitness levels were associated with a
more modest decline in regional brain volume than low fitness levels
with increasing durations of hormone therapy," the researchers
wrote. "High fitness levels also were associated with a significant
sparing of the neural tissue of women not receiving hormone
Durations of therapy of less than 10 years showed enhanced tissue
volume compared with all other groups, and the decline in tissue
volume began only after 11 to 15 years of hormone-replacement
Erickson and Kramer noted that their findings in women were in
line with previous animal studies that have found that estrogen and
fitness have similar mechanisms in the brain. Estrogen and fitness
both stimulate brain-derived neurotropic factor, a molecule tied to
the production of capillaries, plasticity and neurons.
These preliminary findings are based on only a small sampling of
women and need to be considered in a much broader clinical setting,
Kramer said. However, the findings mirror similar studies in his lab
that are continuing to show the benefits of physical fitness in
Co-authors with Erickson and Kramer were Stanley J. Colcombe, a
research scientist at the Beckman Institute; Paige E. Scalf, a
postdoctoral researcher in Kramer's lab; Edward McAuley, a Beckman
researcher and professor of
and psychology; McAuley's former doctoral student Steriani Elavsky;
and Donna L. Korol, professor of psychology.
The research was funded by the National Institute on Aging and
the Institute for the Study of Aging.
[News release from
University of Illinois at Urbana-Champaign]