On October 10th, nine days before the National Institutes on Aging released a national strategy document on inclusion and representation of minority participants in research into Alzheimer's disease and related dementias (ADRD), 394 stakeholders gathered to discuss the issue at the Charles F. and Joanne Knight Alzheimer’s Disease Research Center at Washington University, St. Louis. Convened by WashU’s John Morris and colleagues, the assembled audience focused on how to boost participation specifically of African-Americans and other black Americans in Alzheimer’s research studies across the country. Representatives of all 30 federally funded Alzheimer’s Disease Centers (ADCs) sat next to patient advocates, funders, clinicians, and scientists who study recruitment and retention of minority participants.
They had frank discussions of what works, what doesn’t, and what needs to be done. The frankness was at times discomforting to some. It also drew praise. “I have been at plenty of meetings on race and research, where things were talked around but never addressed,” said Stephen Thomas, a professor of health services administration at University of Maryland, College Park.
The problem is beyond dispute. Even as black Americans are disproportionately affected by Alzheimer’s and related dementias, they participate in research studies on ADRDs at far below their population fraction of about 13 percent nationally across all age groups. For example, African-Americans contribute only 3.7 percent of autopsy data collected at the National Alzheimer’s Coordinating Center, aka NACC. Even when they do join a study, African-American participants decline tissue sample donation, and leave studies early, at higher rates than whites. “We all agree this is not where we want to be,” said Krista Moulder, executive director of the WashU ADRC.
This underrepresentation means data are lacking on whether AD or other dementias unfold in the same way or differently in black versus white, Latino, or Asian people. Social determinants are thought to be important, and some biological differences may exist. For example, there appear to be differences in CSF tau and sVCAM1, a leukocyte biomarker of brain aging and neuroinflammation. But data sets are tiny; they need replication and deeper exploration in larger, independent samples that do not yet exist (for more on research results, see Part 2 of this series)
African-American underrepresentation is also common in therapeutic trials across disease areas, including Alzheimer’s and cancer (Chen & Wong, ProPublica 2018). The recent Expedition Phase 3 program for solanezumab, for example, included only 1.6 percent African-American participants. Some drug sponsors make additional funds available to recruit black participants, but often, trial sites fail to meet desired quotas. This means when a drug finally works, doctors won’t know if it works as well, or better or worse, for their black patients.
Taking note of the problem, the National Institute of Health in November 2017 tightened policy around the Revitalization Act, which was first issued in 1993 to mandate inclusion of women and minorities. The law was updated once before, in 2000. On including women in dementia research, great strides have been made since then. These days, women typically are at parity in clinical trials and are often a majority in observational studies. For African-Americans, some progress has been made, said Rachel Whitmer of the University of California, Davis. But not enough.
The solution would seem obvious—increase recruitment and retention. But that’s easier said than done. A legacy of exploitation by medical science has left especially older African-Americans distrustful of research, and this feeling is confounded for many by a continuing experience of racism today. “You can’t simply mail a flyer and expect that black people will come to your center,” said Lisa Barnes at Rush University, Chicago.
That said, barriers to research participation can be overcome, as illustrated by examples of success that dominated the workshop. In essence, recruiting and retaining minority participants requires a dedicated, sustained, funded effort. Cycles of engaging, giving, and fostering relationships are key, as is cultural competency. “Respect is the minimum. We also must understand the population that we want to study,” said Crystal Glover, also at Rush. A recruiter at the University of Pittsburgh Medical School told Alzforum that with each potential participant, she invests time for multiple personal contacts. She answers their phone calls at all hours, trying to get to know them, learn what’s important in their lives, and address concerns in a personalized way.
The commitment, the money, and the teeth behind recruiting and retaining more minorities are there. At NIA, Cerise Elliott is a program director who focuses on health disparities. This past May, Elliott issued a request for applications for an R24 grant to examine diversity, recruitment, and retention in aging research. Elliott works alongside Carl Hill, director of NIA’s Office of Special Populations. He oversees the Butler-Williams Scholars program, which funds young scientists interested in health disparities in aging. In St. Louis, Hill said that after a slow start, there is now hope that the minority gap can be closed for good. Elliott agreed. “I am thankful we are having this conversation today, so in the future we no longer need it,” she said. “In the future, inclusion, diversity, representation will be part of the scientific process and scientific literature,” Elliott added. Trying to engage a broader audience in their effort, NIA officers on October 23 hosted public discussion on Twitter at #researchdiversity.
To foster a generation of recruitment researchers, the Alzheimer’s Association sponsored 11 junior investigators’ travel to the workshop. Priorities for clinical, neuroscience, and biomarker research were hashed out in advance by working groups sponsored by the Cure Alzheimer’s Fund, and led by Morris and Moulder. Afterwards, WashU’s ADRC has posted a video recording of the workshop on its website. In the near future, Morris said, the organizers will publish a formal report to serve as a reference for the field at large of which recruitment strategies appear to work at some sites in the country already.
The organizers also hope to develop multicenter recruitment and retention protocols that can be formally tested. “Recruitment is a science,” said Barnes, who encouraged the researchers in the room to make a pitch for the R24. Toward that end, Roger Wong, a social work and occupational health researcher who works with Susy Stark at WashU, presented a literature review of published minority recruitment and retention methods in the field. Stark then primed the pump by offering for discussion a straw-man proposal for a multicenter protocol to determine and standardize best practices.
The WashU ADRC has been a leader in including African-Americans in AD research, said Joyce Balls-Berry, Mayo Clinic Rochester, Minnesota. The evening before the workshop, Balls-Berry and Hill spoke at the 13th annual public lecture in honor of Norman R. Seay, a veteran Civil Rights leader in St. Louis. Morris approached Seay soon after taking over WashU’s ADRC in 1997, when he realized he needed to diversify its work. In the year 2000, Seay convened an African-American Advisory Board for the center, on which he still serves. The board helped WashU ADRC grow its African-American representation from 3 percent at the time to 18 percent now (Williams et al., 2010; Williams et al., 2011).
Even so, Morris said, African-Americans participate less fully in WashU studies. More black than white people drop out of WashU studies, and though blood draws and brain scans are increasingly acceptable to black participants, their 38 percent CSF donation rate is half that of non-Hispanic whites. What’s more, fewer black than white people donate their brains for autopsy, at WashU and elsewhere (Boise et al., 2016). “We are not addressing all of the concerns needed for full participation,” Morris said.
In 2004, when the ADRC started an intensive biomarker study that required lumbar puncture, the center’s African-American enrollment plummeted. Two years later, Morris dropped this requirement for blacks only and regained 18 percent representation. “We hope that if we do not require lumbar puncture for enrollment, and if African-Americans participate for some time, we may gain their trust and will be better able to explain the rationale for spinal fluid sampling and answer all questions,” Morris said. The hope is this will generate more CSF donation over time.
What Works? Do Research Before the Research
Looking beyond WashU’s record, ongoing community engagement emerged as the prevailing theme at this workshop. Sites that have built thriving research programs in black communities are doing far more than issuing study invitations, scheduling appointments, and executing assessments. They invest effort getting to know black communities in their catchment area, and meeting some of their needs before they ask prospective participants to join an invasive dementia study. This can take years of active, structured work.
The work is necessary because the barriers to research participation among African-Americans are manifold. One is lingering distrust of medical institutions, said Balls-Berry. It was engendered not only by the infamous Tuskegee project that withheld syphilis treatment from infected men in Alabama, but also by other instances of abusive medical experimentation on African-Americans, especially their boys (e.g., Washington H, Medical Apartheid, 2008). “We still feel the consequences,” said Glover.
For many African-Americans, the cultural memory of medical science evokes fear. This is a far cry from the feeling of empowerment, and agency in a shared fight against a common foe, that researchers like to associate with study participation. Barriers to joining research exist at the systemic, community, institutional, interpersonal, and even intrapersonal level, Glover said. They stem from stigma and low self-esteem, educational disparities, or lack of transportation, to name a few. In essence, the barriers mean that successful research inclusion, to many African-American people, is a broader concept that requires listening to them and even making their needs an integral part of the process. Balls-Berry, Hill, and Glover all urged the audience to acknowledge the silencing that has resulted from historical oppression and continuing health disparities.
Some centers have made this work. In the Chicago metropolitan area, Barnes has built two cohort studies that together enrolled 1,000 African-Americans without dementia into observational research. Called Minority Aging Research Study (MARS) and Rush Clinical Core (CORE), they require annual clinical/cognitive exams using batteries harmonized with other studies at Rush so that results can be compared across race.
How about biomarkers? Barnes considers them a priority. “As we move in our field toward a biological definition of AD, in which the disease is defined by pathology that can be documented by postmortem autopsy or biomarkers, we have to ask what does this mean for older African-Americans who are not usually included in biomarker studies? There are few biomarker studies with African-Americans, and at Rush we are working hard to change that,” Barnes said. MARS and CORE do not request CSF, but everyone gives blood. Brain donation, which is optional, is creeping up as participants become engaged and build trust together with the researchers. Thus far, more than half of participants have expressed interest, a similar rate as at WashU, and 70 brains have come to autopsy, Barnes said.
Barnes stressed that researchers must work in the community before making organ requests. Her team uses Glover’s NGAGE model, which stands for Network, Give first, Advocate for research, Give back, Evaluate. In practice, this means meeting with African-American community leaders, partnering in health fairs, engaging early study participants as “ambassadors,” sharing research updates with individual participants and the community, and doing pre- and post-enrollment surveys. The Rush team fosters bidirectional community relationships through a range of activities that support the community’s needs. A social worker on the team connects people to services. Indeed, Elliott encouraged the audience to include funds for a social worker and community support services in their R24 NIA grant application.
Barnes highlighted the cyclical nature of this “research-before-the-research.” Engaging and supporting the community builds opportunities to educate, encouraging interest to join a study down the line. Regardless of whether a person agrees to a specific test, answering every one of their questions builds the trust that allows the scientist to explain how their blood will be used, or why lying in a scanner will eventually benefit the volunteer, their loved ones, or the wider African-American community.
Equally important is sustainability, Barnes said. To make staying with the study easier for participants, her research staff visit them in their homes for cognitive and clinical exams, and the study pays transportation for brain-imaging visits. The team has a retention specialist whose job it is to come up with creative ways to foster people’s motivation to return; this can take the form of tokens of appreciation, checking in between visits, greeting cards for special occasions, etc.
Finally, it’s critical that the staff be culturally competent. At least some of them should be African-American, and all must be comfortable working in prospective participants’ neighborhoods. At the St. Louis workshop, a black recruiter spoke about motivating community elders to visit the center, only to have a perceived insensitivity on the part of white center staff make them turn back. It helps if the staff is aware of social and cultural risk factors of the participants they interact with, perhaps birth region, early life conditions, and quality of education. Participants, investigators, and staff should know each other. When Barnes started MARS in 2004, she visited every study volunteer at home. “Research participation is a lived experience. It is what works for us in Chicago,” Barnes said.
In North Carolina, Goldie Byrd, while working at North Carolina A&T State University in Greensborough, created its Center for Outreach in Alzheimer’s, Aging, and Community Health. COAACH enables recruitment as part of a broader mission to improve literacy, care, training, and research on aging-related diseases. At the St. Louis workshop, Byrd, who last September became director of the Maya Angelou Center for Health Equity at Wake Forest University in nearby Winston-Salem, reviewed the prep work required to be able to start genetics research. Though ApoE4 is more frequent in African-Americans than non-Hispanic whites, the allele increases AD risk less in African-Americans than it does in whites. Not enough samples exist to work out the reason for this apparent contradiction, or to explore AD genetics in African-Americans more broadly.
A geneticist by training, Byrd knew she needed to put community before genetics research. She ran a feasibility study with 500 intergenerational local people. Two-thirds were under 40, and three-quarters had less education than a bachelor’s degree. Lo and behold, a majority said they wanted to participate in research, with the number reaching 85 percent among 18- to 24-year-olds. They were motivated by having a relative with the disease, and the younger people by monetary compensation. “These surveys are much more positive than the common perception that African-Americans won’t participate. They want to,” Byrd told the audience. Pedigrees of local families showed that some have a high burden of Alzheimer’s, yet they are not fully aware of the disease’s role in their family, Byrd said.
Having established both need and motivation, Byrd in 2013 created COACCH with a grant from the Merck Foundation. Its all-black staff host support groups, educational luncheons, galas, town hall meetings, an annual caregiver education conference, celebrity events, and a program that connects family members to web-based resources and health information. “Our recruitment went through the roof,” Byrd said. People stick with it, too. Retention stands above 90 percent, as people derive a sense of dignity and meaning from their work with the center.
In Atlanta, a successful recruitment hub is called Registry for Remembrance. Built as a partnership between the Emory University ADRC and its local community, the registry informs black elders about cognitive disorders and engages them in ADRD research. Speaking in St. Louis, William Hu at Emory noted that the registry started in response to focus groups that, like Byrd, had found black citizens in and around Atlanta were interested in volunteering for AD research. By 2011, it had enrolled 130 participants. The post-2008 NIA funding crunch delayed comprehensive phenotyping until 2012, when Hu got an R21 grant in for that purpose.
Hu noted that while he is keen to get to know his study participants personally, early registry members who champion the study in their community are more effective recruiters. Like Barnes and Byrd, Hu found that returning information in the form of newsletters, forums, and luncheons is critical to retain volunteers. He found differences to Glover and Balls-Berry’s experience in that his volunteers rarely bring up Tuskegee when they decline biomarker procedures. Hu showed that fear of side effects from a lumbar puncture, and claustrophobia about entering a scanner, were the only two factors that prompted more black than white research volunteers at Emory to say no (Howell et al., 2016).
In Portland, creating a culture of belonging was the primary goal of Raina Croff at the Layton Aging and Alzheimer’s Disease Center at Oregon Health & Science University. Croff approached engaging African-Americans in brain health research from a cultural perspective. She heard from black elders that gentrification had displaced them from their former Portland neighborhood to less-walkable suburbs, cutting them off from their social networks and physical activity. So Croff’s all-black team developed maps of 72 walks in those formerly black neighborhoods, annotated the maps with markers celebrating black history there from 1940 to 2010, and put them on iPads for small groups of volunteers to use together. Croff measured health indicators such as mood and cognitive status before and after the walking program. Besides improving mood and MoCA scores, the group walks engendered in the participants a sense of belonging and pride in the center’s work, which may motivate further participation in subsequent research studies (Croff et al, 2018).
In New York City, Jennifer Manly of Columbia University has built trusting relationships with participants in the Washington-Heights Inwood Community Aging Project, which has been recruiting African-Americans in northern New York City since 1989. Like Barnes, Manly visited participants in their homes in her early work with WHICAP. Getting to know them personally gave her an opening to ask about their childhood and youth, where Manly places the origin for social determinants of dementia (see Part 2).—Gabrielle Strobel
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