In the whitewashed world of Alzheimer’s research, one scientist is on a quest to understand the diversity of brains

CHICAGO — When she entered the field of Alzheimer’s research a quarter century ago, Lisa Barnes was deeply disappointed to find few Black people like her family members with dementia were being studied. A rarity herself — as a Black female cognitive neuropsychologist — she’s spent her career quietly pushing back.

Since 2004, Barnes has been running the Minority Aging Research Study, one of the nation’s largest studies of Alzheimer’s focused exclusively on Black people and has created a brain bank used by other researchers to understand the illness in this population. This was no easy feat, given that many of the people she hoped to study grew up amid Jim Crow laws and often held a deep mistrust of medical science and its experiments.

“We were learning a lot about Alzheimer’s and cognitive decline but those studies didn’t have people of color, African Americans in particular,” said Barnes. “I wanted to interrogate some of the lived experiences of older African Americans based on what I knew about my own family,” she said in a recent interview at her office at Rush University.

It’s critical work with the population of older Black Americans expected to double in coming decades. Some studies suggest Black Americans are more likely to develop Alzheimer’s disease or other dementias, yet are far less likely to be diagnosed with the disease, and they are still barely represented in many clinical trials for new dementia drugs. There are hints that in Black populations, the disease may progress differently, have different causes and biomarkers, and may not always be so closely tied to the amyloid pathology that’s the focus of many new treatments.

But because there’s been scant research in Black populations, and barely any brains from Black people without dementia to study, understanding these critical differences — and potential treatments they may lead to — remains a distant goal. Barnes isn’t convinced that a widely cited statistic, that Black Americans are twice as likely to get the disease, is true, because there’s a dearth of data from brains of Black people and Black older adults tend to perform more poorly on the standard cognitive testing used to assess people for the disease due to a host of educational and cultural differences.

That’s not to say Barnes hasn’t made significant strides. Among the most cited of the nearly 300 research papers she’s written or co-authored is a genomics study showing that the APOE4 gene variant that’s tightly linked to Alzheimer’s in white populations does not have the same effect in Black populations. But for Barnes, the most important work has been on social factors that impact cognition, from studies showing the effects of school segregation and discrimination can lead to lower cognition later in life, to research showing other factors, such as spending time with friends and family, can be protective. (She and other researchers emphasize that any differences between populations in Alzheimer’s are largely due not to genetics but to social factors associated with racial categories, such as wealth, education, discrimination, and access to health care.)

“Lisa and her cohort studies made it clear that Alzheimer’s does not progress the same way for all people. It helps us not just understand Alzheimer’s disease in Black people but Alzheimer’s disease in general,” said Jonathan Jackson, who directs a center at Massachusetts General Hospital that studies the impact of diversity on human subjects research. “The rest of the field is just now catching up to her wisdom.”

Barnes’ research, along with the work of two other pioneering Black psychologists — Jennifer Manly of Columbia University and Keith Whitfield, now the president of the University of Nevada, Las Vegas — has raised a slew of critical questions about how the disease differs in Black populations, why cognitive testing relied on to clinically diagnose dementia may fail Black patients, and whether the disease progresses differently in them.

These are questions Barnes has been asking for decades, while quietly emphasizing to her mainly white research peers that Black populations are not a monolith — they vary in socioeconomic status, education levels, and life experiences just like white populations — and despite the pushback she receives to this day, that there is value in studying Black populations for themselves.

A second-generation practicing Buddhist, Barnes is exceedingly calm. But if one thing gets to her, it’s grant and peer reviewers questioning the validity of her studies because they include no white comparison groups.

“My studies aren’t valid because they can’t be compared to white people? The answer is why are white people considered the gold standard?” she asked. “It’s a constant battle — it’s the whole field that’s like this. And it’s hard to change a whole field.”

But Barnes is trying.

Barnes’ interest in medicine was borne of tragedy. A Chicago native, she lost her father to a shooting at the age of 4. She couldn’t save him, of course, but grew up thinking she might be able to save others if she became a doctor. She realized rather quickly that medicine was not for her, but studying the brain was. “I decided instead I could be a really good book doctor,” she said.

Throughout her studies at Wellesley College and then Clark Atlanta University, she never shook that early fascination with the brain. And though it wasn’t in her science textbooks, she thought a lot about race as well. These were the years when ideas presented in the controversial book “The Bell Curve,” with its now-debunked premise that racial differences in IQ tests were genetic, were roiling public debate. “There was all this craziness around cognitive testing, racist theories,” Barnes said. “People just didn’t want to touch it because obviously it’s difficult to talk about.”

Later at the University of Michigan, she was the only Black Ph.D. student in biopsychology and the second to ever graduate from the program, she said. She had chosen the university because it graduated the most Black Ph.D.s overall after Howard, and she was able to lean on Black students studying other areas of psychology for support.

She was researching memory and the hippocampus and noticed right away that the studies in her field were conducted primarily on white people, often on college students. “In biopsychology and neuropsychology, race wasn’t even a construct people really talked about,” she said.

When she moved into studying Alzheimer’s in the job she took at Rush in 1999, it was the same. “You could count on one hand the number of studies that included large numbers of African Americans,” she said.

She knew — even from her own family, where there is a history of dementia on both sides — that Black people were affected by Alzheimer’s as well. She wasn’t surprised not to see them included in research. “But I thought, ‘Here’s something I can do something about,’” she said.

“It wasn’t an aha moment, it was more like a duh moment,” she said of her decision to focus on studying Black populations. “Why wouldn’t we?”

It’s this perspective — or perhaps simply the clearsightedness about long overlooked research gaps — that’s such a strength of Barnes, said Damali Martin, chief of the population and genetics branch in the division of neuroscience within the National Institute of Aging, the agency that funds her. “When you have diversity within the workforce, it brings different perspectives,” she said. “It helps accelerate the research. It’s just really good for science.”

What Barnes needed was brains.

Brains from deceased patients have long been key to understanding the pathology of Alzheimer’s because until recently, they were the only way to see the amyloid plaques and tangled masses of proteins within nerve cells that are the hallmarks of disease. With today’s modern analysis techniques, brain tissue can also provide detailed cellular and genetic information that might provide clues into how and why the disease progresses.

Rush University has a long history in treating and studying Alzheimer’s; it’s home to one of the nation’s oldest Alzheimer’s Disease Research Centers and runs major long-term studies, including the Religious Orders Study, which tracks the physical and cognitive health of 1,100 older Catholic clergy, and the Rush Memory and Aging Project, which follows 2,200 older Chicago residents. Neither study includes a large number of Black participants, partly because they both require participants to agree to donate their brain.

Barnes started her work knowing you just don’t go asking Black people, who have lived through a history of horrendous medical experimentation — from the father of gynecology, J. Marion Sims, conducting surgery on enslaved Black women without anesthesia, to the U.S. Public Health Service leaving Black men in Tuskegee, Ala., untreated for syphilis — for their brains. Asking for cerebrospinal fluid samples, another target for Alzheimer’s researchers, is also a tough ask. Not only are they painful, lumbar punctures were a key part of the Tuskegee experiments.

“People still remember those studies. It’s an oral history that’s passed down — ‘Don’t trust these researchers, they’re going to do something to you,’” Barnes said. It’s something she has to overcome. “I might be a Black person, but I represent a white institution. I have to earn that trust — it’s not just given to me because I’m Black.”

If she were to succeed, Barnes would have to start slowly and develop relationships with the people she hoped to study. “The model we have is give first before you ask for anything,” she said.

She set up memory fairs and educational events, where she met hundreds of people. She asked for letters from the community to use in her grant applications. It’s a show of patience unusual for science, where researchers often scramble to meet grant deadlines, publish papers, and recruit patients on accelerated schedules.

Not Barnes. “I spent two to three years giving first before we asked for anything,” she said. It paid off. She recruited 200 Black participants to join the study in the first year because of the foundation she’d laid. Brain donation is not required; while participants can agree to it, Barnes doesn’t ever push.

Then she did something virtually unheard of for a study’s principal investigator: She visited every single participant, driving to homes all over the Chicago area to thank them. She asked her assistant to schedule 15 minutes with each participant. It wasn’t nearly enough. “They were so excited I was there, they wanted to make me lunch and show me pictures of their grandchildren,” she said.

The visits ended up taking half of her work schedule those early years. “People don’t do that. You don’t get tenure for that,” she said. But she continued, seeing how much impact she was having.

Barnes also made sure the research was as easy as possible for participants, who must have no signs of Alzheimer’s disease to enroll. The study includes cognitive and physical exams and blood collection each year. These are done at the participants’ homes and divided into several visits so as not to be overwhelming. While many research projects conducted on communities historically overlooked in medical science have trouble recruiting participants, Barnes has no such problem. Her study population has grown to more than 800 people. “A lot of it is word of mouth,” she said.

Some of those words come from Eugene Leonard, 75, a retiree who formerly worked in social services and lives on Chicago’s South Side. He first learned of the study during a talk for seniors Barnes gave in the building where he lives. He listened and took a pamphlet. After thinking some more, he decided to sign up.

“I said, I have to do my part. As an African American man, doctors are something we shy away from,” he said. “There’s the fear factor — you don’t want to know, and machoism, thinking I’m healthy, I’m strong.”

Males have been difficult to recruit; the population is 75% female, said Barnes, a gender imbalance seen in studies of white populations as well.

Leonard said he was comfortable with the study right away because of the caring nature of the researchers. “Being the same race is a positive,” he said. “I think they understand the psyche of African American males.”

Enrolled since 2012, Leonard said the process has been effortless. “They come visit on my time frame, there’s no pressure. You feel very comfortable,” he said.

When asked whether he’d donate his brain to the study after his death, Leonard took his time. “I had to think about it and talk to my children about it,” he said. “They said, ‘why not?’”

“We all have a responsibility to do what we can to help researchers understand how the disease progresses,” he said. “It may not necessarily help me, but it will help generations behind me.”

What Barnes has been focusing on more recently is keeping people enrolled in the study. It’s critical, especially for brain donation, that older participants remain involved. She realized that many of the participants she works with are dealing with a lot, medically, legally, and financially, so in addition to celebrations and events where she presents her research findings to participants, she took another unusual step for a research scientist: She wrote a supplemental grant to include a social worker on her team.

“People said, you can’t do that, but Dr. Barnes said yes you can, and it’s perfect,” said Janice Layne, the project’s community engagement and retention coordinator.

The social worker, Charon Cannon, checks in and can help with things participants need. “She spent days on the phone trying to get people their Covid vaccinations,” said Karen Graham, who manages community engagement for the project. “Things like that keep people retained.”

While some researchers neglect to share results of studies once they’ve gotten the data or blood samples they need, Barnes makes a point of sharing research findings. That’s something Minnie Jefferson, an 80-year-old former Chicago school teacher, says she appreciates.

It’s clear seeing the team interact with participants like Jefferson — on a recent day they fawned over her new braids — that there is a lot of mutual respect, you might even call it love, between the researchers and the people they study. “We’re not like, ‘Oh god, there’s Miss Jones calling us again,’” said Judy Phillips, the project’s senior engagement outreach coordinator.

It goes both ways. Leonard sings the praises of the research team at events about the research. “I was able to give testimony and 20 people signed up,” he said. “They see these individuals as trusted individuals.”

The Alzheimer’s research community has begun to realize what Barnes saw so long ago: There is not enough diversity in Alzheimer’s studies and this deficiency has undermined efforts to understand how the disease unfolds in different populations.

“The field has fallen short in efforts to recruit and retain diverse research cohorts,” the authors of one recent review paper said in assessing whether Alzheimer’s biomarkers differ between Black and white populations, adding, “as we have repeatedly emphasized, more research in this area, and in larger and more representative samples, is greatly needed.”

The findings on racial differences so far are intriguing, but conflicting. Several studies have shown that Black people have lower levels of tau proteins linked to Alzheimer’s in their cerebrospinal fluid, but these papers are limited by the small number of Black participants willing to have the lumbar punctures needed to get these data. Some studies show a reduced burden of amyloid in Black populations, others show no differences. Studies in patients recruited from memory clinics often yield largely different results than population studies where participants include more of a random sample from the community.

While it’s known that Black populations have a higher rate of vascular disease, which has been linked to dementia, some studies show they don’t have the related lesions in the brain that would be expected from this. Also puzzling to researchers is the fact that while the APOE4 gene variant is found to be the most potent driver of Alzheimer’s pathology in white people, and is found more frequently in Black people, it seems to do less damage in them.

It’s all kind of a mess, primarily because there haven’t been enough studies — or people to study. “What we need to know is, is the underlying pathology of the disease in the brain different? We can’t answer that because we don’t have the data,” Barnes said. “When you’re going to recommend treatments, you need to make sure you have inclusive science.”

Barnes is trying to do just that. Her collection now includes the donated brains of 150 Black participants compared to 2,000 donated brains of white participants at Rush. “It’s just really, really harder,” said Barnes. “But the numbers are growing.”

After death, brains are removed during a rapid autopsy protocol so that bodies can be returned to families as quickly as possible for funerals. Ryan Johnson, pathologist and assistant manager of the Rush Alzheimer’s Disease Center lab, manages a team that’s on call 24/7 to respond.

Once a brain is removed, half of it is cut into slices, flash-frozen, and stored in an ultracold freezer. The other half is fixed in formalin, then cut into one-centimeter slabs before the tissue is preserved and sectioned for analysis. The specimens are shared with researchers around the world.

The team is blinded to whether or not donors have Alzheimer’s and the disease can’t be officially diagnosed without a closer analysis under the microscope, but sometimes the ravages of the disease are visible to the eye. In a brain Johnson held in his gloved hands recently, the ventricles were enormous; these cavities filled with cerebrospinal fluid had expanded as the brain atrophied.

The many brain slices, tissue, and blood samples are stored in Rush’s massive “freezer farm,” where there’s backup after backup to protect the samples: alarm systems, carbon dioxide tanks, and backup generators. “This is 25 years of specimens,” said Barnes. “The last thing you want is someone you’ve been following for 20 years and it’s all for naught.”

Barnes is happy to share whatever stories these brains can tell with fellow researchers. She can’t get to all the data she wants to write up, she said. Over the years, her work has garnered plenty of awards. There’s the NIH Pioneer Award she received in 2017, the endowed chair she holds at Rush, and the hundreds of publications. But all the credit, she insists, should go to the study participants. “I’m able to do what I’m doing because of them,” she said.

They are also what keeps her going. There was one woman, now in her 70s, who told Barnes she had marched with Dr. Martin Luther King when he came to Chicago’s Garfield Park in 1966. She’d been hit by rocks that day, and been spat on. But she told Barnes: “I would do all of that again if I knew there was someone like you, African American, doing research and helping us.” Said Barnes: “I was bawling.”

This is part of a series of articles exploring racism in health and medicine that is funded by a grant from the Commonwealth Fund.