Black and Hispanic people are up to twice as likely as white people to develop Alzheimer’s disease, but they have a much lower chance of being included in clinical trials for Alzheimer’s treatments.
People of colour made up only 20% of participants in trials1 for the Alzheimer’s drug lecanemab, approved in July 2023, and less than 10% in the trial2 for donanemab. The 1,736-person donanemab trial — which was presented by the pharmaceutical company Eli Lilly, based in Indianapolis, Indiana, at last month’s Alzheimer’s Association International Conference (AAIC) in Amsterdam — included only 19 Black participants who got the drug.
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The low numbers are making some researchers worry about whether these drugs — the first to show improvements to clinical outcomes for people with Alzheimer’s — will work for people of colour, and whether these trials fully address the causes of dementia, which might differ across demographics.
“I don’t think it should be acceptable that clinical trials are so non-representative,” says neurologist Gil Rabinovici at the University of California, San Francisco. “This is a call to arms.”
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In April 2022, the US Food and Drug Administration, based in Silver Spring, Maryland, instituted guidelines recommending that trials reflect the diversity of people who will use the drug — but this doesn’t always happen. The lack of diversity is particularly acute for Alzheimer’s disease. This is because participants in trials testing monoclonal antibody drugs such as lecanemab and donanemab must have sufficient levels of the sticky amyloid protein that accumulates in the brains of people with Alzheimer’s.
At the AAIC, neurologist Doris Molina-Henry, at the University of Southern California in Los Angeles, presented a study which found that having low amyloid levels made people of colour two to four times less likely than their white counterparts to qualify for an ongoing trial testing whether lecanemab could prevent Alzheimer’s. A study3 presented at the 2022 AAIC meeting found similar trends in data from nearly 11,000 people in the early stages of Alzheimer’s who underwent positron emission tomography (PET) scans to determine whether they could participate in four separate Alzheimer’s trials run by Eisai, a bio-pharmaceutical company based in Tokyo.
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Qualifying for the latest donanemab trial was even more difficult, says Lilly’s senior medical director, John Sims, because the company was screening for both amyloid and tau, another Alzheimer’s-related protein. Only one in 8 Black and one in 17 Hispanic volunteers qualified, he says, compared with one in 4 white applicants.
“The field really needs to understand why this keeps happening,” says Alzheimer’s researcher Joshua Grill at the University of California, Irvine. It is unclear why people of colour would have lower amyloid or tau levels than their white counterparts with the same amount of cognitive impairment. Grill speculates that dementia in people of colour might often be caused by other conditions such as vascular disorders or inflammation. External factors such as education levels and stress could also contribute to dementia risk, and some evidence suggests that certain genetic variants involved in Alzheimer’s risk differ between people of European and African ancestry4,5.
Amyloid levels are not the only reason that Alzheimer’s trials lack racial diversity, says Reisa Sperling, a neurologist at Harvard University in Cambridge, Massachusetts. People of colour are less likely than white people to live near hospitals with PET scanners that are used to determine whether a drug is working, and recruitment campaigns typically target white communities. People of colour also face higher rates of disorders that disqualify them from trials, such as cardiovascular disease and lupus. “We need to look at all our inclusion and exclusion criteria: which are necessary and which are contributing to disparities in who we bring in,” Sperling says.
Grill and others are concerned about whether lecanemab and donanemab will be safe and effective in diverse populations. Recent trials have shown that monoclonal antibodies can slow cognitive decline by around 30% in selected groups of people with Alzheimer’s who have mild cognitive impairment. But neither drug stops the progression of the disease, and both frequently cause brain abnormalities that can lead to haemorrhages, seizures or death. Sims says that Lilly’s latest donanemab trial had too few participants who were people of colour to determine whether these risks, or even the drug’s effectiveness, differ by race.
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That concerns Jennifer Manly, a neuropsychologist at Columbia University in New York City, who says that she would hesitate to recommend monoclonal antibodies if a Black family member had Alzheimer’s. “I’d want to know people in the clinical trials were as close to my family members as they can get — their lived experience, background and health risks,” she says. “We don’t have that for Black and Hispanic people right now.”
The lack of diversity in clinical trials is not only an equity problem but also a scientific one, Manly says, because it could prevent researchers from determining the causes of Alzheimer’s and other forms of dementia. The limited success of monoclonal antibodies against amyloid has made it increasingly clear that Alzheimer’s is not just driven by amyloid or tau, she says. Focusing drugs only on these proteins might miss other factors that contribute to the disease across populations. “It’s not solely about developing the treatment but understanding the differences so they can inform the design of future studies,” says Molina-Henry.
Eisai is now working with community groups such as churches to advertise its trials more widely, says Shobha Dhadda, Eisai’s senior vice-president of biostatistics and clinical development operations for neurology. The first step of its Alzheimer’s prevention trial will screen potential participants for amyloid levels with a new blood-based test, which should help to rule out people who don’t qualify without forcing them to go through cognitive tests or PET scans. Lilly is also ramping up similar recruitment strategies in its donanemab trials: Sims says that it has doubled the number of people of colour participating in a 1,000-person safety trial, which will conclude later this year. It is also switching from PET scans to blood tests in an ongoing trial testing whether donanemab can prevent Alzheimer’s.
Grill would also like to see more infrastructure for Alzheimer’s registries that can direct disqualified individuals to other trials that could help them more. “I have great concern that by turning them away they’ll go back to their community and say, ‘They didn’t want me,’” he says. “We don’t want to add to the stigma of disease or lower trust in the community.”