Abstract
Introduction:
The steps of participant recruitment are described as a “funnel.” In AD secondary prevention trials, the funnel typically yields an unrepresentative study population.
Methods:
A national survey of U.S. adults aged 65 and over assessed intention to enroll in a hypothetical secondary prevention trial. Among those intending to enroll, intention to ask someone to serve as their study partner was also measured.
Results:
In the full sample (n=603), intention to enroll – measured on a scale of 1 (very unlikely) to 5 (very likely) – was low (M: 2.37, SD: 1.31). Among those somewhat or very likely to enroll (24%, n=168), mean intention to ask a study partner was 3.45 out of 5 (SD 1.44). There were no significant differences between Black and White respondents.
Discussion:
Our results suggest underrepresentation of Black older adults in secondary prevention trials is not attributable to lower intention to participate or ask a study partner.
Keywords: Alzheimer’s, prevention, diversity, recruitment, participant, study partner
Introduction
The aging of the U.S. population is contributing to an increase in late-life diseases, including dementia.[1] Dementia places a heavy burden on those living with the disease, as well as on their families and society. There is substantial agreement amongst experts that reducing these burdens will require evidence-based interventions for both primary prevention (modification of risk factors) and secondary prevention (early disease detection and treatment).[2,3]
In recent decades, there have been substantial advancements in our understanding of the pathophysiology and course of Alzheimer’s disease (AD), one of the most common causes of dementia.[4,5] AD-related changes begin accumulating in the brain many years before the onset of symptoms, during a long “preclinical” stage.[4] It is estimated that, by 2060, over 75 million older adults in the United States will live with preclinical AD.[6,7]
Though not all individuals with preclinical AD will become symptomatic in their lifetime, this preclinical stage is thought to provide a critical opportunity for intervention.[8] Researchers have, therefore, increasingly focused on secondary prevention: understanding how to better predict progression to symptomatic disease and identifying disease-modifying therapies that could, if administered in the preclinical stage, slow or even prevent onset of overt cognitive impairment. Unfortunately, participant recruitment is a persistent obstacle to the success of such secondary prevention trials.[9,10]
The participant recruitment process can be conceived of as a funnel. At the wide end, investigators seek broadly to raise awareness of the opportunity to participate in research. At each intermediate step – such as pre-screening or seeking informed consent – potential participants are lost. The narrow end of the funnel ultimately yields the study sample – those aware, eligible, willing, and able to participate. Problematically, the funnel for AD secondary prevention trials often yields samples that are neither representative of the general population nor of those who bear the burden of AD.[11–13] Participants are typically whiter, wealthier, and more educated; they are also more likely to be married or partnered and to express concern about AD.[14]
Past studies have examined barriers to and facilitators of individuals’ participation in secondary prevention trials, often with particular attention to Black older adults.[10,15–19] Here, we advance on that work by reporting the results of a nationally representative survey of U.S. older adults that assessed intention both to enroll in a hypothetical AD secondary prevention trial and also intention to ask someone to serve as a study partner. Our goal was to characterize the AD secondary prevention trial recruitment funnel (Figure 1, left), with particular attention to when, to which, and to how many prospective participants were lost as they passed through the funnel.
Figure 1. The AD Secondary Prevention Trial Participant Recruitment Funnel.
On the left, we provide a general overview of the recruitment funnel. At each step, the pool of potential participants becomes smaller and less representative of the general population. As seen on the right, our study focused on the first three steps of the recruitment funnel. Only 17% of survey respondents made it to the third step. As described elsewhere in the article, there were significant differences on sample characteristics between those who did and did not make it to the third step..
Methods
Data were collected as part of a project to design evidence-based recruitment messages for AD secondary prevention trials. First, we conducted qualitative interviews characterizing older adults’ views on joining AD secondary prevention trials, as well as how they identify potential study partners. Those results, reported elsewhere, They informed the creation of a quantitative survey for the target behaviors of enrolling in a secondary prevention trial and asking someone to be a study partner.[19]
Data Collection
All procedures were approved the University of Pennsylvania Institutional Review Board.
Data were collected from English-speaking adults ages 65 and over (n = 603) living in the United States who, per self-report, had not previously been diagnosed with Mild Cognitive Impairment (MCI), dementia, or AD. Non-Hispanic Black adults were oversampled (n = 148) for group comparisons, as Black older adults’ participation rates in AD studies are significantly lower than their White counterparts’.[20] The survey was fielded by SSRS (www.ssrs.com) from January 30 to February 13, 2023. The survey was completed online and – to ensure coverage of individuals who do not use the internet – telephonically in English. Respondents were reached online through the SSRS Opinion Panel, a nationally representative probability-based panel.[21] For the online panel component, the completion rate among invited panelists was 44%.
Data were weighted in two stages. The first stage was the application of a base weight to account for different selection probabilities and response rates across sample strata. In the second stage, sample demographics were post-stratified to match population parameters. Weighting ensures the demographic profile of the sample matches the profile of the target population.
Measures
Intention.
Respondents were asked about their intention to join a hypothetical secondary prevention trial, the HEALTHY MIND Study. Much of the language describing the HEALTHY MIND Study (Box 1, top) was drawn from the AHEAD 3-45 Study’s (NCT04468659) participant-facing website (www.aheadstudy.org) and recruitment materials from other AD secondary prevention trials. The AHEAD 3-45 Study is a pair of preclinical clinical trials, conducted under a single protocol, in cognitively unimpaired older adults, ages 55 to 80. The trials are testing whether treatment with intravenous lecanemab is superior to placebo in reducing brain amyloid accumulation (A3) and change from baseline on the Preclinical Alzheimer Cognitive Composite 5 (A45). Before enrolling, prospective participants undergo screening positron emission tomography (PET) brain scans to determine eligibility.[22]
Box 1. Descriptions of the HEALTHY MIND Study and Study Partner Requirement.
The HEALTHY MIND Study is an Alzheimer’s disease prevention study. It tests whether an investigational treatment can slow or stop the earliest brain changes due to Alzheimer’s disease.
The study is looking for people ages 65-80 who do not yet have symptoms of dementia caused by Alzheimer’s disease. Participants will receive monthly intravenous (or IV) infusions of either an investigational drug or a placebo (an inactive substance). At diOerent points in the study, participants will have memory testing and a brain scan. The brain scan looks for signs of Alzheimer’s disease. The results of these memory tests and brain scans will be shared with participants and help the participants and researchers track the participants’ brain health.
***
The HEALTHY MIND Study requires participants to enroll with a “study partner.” The study partner will accompany the participant to some of the research visits. The study partner must be someone the participant sees or talks to at least weekly and who would notice if the participant was having memory or thinking problems. The study partner will be asked to share observations about the participant’s memory with the researchers. The study partner might also provide the participant with emotional and logistical support. Additionally, the study partner will learn information about the participant’s brain health and risk of developing dementia caused by Alzheimer’s disease.
Survey respondents were given 3 comprehension questions to ensure they understood key features of the HEALTHY MIND Study; if they answered incorrectly, they were given the correct information. They were then asked: “How likely would you be to enroll in the HEALTHY MIND Study if you are asked to participate in the next 3 months?” The intention measures were asked on a scale from 1 to 5 (very unlikely to very likely) to facilitate telephonic survey administration. Mean scores below the midpoint are considered low/unlikely.
Our past research suggests that, for cognitively normal individuals, the decision to participate in research is made before the decision to ask a study partner (rather than being made simultaneously, as typically occurs for cognitively impaired individuals).[19] So, for the next set of intention measures, only the subset of respondents who answered that they were somewhat or very likely to enroll (i.e., those who answered 4 or 5) was told that the HEALTHY MIND Study requires participants to enroll with a study partner (Box 1, bottom). Respondents were asked on a scale of 1 to 5 (very unlikely to very likely): “How likely would you be to ask someone to be your study partner for the HEALTHY MIND Study in the next 3 months?”
Perceived threat of AD.
In prior work, perceived threat of AD and AD stigma have been shown to be related to research participation.[23–25] Therefore, all respondents were asked 7-items about their perceived threat of AD.[26] They were asked on a 5-point scale (strongly disagree to strongly agree) about the extent to which they agreed with the following statements: (1) You believe that you will get Alzheimer’s disease someday; (2) You worry about getting Alzheimer’s disease someday; (3) You worry about getting Alzheimer’s disease in the next few years; (4) If you got Alzheimer’s disease, it would be extremely stressful for you and your loved ones; (5) Alzheimer’s disease is just part of growing older; (6) Alzheimer’s disease is one of the worst diseases you can think of; and (7) You would like to know if you are going to get Alzheimer’s disease at some point later in life. We averaged these items into one measure of threat (M: 3.11 SD: .69; Alpha: .70).
AD Stigma.
The following three items, also on a 5-point scale (strongly disagree to strongly agree), assessed AD stigma: (1) If you had Alzheimer’s disease, people would avoid you; (2) If you had Alzheimer’s disease, people would think badly of you; and (3) If you had Alzheimer’s disease, people would be uncomfortable around you. We combined these into one measure of stigma. These items were averaged together (M: 2.95 SD: .90; Alpha: .75).
Respondents were asked demographic questions including gender identity (man, woman, other), race (Asian, Black or African American, White, Other or mixed race), ethnicity (Hispanic or not), education level, income, and marital status.
Study Partner Measures.
Only the subset of respondents indicating they were somewhat likely or very likely to enroll in the HEALTHY MIND Study was asked how likely they would be on a scale from 1 to 5 (very unlikely to very likely) to ask the following kinds of people to be their study partner: spouse or partner (if applicable), close friend, neighbor, adult child (if applicable), sibling, or member of their extended family. They were also asked how many people total they would be willing to ask and, if asked, how likely these individuals were on a scale from 1 to 5 (very unlikely to very likely) to agree.
Statistical Analyses
Descriptive statistics were calculated on all measures for the full sample (n=603) and also for those who intended to enroll in the HEALTHY MIND Study (n=168) and those who intended to ask a study partner (n=103). Differences were calculated between those somewhat or very likely to enroll (“intenders”) and those who were not (“non-intenders”) and also between those who did and did not intend to ask a study partner. Bivariate analyses using Adjusted Wald tests (based on cross-tabs or mean differences depending on the variable type) were used to calculate the differences with the weighted data.
Results
Unweighted and weighted participant demographics are shown in Table 1. Of the 603 individuals who completed the survey, just over half were women, approximately two-thirds were White, and the mean age was 73.9 years. In the overall sample, 56.8% of respondents reported they were married or partnered; 59.5% of White respondents were, compared to 38.9% of Black respondents (F(1,553)=11.64, p<.001).
Table 1.
Overall sample demographics
| Unweighted %or Mean (SD) | Weighted % or Mean (SD) | |
|---|---|---|
| Female | 56.6% | 53.8% |
| Mean age | 73.9 (6.42) | 73.80 (6.88) |
| Marital status | ||
| Never been married | 9.1% | 7.5% |
| Married/partnered | 51.0% | 56.9% |
| Widowed | 21.8% | 20.5% |
| Divorced/separated | 18.1% | 15.1% |
| Income | ||
| Less than $30,000 | 23.2% | 24.0% |
| $30,000- less than $50,000 | 22.7% | 22.9% |
| $50,000- less than $90,000 | 30.3% | 30.9% |
| $90,000 or more | 23.9% | 22.2% |
| Education level | ||
| High school or less | 22.1% | 38.6% |
| Some college | 31.5% | 28.2% |
| College + | 46.4% | 33.2% |
| Race/ethnicity | ||
| Black | 24.6% | 9.7% |
| Hispanic | 5.8% | 8.9% |
| Other | 2.0% | 5.3% |
| White | 67.6% | 76.1% |
| Family history of AD | 23.3% | 24.0% |
| Mean AD stigma* (SD) | 2.96 (.93) | 2.95 (.90) |
| Mean AD threat* (SD) | 3.14 (.70) | 3.12 (.69) |
| Answered All 3 Comprehension Questions about the HEALTHY MIND Study Correctly | 71.8% | 67.8% |
Range 1-5
Intention to enroll in the HEALTHY MIND Study
The mean overall intention to enroll in the HEALTHY MIND Study was 2.37 (SD: 1.31). Only a quarter (24.4%, n=168) of all respondents indicated that they were somewhat or very likely to enroll (Figure 1, right). The mean intention to enroll in the HEALTHY MIND Study was higher among those who answered all three comprehension questions about the study correctly than among those who did not (M: 2.53 SD 1.31 vs. M: 2.02 SD 1.24; F(1,601)=10.8, p<.01).
Comparison of those likely and those not likely to enroll in the HEALTHY MIND Study
As Table 2 shows, there were differences between respondents somewhat or very likely to enroll in the HEALTHY MIND Study (n=168) and those not likely to enroll (n=434) with respect to education (F(2,600)=6.73, p<.01) and income (F(3,574)=5.69, p<.001). Intenders were more likely than non-intenders to have at least a college education (49.0% vs. 28.1%) and to report an income of $90,000 or more (30.1% vs. 19.6%). Additionally, intenders perceived AD as a greater threat compared to non-intenders (M: 3.38 SD .71 vs. M: 3.03 SD .65; F( 1,601)=14.07, p<.001). There was no significant difference between intenders and non-intenders by racial or ethnic group.
Table 2.
Characteristics of those who intend and do not intend to enroll in the HEALTHY MIND study
| Intend to enroll in the HEALTHY MIND Study (n=168) | Do not intend to enroll in HEALTHY MIND (n=434) | Adjusted Wald test | |
|---|---|---|---|
| Mean age (SD) | 74.27 (6.41) | 73.65 (6.86) | F(1,589)=.50, p=.48 |
| Female | 51.3% | 54.6% | F(1,600)=.27, p=.60 |
| Married | 61.0% | 55.6% | F(1,600)=.81, p=.37 |
| Income | F(3,574)=5.69, p<.001 | ||
| Less than $30,000 | 11.0% | 28.3% | |
| $30,000- less than $50,000 | 26.6% | 21.7% | |
| $50,000- less than $90,000 | 32.2% | 30.5% | |
| $90,000 or more | 30.1% | 19.6% | |
| Education level | F(2,600)=6.73, p<.01 | ||
| High school or less | 25.1% | 42.9% | |
| Some college | 25.9% | 29.0% | |
| College + | 49.0% | 28.1% | |
| Race/ethnicity | F(3,598)=.19, p=.90 | ||
| Black | 10.6% | 9.5% | |
| Hispanic | 10.4% | 8.5% | |
| Other | 6.2% | 5.0% | |
| White | 73.2% | 77.1% | |
| Family history of AD | 30.1% | 22.2% | F(1,581)=2.09, p=.14 |
| Mean AD stigma* (SD) | 3.02 (.99) | 2.92 (.85) | F(1,601)=.71, p= 0.40 |
| Mean AD threat* (SD) | 3.38 (.71) | 3.03 (.65) | F(1,601)=14.07, p<.001 |
Range 1-5
Intention to enroll in the HEALTHY MIND Study and to ask a study partner
Within the subset of respondents somewhat or very likely to enroll in the HEALTHY MIND Study (n=168), the mean overall intention to ask someone to be their study partner was 3.45 (SD 1.44). Less than two-thirds of respondents who intended to participate in the HEALTHY MIND Study also indicated that they were somewhat or very likely to ask a study partner (61.3%, n=103). Table 3 shows the sample characteristics for those who intended to enroll in the HEALTHY MIND Study and the smaller subgroup of those who intended both to enroll and to ask a study partner.
Table 3.
The HEALTHY MIND Study Recruitment Funnel (Weighted)
| Intention to participate in the HEALTHY MIND Study (n=168) | Intention to participate in the HEALTHY MIND Study and ask a study partner (n=103) | |
|---|---|---|
| Mean age (SD) | 74.27 (6.41) | 73.91 (6.13) |
| Female | 51.3% | 48.2% |
| Married or other | 61.0% | 66.7% |
| Income | ||
| Less than $30,000 | 11.0% | 11.0% |
| $30,000- less than $50,000 | 26.6% | 24.2% |
| $50,000- less than $90,000 | 32.2% | 27.3% |
| $90,000 or more | 30.1% | 37.0% |
| Education level | ||
| High school or less | 25.1% | 25.4% |
| Some college | 25.9% | 23.1% |
| College + | 49.0% | 51.5% |
| Race/ethnicity | ||
| Black | 10.6% | 10.6% |
| Hispanic | 10.4% | 10.3% |
| Other | 6.2% | 2.1% |
| White | 73.2% | 77.1% |
| Family history of AD | 30.1% | 32.6% |
| Mean AD stigma* (SD) | 3.02 (.99) | 3.13 (.93) |
| Mean AD threat* (SD) | 3.38 (.71) | 3.51 (.62) |
Range 1-5
Comparison of those likely to ask a study partner and those not likely to ask
As seen in Table 4, among the sub-sample of respondents somewhat or very likely to enroll in the HEALTHY MIND Study, there were no differences on any of the sample characteristics between those somewhat or very likely to ask a study partner (n=103) and those not likely to ask (n=65). Perceived AD threat was marginally (p=.07) higher among intenders (M: 3.51 SD .62) compared to non-intenders (M: 3.20 SD .78). There was no significant difference in intention to ask someone to be a study partner by racial or ethnic group.
Table 4.
Of those who intend to participate in the HEALTHY MIND Study, characteristics of those who intend and do not intend to ask a study partner
| Intend to ask study partner (n=103) | Do not intend to ask study partner (n=65) | Adjusted Wald test | |
|---|---|---|---|
| Mean age (SD) | 73.91 (6.13) | 74.8 (6.67) | F(1,163)=0.33, p=.57 |
| Female | 48.2% | 55.8% | F(1,167)=0.49, p=.49 |
| Married/living with partner | 66.7% | 53.1% | F(1,16)=1.69, p=.20 |
| Income | F(3,161)1.17, p=.32 | ||
| Less than $30,000 | 11.5% | 10.4% | |
| $30,000- less than $50,000 | 24% | 30.3% | |
| $50,000- less than $90,000 | 1% | 39.5% | |
| $90,000 or more | 27.3% | 19.8% | |
| Education level | F(2,166)=.29, p=.75 | ||
| High school or less | 25.5% | 24.5% | |
| Some college | 23.1% | 29.9% | |
| College + | 51.5% | 45.6% | |
| Race/ethnicity | F(3,165)=.49, p=.69 | ||
| Black | 10.6% | 10.5% | |
| Hispanic | 10.3% | 9.8% | |
| Other | 2.1% | 12.0% | |
| White | 77.1% | 67.7% | |
| Family history of AD | 32.6% | 26.4% | F(1,158)=0.35, p=.56 |
| Mean AD stigma* (SD) | 3.13 (.93) | 2.88 (1.03) | F( 1, 167) = 1.31, p= 0.25 |
| Mean AD threat* (SD) | 3.51 (.62) | 3.20 (.78) | F(1, 167) = 3.27, p= 0.07 |
| Likely to ask ______ to be their study partner | |||
| Spouse/partner (n=94, are married/ partnered) | (n=68) 84.2% |
(n=26) 26.0% |
F(1,110)=18.82, p<.001 |
| Close friend | 25.2% | 8.0% | F(1,167)=5.49, p<.05 |
| Neighbor | 7.1% | 2.3% | F(1,158)=0.74, p=.39 |
| Adult child aged 18 or older (n=143, have child(ren)) | (n=91) 19.9% |
(n=52) 6.8% |
F(1,142)=2.91, p=.09 |
| Sibling | 7.8% | 11.3% | F(1,142)=.286, p=.59 |
| Member of extended family | 15.2% | 7.5% | F(1,146)=.96, p=.33 |
| Mean number of people they would ask to be their study partnerǂ (SD) | 2.22 (1.16) | 1.14 (1.24) | F(1,167)=17.09.96, p<.001 |
| Mean likelihood that, if asked, ___ would agree to be their study partner* (SD) | |||
| Spouse/partner (n=94) | 4.38 (1.14) | 2.30 (1.42) | F(1,93)=20.85, p<.001 |
| Close friend | 3.32 (1.41) | 2.25 (1.22) | F(1,167)=13.63, p<.001 |
| Neighbor | 1.94 (1.23) | 1.87 (1.07) | F(1,158)=0.11, p=.74 |
| Adult child aged 18 or older (n=143) | 2.74 (1.54) | 1.98 (1.27) | F(1,142)=5.73, p<.05 |
| Sibling | 2.20 (1.43) | 2.06 (1.34) | F(1,165)=.24, p=.62 |
| Member of extended family | 2.36 (1.39) | 1.91 (1.11) | F(1,147)=2.49, p=.12 |
Range 1-5
Although the data are presented as a mean for ease of interpretation, the variable was originally not categorical in that the last category was “5 or more” but was treated as a 5.
On average, intenders expressed willingness to ask more people to be their study partner (M: 2.26 SD 1.16) than non-intenders (M: 1.14 SD 1.24).
Amongst just those respondents who reported having a spouse or partner (n=94), intenders were significantly more likely than non-intenders to say they would ask that individual to be their study partner (F(1,110)=18.82, p<.001). Intenders were significantly more likely than non-intenders to say they would ask a close friend (F(1,167)=5.49, p<.05). Intention to ask an adult child was marginally (p=.09) higher among intenders compared non-intenders (19.9% v. 6.8%).
Those who were somewhat or very likely to ask someone to be their study partner were significantly more likely to think that, if asked, their spouse or partner (p<.001) or close friend (p<.001) would agree than those who were not likely to ask. Willingness to ask a spouse or partner and the perceived likelihood of them agreeing was correlated at .64; for close friends, it was .45.
Racial differences among intenders were not possible to calculate because of the small cell sizes. However, among intenders who were White and married or partnered (n=50), about 86% (n=42) indicated they would ask that individual; among intenders who were Black and married or partnered (n=14), 64.3% (n=9) reported they would ask that individual. Black intenders were relatively more likely than White intenders to indicate they would ask an adult child, sibling, or member of their extended family.
Discussion
We surveyed older adults to better characterize the recruitment funnel in AD secondary prevention trials. We assessed intention to enroll in a hypothetical trial, the HEALTHY MIND Study, and – among those who intended to enroll – intention to ask someone to serve as their study partner. Three quarters of respondents indicated an unwillingness to enroll in the HEALTHY MIND Study. Less than two-thirds of those respondents intending to enroll also intended to ask a study partner.
We found significant differences between those who did and did not intend to enroll in our hypothetical trial. Consistent with sample demographics in actual AD secondary prevention trials,[14] survey respondents who intended to enroll were wealthier, more educated, and felt more threatened by AD than non-intenders. We did not, however, see statistically significant differences in intention to enroll by race or ethnicity. This is notable, as other studies have found lower willingness to be contacted about or to participate in AD secondary prevention trials among Black older adults.[14,16,27] Our result is not, however, entirely anomalous. Leggins et al, for example, surveyed dementia caregivers and found that non-Hispanic Black caregivers were not less likely than non-Hispanic White caregivers to participate in a hypothetical dementia trial.[28]
Study partners play an important role in AD secondary prevention trials, providing investigators with key information about cognition and function and providing participants with emotional and logistical support.[29,30] Despite these advantages, the study partner requirement is also a barrier to participation.[17]
Two ways in which the study partner requirement functions as a barrier are evident here. First, some prospective participants may be unwilling to ask anyone to fill the study partner role. Roughly a third of respondents who indicated that they intended to enroll in the HEALTHY MIND Study subsequently indicated that they were not willing to ask someone to be their study partner despite being told that having a study partner was required for participation. Whereas a prior study found that Black individuals rated the study partner requirement as a more important factor in their decision to enroll in a hypothetical preclinical AD study than did White individuals,[16] we did not find statistically significant differences in intention to ask a study partner by race or ethnicity. In light of the association between willingness to ask and thinking that person would, if asked, agree, we speculate that anticipation of rejection is a barrier to asking.
Second, even if prospective participants ask someone to be their study partner, that individual might decline. As we did not survey potential study partners, we cannot report how many would actually decline. Survey respondents, however, expressed a belief many would. In our survey, even those who intended to ask someone to be their study partner reported that, on average, neighbors, siblings, and members of their extended family were unlikely to say ‘yes.’ Notably, Black respondents were relatively more likely than White respondents to say they would ask members of these groups. Respondents were willing to ask one or two people to be their study partner, on average. Thus, a prospective participant confronted with one or two ‘no’s might quickly exhaust their pool of potential study partners, rendering them unable to participate.
Amongst those respondents intending to ask someone to be their study partner, a majority of those in a relationship indicated they would ask their spouse or partner. They also expressed high confidence their spouse or partner would agree. This is consistent with actual AD trials, in which as many as two-thirds of participants enroll with a spouse or partner.[31,32] Notably, individuals without a spouse or partner comprise the majority of the overall pool of potential secondary prevention trial research participants.[29] Overrepresentation of ‘spousal’ study partners might be explained, in part, by the perception that the study partner role is relatively less burdensome for spouses and partners – who are often retired and living with the prospective participant – than for others, like adult children, who are shouldering family and work responsibilities and live apart from the prospective participant.[19] Supportive of this idea, spousal study partners were marginally associated with retention in A4.[33]
Prior work suggests the study partner requirement may disproportionately affect Black participants, given lower rates of marriage and higher rates of divorce within the Black community.[34,35] In our overall sample, Black respondents were significantly less likely to be married or partnered than White respondents. While the results must be interpreted with caution given small cell sizes, Black respondents who intended to enroll in the HEALTHY MIND Study and to ask someone to be their study partner were less likely than White intenders to indicate they would ask a spouse or partner and more likely to indicate they would ask an adult child, sibling, or member of their extended family. In practice, this may lead to a decreased ability to find a study partner, given the overall perception that members of the latter groups are more likely to say ‘no.’
Our survey does not speak to other factors further narrowing the recruitment funnel or affecting representation. Restrictive inclusion criteria contribute to screen-failure rates of 88% in preclinical AD trials.[36] For instance, in the A4 study, 69% of those who underwent amyloid imaging to assess eligibility were excluded because they did not have elevated amyloid; Black individuals were more likely than White individuals to be excluded.[10] In the AHEAD 3-45 Study, plasma amyloid eligibility was lower for Black individuals.[37] Compared to their White counterparts, prospective A4 participants from underrepresented groups were more frequently excluded for failure to meet cognitive inclusion criteria.[10] Further, researchers running AD secondary prevention trials often define comorbid medical conditions—including cardiovascular disease—as exclusion criteria; this practice disproportionately excludes Black individuals given the higher prevalence of cardiovascular disease in the Black community.[38]
Going forward, it is important to consider how the study partner role might be modified to retain its important and necessary features while also empowering more individuals to serve in it. Such steps should be understood as complementary to efforts to address modifiable barriers to recruitment of underrepresented groups, such as addressing financial barriers and questioning the rationale for specific exclusion criteria.[38–40]
Limitations
This study has at least four limitations. First, respondents were recruited from volunteer, opt-in panels and may be predisposed to having more positive attitudes about research, particularly online research; however, we were interested in AD secondary prevention trials, which are qualitatively different.
Second, we described the HEALTHY MIND Study using language drawn from participant-facing materials for actual AD secondary prevention trials. Had we described the HEALTHY MIND Study differently – particularly using more accessible language – respondents’ reported intention to participate might have differed. It is suggestive that the mean intention to participate was higher amongst those who could answer all three comprehension questions correctly than among those who could not. Because designing materials to account for populations with various literacy levels can improve recruitment, it is worth exploring whether there are better means of describing secondary prevention trials.[41]
Third, because the sample was limited to English-speaking older adults, the results may not generalize to non-English speakers. This should be a topic of future research, as it is recognized that recruitment approaches need to be culturally and linguistically tailored.[42–44]
Fourth, we asked about intention to participate in a hypothetical study and intention to ask a study partner; it remains unknown what respondents would do if presented with these opportunities in a real-world setting.
Conclusion
Potential participants are lost at each step of the recruitment funnel. In this survey study, we found that differences in intention to enroll in an AD secondary prevention study and in intention to ask a study partner help to explain both the narrowing of the funnel and also why enrolled participants tend to be wealthier, better educated, and more worried about AD than others. Black respondents were not, however, less likely than White respondents to intend to participate or to ask a study partner. This suggests an essential role for addressing structural barriers to improve representation.
Funding:
Dr. Largent was supported by the National Institute on Aging (K01-AG064123; P30-AG072929). Dr. Grill was supported by the National Institute on Aging (P30-AG066519). Dr. Karlawish was supported by the National Institute on Aging (P30-AG072929).
Footnotes
Conflicts of Interest
None
Consent Statement
All human subjects provided informed consent.
Contributor Information
Emily A. Largent, Department of Medical Ethics and Health Policy, University of Pennsylvania, Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.
Joshua D. Grill, Institute for Memory Impairments and Neurological Disorders, University of California Irvine, 3204 Biological Sciences III, Mail Code: 4545, Irvine, CA 92697.
Jason Karlawish, Department of Medicine, Department of Medical Ethics and Health Policy, University of Pennsylvania, Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.
Amy Bleakley, Department of Communication, University of Delaware, 238 Pearson Hall, Newark, DE 19716.
Works Cited
- [1].Fang M, Hu J, Weiss J, Knopman DS, Albert M, Windham BG, et al. Lifetime risk and projected burden of dementia. Nat Med 2025. 10.1038/s41591-024-03340-9. [DOI] [Google Scholar]
- [2].Shah H, Albanese E, Duggan C, Rudan I, Langa KM, Carrillo MC, et al. Research priorities to reduce the global burden of dementia by 2025. The Lancet Neurology 2016;15:1285–94. 10.1016/S1474-4422(16)30235-6. [DOI] [PubMed] [Google Scholar]
- [3].Van Rosmalen L, Brück CC, Wolters FJ, Handels R, De Kok IMCM. Comparing the short-term and long-term impact of primary and secondary prevention strategies on population-level dementia burden: A microsimulation modelling study. Alzheimer’s & Dementia 2024;20:e091332. 10.1002/alz.091332. [DOI] [Google Scholar]
- [4].Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association 2018;14:535–62. 10.1016/j.jalz.2018.02.018. [DOI] [Google Scholar]
- [5].NIA-AA Revised Criteria for Diagnosis and Staging of Alzheimer’s Disease n.d. https://aaic.alz.org/nia-aa.asp (accessed October 25, 2023).
- [6].Gustavsson A, Norton N, Fast T, Frölich L, Georges J, Holzapfel D, et al. Global estimates on the number of persons across the Alzheimer’s disease continuum. Alzheimer’s & Dementia 2023;19:658–70. 10.1002/alz.12694. [DOI] [Google Scholar]
- [7].Brookmeyer R, Abdalla N, Kawas CH, Corrada MM. Forecasting the prevalence of preclinical and clinical Alzheimer’s disease in the United States. Alzheimers Dement 2018;14:121–9. 10.1016/j.jalz.2017.10.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [8].Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association 2011;7:280–92. 10.1016/j.jalz.2011.03.003. [DOI] [Google Scholar]
- [9].Elliott CL. Together We Make the Difference: National Strategy for Recruitment and Participation in Alzheimer’s and Related Dementias Clinical Research. Ethn Dis 2020;30:705–8. 10.18865/ed.30.S2.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [10].Raman R, Quiroz YT, Langford O, Choi J, Ritchie M, Baumgartner M, et al. Disparities by Race and Ethnicity Among Adults Recruited for a Preclinical Alzheimer Disease Trial. JAMA Netw Open 2021;4:e2114364. 10.1001/jamanetworkopen.2021.14364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [11].Shin J, Doraiswamy PM. Underrepresentation of African-Americans in Alzheimer’s Trials: A Call for Affirmative Action. Front Aging Neurosci 2016;8. 10.3389/fnagi.2016.00123. [DOI] [Google Scholar]
- [12].Wilkins CH, Schindler SE, Morris JC. Addressing Health Disparities Among Minority Populations: Why Clinical Trial Recruitment Is Not Enough. JAMA Neurol 2020;77:1063. 10.1001/jamaneurol.2020.1614. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [13].Mooldijk SS, Licher S, Wolters FJ. Characterizing Demographic, Racial, and Geographic Diversity in Dementia Research: A Systematic Review. JAMA Neurol 2021;78:1255. 10.1001/jamaneurol.2021.2943. [DOI] [PubMed] [Google Scholar]
- [14].Cox CG, Davis MA, Grill JD, Roberts JS. US Adults’ Likelihood to Participate in Dementia Prevention Drug Trials: Results from the National Poll on Healthy Aging. J Prev Alzheimers Dis 2023;10:34–40. 10.14283/jpad.2022.86. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [15].Ketchum FB, Erickson CM, Chin NA, Gleason CE, Lambrou NH, Benton SF, et al. What Influences the Willingness of Blacks and African Americans to Enroll in Preclinical Alzheimer’s Disease Biomarker Research? A Qualitative Vignette Analysis. JAD 2022;87:1167–79. 10.3233/JAD-215521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [16].Zhou Y, Elashoff D, Kremen S, Teng E, Karlawish J, Grill JD. African Americans are less likely to enroll in preclinical Alzheimer’s disease clinical trials. Alzheimer’s & Dementia: Translational Research & Clinical Interventions 2017;3:57–64. 10.1016/j.trci.2016.09.004. [DOI] [Google Scholar]
- [17].Grill J, Zhou Y, Elashoff D, Karlawish J. Disclosure of amyloid status is not a barrier to recruitment in preclinical Alzheimer’s disease clinical trials. Neurobiol Aging 2016;39:147–53. 10.1016/j.neurobiolaging.2015.11.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [18].Ryan MM, Gillen DL, Grill JD. Reasons for undergoing amyloid imaging among cognitively unimpaired older adults. Ann Clin Transl Neurol 2021;8:1646–55. 10.1002/acn3.51414. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [19].Largent EA, Bhardwaj T, Clapp JT, Sykes OS, Harkins K, Grill JD. You’ve Got a Friend in Me: How Cognitively Unimpaired Older Adults Select a Study Partner to Participate with Them in Alzheimer’s Disease Research. J Alzheimers Dis 2022;90:1021–33. 10.3233/JAD-220061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [20].Eliacin J, Polsinelli AJ, Epperson F, Gao S, Van Heiden S, Westmoreland G, et al. Barriers and facilitators to participating in Alzheimer’s disease biomarker research in black and white older adults. A&D Transl Res & Clin Interv 2023;9:e12399. 10.1002/trc2.12399. [DOI] [Google Scholar]
- [21].SSRS Solutions. SSRS Opinion Panel n.d. https://ssrs.com/opinion-panel/ (accessed October 24, 2023).
- [22].Rafii MS, Sperling RA, Donohue MC, Zhou J, Roberts C, Irizarry MC, et al. The AHEAD 3-45 Study: Design of a prevention trial for Alzheimer’s disease. Alzheimer’s & Dementia 2023;19:1227–33. 10.1002/alz.12748. [DOI] [Google Scholar]
- [23].Bardach SH, Kent S, Jicha GA. Alzheimer Disease Worries, Fears, and Stigma and Their Relationship to Genetic and Interventional Research Engagement. Alzheimer Disease & Associated Disorders 2021;35:75–9. 10.1097/WAD.0000000000000413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [24].Garand L, Lingler JH, Conner KO, Dew MA. Diagnostic Labels, Stigma, and Participation in Research Related to Dementia and Mild Cognitive Impairment. Research in Gerontological Nursing 2009;2:112–21. 10.3928/19404921-20090401-04. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [25].Rosenberg A, Coley N, Soulier A, Kulmala J, Soininen H, Andrieu S, et al. Experiences of dementia and attitude towards prevention: a qualitative study among older adults participating in a prevention trial. BMC Geriatr 2020;20:99. 10.1186/s12877-020-1493-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [26].Roberts JS. Anticipating response to predictive genetic testing for Alzheimer’sdisease: a survey of first-degree relatives. The Gerontologist 2000;40:43–52. 10.1093/geront/40.1.43. [DOI] [PubMed] [Google Scholar]
- [27].Salazar CR, Hoang D, Gillen DL, Grill JD. Racial and ethnic differences in older adults’ willingness to be contacted about Alzheimer’s disease research participation. Alzheimers Dement (N Y) 2020;6:e12023. 10.1002/trc2.12023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [28].Leggins B, Hart DM, Jackson AJ, Levenson RW, Windon CC, Merrilees J, et al. Perceptions about dementia clinical trials among underrepresented populations: a nationally representative survey of U.S. dementia caregivers. Alz Res Therapy 2024;16:224. 10.1186/s13195-024-01579-5. [DOI] [Google Scholar]
- [29].Largent EA, Karlawish J, Grill JD. Study partners: essential collaborators in discovering treatments for Alzheimer’s disease. Alzheimer’s Research & Therapy 2018;10:101. 10.1186/s13195-018-0425-4. [DOI] [Google Scholar]
- [30].Grill JD, Karlawish J. Study partners should be required in preclinical Alzheimer’s disease trials. Alzheimer’s Research & Therapy 2017;9:93. 10.1186/s13195-017-0327-x. [DOI] [Google Scholar]
- [31].Watson JL, Ryan L, Silverberg N, Cahan V, Bernard MA. Obstacles And Opportunities In Alzheimer’s Clinical Trial Recruitment. Health Affairs 2014;33:574–9. 10.1377/hlthaff.2013.1314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [32].Cary MS, Rubright JD, Grill JD, Karlawish J. Why are spousal caregivers more prevalent than nonspousal caregivers as study partners in AD dementia clinical trials? Alzheimer Dis Assoc Disord 2015;29:70–4. 10.1097/WAD.0000000000000047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [33].Raman R, Hussen K, Donohue MC, Ernstrom K, Holdridge KC, Langford O, et al. Pre-Randomization Predictors of Study Discontinuation in a Preclinical Alzheimer’s Disease Randomized Controlled Trial. The Journal of Prevention of Alzheimer’s Disease 2024;11:874–80. 10.14283/jpad.2024.136. [DOI] [Google Scholar]
- [34].Manly JJ, Gilmore-Bykovskyi A, Deters KD. Inclusion of Underrepresented Groups in Preclinical Alzheimer Disease Trials—Opportunities Abound. JAMA Netw Open 2021;4:e2114606. 10.1001/jamanetworkopen.2021.14606. [DOI] [PubMed] [Google Scholar]
- [35].Raley RK, Sweeney MM, Wondra D. The Growing Racial and Ethnic Divide in U.S. Marriage Patterns. Future Child 2015;25:89–109. 10.1353/foc.2015.0014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [36].Langbaum JB, Zissimopoulos J, Au R, Bose N, Edgar CJ, Ehrenberg E, et al. Recommendations to address key recruitment challenges of Alzheimer’s disease clinical trials. Alzheimer’s & Dementia 2023;19:696–707. 10.1002/alz.12737. [DOI] [Google Scholar]
- [37].Molina-Henry DP, Raman R, Liu A, Langford O, Johnson K, Shum LK, et al. Racial and ethnic differences in plasma biomarker eligibility for a preclinical Alzheimer’s disease trial. Alzheimer’s & Dementia 2024;20:3827–38. 10.1002/alz.13803. [DOI] [Google Scholar]
- [38].Indorewalla KK, O’Connor MK, Budson AE, Guess C, Jackson J. Modifiable Barriers for Recruitment and Retention of Older Adults Participants from Underrepresented Minorities in Alzheimer’s Disease Research. JAD 2021;80:927–40. 10.3233/JAD-201081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [39].Franzen S, Smith JE, Van Den Berg E, Rivera Mindt M, Van Bruchem-Visser RL, Abner EL, et al. Diversity in Alzheimer’s disease drug trials: The importance of eligibility criteria. Alzheimer’s & Dementia 2022;18:810–23. 10.1002/alz.12433. [DOI] [Google Scholar]
- [40].Mehl KR, Morain SR, Largent EA. The Importance of Including Underserved Populations in Research. Pharmaceut Med 2025;39:59–71. 10.1007/s40290-025-00562-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [41].Bader M, Zheng L, Rao D, Shiyanbola O, Myers L, Davis T, et al. Towards a more patient-centered clinical trial process: A systematic review of interventions incorporating health literacy best practices. Contemporary Clinical Trials 2022;116:106733. 10.1016/j.cct.2022.106733. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [42].Ta Park V, Grill JD, Zhu J, Nguyen K, Nam B, Tsoh J, et al. Asian Americans and Pacific Islanders’ perspectives on participating in the CARE recruitment research registry for Alzheimer’s disease and related dementias, aging, and caregiving research. A&D Transl Res & Clin Interv 2021;7:e12195. 10.1002/trc2.12195. [DOI] [Google Scholar]
- [43].Massett HA, Mitchell AK, Alley L, Simoneau E, Burke P, Han SH, et al. Facilitators, Challenges, and Messaging Strategies for Hispanic/Latino Populations Participating in Alzheimer’s Disease and Related Dementias Clinical Research: A Literature Review. JAD 2021;82:107–27. 10.3233/JAD-201463. [DOI] [PubMed] [Google Scholar]
- [44].Wong R, Amano T, Lin S-Y, Zhou Y, Morrow-Howell N. Strategies for the Recruitment and Retention of Racial/Ethnic Minorities in Alzheimer Disease and Dementia Clinical Research. CAR 2019;16:458–71. 10.2174/1567205016666190321161901. [DOI] [Google Scholar]