Study illuminates memory loss

Yale researchers may be able to explain why people lose their memory as they get older.

A team at the Yale School of Medicine has shown that a specific neural dysfunction in the prefrontal cortex of the brain is responsible, in part, for age-related memory loss. In a study published last month in the journal Nature, researchers linked these cognitive deficits to disruptive signaling in normal pathways.

“In the old days working memory loss really didn’t matter that much because life was so much simpler. But in the Information Age these disabilities are to our disadvantage,” Amy Arnsten, professor of neurobiology and psychology, said. “Many elderly people lose their independence as they lose their executive abilities, and need their children to help them manage their money and medical needs.”

The good news is that targeted treatment may ease, and even reverse, many symptoms of cognitive aging, the researchers said. Working memory, which is associated with the quality of recall and ability to process multiple tasks at once, disintegrates as humans age and requires a sensitive neurochemical environment to function properly.

The results of ongoing clinical trials on healthy elderly patients taking place at the medical school, which are partially funded by the National Institute on Aging, now hope to determine whether patients receiving Guanificine treatment show improved cognitive function and more youthful memory recall. Guanificine inhibits the messenger protein cAMP, this study’s target for disruptive signaling, and is currently approved by the Food and Drug Administration to treat children with Attention Deficit Hyperactive Disorder.

“We’re very interested to see how the basic research findings will transfer into benefits for older people in terms of their cognitive function and the way they’re living,” said principal investigator and psychiatry and neurobiology professor Christopher van Dyck.

The study has larger implications for treating other diseases that likewise involve the prefrontal cortex, such as schizophrenia and Alzheimer’s, in which the same circuits degenerate. Arnsten said that one of the article’s most important findings is the discovery of physiological vulnerabilities in higher cognitive circuits specific to advancing age, as the dysregulation of cAMP signaling is unique to high-order brain circuits.

And further research in this field may lead to reduced health costs as well.

“Our society is rapidly aging, and thus the number of people with Alzheimer’s disease is expected to increase dramatically in the next few decades,” Arnsten said. “The medical cost for caring for huge numbers of people with Alzheimer’s is mind-boggling. So, if you can slow it or stop it you’re rescuing the future in a major way. Right now, there’s relatively very little money dedicated for Alzheimer’s disease research.”

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