How memory is lost — and re-found

A new study published July 27 in the journal Nature shows that the neural networks in the brains of the middle-aged and elderly have weaker connections and fire less robustly than in youthful ones.

Intriguingly, note the scientists, the research suggests that this condition is reversible.

“Age-related cognitive deficits can have a serious impact on our lives in the Information Age, as people often need higher cognitive functions to meet even basic needs, such as paying bills or accessing medical care,” says Amy Arnsten, professor of neurobiology and psychology and a member of the Kavli Institute for Neuroscience.

“These abilities are critical for maintaining demanding careers and being able to live independently as we grow older.”

Arnsten and her team studied the firing of prefrontal cortical neurons in young, middle-aged and old animals as they performed a working memory task. Neurons in the prefrontal cortex of the young animals were able to maintain firing at a high rate during working memory, while neurons in older animals showed slower firing rates.

However, when the researchers adjusted the neurochemical environment around the neurons to be more similar to that of a younger subject, the neuronal firing rates were restored to more youthful levels.

Arnsten says that the aging prefrontal cortex appears to accumulate excessive levels of a signaling molecule called cAMP, which can open ion channels and weaken prefrontal neuronal firing. Agents that either inhibited cAMP or blocked cAMP-sensitive ion channels were able to restore more youthful firing patterns in the aged neurons.

One of the compounds that enhanced neuronal firing was guanfacine, a medication that is already approved for treating hypertension in adults and prefrontal deficits in children, suggesting that it may be helpful in the elderly as well, note the researchers.

Arnsten’s finding is already moving to the clinical setting. Christopher vn Dyck of the Yale School of Medicine is enrolling subjects in a clinical trial testing guanfacine’s ability to improve working memory and executive functions in elderly subjects who do not have Alzheimer’s disease or other dementias.

Information about the clinical trial can be found online,