OU College of Medicine Researchers Identify Unique Behavior of Aging Brain

What causes memory problems as people age, and can anything be done to slow the rate of cognitive decline? Researchers at the University of Oklahoma College of Medicine have discovered a key difference in the brains of older adults and recently launched a clinical trial to test a vitamin supplement for its potential to improve memory.

By placing what looks like a swim cap with light sensors on a person’s head, researchers can measure blood flow to the brain and the amount of oxygen it contains. Because people cannot store extra oxygen in their brains, a constant supply is necessary for functions like short-term memory. In a recently published study, OU College of Medicine researchers demonstrated that blood flow to the brain diminishes with age, which correlates with deterioration of memory. Further, they discovered that the brains of older adults compensate for the decrease in blood flow by calling on other parts of the brain for help.

“By using a piece of equipment called functional near-infrared spectroscopy, we can take four images of the brain every second, which allows us to measure brain activity and blood flow at a fast rate. This paper is foundational for us because, by identifying a mechanism of cognitive dysfunction in aging, we have a strong justification for clinical trials that test interventions for improving cognitive function, such as the vitamin supplement that we hope will improve memory in older adults,” said Peter Mukli, M.D., Ph.D., who wrote the research team’s paper in the journal Advanced Science. He is a research assistant professor in the Department of Neurosurgery in the OU College of Medicine

Researchers conducted the study in the Translational Geroscience Laboratory at OU Health Sciences, which contains a variety of equipment for analyzing the biology of aging. In the study, healthy older adults, along with younger adults for comparison, were recruited to participate in a short memory challenge game on a computer while their brains were monitored by functional near-infrared spectroscopy. The game begins simply, requiring participants to remember individual letters and click when they see them again. Then it becomes progressively harder, asking people to memorize sequences of letters.

During the memory challenge, researchers noticed striking differences between the brains of younger and older adults. As soon as younger adults began the challenge, their blood flow increased for 30 seconds to brain regions corresponding to the task, then plateaued and maintained that level throughout the game. In older adults, blood flow increased somewhat during the first 30 seconds, but then died back down quickly. The process of regulating blood flow to the brain is known as neurovascular coupling.

Next, the brains of older adults reacted in yet another distinct way than those of younger adults. To compensate for insufficient blood flow in brain regions dedicated to the task, the brains of older adults essentially recruited other areas to help with the memory challenge. However, multiple brain regions working on a memory challenge — some of them unrelated to the task at hand — are considered less efficient than if blood flow is adequate in the area of the brain that needs it. The brain’s attempt to activate several brain regions simultaneously is described as an increase in functional connectivity.

“Increased functional connectivity characterizes a less efficient brain architecture in older adults,” Mukli said. “It could be compared to our early computers, which were much larger than today’s smaller, more efficient computers. Even though older adults use a larger amount of their brain for memory tasks, that doesn’t mean they are more proficient.”

Because of increased functional connectivity, older adults may still have normal cognitive function, at least according to measures commonly used in clinical practice. However, because functional near-infrared spectroscopy is sensitive enough to capture changes in the aging brain, it could be used to detect memory problems before they appear.

“There is an association between the magnitude of these changes and cognitive performance, which sheds light on the mechanism of cognitive deterioration with aging. So, this imaging technique potentially could be used as an early detection tool to find changes before they manifest into a cognitive problem,” said Andriy Yabluchanskiy, M.D., Ph.D., an assistant professor of neurosurgery in the OU College of Medicine and director of the Translational Geroscience Laboratory.

Understanding what happens in the brains of older adults is crucial because it allows researchers to then develop methods of preventing or delaying cognitive problems. The OU research team is now recruiting participants for a clinical trial that will test whether a form of vitamin B3, called nicotinamide riboside, can help improve blood flow to the brain. In previous studies in mice, the vitamin improved cognitive performance. Nicotinamide riboside is used by every cell in the body as a source of energy. The study is funded by a $3.1 million grant from the National Institutes of Health.

The study is open to adults ages 60 to 85. Participants will be randomly assigned to receive either nicotinamide riboside or a placebo pill. For more information about the study, call (405) 271-8130 or email gerolab@ouhsc.edu.