Spring 2023

Inclusive investigation

Chippewa elders step forward to take part in crucial U of M research that will make knowledge about dementia more relevant for all people


In far Northern Minnesota, the Nett Lake sector of the Bois Forte Band of Chippewa Reservation sprawls across 80,000 acres of remote wetlands, lakes, and dwindling forest. The sense of isolation is palpable here, just 40 miles south of the Canadian border, where medical services are limited.

“Being so isolated is one of our biggest challenges as a tribe,” says Bois Forte band member Corey Strong, who also serves as patient benefits case manager for Bois Forte Health and Human Services. “Our band members have to travel 60 miles to the closest full-service hospital for most specialized care.”

So when the University of Minnesota Medical School’s William Mantyh, M.D., reached out for help with a new Indigenous-focused dementia research project, leaders of the Bois Forte community were eager to participate.

“Although some of our tribal elders are distrustful because of things done in the past, in general we were very receptive to this research,” says Cathy Chavers, Bois Forte tribal chairwoman, president of the Minnesota Chippewa tribe, and a participant in Mantyh’s study. 

Chavers has worked in health care for almost three decades and knows well the importance of clinical research. “There is very little research specifically about Native Americans, and we urgently need more data about the many health problems—dementia, substance abuse, diabetes, heart disease—that are so common on reservations.”

The University also has a powerful resource that made Mantyh’s search for a tribal connection much easier: the Duluth-based Memory Keepers Medical Discovery Team (see sidebar below). This team focuses on reducing health disparities in Indigenous communities and has considerable expertise working with Indigenous people on research that is valuable to them. 

One size does not fit all

Because Alzheimer’s disease (AD) makes up  60 to 80% of dementia diagnoses, many researchers have targeted their efforts there. And that work has been fruitful.

“There’s a commercially available blood test for diagnosing AD, but it’s expensive and requires significant expertise to run,” Mantyh says. “More accurate, easy-to-use, and affordable tests are coming out in the next one to two years that will truly revolutionize our ability to diagnose AD.”

The blood test does two things: First, it quantifies the level of AD proteins (amyloid and tau) in the bloodstream. Second, it identifies an AD gene, APOE4, the most significant genetic risk factor for Alzheimer’s. 

If you have the APOE4 gene, Mantyh says, research has found that you’re three times more likely to get AD than those who don’t carry the gene. If you have two APOE4 genes—meaning you got one copy from each parent—your risk of getting AD is 14 times higher. 

“This is research that won’t just, ultimately, benefit Bois Forte or even just Minnesota, it will benefit everyone.”
Corey Strong

But while dementia experts cheered this promising new test, researchers like Mantyh had questions, most critically: Does having the APOE4 gene mean higher AD risk for everyone? And the answer appears to be no. 

The initial investigation studied mostly European Americans. Further studies have found that people of Japanese descent, for instance, possibly have an even higher risk of developing AD if they carry the APOE4 gene. Africans and Native Americans, on the other hand, might have no increased risk of disease at all.

Essential for everyone

One stat stands out as Mantyh sketches out the prelude to his current dementia research: In the largest Alzheimer’s disease blood test research study in the United States, which included several thousand participants, only two were Native American.

Memory keepers

Memory Keepers, one of four University of Minnesota Medical School Medical Discovery Teams established with targeted funds from the Minnesota legislature in 2015, works to eliminate rural and American Indian health disparities. The team, led by Kristen Jacklin, Ph.D., largely focuses on Alzheimer’s disease and other dementia-related research.

According to Jacklin, the history of unethical medical research with Indigenous communities led to a justified distrust of academic- or clinic-based research. “Our approach to research at Memory Keepers is to work within a community-based participatory research framework and Two-Eyed Seeing model, which means the Western biomedical science lens and Indigenous science lens are equally valued.”

The Memory Keepers team supported Mantyh’s dementia research through this community-engaged structure, which involved cultural advisers Annamarie Hill and Rick Smith, members of the Red Lake Nation, and J. Neil Henderson, Ph.D., a member of the Choctaw Nation of Oklahoma and former executive director of Memory Keepers. Mantyh credits all three with providing the crucial guidance that enabled him to create a successful partnership with Bois Forte.

“Ultimately, if we want to ensure equity in access to the outcomes of research,” Jacklin says, “we have to create equitable pathways for participation in research.”

“Plus, a lot of AD clinical trials include mostly people who are otherwise healthy,” Mantyh says. “Those trials don’t reflect the real world. And that’s the overarching goal of our work: Build on the success and promise of this blood test, but make sure it works for all populations.”

That’s how Mantyh and his team ended up heading northwest on Route 23 out of Orr, Minnesota, in the fall of 2021  and again in the summer of 2022 to the Bois Forte Reservation, where 38 tribal elders had agreed to participate in his research.

Funded with a grant from the Winston and Maxine Wallin Neuroscience Discovery Fund, Mantyh’s study included 90-minute visits with each tribal elder (those age 55 or older), plus a memory test, blood draw, and MRI. Mantyh then went over the results of the tests with each participant. 

Initial results suggest that, as he suspected, the promising diagnostic blood test for AD may not deliver accurate results for Native Americans.

“This research is one of the coolest things Bois Forte has been part of,” says Strong, who oversaw logistics and recruited elders for the study. “This is research that won’t just, ultimately, benefit Bois Forte or even just Minnesota, it will benefit everyone.”

Just the beginning

Now a second phase of the work is beginning. Strong is reaching out to nearby assisted-living facilities to see if any additional band members who have memory concerns would be willing to participate in the study.

“We owe a tremendous debt to the Wallin Fund,” Mantyh says. “Their generosity enabled us to gather pilot data and, using that, we’ve applied for a five-year NIH [National Institutes of Health] grant to explore the issue in greater detail.”

But Mantyh hopes this research is just the beginning of more dialogue between academia and tribal communities. 

“Dementia is very underserved across the board,” he says, “but that’s magnified in Native American communities, where there’s little care available.”

Chavers agrees. While there is no dementia care available on the Bois Forte Reservation—families care for elders with AD in their homes, or patients move to memory-care facilities off the reservation—she says the elders who participated in the study expressed keen interest in learning more about their brains and about dementia.

“Tribes really have to battle for funding, but we still want to offer more in prevention, care, and education for our people,” Chavers says. “Research studies like this can help us do that. I was honored to be part of it.”