Most scientists who study aging do so by studying older adults. That makes perfect sense, but Denise Park, PhD, isn’t most scientists. Park, who heads the Aging Mind Laboratory at the University of Texas at Dallas (UT Dallas), combines neuroimaging techniques and behavioral research to study the aging process across the life span.
"It’s very clear that there are age differences by decade, starting in your 20s and all the way through to your 90s," she says.
Understanding those changes, Park believes, will be the key to discovering new ways to maintain a healthy mind for a lifetime. Rates of Alzheimer’s disease are increasing as the U.S. population ages, making it one of the most pressing public health challenges of our era, Park says. To better understand and prevent the disease, she aims to learn more about what healthy aging looks like in the brain. At the same time, she’s exploring possible interventions to slow cognitive decline.
From any angle, the aging brain presents almost endless puzzles to solve, Park says. "I have spent my entire professional life studying cognition, beginning my freshman year in college, and I’m still not tired of it."
Brains across the life span
Park’s research helps explain why aging brains continue functioning well even as they show physical signs of aging. Numerous studies by multiple scientists, including Park, have shown that processing speed, inhibitory function, working memory and long-term memory decline with age, while certain brain structures also decrease in size. Yet imaging studies have found that older people have greater activity in the brain’s frontal lobes, the region in charge of planning, decision-making and other complex mental processes.
In an influential paper, Park and her colleague Patricia Reuter-Lorenz, PhD, of the University of Michigan, reviewed those findings and proposed a "scaffolding theory of aging and cognition" to explain them (Annual Review of Psychologyopens in new window, Vol. 60, No. 1, 2009). The theory posits that as the brain shows age-related structural degradation, there is an increase in brain activation. "In this paper, we specifically linked structure to function and suggested that older adults forge new neural circuits to compensate for some of the degradation in their brains," Park says. "We believe that the younger this compensation begins, the faster a person will decline cognitively." In other words, researchers and clinicians might one day be able to predict cognitive decline by identifying these compensation patterns years before cognition falters.
The scaffolding theory guides Park’s current project, the Dallas Lifespan Brain Study, a large, longitudinal study launched shortly after she joined UT Dallas in 2008. Park and her lab members are using fMRI, PET scanning and neuropsychological testing to follow some 500 people ages 20 to 90 to understand how a healthy brain looks and functions over time and to identify neural signatures that might predict future cognitive decline. Using new PET imaging techniques, the researchers are able to collect multiple measures of brain degradation—including deposits of amyloid, the protein associated with Alzheimer’s disease.
Predicting cognitive decline
Amyloid deposits in the brain have long been associated with Alzheimer’s pathology, but only in the last 15 years or so have scientists been able to view amyloid in living brains, using PET imaging. Those first PET results were surprising: Many older adults with normal cognitive function actually have quite high levels of amyloid in their brains (Neurologyopens in new window, Vol. 78, No. 6, 2012).
Now, Park is investigating what amyloid means for adults of all ages. In one recent example, she and her colleagues explored the relationship between amyloid deposits and episodic memory in three groups of participants from the Dallas Lifespan Brain Study: younger adults ages 30 to 49, middle-older adults ages 50 to 69 and older adults ages 70 to 89. They found that among the younger adults, those with a high amyloid burden had significantly lower performance in recall and recognition memory relative to their peers—a relationship that wasn’t present in the two older groups (Neurologyopens in new window, Vol. 87, No. 24, 2016). The finding suggests that amyloid may be influencing memory in young adults, even when it is present in subclinical levels. In related work, Park and her colleagues showed the amount of amyloid in the brains of people ages 40 to 89 could predict the rate at which they showed cognitive decline over the next four years (JAMA Neurologyopens in new window, Vol. 74, No. 7, 2017).
Ultimately, Park hopes this line of research will lead to screening techniques that can forecast dementia well before symptoms appear. "Evidence is mounting that amyloid is an early harbinger of Alzheimer’s disease, and it may take as long as 20 years before people [show symptoms]," she says.
While Park works to better understand the aging brain, she’s simultaneously undertaking efforts to help keep brains healthy well into late life. In one line of research, she’s investigating whether an engaged lifestyle can improve cognitive function.
She created an intervention called "Synapse," in which participants age 60 and older took classes in quilting or digital photography for 16 hours a week for three months. The classes were challenging, involving complicated sewing machines that required programming or technical photography and computer skills. Two control groups either got together regularly for social events or worked on cognitive tasks that required using previous knowledge but not new skills. At the end of the study, those in the quilting and photography groups showed significantly improved episodic memory and enhanced neural function relative to the controls—and some effects persisted up to a year (Psychological Scienceopens in new window, Vol. 25, No. 1, 2014; Restorative Neurology and Neuroscienceopens in new window, Vol. 33, No. 6, 2015).
Park believes the mechanisms underlying the positive effects of engagement are related to the sustained mental effort of learning. Now, she’s planning a clinical trial to further explore whether learning challenging new skills can help keep the mind sharp.
New colleagues, new paradigms
Park’s research has been (and continues to be) funded primarily by the National Institute on Aging. That support has been an important constant in a varied career, Park says. After completing her PhD in experimental psychology at the State University of New York at Albany in 1977, Park took a faculty position at the University of North Carolina at Charlotte. She held tenured positions as professor of psychology at the University of Georgia, the University of Michigan and the University of Illinois at Urbana-Champaign before moving to UT Dallas.
While some academics prefer to settle into one institution, Park says her relocations have been key to creativity and innovation in her research. "Moving around has been very productive for me," she says. "Every time I’ve moved I’ve been exposed to new colleagues and new paradigms, and I find there are interesting combinations of ideas that wouldn’t happen if you stayed in the same place."
Currently, Park directs a large and diverse group of lab members, including two graduate students, four post-doctoral researchers, a PhD-level physicist, three research assistants and a team of talented undergraduates.
Most labs that study cognitive aging tend to focus primarily on longitudinal research, or just on brain imaging, says Avanti Dey, PhD, a postdoctoral fellow who joined the Park lab in the fall of 2017, so she was attracted to the breadth of the lab’s research. "It’s one of the few labs that is truly interdisciplinary in its approach to cognitive aging," Dey says. "Having the expertise at our fingertips to use multiple techniques and methods, in our lab and with our collaborators, feels like an embarrassment of riches."
Park says collaboration ignites her natural curiosity. "There’s nothing I like better than sitting around a table and talking to people about different ideas to consider our findings and plan next steps in the research process."
That natural affinity for collaboration explains why one of Park’s students is from the nearby University of Texas Southwestern Medical Center (UT Southwestern). Catherine Munro, a doctoral candidate in clinical psychology, joined the lab under a cross-campus mentoring arrangement with C. Munro Cullum, PhD, a clinical neuropsychologist who studies dementia and sports concussions at UT Southwestern. Drawing from both of her advisors’ interests, Munro’s NIH-funded doctoral research involves identifying biomarkers associated with a history of concussion and head injury that might predict future cognitive decline. "It’s definitely not a small thing to [advise a student] across different institutions, but Dr. Park was immediately excited about the opportunity to collaborate," Munro says.
Breathtaking science
Park makes mentoring a high priority. On her lab’s website, she lists "training the best new scientists" as one of her primary goals. She approaches those relationships by working with students to find out what excites them and letting them propose studies that fit their interests and expertise.
While it could become almost easy to take Park’s rich longitudinal data sets for granted, she ensures that her students make the best use of those data. "You need to show the motivation and logic behind your question and set up the studies well," says current PhD student Xi Chen. "She has high standards for the work, but I appreciate that. Graduate school isn’t supposed to be easy."
Although the research is rigorous, it isn’t rigid, Park says. "I think one strength of my lab is flexibility. We can respond quickly to different ideas and initiatives."
Although there’s much left to learn about the aging mind, Park says it’s been a thrill to see how far the field has come in just a few decades, as new neuroimaging tools and techniques have transformed our understanding of the human brain. "Every time someone gets into the magnet and we look at their brain, that first moment we see the structure of their brain—it takes my breath away."
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