On the Texas-Mexico border, a bold plan to diversify Alzheimer’s research takes shape

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BROWNSVILLE, Texas — Gladys Maestre is on a scouting mission. The Alzheimer’s disease researcher is driving through Southmost, a Mexican American neighborhood just north of looming sections of the border wall and a checkpoint that leads to Mexico. She passes barking dogs and “no trespassing” signs, but doesn’t see a single person outside, despite the comfortable stuffed recliners, refrigerators, and shade canopies that furnish many yards.

“A house outside the house,” Maestre laughs, delighting in seeing these elaborate living spaces while acknowledging that the clear wariness of outsiders here demonstrates the need for her unorthodox approach to engaging the people she studies. “That’s where we could put a community center,” she says, pointing to a vacant house. “For yoga, or art classes.”

For decades, and really for as long as the field has existed, Alzheimer’s researchers have recruited patients for clinical trials in largely the same way: pulling them from specialty clinics, often at elite medical institutions that house the bulk of the nation’s federally funded Alzheimer’s Disease Research Centers. That’s led to patients in these trials, which sometimes offer new therapies available through no other channels, being overwhelmingly privileged, well-insured, and white.

It’s an approach that’s been increasingly criticized for its lack of inclusion. Hispanic people, for example, make up more than 18% of the U.S. population, and are among groups more likely to get Alzheimer’s disease, yet accounted for just 2% of participants in Alzheimer’s clinical trials as of 2019.

Maestre came to Texas’ Rio Grande Valley to change that. With some of the nation’s highest rates of Alzheimer’s disease among Hispanic people and a population that’s more than 90% Mexican American, this would seem to be an easy place to recruit Hispanic patients to join studies. But that hasn’t been the case. When Maestre met with colleagues recently to analyze recruitment data, they realized that even here, where Spanish is the lingua franca and some towns have almost no white residents, 60% of patients interested in taking part in research are white — likely because they, too, were recruited from university health clinics.

While her team still has recruited far more Hispanic people than other centers have, the numbers are clear evidence, said Maestre, that the standard method of enlisting people for Alzheimer’s research is broken.

“It is the modus operandi of 99% of Alzheimer’s centers. High-risk patients get sick, go to the doctor, and get invited to participate,” she said. “It’s encouraged by the NIH because it’s cheaper, but this is why there are no Hispanics. You need to go to the population.”

That’s exactly what Maestre plans to do. A deeply respected Alzheimer’s researcher, Maestre left a faculty position at Columbia University in New York City in 2016 to join the fledgling University of Texas Rio Grande Valley School of Medicine and immediately started building an ambitious research program with more than $6 million she received from the National Institutes of Health. Then in 2021, Maestre was awarded, with Sudha Seshadri, a professor of neurology at the University of Texas Health Science Center at San Antonio, $14.8 million to open an Alzheimer’s Disease Research Center (ADRC) with locations in the Rio Grande Valley and in San Antonio.

That center’s new clinics and research labs opened last fall just north of Brownsville, in Harlingen. Maestre plans to use the new facility and funding to rethink, and perhaps upend, who is studied in Alzheimer’s research and how. Her team is starting to go door-to-door through the Southmost neighborhood to tell them about available resources for health issues including Alzheimer’s disease, and about opportunities to take part in research. She’s hoping to include people as young as 40 who may be at different stages of Alzheimer’s, making sure not to study only people with disease so advanced they’ve had to seek medical care. She’s also looking for clusters of disease, signs that the environment may play a larger role in the development of Alzheimer’s than traditionally believed.

Her goal is to broaden the focus many Alzheimer’s researchers have had on a single gene or protein — work she sees as counterproductive shortcuts that haven’t yielded a deep understanding of the disease. And don’t get her started on the field’s long-held obsession with clumps of amyloid proteins as a precursor of disease, a clubby focus that sucked oxygen, and grant money, from those who wanted to study other factors. “We want to cure Alzheimer’s disease without understanding it, without walking the path,” she said.

While researchers at her center and in San Antonio are studying a host of genes and biomarkers that may be involved in the disease, Maestre is also pursuing a more holistic approach — using state-of-the-art techniques to examine the contributions of vascular disease, strength of family ties, environmental pollutants, and the fabric of neighborhoods, and doing so in a population that has long been overlooked. The work here, she hopes, could speed the hunt for therapies and ways to prevent Alzheimer’s.

“If we bring diversity, not just check the box, but include the experiences of these people, we’ll have a better chance of understanding what’s affecting memory,” she said.

That could benefit all populations. Once patients are recruited here, their blood samples and brain images will be sent to a national tissue repository, helping to diversify a collection used in numerous Alzheimer’s studies.

Seshadri notes that looking at individual groups can serve a larger population; a class of cholesterol drugs called PCSK9 inhibitors arose from findings that some Black participants enrolled in the Dallas Heart Study had genetic mutations that led to extremely low cholesterol levels. “Answers you find hiding in people you haven’t studied could be valuable answers not just to them but to everyone. That’s the value of diversity,” she said.

It’s not as though Maestre is the only scientist studying Alzheimer’s in Hispanic populations. (Biogen and Eisai, for example, said Tuesday night that about 25% of participants in their clinical trial of an experimental treatment called lecanemab were Hispanic or Black people.) But most ADRCs have no more than a smattering of researchers focused on such groups. Here, geography is key, the work is community-based, and the local Mexican American population is the singular focus.

Alzheimer’s researchers around the country are eagerly awaiting the new samples that come from this population but also avidly watching how and what Maestre does. The nation’s major funder of Alzheimer’s research, the National Institute on Aging, has bet on Maestre with millions in funding, hoping her work improves, and even revolutionizes, how research is conducted.

“She knows this is her moment,” said Cerise Elliott, who co-leads the ADRC program at the institute. “If she’s going to make a difference, now is the time. She’s using this runway to be bold and really visionary.”

First, though, she has to get people to open their doors.

Maestre’s adopted home is a place of deep natural beauty. Native grasses and palm trees sway in the wind. Green waters lap in resacas, former meanderings of the Rio Grande now cut off from the river, which cool neighborhoods along their banks. But it’s also an area with entrenched poverty, a severe shortage of medical care, and staggeringly high rates of Alzheimer’s disease: Two of the valley’s counties rank among the highest in the nation for rates of the disease among Hispanic people.

It’s unclear exactly why cases in the valley are so common. The risk factors for residents jumble against each other like so many fallen blocks: Low education. Low household income. Lack of access to safe spaces for walking or exercise. High rates of diabetes. Obesity. Addiction. Air pollution. Toxic metals in the drinking water.

Many residents, like 51-year-old Alma Castor, live in colonias, neighborhoods of mobile homes and self-built structures that lie outside of city limits and often lack basic services such as running water, sewers, and trash disposal. Medical care, as it is for Castor, is often an afterthought.

She hasn’t seen a physician locally for 14 years, Castor said, since she had her last child, but will sometimes cross the border for medical care she can afford in Mexico: $25 for a doctor’s visit and $15 for prescriptions like the albuterol inhalers so many in her family need to breathe amid asthma attacks.

Castor, who forded the Rio Grande as a young woman and is now a legal U.S. resident, has worked hard all her life. She put most of her children through college, but still cares for her youngest, who are in high school, and a grandson with Down syndrome in a small home that carries watermarks from recent flooding.

Like almost everyone here, Castor knows several people with dementia. A man she works with no longer recognizes her. A neighbor she used to see wandering among the horses and goats that roam the colonia walked off one day and was never seen again. Her own children are worried she may have dementia as well. She’s gotten confused and lost a few times while out driving, she said. Her sons now track her phone so she can call them if she needs to be guided home. But it’s nothing she’s planning to see a doctor about.

Given how difficult it is for residents like Castor to access health care, Maestre thinks the disturbingly high rates of Alzheimer’s here are likely an undercount. Whatever the true numbers, they are likely to rise. With the U.S. Hispanic population expected to triple by 2050 — and age — the Centers for Disease Control and Prevention estimates that 3.2 million Hispanic people may have Alzheimer’s by 2060. Many of them are expected to live in the south, and in rural areas like this one.

Yet the nation’s 33 Alzheimer’s Disease Research Centers, which study causes of the disease and offer access to clinical trials of experimental treatments, are located mostly in more privileged settings in urban centers and along the coasts — and not necessarily in areas with the highest Alzheimer’s case rates. California has six, New York City has three, and Boston has two. Until the South Texas Alzheimer’s Disease Research Center opened here last fall, Texas didn’t have a single one.

To say Maestre thinks and operates differently than the typical researcher is an understatement. She’s as likely to be found presenting at a scientific conference as she is judging a fajita contest. She’ll mention tau proteins and the Renaissance artist Tintoretto in the same breath. She thinks scientists need to talk less about molecules and more about love.

On a recent day, she drove nearly 300 miles across her massive territory: the 43,000-square-mile Rio Grande Valley. First she met with Tony Falcon, who has practiced family medicine for 43 years in rural Starr County, one of Texas’ poorest, where 18.9% of Latino residents on Medicare are estimated to have Alzheimer’s disease; that’s the second highest county rate for Latinos in the nation after Miami-Dade.

Falcon was so frustrated at not being able to offer his patients anything for their dementia — he calls it “a death penalty diagnosis” — that he’s devoted many hours to set up a clinical trial site in a building near his practice in Rio Grande City. His office is so remote he can’t get the radioactive chemicals needed to run a PET scan to confirm a patient has Alzheimer’s, so he must use more painful lumbar punctures instead. “At least I have something available,” he said of the experimental drugs he can offer patients through the trials, “other than nothing but bad news.”

Maestre then traveled with an architect to San Ygnacio, a nearly 200-year-old outpost of sandstone buildings in Zapata County on the banks of the Rio Grande. It’s home to artists, historical preservationists, and a few hundred people, many of them healthy centenarians. They met with local artists and civic leaders to develop plans to use the unique community to test her theory that its labyrinthian streets may require memory tasks and navigation that keep aging brains healthy.

With a relentless intellectual curiosity and a penchant for asking questions outside, as well as inside, the lab, there seems no end to the connections Maestre makes, or the questions she asks in her lilting Venezuelan accent. What is the psychological impact of looking at a border wall? Why have human brains appreciated some painters — Tintoretto, for example — for 600 years? Could “reverse dippers,” people who have lower blood pressure at night than they do during the day, be at risk? Is sleep apnea a missing piece of the puzzle?

“Dr. Maestre is a force of nature. What she is building is going to resonate across ADRCs — and across the country,” said Jonathan Jackson, who directs the Community Access, Recruitment, and Engagement Research Center at Massachusetts General Hospital and has been a fierce critic of both the lack of diversity in Alzheimer’s research and the reluctance of many established researchers to change the status quo. “She doesn’t get the credit she deserves.”

Maestre was born in Venezuela, where she received a medical degree from the University of Zulia in her hometown of Maracaibo, and is still known for her long-term study of memory disorders among the coastal city’s residents. She found high rates of Alzheimer’s among residents and was among the first researchers — decades ago — to look for connections between cardiovascular and brain health. In a time when most researchers focused on brains from autopsies, she helped pioneer the use of 24-hour blood pressure monitors in aging, a tool now seen as increasingly promising.

She came to the U.S. to get her Ph.D. in neurobiology and behavior from Columbia, then did research at the Harvard-affiliated Mass. General and worked at Columbia. She was on the traditional path to academic success, and colleagues there told her she was crazy to leave back in 2016. But when she visited South Texas, she was captivated by the warm climate, abundant hospitality, and people with deep connections to family, all things that seemed so much like Venezuela. “It was déjà vu, like coming home,” she said. (Returning to Venezuela was not an option given the lack of support for science under recent government leaders and the lawlessness; carefully collected tissue samples from her Maracaibo project have fallen prey to highway bandits when being shipped by truck.)

“A few folks always get mentioned, they get the biggest grants and work at the biggest institutions, then you have someone like Gladys, who bucks that trend, who leaves Columbia to go to a Hispanic-serving institution in a place surrounded by disease where people really need help,” said Jason Resendez, who worked closely with Maestre as the founding director of the UsAgainstAlzheimer’s Center for Brain Health Equity. “She has a grit about her and a commitment to community.”

Maestre’s work is rooted in a deep humanism and care for the people she studies. When walking through the Brownsville neighborhood, for example, she lamented the trucks barreling toward the border on an adjacent street and the endless stream of cars and fast-food restaurants that stretched as far as the eye could see. The impact of such environments, with no sidewalks or places to gather, must impact brain health, she thinks. “Where are the cafes?” Maestre asked wistfully. “Where can they walk?”

“She talks about how everything Venezuela has gone through has somehow prepared her for this, for working at the U.S.-Mexican border, an area of deep human need and crisis,” said her co-director Seshadri, a noted neurologist who was recruited to Texas from Boston where she helped run the famous Framingham Heart Study. “She has an ability to see challenges on the ground and find the best way to answer those challenges.”

Those challenges include untangling the mosaic of diseases here, including diabetes and heart disease, that may be part of the reason for high Alzheimer’s rates. Many people with these comorbidities have been excluded from studies of the degenerative brain disease in the past because their health issues complicated analyses. This multifactorial complexity has been an issue for the field, but Maestre said she has recruited a team of scientists who have the statistical chops to power through the analyses she’s proposing.

Maestre knows the work here won’t be easy. She knows many doors in Southmost and elsewhere will stay closed despite her best efforts, and that answers to many of the questions she is asking will take years to unravel, certainly much longer than the typical length of an Alzheimer’s research grant. “The best story you will get from me,” she told STAT, “will be in 10 years.”

It’s not surprising that Maestre has found people reluctant to sign up for research studies. For one, there’s an understandable wariness of strangers here, where getting stopped by the border patrol is common, and the river is monitored by massive blimps. Many residents are fearful of Alzheimer’s and in denial. Their first instinct is not to seek help but to keep affected relatives hidden away. “They think if they don’t talk about it, it will go away,” Maestre said.

And many don’t rely on the American health care system because it’s too expensive or not to be trusted. They cross the border to see physicians, rely on folk healers called curanderos, or visit herbalists to get remedies like Yerba santa, “the holy herb.” Maestre is often surprised by the questions she gets about what she’ll do with blood samples. “They say, ‘Is this like Jurassic Park? Will you make my twin?’” she said.

Her secret weapons are promotoras, trained community health workers who live in the areas where they work. They have traditionally focused on helping neighbors with diabetes and cancer, but are being trained here about Alzheimer’s and other mental health conditions such as depression and substance use disorder. They have begun knocking on doors in Southmost to introduce themselves and inquire about who may be impacted by Alzheimer’s and interested in learning about Maestre’s research. It’s slow, careful work because many people here are nervous, afraid of both the disease and the interest of outsiders.

Maestre’s team has been holding focus groups to learn why people are staying away and what might help bring them in. “They said they don’t want to be touched,” Karla Lopez, a research associate and doctoral candidate, said at a recent meeting the team held to discuss patient enrollment. “They said, ‘Blood sample? No.’”

For Maestre, that means seeking out phlebotomists with “the softest hands.” For people who are afraid of the word Alzheimer’s, it means discussing “memory problems” instead. For older people who say they are too scared to be scanned inside an MRI machine, it means finding staff who will hold their hands throughout the procedure.

Another challenge comes from the for-profit plasma centers that dot the valley, where billboards read “Plasma: Good for You. Great for Life” and people can earn $700 to $900 a month selling their plasma. For some residents, said Maestre, “it’s a job.” And it means people willing to give blood samples to researchers often expect to be paid large sums. Her budget doesn’t permit paying such fees so she’s looking for other incentives she can offer.

Some people ask if Maestre can get their family members new drugs like Aduhelm, even though it’s seen as having questionable benefit. She can’t at this point because it’s only given at specific clinical trial sites, but she’s eager to listen to what else they may need. “They want to talk, to cry, to share,” she said. “I may be interested in Alzheimer’s. They may be interested in how to get their grandson treatment for addiction, or in vision, glaucoma treatment, and cataracts.”

She wants residents to see the research center as not just a medical office, but as a valuable part of their community. She’s arranged for patients and their families to get free access to a local zoo and art museum. She’s trying to find a venue for abuelas — grandmothers — to sell their arts and crafts to earn money. She gives research participants beautiful china dolls she’s collected. Accustomed to writing scientific grants that bring in millions, she’s been known to help community groups write grants that net just a few thousand dollars. “For them, it’s big,” she said. “I want people to see us as a resource. Our doors are open. Everyone has my cell.”

Yet another recruitment problem here is machismo. Alzheimer’s is more common in women, but in nearly all Alzheimer’s studies, men make up the majority of participants. Here, men are not that interested; they account for just 33% of people who have signed up. “They think if they ask for help, it will take their manhood,” Lopez told STAT.

To Maestre, it’s not only a logistical problem, it’s yet another research question to probe. “Let’s think about this, what are the reasons?” she asked the team during its recent meeting. “Let’s look under the hood.”

To get around the resistance, she’s trying to appeal to men’s groups and the altruism that runs through this community, where local charities gave $15 million toward the new Institute of Neuroscience where the ADRC is housed and donated the 35 acres that the building stands on. She asks her husband, an immigration lawyer, to give presentations about Alzheimer’s research at men’s church groups. Alan Francis, a neuroscientist who recently moved here from Harvard, recently spoke about the need for research subjects at the Harlingen Chamber of Commerce. “They took my cards and said they would call us back,” he told Maestre.

“I already got five emails,” Maestre said triumphantly. “We’re going to learn how to talk to men.”

The Institute of Neuroscience building in Harlingen has Maestre’s touch all over it. As a part of the design team, she insisted on the use of bricks that echoed the historic architecture of the region and asked for the building’s art selections to include the work of local artists. The windows overlook fields of sunflowers, and there are benches for patients and caregivers to sit outside. The inside has a pharmacy, MRI, labs, and tools ranging from eye-tracking machines to Maestre’s beloved 24-hour blood pressure trackers.

The ambitious work here will, of course, take much more than a gleaming building and shiny machinery. It will take researchers who not only understand, but are part of, this community. Maestre is fond of mentioning, even in the midst of a scientific talk, that fewer than 5% of researchers funded by the NIH are Hispanic. Here, the faculty list looks very different.

Mario Gil is studying the role of a gene called AVPR1A in cognitive performance. Juan Lopez-Alvarenga is studying vascular dementia. Marcio Almeida is looking for new biomarkers that predict dementia risk. Romeo Luis Escobar is studying stresses on Mexican American caregivers. Ney Alliey Rodriguez is combining research on the genetic underpinnings of Alzheimer’s with work on biomarkers and lifestyle factors to learn when people start to decline, and why. Alvaro Diaz-Badillo is testing whether eye tracking may help predict dementia. Candace Robledo, who was born here in the Rio Grande Valley but left to earn her doctorate and complete an NIH postdoctoral stint, has returned to study what role the pesticides and other industrial or carcinogenic chemicals implicated in the high rate of birth defects here may play in Alzheimer’s. Two more Hispanic scientists, one from Venezuela and one from Tijuana, were just hired.

In the past, many researchers from the north would descend on the region to conduct studies on the local population, often with a brusqueness and lack of regard locals still complain about. They often wouldn’t even inform people here about the results of their studies.

“They came, did the research, whatever they wanted, and left. It left a bad taste,” said Noe Garza, the center’s community liaison. “We’re here. It’s different. We’re not going to leave. Never.”

The work, this intensive and personal recruitment of patients, the goal of developing a broader view of the many factors that may interact to cause Alzheimer’s disease and also what may prevent it, can be exhausting.

At times, Maestre asks herself why she’s pushing so hard. It would be so much easier to conduct research the way it’s always been done, simply focusing on established clinic patients. It would also make financial sense. Many centers, she noted, get reimbursed by insurers to treat or assess patients, and are then paid again to research them. “Why do I want to make my life harder? Am I paying some imaginary debt?” she asked.

But she knows the answer. In this valley that’s now Maestre’s permanent home, Alzheimer’s and the devastation it wreaks are so palpable it can hurt. And the people here look like her.

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

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