Memory Loss May Soon Be Reversible

by Carole Jackson, Bottom Line Health

If you can’t remember where you put your glasses or the last name of the couple that you’ve just been introduced to, be sure to remember this one word — guanfacine. It’s the name of a drug, currently used to treat high blood pressure, attention deficit hyperactivity disorder (ADHD) and anxiety, that might be able to reverse a major type of short-term memory loss in older people, according to a new study. That’s right — reverse memory loss. Even if an elderly person’s ability to remember has deteriorated over 15 or 20 years, doctors may soon be able to prescribe guanfacine to restore the memory to the way it was during young adulthood. Now, we’re not talking about memory loss due to Alzheimer’s disease or other forms of dementia — we’re talking about the loss of working memory, which occurs in nearly everyone, sometimes starting as early as age 50 and almost certainly after the mid-60s.

I spoke with Amy Arnsten, PhD, the study’s lead researcher and a professor of neurobiology and psychology at Yale University School of Medicine in New Haven, Connecticut, to find out how this drug works.


Prior studies have shown that the faster neurons fire, the better the working memory. What Dr. Arnsten and her colleagues explored is how aging affects the firing of the neurons — and whether guanfacine might help speed up the firing.

For the study, she gathered six rhesus monkeys of three different age groups. Two were “young adults,” two were “middle-aged” and two were “aged.” The monkeys played a game that required them to remember the locations of objects on computer screens. During the game, a tiny electrode that had been painlessly inserted into each monkey’s prefrontal cortex allowed researchers to monitor their brain function. Compared with the young adult monkeys, the neurons in the middle-aged and aged monkeys fired more slowly.

Earlier tests done by Dr. Arnsten’s lab had shown that neurons in the prefrontal cortex of humans and other animals fire more slowly when there’s a buildup there of a substance called cyclic adenosine monophosphate (cAMP). So in this study, researchers injected the monkeys with guanfacine, which is known to inhibit the production of cAMP in the prefrontal cortex. Afterward, neuron firing doubled, on average, in both the middle-aged and aged monkeys, compared with the firing speed of their neurons when they weren’t given the guanfacine injection. These results appeared in the July 27, 2011 issue of Nature.


The question remains: Would guanfacine have the same effect on humans? Dr. Arnsten said that she and her colleagues are optimistic because the prefrontal cortex functions similarly in both species. In fact, researchers at Yale have already begun clinical trials on the effect of guanfacine on the working memory of people age 75 or older (who don’t suffer from dementia or Alzheimer’s). Results of these tests are expected in the fall of 2012.

Meanwhile, there’s the question of whether guanfacine could or should be prescribed now, off-label, for memory loss. Dr. Arnsten thinks that it’s too early to try this — because it hasn’t yet been proven to reduce memory loss in humans. However, if future studies show that it’s a good idea, you can be sure that I’ll remember to tell you about it.


Amy Arnsten, PhD, professor of neurobiology and psychology at Yale School of Medicine, New Haven, Connecticut. Dr. Arnsten is a member of Yale’s Kavli Institute of Neuroscience, a group that focuses on innovative approaches to study of the human brain.