Stress hormone elevation is associated with working memory deficits in aging

 A new study published in the June 18 issue of The Journal of Neuroscience adds to a body of evidence suggesting stress may accelerate cognitive decline later in life. The study found that aged rats with high levels of the stress hormone corticosterone showed structural changes in the brain and short-term memory deficits.

While most people will experience some cognitive decline as they get older, the extent of these changes and how rapidly they progress varies greatly from one person to the next. Scientists are interested in understanding the factors that contribute to these differences. Research suggests that how the body responds to stress may be one of the factors influencing how the brain ages. Multiple animal studies have linked high levels of the stress hormone corticosterone (similar to the human stress hormone cortisol) with age-related structural and functional decline in the hippocampus, a region that plays a key role in long-term memory.

Jason J. Radley of the University of Iowa wanted to know whether exposure to high levels of corticosterone is associated with other changes in the brain and memory deficits. In the current study, he and others measured the amount of the stress hormone in the blood of young and old rats and examined cells in the prefrontal cortex, a region of the brain involved in short-term memory. The researchers found that older animals with high levels of the stress hormone had fewer connections between prefrontal cortex cells than the older animals with lower levels of the hormone. In contrast, prefrontal cortex cells appeared similar in younger animals regardless of stress hormone levels.

“Older animals with higher levels of stress hormones in their blood have 'older' frontal cortexes than animals with less stress hormones,” explained Stanford University professor Robert Sapolsky, PhD, an expert on the damaging effects of long-term stress who was not involved with this study. “Thus, stress may act as a pacemaker of aging in this key brain region.”

Older rats with higher levels of stress hormone displayed a 20 percent reduction in the density of dendritic spines (the small protrusions on neurons that come into close contact with other cells to form synapses, the connections between cells) relative to age-matched rats with less stress hormone.

The researchers also compared how the young and old rats performed on a simple working memory task, where the animals had to remember which arm of a two-arm maze contained a food reward following varying periods of delay. Older animals with higher levels of corticosterone made more errors when attempting to predict the location of the reward than age-matched animals with less of the stress hormone after a brief period of delay.

“These findings are not meant to indicate that high stress hormones are the only factor in determining the decline of mental abilities during aging,” Radley cautioned. “Nonetheless, this study suggests that the effects of these stress hormones on the brain may be much more widespread than we previously thought.”

This research was funded by the National Institute of Mental Health.

The Journal of Neuroscience is published by the Society for Neuroscience, an organization of nearly 40,000 basic scientists and clinicians who study the brain and nervous system. Radley can be reached at jason-radley@uiowa.edu. More information on aging, stress, and memory can be found on BrainFacts.org.