15 Oct 2016

In aging research, scientists often search for abnormalities that could explain why things go wrong. What about the other side of the coin? A growing trend to look at abnormalities that keep things going right got a boost from a recent study that evaluated brain thickness in older adults with unusually sharp memories. In the September 14 Journal of Neuroscience, researchers including senior author Brad Dickerson at Massachusetts General Hospital, Charlestown, report that older adults who exhibited superb memory abilities had thicker cortices in certain parts of their brains than did their more forgetful peers. While it’s unclear what leads to such differences, the authors think these so-called “superagers” could help unlock the secrets to healthy brain aging, and improve our understanding of what happens when brain aging goes awry. Some of the brain regions identified play key roles in learning and memory.

“What we learn from working with these gifted people could help us build or maintain resilience in people who have degenerative diseases that ultimately lead to dementia,” said Dickerson.

It is well established that as people age, their cerebral cortices thin. This thinning typically does not spare regions that support cognition and memory. But some older adults seem to buck this trend. Recently, researchers at Northwestern University found adults over 80 who exhibited memory abilities far superior to their peers. Dubbed superagers, these adults had thicker anterior cingulate cortices (see Rogalski et al., 2013). Inspired in part by those findings, Dickerson and colleagues set out to compare cortical thickness among adults of retirement age and young adults. He hoped to identify older adults who would score as well as those in the younger group, and to search for underlying neuroanatomical properties that might support their superior performances, even at an age often accompanied by a drop in memory and cognitive abilities.

Dickerson’s team evaluated 41 adults between the ages of 18 and 35 and another 40 between 60 and 80 years old. About 40 percent of the older adults scored high enough on a memory test to be classified as superagers. Using MRI, first author Felicia Sun and colleagues then looked for regions of the brain where the superagers might have thicker cortices. The scientists focused on regions traversed by two brain circuits widely recognized as important in memory and other cognitive functions: the default mode network, which coopts the medial prefrontal cortex and hippocampus and helps store and recall new information, and the salience network, which calls on portions of the anterior cingulate cortex and is associated with directing attention and identifying important details. Sun and her colleagues found a number of regions where cortical thickness in the superagers was higher than in other older adults, approaching—and sometimes matching—thicknesses seen in much younger participants. These included portions of the prefrontal cortex, midcingulate cortex, and middle temporal gyrus. Superagers had preserved thickness in four regions of the sensory cortex as well, but this was not as robust, Dickerson said. In some of those regions, including the midcingulate cortex and portions of the prefrontal cortex, thickness and memory abilities correlated across the whole group of older adults, raising the possibility that preserved thickness in these areas might support the preservation of processes underlying memory function. Volume and memory abilities in older adults were also correlated in the hippocampus, a critical region for memory and a key node in the default mode network.

“The results are very interesting because not only did they show brain regions where the superagers had a thicker cortex, but they also showed that this [thickness] was related to their cognitive function,” said Bill Jagust of the University of California, Berkeley. “It really is a pretty good story, identifying an important set of brain regions that has meaning for aging.”

Do superagers have thicker cortices from early in life, or might they have greater resilience in the face of age-related atrophy? Dickerson and his colleagues hope to answer this question in a two-year follow-up study of the older adults that will monitor how cortical thickness and memory ability change over time. If superagers turn out to be more resilient, understanding why might eventually allow us to protect other older adults from cognitive decline, said Dickerson.

The study does not address why some brain areas might be spared while others seem to show typical rates of thinning said Marcus Raichle of Washington University in St. Louis. One possibility, he noted, is that preservation of specific areas in the brain might be influenced by differing metabolism across the brain, something that has been previously shown to coincide with the deposition of amyloid plaque (see Vaishnavi et al., 2010). 

Emily Rogalski of Northwestern University in Chicago thinks the follow-up studies will be particularly important since the study cohort is relatively young. Age is the biggest risk factor for cognitive decline and dementia, and it’s not clear how exceptional performance in this study’s cohort will translate into exceptional aging at later stages, where she and her colleagues have chosen to focus their research. While more than 40 percent of the retirement-age adults in this study were determined to be superagers, only 5 percent of Rogalski’s participants (all older than 80 years old) met the Northwestern group’s criteria for superaging. Despite the differing approaches, Rogalski was encouraged to see that the study replicated some of her own findings. Both research groups found superagers had increased thickness in the anterior cingulate cortex, she noted.

“I think it’s exciting that they are confirming some of the findings in our study but in a slightly different cohort,” she said. “Even if there are some methodological differences, it’s showing us the anterior cingulate may be important enough to spend a little more time looking at.”

One potential weakness of the study noted by Rogalski and echoed by Bill Seeley of the University of California, San Francisco, was within the statistical approach, which Seeley described as having a “degree of circularity.” Differences in memory were used to define the normal and superaging groups, regional differences in thickness were found between them, and then those regions were probed for a relationship to memory, he noted. As with any study, he said, replication in an independent sample would help to address these concerns.

Still, both researchers described the study as thoughtful overall, and expressed enthusiasm about the findings.

“It sets the stage for future, larger studies that get at an underlying mechanism,” said Seeley. “I think this is a really interesting topic and I would like to see more and more studies focusing on successful aging.”—Lindzi Wessel

Lindzi Wessel is a freelance science writer based in San Jose, California.

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References

Paper Citations

1. Rogalski EJ, Gefen T, Shi J, Samimi M, Bigio E, Weintraub S, Geula C, Mesulam MM. Youthful memory capacity in old brains: anatomic and genetic clues from the Northwestern SuperAging Project. J Cogn Neurosci. 2013 Jan;25(1):29-36. PubMed.
2. Vaishnavi SN, Vlassenko AG, Rundle MM, Snyder AZ, Mintun MA, Raichle ME. Regional aerobic glycolysis in the human brain. Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17757-62. Epub 2010 Sep 13 PubMed.

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