The stresses of everyday life may start taking a toll on the brain in relatively early middle age, research shows. The study
of more than 2,000 people, most of them in their 40s, found those with
the highest levels of the stress-related hormone cortisol performed
worse on tests of memory, organization, visual perception and attention.
Higher cortisol levels, measured in subjects’ blood, were also found
to be associated with physical changes in the brain that are often seen
as precursors to Alzheimer’s disease and other forms of dementia,
according to the study published in October 2018 in Neurology.
The
link between high cortisol levels and low performance was particularly
strong for women, the study found. But it remains unclear whether women
in midlife are under more stress than men or simply more likely to have
their stress manifested in higher cortisol levels, says lead researcher
Sudha Seshadri. A professor of neurology, she splits her time between
Boston University and The University of Texas Health Science Center at
San Antonio, where she is the founding director of the Glenn Biggs
Institute for Alzheimer's & Neurodegenerative Diseases.
Working
on the study “made me more stressed about not being less stressed,”
Seshadri says, laughing. But, she adds, the bottom line is serious: “An
important message to myself and others is that when challenges come our
way, getting frustrated is very counterproductive—not just to achieving
our aims but perhaps to our capacity to be productive.”
The
study is the largest of its kind to look at these factors and tightens
the link between cortisol, midlife stress and brain changes, says Pierre
Fayad, medical director of the Nebraska Stroke Center at the University
of Nebraska Medical Center, who was not involved in the new research.
“It confirms some of the previous suspicions,” he says. “Because of its
quality, it gives a lot more credibility.”
Bruce
McEwen, a neuroscientist and cortisol expert at The Rockefeller
University who also was not part of the study, says he found it “frankly
remarkable.” Cortisol, he notes, is necessary for life—so it is
obviously not all bad. But stress can lead people to potentially
problematic behaviors such as smoking, drinking and eating unhealthy
food. “Cortisol is itself the tip of the iceberg of things that are
going on in a person’s life and a person’s body,” he says.
The
new research included volunteers from the Framingham Heart Study, a
70-year-old study of residents from a Boston suburb. Researchers are now
studying the grandchildren of the original participants, most of whom
were white, middle class and suburban, Seshadri says. Although the
scientists did not ask participants what kinds of specific stresses they
were under on the day their blood was drawn, she says the volunteers
were able to come in for a three-to-four-hour examination—so “you would
say they were at a reasonably stable point in their life.”
Yet
even these relatively young and apparently well-off people showed signs
of brain changes, both in brain scans and in their performance. “This
is the range of stress that a group of average Americans would
experience,” Seshadri says. The highest cortisol levels were associated
with changes that could be seen on an MRI scan of the brain, the study
found.
Cortisol
does not distinguish between physical and mental stress, so some of the
people with high levels might have had physical illnesses such as
diabetes that drove up their cortisol levels, Seshadri says. It is also
possible levels of the hormone might spike in people’s blood if they are
already undergoing brain changes—that is, the elevated cortisol could
be the result of the changes rather than their cause—she says. But she
thinks this is unlikely because the trial participants were so young.
Each subject’s cortisol level was measured only once (in the morning),
so the measurements do not reflect changes over time or variations
throughout the day, she notes.
The
volunteers were given tasks such as copying a shape they were shown, or
being asked to repeat a story they had been told 20 minutes earlier.
The differences in performance were subtle, Seshadri says. She could not
immediately tell whether subjects had higher or lower cortisol levels
based on how well they carried out the tasks. “It was more that in terms
of group averages there was a real difference,” she explains.
Earlier
research has shown weaker-than-average performances on tests like these
are associated with a higher risk of dementia decades later, and
Seshadri says high stress levels in midlife might be one of many factors
that contribute to dementia. Understanding that link might offer a
potential opportunity to reduce risk—but she cautions research has not
yet shown conclusively that lowering cortisol levels will reduce the
risk of Alzheimer’s.
Other
research has shown cortisol levels can be reduced with adequate sleep,
exercise, socializing and relaxing mental activities such as meditation.
“There are a number of intriguing, fairly simple things that have been
shown to change these levels,” Seshadri says. “But whether they will in
turn translate into better preservation of the brain is something that
can only be determined in a clinical trial.”
Rockefeller
University’s McEwen says other research suggests it is never too late
to adopt a healthier lifestyle by taking steps like reducing stress,
exercising regularly, eating a healthy diet, getting enough good-quality
sleep and finding meaning in one’s life. “The life course is a one-way
street,” he says. But “the brain does have the capacity for repairing.”
Karen
Weintraub is a freelance health and science journalist who writes
regularly for the New York Times, STAT and USA Today, among others.
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