Memory Lost, Memory Regained

We can’t tell you where you left your house keys, but we can most certainly tell you why you can’t find them, say researchers at Yale University.

According to a new study published in the journal Nature, authors report that middle-aged and elderly people have weaker neural networks in their brains causing them to fire less robustly than youthful ones. Interestingly, research reveals that this condition is reversible.

Professor of Neurobiology and Psychology and a member of the Kavli Institute for Neuroscience, Amy Arnsten, said that: “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. These abilities are critical for maintaining demanding careers and being able to live independently as we grow older.”

With age, people often become forgetful, get easily distracted and disrupted by interference, and have greater difficulty with executive functions. The cellular basis for these common cognitive difficulties has not been fully understood even though these age-related deficits have known to exist for many years. For the first time, this new study examined age-related alterations in neuronal activity of the prefrontal cortex (PFC), which is that portion of the brain responsible for higher cognitive and executive functions.

Even in the absence of a signal from the environment, the neuronal network in the prefrontal cortex relentlessly fires impulses to keep information “in mind.” This process known as “working memory,” allows us to recollect information, such as where you left your house keys, even when that information requires constant updating. This ability, often referred to as the “Mental Sketch Pad,” forms the basis for abstract thought and reasoning, and is integral for executive functions such as multi-tasking, organizing, and inhibiting inappropriate thoughts and actions.

A group of young, middle-aged, and aged animals performing a working memory task were studied by Arnsten and her team to understand the firing of prefrontal cortical neurons. While the prefrontal cortex neurons of older animals displayed slower firing rates, those of young animals were able to maintain high firing rates during working memory. Further, when the neurochemical environment surrounding the neurons in older animals was regulated to resemble that of a younger subject, the neuronal firing rates were restored to more youthful levels.

Arnsten said that an excessive level of a signaling molecule called cAMP (which opens ion channels and weakens prefrontal neuronal firing) appears to accumulate in the aging prefrontal cortex. When cAMP was inhibited or cAMP-sensitive ion channels were blocked using certain agents, youthful firing patterns were restored in the aged neurons. Guanfacine is an approved medication for treating hypertension in adults and prefrontal deficits in children, and it is one of the compounds that enhanced neuronal firing which suggests that it may also be helpful in the elderly.

With the aim of testing guanfacine’s ability to improve working memory and executive functions in elderly subjects who do not have Alzheimer’s Disease or other dementias, Yale is already enrolling subjects in a clinical trial thereby progressing Arnsten’s finding into the clinical setting.