Memory Loss: A Reversible Problem?

It’s well known that our working memory capacity decreases as we age (by about 1% per year after we turn 40). But now Min Wang from the Yale University School of Medicine has found that the environment around the neurons that process working memory seems to be the culprit, not the neurons themselves. And, by suppressing these changes in monkeys, he has been able to reverse some of the age-related decline in their working memory.

Monkeys, like humans, have a highly developed pre-frontal cortex. After training a group of monkeys to remember the location of a visual display, Wang recorded the level of activity in their pre-frontal cortex after the display flashed on and off. This activity is typical of working memory activity as the monkeys tried to remember the location of the display long enough to enjoy a reward.

In older monkeys Wang found that the delay neurons fired less strongly and became less sensitive. They found it correspondingly harder to remember the location from test to test.

Graphic Courtesy of Scientific American

While working memory decline likely has several causes, Wang looked at the impact of changes in the surrounding cells, in particular an increase in the level of a protein known as cAMP, a multipurpose molecule that carries signals around the body. cAMP inhibits neural activity.

When Wang used a drug called guanfacine to block the effects of cAMP, the neurons fired more strongly. Conversely, using etazolate to amplify the effects of cAMP, he was able to suppress the response of the delay neurons.

Guanfacine is already used to treat attention-deficit hyperactivity disorder, Tourette’s syndrome and some of the behavioural problems associated with autism. “We have found that guanfacine improves self-control in young adults, which is also a prefrontal ability,” says Amy Arnsten, lead on Wang’s new study. “It is currently being tested in people who want to quit smoking or other types of substance abuse, and appears to be having positive results.”

Personally, I’d like to see a similar study using working memory training to stimulate the response of delay neurons. Brain exercise is a great alternative to medication in reversing the effects of age-related memory loss.


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