This is part two of a two-part story on diversity in Alzheimer's disease research, which will explore the importance of long-term engagement to recruit diverse patients in need of timely diagnosis and treatment. The first story, available here, examined the lack of basic research in nonwhite and female patients.
This story is part of a series on Diversity in Clinical Trials, which will explore the impacts of drug development using data that does not reflect the diverse U.S. population.
To read more in this series, please visit the "Diversity in Clinical Trials" Issue in Focus page here.
In the 1,169-patient A4 study on memory loss in Alzheimer's disease, Harvard University neurology professor and study lead Reisa Sperling set a goal of one person of color for every five screened candidates — and ended up with single-digit percentage enrollment among minorities.
"She tried everything," Global Alzheimer's Platform Foundation President John Dwyer said. "But that study suffered from [a] sine curve. ... No matter how hard the doctors try, the community won't respond at the rate you want if you haven't built long-standing relations of trust."
Dwyer said outreach to potential clinical trial participants "goes up and then it comes down," like a sine curve: Researchers — or "the guys in the suits," as one African American primary care physician put it to Dwyer — tend to parachute in to an underserved community to recruit for clinical trials and pack up and leave after.
"You have to be in the community every month, you have to be telling folks ... why [brain health is] important," Dwyer said. "They're not going to trust a 90-day wonder, or once-in-a-blue-moon conversation."
On top of that are clinical trial exclusion criteria that might leave out underrepresented populations. Clinical trials are carefully designed to examine a particular condition, and since Alzheimer's often comes with comorbidities, or co-occurring diseases, patients are often found to be ineligible under traditional entry requirements.
Global Alzheimer's Platform Foundation President John Dwyer compared clinical trial recruitment to a sine curve, alluding to the ebb and flow of researchers engaging with underrepresented populations.
For example, Alzheimer's trials often bar patients with diabetes, which would disqualify about 40% of African Americans from participating, according to Stephanie Monroe, executive director of Us Against Alzheimer's African American network.
"We need to make sure that the barriers designed to assess efficacy and safety [are there] but that we're not unnecessarily leaving people behind," Monroe said.
Sperling's trial was an exception to the norm, as Alzheimer's trials, like many other disease studies, rarely include targets for enrollment by specific demographics.
"If we don't hold ourselves to quantitative answers, we don't know how short we fell," Dwyer said.
Monroe added that if a target goal is not set, "you're assured not to hit it." She would like to see a representative sample of at least 13.4% of African Americans alone in Alzheimer's trials.
Cerise Elliott, National Institute of Aging program director for the dementias of aging branch of the division of neuroscience, said clinical trial investigators receiving funding from her organization must justify target goals using science or according to their local catchment areas for potential participants.
But minorities who might benefit from these trials are not necessarily in the same region as the clinical trial.
"You've got to put the trials where [diverse populations] live, not where you have research," Dwyer said.
Dwyer's organization, the GAP, Global Alzheimer's Platform, Foundation, is aiming for a 5% to 8% range of African American and Latino enrollment in clinical trials for Alzheimer's while building an infrastructure focused on high-density underrepresented populations.
"Is that a take-your-breath-away answer? No," Dwyer acknowledged. "But is it better than the field on average? It really is."
The Pixar film "Coco" has been leveraged in conversations on Alzheimer's because of its depiction of dementia and memory.
Seize your moment
Establishing relationships based on trust is easier said than done, and organizations such as Us Against Alzheimer's sometimes have to get creative, said Monroe and Jason Resendez, Us Against Alzheimer's chief of staff and executive director of Latino's Against Alzheimer's.
Us Against Alzheimer's capitalized on the Pixar film "Coco," which won the Academy Award for Best Animated Feature in 2018, and draws on themes of memory. The film centers on a Mexican child and the celebration of Day of the Dead.
Resendez said the movie was a vital cultural moment. Us Against Alzheimer's hosted screenings of "Coco" in Kansas City, Kan., and other cities and authored op-eds in Spanish-language and National Public Radio outlets to raise awareness of dementia and memory loss, which the movie focused on.
"That kind of precision approach, leveraging culture, has been really important in … opening up the conversation around stigmatized disease in these communities," Resendez said.
Us Against Alzheimer's also organized a play with an all-black cast called "Forget Me Not," depicting a man who experiences memory issues and how his cognitive health impacts his wife, who is a cancer patient, and daughter, a primary care physician.
According to Monroe, "Forget Me Not" has been performed in 27 cities across the U.S. and includes a panel discussion with patients and physicians who talk about their own experiences. Monroe said about 80% of attendees signed up to be contacted about potential research opportunities.
Monroe also said diversity in healthcare needs to start at the beginning: recruiting diverse staff to medical schools and research sites.
"That's an immediate way to examine the trust factor," Monroe said.
According to Elliott, the National Institute of Aging has a funding program aimed at supporting undergraduate aging research projects, with the hope that by graduation, the funded students will be motivated to further study aging in graduate school or medical school.
Dwyer, who is based in Washington, D.C., pointed to Howard University, a historically black college, which is also in a diverse neighborhood of the city.
"[People] are entitled to go to places, if they can, that look like them," he said.