Redefining the “aging brain” through diverse data

Age is more than just one number. While neuroscientists used to think of cognitive aging as a single trendline, they now realize that vast individual differences require a more predictive and personalized approach. As they uncover more factors that affect cognition over time, they are realizing that modeling the aging brain requires more diverse data than traditionally captured. 

“We need to appreciate that how people age is as much a biological process as it is a social process,” says Randy McIntosh of Simon Fraser University, who is chairing a symposium at the annual meeting of the Cognitive Neuroscience Society (CNS) on brain resilience.

“It means there is no single molecule or a single protein that is a biomarker of healthy brain aging; there is going to be some combination. And capturing that intersection between what happens in our brains and what happens in our environment and in our culture is hard to do, but it’s also an exciting opportunity, especially in this age of machine learning.”

Indeed, as will be presented today at the CNS conference in Vancouver, B.C., researchers are now looking beyond the fMRI scanner to incorporate a wide range of data into their studies of cognition over the lifespan, everything from sleep and vascular health to religiosity and lifestyle.

At the same time, they are also widening who they study, moving toward more population-representative samples, as well as the conditions in which they test brain health, moving from solely controlled lab tasks to more naturalistic settings, like watching movies. New data is showing how, for example, even low levels of depression can influence cognitive decline. 

Together, these efforts are creating a broader picture of the aging brain, one that can not only help inform diagnosis and treatment of clinical disorders like depression, dementia, and Alzheimer’s disease but that can also help healthy individuals better optimize their cognition.

Uncovering the role of depression

Cognitive neuroscientist Audrey Duarte has seen a tremendous shift in cognitive aging over the last few decades.

Back in the day, we were really looking at age as young versus old, but when we would look at our data, two 70-year-olds could be incredibly different in how they perform on the cognitive assessments, their overall health, age-related diseases, and so forth. And our cognitive aging models just didn’t incorporate individual difference factors.”

Audrey Duarte, Cognitive Neuroscientist, Cognitive Neuroscience Society

For Duarte and her team at the University of Texas at Austin, this shift has meant looking beyond the genetic factors that contribute to aging to understand some of the more “malleable” factors, things that people can change or do at any age to help confer brain resilience over time. Importantly, her team also wants to broaden from whom they are capturing data, with a large multisite study of some 330 participants, aged 18-75, from diverse racial and ethnic backgrounds.

Now in year two of this five-year project, Duarte’s team is already uncovering new insights about the aging brain. As they will present at CNS, new unpublished findings show that even minimal levels of depression can lead to executive dysfunction that underlies memory impairments as people age. They are finding that this effect can be exacerbated in Black and Mexican Americans, who evidence finds experience higher levels of depression and Alzheimer’s disease prevalence than non-Hispanic Whites. 

In work from Duarte’s postdoctoral researcher Sarah Henderson, also being presented at CNS, they have also been looking at the mechanisms by which depression-related memory deficits occur. Linking the reported depression symptoms in their research cohort to a series of memory tasks participants undertook while in an fMRI scanner, the researchers found that an impaired ability to combat interference from competing information contributes to depression-related memory decline. 

Other findings from Duarte’s work have uncovered social factors, like religiosity, that seem to confer cognitive resilience in aging, and have uncovered insights from lifestyle factors like sleep. Making these connections has required a sustained effort in local communities to build trust with groups that have been underrepresented in neuroscience research. “By listening to people talk about their experiences with aging and their parents’ experiences, we’ve learned a lot about social support factors and other emotional support factors, as well as lifestyle factors that all contribute to how people age,” Duarte says.

The overall goal is to link these new data to executive function demands in the brain, so that the researchers can understand how aging across the lifespan differs as a function of different racial, ethnic, or social backgrounds. “Are there factors that may confer more resilience or exacerbate depression-related memory impairments, for example?” Duarte posits. 

Answering such questions can lead to a personalized approach to enhancing cognitive aging. For example, in participants whose brain scans showed high white matter vascular burden, physical activity could be an effective treatment for their depression, either instead of or along with medication.. “We’re aiming to build a decision tree that can help navigate all these individual differences,” Duarte said.

Uncovering the power of the natural setting

Karen Campbell’s work on cognitive aging began in a personal way, observing how her grandmother maintained her memory until the end – able to recount memories of growing up in Poland, her time at the Auschwitz concentration camp in World War II, and finally moving to Canada to make a new life. “That sparked my fascination with aging and memory and what makes some people resilient to age-related declines in the face of trauma,” says Campbell of Brock University in Ontario.

As Campbell began studying aging during her PhD research, she quickly realized how memory studies differ from how people use memory in everyday life. Whereas lab tasks ask study participants to study lists of words or pictures and then intentionally recall or recognize them, “in the real world, people are more often guided by their knowledge of a given situation and allow things to come to mind unintentionally,” she says. That realization prompted Campbell to seek opportunities to study memory and perception in more naturalistic settings, such as while people watch movies or read stories. 

As she will present today at the CNS conference, Campbell’s team’s findings have revealed that younger and older adult brains do not differ as much as previously reported when under natural conditions. Building on past work that shows that artificial lab tasks may induce a different type of brain activity than natural language processing, their recent work shows that older and younger study participants who watched a movie similarly perceived and remembered it. The participants watched the film naturally, without any tasks, and later answered questions about the movie, including identifying shifts in the story. “The findings suggest that a similar neural mechanism underlies better memory in both groups,” Campbell says.

Overall, Campbell’s research finds that “aging is not all bad,” she says. “Most older people are functioning just fine in everyday life, especially when they can make use of existing knowledge and their accumulated expertise,” Campbell explains. “We still need to figure out what leads some people toward pathological aging, but we do have some clues – exercise, get hearing aids if you need to, and try to maintain social connections.”

Now Campbell’s team is working on an intervention to help with memory for everyday life: Participants watch a movie and pause it at specific points to prompt them to come up with keywords that describe the event they just saw. “For instance, we are using BBC’s Sherlock, so at the end of one scene, participants might say, ‘Sherlock, morgue, riding crop,'” she says. “We think generating these keywords forces people to reflect on what just happened and rehearse the important bits.” This kind of retrieval practice has boosted memory in more standard list-learning paradigms, for example, but it has not been applied more widely in more naturalistic scenarios, Campbell says. Their preliminary results suggest that this intervention can boost memory and help make individual events more distinct from one another.

“What’s emerging is a view of brain aging that’s fundamentally about possibility,” says McIntosh, who is working to create generative models based on the various new and emerging data sets. “By modeling how biology, experience, and environment interact over time, we’re moving beyond averages and toward a science that respects individual lives, and opens new paths for resilience across the lifespan.”