It happens to the best of us: you walk into the kitchen to get a cup of coffee but get distracted by the mail, and then forget what you were doing in the first place. Aging makes people particularly vulnerable to this kind of forgetfulness, where we fail to maintain a thought in the face of distractions.

New research from Yale University uncovers cellular changes that seem to underlie this type of memory loss in monkeys, and shows that it can be reversed with drugs. By delivering a certain chemical to the brain, researchers could make neurons in old monkeys behave like those in young monkeys. Clinical trials of a generic drug that mimics this effect are already underway.

The findings support the idea that some of the brain changes that occur with aging are very specific—rather than being caused by a general decay throughout the brain—and can potentially be prevented. "It helps us understand that the age-related changes in the brain are malleable," says Molly Wagster, chief of the Behavioral and Systems Neuroscience Branch at the National Institute on Aging, which funded the research. "That's a crucial piece of information, and extremely hopeful."

In the study, Amy Arnsten and collaborators recorded electrical activity from neurons in a part of the brain called the prefrontal cortex, a region especially vulnerable to aging in both humans and primates. It is vital for our most high-level cognitive functions, such as working memory and the ability to multitask and inhibit distractions. "The prefrontal cortex is a mental sketch pad, keeping things in mind even if nothing in the environment is telling us what to do," says Arnsten. "It's the building block of abstract thought."

Previous research has shown that neural circuits in this region are organized to create a sustained level of activity that is crucial for working memory. "By exciting each other, the neurons are able to maintain information that isn't currently in the environment," says Arnsten.

By analyzing activity recorded from young, middle-aged, and old monkeys, the researchers found that the firing rate of the neurons in this area declines with age. They found that other neurons, such as those that respond to cues in the environment, still fired normally even as the monkeys aged. The research was published today in the journal Nature.