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The University of Arizona Alumnus / Fall 2007

Thanks for the Memories
by Tim Vanderpool
Brain scan photo by Jeff Smith/Photosmith
All other photos by Jacob Chinn

“Memory is history recorded in our brain. Memory is a painter — it paints pictures of the past and of the day.”
    — Grandma Moses

That’s certainly true, and beautifully expressed. Still, what if the brain stops recording our personal histories? What if those lovely paintings of memory begin to wither as we age?

For academics who study such things, these are long-vexing questions. But many of those same experts now believe we’re on the verge of a golden age in understanding — and mitigating — normal memory loss. In turn, those breakthroughs will undoubtedly yield precious clues about vicious, memory-robbing diseases such as Alzheimer’s.

Nowhere does that learning curve reach higher than at the UA’s Evelyn F. McKnight Brain Institute. With a five-year, $5 million grant from Florida’s Evelyn F. McKnight Brain Research Foundation — and matching funds from the UA — this high-powered, 14-member consortium is taking sharp aim at aging and the memory changes it sparks.

“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 something of a celebrity in the world of memory research. Her decades of vital work earned her a term as president of the 37,500-member Society for Neurosciences. 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. These elongated ridges on the floor of the brain’s lateral ventricles are considered the centers for emotion and memory. Barnes revolutionized our understanding of their role in switching memory-related genes on and off.

Dr. Carol Barnes, Regents’ professor of psychology and neurology and director of the UA Evelyn F. McKnight Brain Institute.

“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 to the institute’s mission. But reaching that goal is an equally sweeping affair; faculty expertise ranges from psychology and medicine to neurology and microbiology. This science stronghold — 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 chair William McKnight. Its sole purpose: researching and investigating memory loss due to aging.

And that’s a very good fit with the UA. “Most of us at the institute have been thinking about aging for quite a while,” 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 the huge glut of 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. It may sound awfully 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.”

That’s only the beginning. 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.

Dr. Lee Ryan, associate professor of psychology and director of UA’s Cognition and Neuroimaging Labs.

“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 (MRI) 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 as well. “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 challenge researchers face. “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 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.”

Dr. Alfred Kaszniak couldn’t agree more. Along with his slot on the institute faculty, he heads the UA’s Psychology Department and the Coordinated Clinical Neuropsychology Program. Over years of research, his research has focused on different types of memory tasks and different types of neuronimaging approaches.

Kaszniak achieves his measurements through spatially oriented tasks, “both with navigating around relatively large spaces, and spatial navigation tasks that look like computer games,” he says.

The goal is to compare people who seem to be aging normally “and those we know to be in the early stages of Alzheimer’s. That’s so we can see qualitative differences in what composes their memory performance. It’s analyzed at a fine-grain level.”

Dr. Alfred Kaszniak, head of the UA Psychology Department and the Coordinated Neuropsychology Program.

The implications are enormous: those of us fortunate to escape the ravages of disease will still be dealing with memory loss and age-related changes, says Kaszniak. “So even if I don’t develop Alzheimer’s in older age, I’ll still have less-efficient memory functioning than I currently have in my late 50s. That may not be disabling, but it’s a pain in the butt. I’d like to be able to recall everything I’ve read as effectively as I did in my earlier years.”

Learning to maintain that effectiveness illustrates “the practical applications from working exclusively on normal aging changes,” he says.

It also gets us closer to effective Alzheimer’s treatments. “Separating out normal memory change from Alzheimer’s (symptoms) very clearly is part of the institute’s mission,” says Kaszniak. “Even at the point where someone’s day-to-day functioning is not demonstrably disturbed, can we predict who will eventually develop this illness? And then how do we separate that from normal changes in memory functioning?”

“Those questions,” Barnes notes, “grow only more complicated when we realize the endless ways brain changes can manifest.” Further snarling things, it’s not so much the disappearance of brain matter that affects memory. Rather, changes in connections — the synapses — are likely at the heart of memory loss in older adults.

Barnes and other faculty members are busily ferreting out those synaptic shifts. “One thing we’re able to do at the institute is monitor the activity of many, many, many (brain) cells at once,” she says. “That a specialty of (the institute’s) Dr. Bruce McNaughton. He developed recording devices that are really quite remarkable. Now we can determine not just how single cells change, but how brain circuits are interacting and changing as we age.”

And in the end, those determinations just may help us keep our memories humming — and keep painting those lovely pictures of the past.

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