Come Monday, we should learn whether the Food and Drug Administration will approve the first new drug since 2003 to help slow the relentless cognitive decline caused by Alzheimer’s disease.
While there is much uncertainty swirling over whether the drug will be approved, how effective it is, how much it should cost, and how it could be administered given the shortage of memory specialists and brain imaging machines required to identify eligible patients, one thing is abundantly clear: Approval of Biogen’s aducanumab, or other similar medications rising through the drug development pipeline, is likely to only increase massive racial inequities in the treatment of the more than 6 million Americans with Alzheimer’s.
Black people are twice as likely, and Hispanic people are 1.5 times more likely, than white people to have Alzheimer’s or other dementias. But they are far less likely to have the condition diagnosed. And patients of color are less likely to be referred to specialists, something that’s especially key for Alzheimer’s care.
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“The emergence of any new drug could really widen health care disparities that already exist,” said Allan Levey, a professor of neurology at Emory University School of Medicine who directs the university’s Alzheimer’s Disease Research Center and wrote a recent editorial describing many of the issues raised by the looming Alzheimer’s treatments. “Covid provided examples of exactly the same issues we could face here — disparities in detection, testing, and treatment. … Even if the treatment gets approved tomorrow, there could be years of delay to get treatment.”
Early diagnosis will be critical for aducanumab or similar drugs that clear away clumps of a misshapen protein called beta-amyloid. These drugs work best before patients show signs of dementia, and so many doctors rely on a type of brain imaging called a PET scan to spot the amyloid plaques that are telltale signs of Alzheimer’s. But Medicare does not reimburse for such scans, putting them out of reach for many patients. Various proteins related to Alzheimer’s can also be found in cerebrospinal fluid and measured through more invasive spinal taps, but both imaging and spinal taps require the expensive specialty care that patients 0f color are less likely to receive.
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Many Alzheimer’s patients and caregivers also report that racism is a barrier to their getting adequate care. A report released by the Alzheimer’s Association in March showed that 66% of Black Americans believed discrimination made it harder for them to access good care for Alzheimer’s; about 40% of Hispanic and Native American people reported the same barriers. The discrimination detailed in the report included providers not listening to patients or caregivers of color, talking down to them, and treating them discourteously.
“We knew access was a problem, we didn’t realize discrimination when receiving care was a barrier as well,” Carl Hill, the association’s chief diversity, equity, and inclusion officer, told STAT.
The misdiagnosis of Sonia Cardona, a former teacher’s aide in Chicago who was originally from Puerto Rico, is just one example of the subpar care many Black and Latinx patients may receive. Doctors missed her early-onset Alzheimer’s for at least five years despite increasingly severe symptoms characteristic of the disease. “They kept telling her she was depressed, depressed, depressed,” said Cardona’s daughter, Daisy Duarte.
Cardona was in her mid-50s at the time, so she may have seemed young for an Alzheimer’s diagnosis. But if her physician had taken the time, he would have learned she came from a family with a history of early-onset Alzheimer’s; her mother, and all 10 of her mother’s siblings in Puerto Rico had suffered from dementia. “That doctor in Chicago really dropped the ball,” Duarte said.
The problems were compounded by her family’s refusal — which Duarte said she believes is widespread among Hispanics — to acknowledge that her mother might have dementia or to seek medical care. “They just say, ‘Oh she’s crazy,’ and don’t take them to the hospital.”
The symptoms, including the formerly sweet-natured Cardona becoming increasingly spiteful toward family members, worsened to the point that Duarte’s brother, a Chicago police officer, could no longer care for her. That was 11 years ago. Duarte and her sister brought Cardona to live in Springfield, Mo., with Duarte’s sister, who planned to care for her while raising a family, working, and starting a new business. Within a week, Cardona was at Duarte’s front door with her suitcase. “My sister just couldn’t handle her,” Duarte said.
Duarte, an avid Chicago Cubs fan, was at the time running a sports bar called Da Cubby Hole, a business that had been her lifelong dream to open. She cared for her mom at home and brought her everywhere, including to work, where, despite her mom’s increasing confusion and depression, Duarte gave her small tasks and a title. “I told her she was the manager and fellow employees played along, asking her questions even though they knew the answers. Every Friday, I gave her $10 or $15 in cash in an envelope as a paycheck and she thought she won the lottery. She was so happy.”
But Cardona’s behavior deteriorated rapidly during that first year with Duarte. One night, she found her mom screaming desperately: “I can’t do this anymore. They want me to kill myself.”
Thinking she might have bipolar disorder or schizophrenia, Duarte took her to an emergency room. From there, Cardona was placed in a mental health facility. When Duarte saw the severe psychiatric issues of other residents, she knew there had been a mistake. “I knew she didn’t belong in there,” she said. “And they had her so drugged up, she looked like a zombie.” To make matters worse, Cardona could no longer speak English, which she had once spoken perfectly — and taught to scores of ESL students over the years. She now spoke only Spanish, which none of the medical staff spoke, so she couldn’t communicate.
After completing paperwork to become Cardona’s power of attorney, Duarte was able to get her mother released. When she asked for a diagnosis, a neurologist at the hospital told Duarte that Cardona had Creutzfeldt-Jakob disease, a neurodegenerative disorder — and less than nine months to live. “I was like ‘Oh God,’” said Duarte.
The incorrect diagnosis was the beginning of what would be a long and difficult journey for Duarte, as a caretaker and as someone who — though she didn’t know it yet — was at high risk of inheriting Alzheimer’s herself.
Clinical trials of potential Alzheimer’s treatments have been conducted with largely white patients, and that means our understanding of how well the drugs work is based on the biology of the disease in white people.
The 257 participants in a recently published Phase 2 study of Eli Lilly’s plaque-clearing Alzheimer’s drug donanemab included just 3% who were Black, 3% who were Hispanic, and 1% who were Asian. In one Phase 3 trial for another Lilly drug, solanezumab, just 1.6% of 2,129 participants were Black. For the global aducanumab trials, information released by Biogen includes only Asian people, who made up roughly 10% of participants, and white individuals, who made up 80%, a lack of diversity that was criticized in an Institute for Clinical and Economic Review report about aducanumab released last month.
Such lack of racial and ethnic representation is widespread in Alzheimer’s clinical trials. “If people from underrepresented groups are just 2 to 3% of the trial participants, that’s too few to know whether or how they will respond to the drug or experience side effects,” said John Morris, who directs the Charles F. and Joanne Knight Alzheimer’s Disease Research Center at Washington University School of Medicine in St. Louis. “If we only study white people, we’re only going to learn about Alzheimer’s in white people.”
Lilly and Biogen did not provide comment about the lack of diversity in Alzheimer’s clinical trials, but in November, pharmaceutical manufacturers — through their lobbying group PhRMA — pledged to address the issue and make trials of all kinds more inclusive.
The underrepresentation of people of color in trials is not just a hypothetical concern. Emerging — and controversial — research led by Morris and others points to possible racial differences in some brain biomarker levels that are used as early indicators that Alzheimer’s may be taking hold before symptoms are apparent.
Morris’ recent finding that amounts of the protein tau appear to be lower in Black individuals than in white individuals — and other studies showing that other Alzheimer’s biomarkers may also differ by race — suggests that without changes to current diagnostic guidelines, some Black patients with early Alzheimer’s could be unfairly excluded from clinical trials or getting new treatments once they’re approved. This could be true for other groups as well, but no one knows because so few patients of color have been included in research. Native Americans, for example, are basically unrepresented in clinical trials.
Alzheimer’s experts said the differences in biomarker levels may result not from biology or genetics but from social factors such as poverty or racism. “People of color experience differences in educational opportunities, in the neighborhoods where they live, in exposure to air pollution, and certainly stress-producing discrimination, “ Morris said. “All of these social determinants of health certainly can play a role in observed racial differences.”
Other researchers are not convinced that these biomarkers vary by race, primarily because so little Alzheimer’s research has been conducted on Black and Latinx people. “We don’t know these differences exist and the reason we don’t know is we have an inequitable system,” said Jennifer Manly, a professor in the Columbia University neurology department who studies predictors of Alzheimer’s disease in Black and Hispanic populations. “Not only has research been occurring in clinics with mostly white people, the research is occurring on mostly well-educated and well-resourced white people.”
The resulting uncertainty about a new drug’s effects on people of color is likely to amplify the mistrust many may already have about receiving medical care. “People are going to want to know, is this going to help me?” said Manly, who is the first Black tenured science professor at Columbia University Irving Medical Center. “The answer is with current studies, we don’t know. The effectiveness of these treatments has not been tested in people of our background.”
Morris, who is white, has worked to change that. When he took over Washington University’s Alzheimer’s research center in the late 1990s, less than 3% of people in its clinical studies were Black. He knew that was wrong, especially for an institution in a city where 18% of the population was Black.
Morris also knew he needed help reaching out to the Black community, so he turned to Norman Seay, a revered civil rights icon in St. Louis whose mother had been affected by Alzheimer’s. In 2000, Seay organized and led an African American advisory board to help Morris and the center become more welcoming to Black participants. Seay signed up as a research participant himself, even volunteering to undergo a spinal tap.
“One day, Mr. Seay mentioned to me that throughout his study participation, he didn’t see a single person of color on our staff,” Morris said. “It hadn’t occurred to me until then that we were all white — that’s how naive I was.”
Seay passed away in 2019, but he left important legacies. An annual lecture series in his name at the medical school at Washington University highlights the work of Black Alzheimer’s researchers, and the percentage of Black people enrolled in studies at the center is now 19%, which Morris says is what allowed him to do the research on possible racial differences in Alzheimer’s biomarkers. “We also now can ask important questions about the role of social determinants of health,” said Morris.
When Cardona got the diagnosis of CJD, her daughter had nowhere to turn. “The doctor just said it was a rare disease and no one lives more than nine months,” Duarte recalled. “He didn’t give me any more information, not a pamphlet, nothing. He told me to Google it.”
This was 10 years ago, and information was scarce. She found a foundation in Australia, and it referred her to Beau Ances, a neurologist at Washington University in St. Louis whose lab works on early detection of CJD and other brain disorders. I hope you have insurance, they warned her.
Cardona did not — there had been a mixup with her paperwork when she retired — but Duarte was undeterred. She would sell her sports bar if she had to, and use the proceeds to pay the medical bills. By the time they got an appointment, three months had passed. By the clock, Cardona had six months left to live.
Duarte liked Ances immediately. He met them in the waiting room, shook their hands, and took them into the clinic for a detailed evaluation. “He wasn’t looking at his watch every five minutes,” Duarte said. “We must have spent 45 minutes in there. Let me tell you, that was the best visit of my life.”
Ances told Duarte that her mother may have been diagnosed with CJD because of her rapid frontal lobe deterioration, but that she did not have the disease. Her MRI was filled with the plaques and tangles that are the clear hallmarks of Alzheimer’s.
In what may be one of the few times someone was happy to receive such a dire diagnosis, Duarte was relieved. It meant her mom was not likely to die right away. “It was like a ton of bricks was lifted from my shoulders.” The care the medical team took with her mom was incredible, Duarte said, and something they had not received before.
Ances also told her that her mother had a PSEN1 gene mutation, an inherited trait that indicates with near certainty an affected person will develop Alzheimer’s dementia. It didn’t come as a surprise. “Seventy-five percent of my mom’s family has it,” she said. “I took care of my uncle that had it. We would visit my grandmother in Puerto Rico who had it.” Her grandmother and four aunts and uncles died with Alzheimer’s before they reached the age of 70.
While Cardona had never had the chance to be in a clinical trial because of her late and botched diagnosis, things were different for Duarte. She was told she could enroll in a study of the Alzheimer’s plaque-reducing drug gantenerumab, a Roche drug that researchers hope will prevent cognitive decline if given to patients early enough. The physicians in St. Louis told her to take a few days to think about it.
“There was nothing for me to think about. I said, ‘I’m in,’” said Duarte. She enrolled and underwent extensive genetic counseling. A blood test showed she had the mutation as well. Now 45, Duarte said that without treatment she was likely to have Alzheimer’s by age 65, like so many of her relatives.
“The difference is, I’m in a clinical trial. No one else in my family was,” she said. She now gets the experimental drug infused into her stomach every 28 days by a nurse who travels to her home to administer the 13-minute infusion. All expenses are paid by the clinical trial.
The mother of a 10-year-old adopted son, Jayden, Duarte desperately wants to stay healthy for his sake, and for her own. She has become a vocal advocate, working with the nonprofit group UsAgainstAlzheimer’s to encourage people who are Hispanic and Black to enroll in the clinical trials in which they are so deeply underrepresented.
“The lack of equity in basic research is one of the most damning failures of our field,” said Jason Resendez, executive director of the UsAgainstAlzheimer’s Center for Brain Health Equity. “Billions of dollars are going into this research, but the communities most at risk are not benefiting.”
Duarte became her mother’s full-time caretaker. She closed Da Cubby Hole in 2015 and worked part-time jobs as much as she could. She helped Cardona shower each morning, and put on the makeup and red lipstick her mother had loved, as well as the expensive perfume. “She didn’t like the cheap stuff,” said Duarte. “She liked the $150 bottles. It was killing my budget.”
There were still times when Duarte felt her mother’s love, even as her mind faded. She worried whenever she saw Duarte crying. “‘¿Que te pasa, que te pasa?’ she would say. You could see her face of concern,” Duarte recalled. But her mom would also lash out. “There were times my neck and arms would be covered in scratches,” said Duarte. As she declined, Cardona seemed to disappear. Once a notorious flirt, she would sometimes barely speak to her physicians.
Years passed. The pandemic was incredibly hard and left the gregarious Duarte isolated. “I wouldn’t let anyone in,” she said. “I was adamant she wouldn’t die of Covid.” She didn’t. But Cardona did die, on Jan. 20. Unlike Covid-19, Alzheimer’s disease is 100% fatal.
The last days were excruciating. Cardona was bedridden and couldn’t eat. She couldn’t talk. She had lost so much weight her bones showed through her skin. “The end is the worst thing you want to see,” said Duarte. “I wouldn’t wish this disease on anyone.”
Duarte is grateful that her mom lived to age 65, and that she was able to keep her at home, care for her, and “love on her,” but she’s angry too. She’s angry at a medical system that hasn’t paid attention to people of color and angry at her fellow Hispanics.
“My own race has failed me, the Spanish race. They don’t stand up to the disease,” she said. “If more Spanish people were in clinical trials, I think I would have been reached, I think my mom would have been reached. I think Caucasians get the best of everything because they act quickly. Spanish people just don’t get involved. They’re the first to say no one does anything for Hispanics, but they aren’t willing to step up. I never knew there were clinical trials. I never knew anything,” she said.
“You hear people say, I’m not going to be a guinea pig,” she said. “You know what, all the drugs we have now, someone was a guinea pig. And I’d rather be a guinea pig than just another number with Alzheimer’s.”