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Brain Trust 

UA researchers tap clues about memory and aging

Half the time, we can't remember personal-identification numbers and passwords and how much we dropped on last night's pepperoni pizza. In the big picture, it's no big deal.

On the other hand, when it comes to truly paramount aspects of our lives--recalling good times, important life passages, those we love--memories become vital to our identities.

But what if the brain stops recording those personal histories? What if our precious paintings from memory begin to wither when we get old?

For academics, these are vexing questions. But many experts now believe we're on the verge of a golden age in understanding--and mitigating--normal memory loss. And those breakthroughs will undoubtedly yield powerful clues about memory-robbing diseases such as Alzheimer's.

As it happens, much of that cutting-edge research is occurring right under our noses at the UA's Evelyn F. McKnight Brain Institute. Armed with a five-year, $5 million grant from Florida's Evelyn F. McKnight Brain Research Foundation--and matching funds from the UA--the institute's 14-member team is tackling complex connections between aging and memory loss.

"One target is understanding what makes some people age so successfully," says Carol Barnes, the institute's director. "That's an important question, since it can really help us improve our quality of life."

Therein lies the driver behind such studies, says Barnes. And she should know. The regents' professor of psychology and neurology is a celebrity in the world of memory research. Her decades of groundbreaking work earned her a term as president of the 37,500-member Society for Neuroscience. Since 1990, she's been at the UA, studying how brain changes affect the way we process information.

Barnes is particularly known for her work on the hippocampi, elongated ridges on the floor of the brain's lateral ventricles that are considered the centers for emotion and memory. In fact, she's revolutionized our understanding of their role in switching memory-related genes on and off.

"Very small differences," she says, "can have a large impact on how your brain is wired. If the information and memories are in these connections, then it really matters how your brain is connected."

Tracking those complex networks is key, and that goal involves disciplines ranging from psychology and medicine to neurology and microbiology. This tour de force--one of only four McKnight institutes across the nation--falls under the umbrella of the UA's Arizona Research Laboratories.

The McKnight Brain Research Foundation was formed in 1999 by Evelyn McKnight, widow of long-time 3M Corporation board chairman William McKnight. Its sole purpose: researching and investigate memory loss due to aging.

It was a good fit for the UA. "Most of us at the institute have been thinking about aging for quite awhile," says Barnes. Although her research specifically focuses on biological mechanisms, she also teaches a gerontology course looking at "the psychological, biological and social issues that affect aging. I don't think you can truly understand the aging brain unless you put it in a social context--looking at the more molecular details, but at social factors such as family and support groups as well."

At the same time, by learning more about how normal brains age, researchers expect to gain knowledge about brain diseases. They hope for the ability to diagnose these diseases earlier--and prevent some of their debilitating effects. It's work that only gets more critical as baby boomers get older.

This highly dynamic field has already exposed a few uncomfortable truths about memory loss. For example, a recent study by England's Cognitive Drug Research Center revealed that cognitive abilities in the average male start declining around age 45, as does the quickness of our physical reactions.

That may sound pretty young. But researchers believe that's when the shrinking of key memory centers--and changes in electrical, physiological and chemical aspects of our brains--may actually begin. Those changes slow the retrieval of information from our "memory stores" and spark forgetfulness.

Still, not every brain ages in the same way. About one-third of the changes we experience may be genetically driven, with the remaining two-thirds likely the result of lifestyle and environmental factors.

"We're watching closely, and we know what's being altered," says Barnes. "It's very subtle in the older brain, and so as we understand more, we can selectively target these genes and hopefully optimize our cognition for longer periods."

Over the next decade, researchers believe we'll come to manage memory change just as we do hypertension or high cholesterol. "This area has really been coming into its own." says Dr. Lee Ryan, director of the UA's Cognition and Neuroimaging Labs, and Barnes' institute colleague. In her research, Ryan investigates the interior of white matter, or areas of the brain that harbor connections between different processing regions.

"For example," she says, "we have a certain knowledge that changes we see in the frontal lobe are associated to some degree with slowing and increased difficulty in learning. But we don't have a really good handle on it."

To get a better understanding, she studies memory "using various kinds of magnetic-resonance-imaging methods, to learn how the brain changes across the adult lifespan, and how those changes are related to memory functions in older adults."

That research niche is filling a vital need, she says. "Although functional MRIs have been around for about 10 years now--and made huge changes in neurosciences in general and our understanding of brain functions--there's been less done on understanding the aging process itself."

But that's changing, too. "There's been a lot happening over the past three or four years," she says. "It's an area where people have a lot of interest." In short, there is a greater need to know what's going on with normal older adults, so we can detect abnormal changes early on.

At the same time, oceans of variability between people only heighten the challenges. "When I'm looking at MRI scans," Ryan says, "I see 80-year-olds that have a brain that looks as good as any 40-year-old I see. Then I have people whose brains show lots of degenerative process, lots of damage to the white matter. And the interesting thing is that those two individuals can actually be cognitively functioning very similarly to one another."

In other words, "we don't have a really good understanding of how the brain is changing," she says, "and how it relates to the changes we see in older adults."

Still, armed with a thorough knowledge of the normally aging brain, "we can look for the earliest signs that you can find, that a person is going to develop Alzheimer's disease," Ryan says.

And that would be a blessing, says Barnes. "If we could even delay Alzheimer's disease by five years, it would be an incredible burden lifted."

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