When Anita Kunin heard the idea, she was immediately intrigued. 

“This is a no-brainer,” she thought.

Far from it, actually. Brains, it turned out, were at the center of the proposal in front of her.

It was 2010, and Kunin and her friends and fellow philanthropists Barbara Forster and Sally Kling were meeting with Apostolos Georgopoulos, a Regents Professor and McKnight Presidential Chair in Cognitive Neuroscience at the University of Minnesota Medical School. Georgopoulos was asking for their support in launching a first-of-its-kind study of women’s brain health across the lifespan. 

He wanted to know: Why do some women show signs of cognitive decline as they age while others do not? 

Kunin, Forster, and Kling were interested in helping him find answers. They shared the idea with other like-minded women, hosting small fundraising gatherings and meet-and-greets with Georgopoulos, and sent letters to more than 170 people asking for gifts of any size.

Within six months, they had raised more than $164,000—enough to launch the Minnesota Women’s Healthy Aging Project, which is now in its 10th year. 

Kunin says the idea of coming together to raise money in support of women-specific research was inspiring. And she was intrigued by the idea of helping with a project that specifically addressed the health and well-being of women of all ages.

“So much of what we know about medicine is because of studies of men. And women, for the longest time, were missing from a lot of the basic research on all types of diseases,” says Kunin, who turned 89 this year. “This study—which is really about understanding the structure and organization of women’s brains—allows women to participate in an area of research they’d never been invited to before. And that’s exciting.”

LONG VIEW

Georgopoulos came up with the premise for the project after a conversation with his wife, Lily—an endocrinologist who, at the time, directed the Women Veterans Comprehensive Health Center, part of the Minneapolis Veterans Affairs (VA) Health Care System. 

Lily told him about a handful of women in their 80s and 90s who came in for annual checkups and who, by all appearances, had dodged much of the physical and cognitive decline synonymous with old age. One 97-year-old even harvested her own wild rice and drove herself 40 miles to her appointments at the VA. 

“I said, ‘We must study their brains and find out what’s going on,’” Georgopoulos recalls.

To do that, Georgopoulos teamed up with Lisa James, an assistant professor in the U of M’s Department of Neuroscience and a clinical psychologist at the VA. Together, they devised a longitudinal study. 

Housed at the VA and including five other U of M investigators, it tracks the health and well-being of almost 100 women. The youngest are in their 20s; the oldest is 104. The participants come in once a year for checkups and diet, exercise, and lifestyle assessments; cognitive and language evaluations; genetic testing; and imaging to look at brain structure and activity. 

James says studying the same women year after year for a decade has yielded information and insights that are beginning to paint a rich picture of what it means to age. And that picture is challenging some of what we thought to be true.

“We all have this idea that dementia and memory loss are inevitable,” she says. “You get old enough and you’re going to start to lose brain matter and you start cognitively deteriorating, right? Not necessarily. We’re seeing people where that is definitely not happening."

James and Georgopoulos are beginning to understand why women like the 97-year-old are still sharp as a tack.

PREVENTING BRAIN DRAIN

Although the dynamics behind aging are varied and complex, the researchers have identified an allele (a special form of a gene) they believe plays an outsized role in preserving cognitive health and preventing brain deterioration. It’s known as DRB1*13:02, and it’s located in human leukocyte antigen (HLA) molecules. These molecules protect cells throughout the body—including in the brain—by destroying foreign intruders, like viruses, bacteria, and other germs.

James and Georgopoulos found that women who carried the allele lost far less gray matter—neurons and other brain cells—than women who did not have the allele. 

It’s a significant finding, James says, because it points to a connection between brain health and pathogen exposure, and suggests that certain pathogens might be to blame for brain loss. Further, it indicates that women who have the allele are protected from these pathogens’ harmful effects and explains why some women experience significant memory loss and cognitive decline, while others do not. 

The findings support James’ and Georgopoulos’ previous research on Gulf War veterans who returned from combat. They found those who had the (HLA) DRB1*13:02 allele were better protected than those who did not have it against Gulf War syndrome, a condition marked by headaches, fatigue, and cognitive problems that is thought to be caused by pathogen exposure during deployment. 

Together, the studies suggested that a person’s exposure to harmful bugs, bacteria, and other pathogens might be at the root of brain health over time. “We believe we’re looking at the source of neurodegeneration,” Georgopoulos says. 

PATHWAY TO INTERVENTION

But what about people who don’t have this super-powered allele? James says understanding why some individuals are more naturally resilient to brain deterioration will, in turn, help those who may need to boost their body’s defense system.

And that’s the ultimate goal of the project.

“We want to be able to forecast who might be in trouble down the road and intervene before it’s too late,”  she says.

Although it’s too early to say what that intervention will be, it could take the form of drugs or vaccines that protect people from the specific pathogens their bodies can’t fight on their own.

“We’re really interested in the idea of personalized or precision medicine,” James says. “No matter what our HLA looks like, we all have a limited repertoire in terms of what pathogens we can personally eliminate. Knowing what pathogens you have floating around in your body would give us a pathway to intervene on an individual level.”

HLA testing isn’t widely accessible yet. But she envisions a day when everyone will know their HLA fingerprint and can incorporate that information into a plan for lifelong health. “It’s kind of like knowing your blood type, or knowing your family’s genetics,” she says. “We’ve even thought about there being a mail-in kit that could be available in the future.”

FOR THE DAUGHTERS AND GRANDDAUGHTERS

James and Georgopoulos are optimistic about their initial findings and have no plans of slowing down the Women’s Healthy Aging Project. The longer the study continues and the more data they collect, the more powerful their potential findings will be. “We want to continue this in perpetuity,” James says.

But research is expensive, and securing federal funding for studies that explore what makes people healthy—as opposed to disease-specific investigations—can be challenging. 

That’s why Kunin has since doubled down on her commitment to the project, making a gift to endow a faculty position. Earlier this year, James received the Kunin Chair in Women’s Healthy Brain Aging, which will allow the team to continue their work indefinitely. 

“Over the last few years, I’ve decided that this project is going to be my thing,” Kunin says. “I want to help this study go on and on.”

To that end, James plans to keep expanding the study group to include more non-veterans and younger women, which will diversify the data. 

James says the women in the study are excited about being part of something that could one day help their daughters and granddaughters. “They have so much fun being a part of this,” she says of the participants. “I think they feel empowered and hopeful.” She says their enthusiasm keeps her energized as well.

Kunin is encouraged by the progress Georgopoulos and James are making. Many of her friends and peers have suffered memory loss, which has made her even more aware of the project’s life-changing potential. “We’ve learned so much about the brain just in the last 10 years,” she says. “Just imagine what we’ll know in the next 20.”

Justin Harris is a regular contributor to Legacy.