Michael Yassa
"This suggests that the brain aging process is selective," says Michael Yassa, director of UCI's Center for the Neurobiology of Learning & Memory and the study's senior author. "Our findings are not a reflection of general brain aging but rather of specific neural changes that are linked to specific problems in object but not spatial memory." Steve Zylius / UCI

Irvine, Calif., March 7, 2018 — As we get older, it’s not uncommon to experience “senior moments,” in which we forget where we parked our car or call our children by the wrong names. And we may wonder: Are these memory lapses a normal part of aging, or do they signal the early stages of a severe disorder such as Alzheimer’s disease? Currently, there’s no good way to tell.

University of California, Irvine-led researchers, however, have found that high-resolution functional magnetic resonance imaging of the brain can be used to show some of the underlying causes of differences in memory proficiency between older and younger adults.

The study, which appears today in the journal Neuron, involved 20 young adults (ages 18 to 31) and 20 cognitively healthy older adults (ages 64 to 89). The participants were asked to perform two kinds of tasks while undergoing fMRI scanning – an object memory task and a location memory task. Because fMRI looks at the dynamics of blood flow in the brain, investigators were able to determine which parts of the brain the subjects were using for each activity.

In the first task, participants viewed pictures of everyday objects and were then asked to distinguish them from new pictures. “Some of the images were identical to ones they’d seen before, some were brand-new and others were similar to ones they’d seen earlier – we may have changed the color or the size,” said Michael Yassa, director of UCI’s Center for the Neurobiology of Learning & Memory and the study’s senior author. “We call these tricky items the ‘lures.’ And we found that older adults struggle with them. They’re much more likely than younger adults to think they’ve seen those lures before.”

The second task was nearly the same but required subjects to determine whether the location of objects had been altered. Here, older adults fared quite a bit better than in the prior task.

“This suggests that not all memory changes equally with aging,” said lead author Zachariah Reagh, who participated in the study as a graduate student at UCI and is now a postdoctoral fellow at UC Davis. “Object memory is far more vulnerable than spatial, or location, memory – at least in the early stages.” Other research has shown that problems with spatial memory and navigation do manifest as individuals progress toward Alzheimer’s disease.

Importantly, by scanning the subjects’ brains while they underwent these tests, the scientists were able to establish a cerebral mechanism for that deficit in object memory.

They found that it was linked to a loss of signaling in a part of the brain called the anterolateral entorhinal cortex. This area is already known to mediate communication between the hippocampus, where information is first encoded, and the rest of the neocortex, which plays a role in long-term storage. It’s also an area severely affected in people with Alzheimer’s disease.

“The loss of fMRI signal means there is less blood flow to the region, but we believe the underlying basis for this loss has to do with the fact that the structural integrity of that part of the brain is changing,” Yassa said. “One of the things we know about Alzheimer’s disease is that this region of the brain is one of the very first to exhibit a key hallmark of the disease, deposition of neurofibrillary tangles.”

In contrast, the researchers did not find age-related differences in another area of the brain connected to memory, the posteromedial entorhinal cortex. They demonstrated that this region plays a role in spatial memory, which was not significantly impaired in the older subjects.

“This suggests that the brain aging process is selective,” Yassa said. “Our findings are not a reflection of general brain aging but rather of specific neural changes that are linked to specific problems in object but not spatial memory.”

To determine whether this type of fMRI scan could eventually be used as a tool for early diagnosis, the researchers plan to expand their work to a sample of 150 older adults who will be followed over time. They will also be conducting positron emission tomography, or PET, scans to look for amyloid and tau pathology in their brains as they age.

“We hope this comprehensive imaging and cognitive testing will enable us to figure out whether the deficits we saw in the current study are indicative of what is later to come in some of these individuals,” Yassa said.

“Our results, as well as similar results from other labs, point to a need for carefully designed tasks and paradigms that can reveal different functions in key areas of the brain and different vulnerabilities to the aging process,” Reagh added.

This study was supported by the National Institutes of Health’s National Institute on Aging (grants P50AG05146, R21AG049220 and R01AG053555), a National Science Foundation Graduate Research Fellowship, and fellowships from the UCI Chancellor’s Club and the ARCS and Roche foundations.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 30,000 students and offers 192 degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit www.uci.edu.

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