Middle-aged people with higher-than-average levels of the "stress" hormone cortisol may have fuzzier memories, a new study suggests. The study, of more than 2,000 adults, found those with relatively high cortisol levels in their blood tended to perform worse on memory tests. They also showed less tissue volume in certain areas of the brain, versus people with average cortisol levels. The findings do not prove that higher cortisol levels -- or daily stress -- directly injure the brain.

But researchers said they add to evidence that the hormone might affect brain structure and function, even years before any obvious memory problems arise.

"Cortisol affects many different functions, so it is important to fully investigate how high levels of the hormone may affect the brain," lead researcher Dr. Justin Echouffo-Tcheugui said in a journal news release.

Cortisol may be best known as the body's main "fight-or-flight" hormone, as it's churned out by the adrenal glands in response to stress. But it also helps regulate metabolism, blood pressure, blood sugar, immune responses and inflammation.

Animal research has found that sustained cortisol elevation can alter brain structure and function, according to Echouffo-Tcheugui, who was based at Harvard University at the time of the study.

And in humans, there's some evidence that abnormal cortisol levels -- caused by certain medical conditions, such as Cushing syndrome -- might affect brain structure or mental abilities.

Now the new findings hint that the same could be true of subtler variations in the hormone.

"This is an interesting finding that clearly needs to be investigated further," said Dr. Ezriel Kornel, an assistant clinical professor of neurosurgery at Weill Cornell Medical College in New York City. He wasn't involved with the study.

But, Kornel emphasized, the research does not prove that cortisol -- or, ultimately, daily stress -- is the culprit.

For example, Kornel said, there could be some third factor that caused the higher cortisol levels and lower brain tissue volumes. It's also possible that the brain changes came first, which then raised people's cortisol levels, he said.

It's not only daily psychological stress that boosts cortisol, Kornel pointed out. Certain health conditions and medications can do that, too.

The findings are based on data from more than 2,200 US adults taking part in a long-term health study. At the outset -- when they were around 49 years old, on average -- they had their morning cortisol levels measured once. They also took standard tests of memory and thinking skills, and several years later, most underwent MRI brain scans.

The researchers divided the participants into low, middle and high cortisol groups. Those in the middle group had levels in the normal range (between 10.8 and 15.8 micrograms per deciliter of blood).

Overall, the study found, people with high cortisol levels scored a bit lower on some tests of memory, attention and thinking. On brain scans, they also tended to show slightly reduced volume in certain brain areas, compared with participants with average cortisol levels.

Those patterns were still seen when the researchers excluded people who'd been diagnosed with major depression, which can affect both cortisol levels and mental acuity.

Some of the brain differences were seen in portions of so-called white matter, which is important in information processing, Echouffo-Tcheugui and his team said. That, they speculate, might be one reason for the lower test scores.

 HealthDay