Nothing about us without us? Using public consensus for priority setting in Alzheimer's disease research

Valerie Rico and colleagues used a Delphi process to gather feedback regarding recommendations for disclosing biomarker results in Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) research from a panel of AD/ADRD experts with experience in clinical care and AD/ADRD research. ¹ They integrated ethics and expert consensus into actionable recommendations along six domains, “study design, clinical relevance, results sharing processes, communication and understanding of results, counseling and support, and follow-up.” ¹ In this comment, I will argue that those domains would be an excellent starting point to make AD research more well-ordered toward the discovery of significant truths that the community cares about.

Rico et al.'s expert-led study contrasts with recent findings from Goswami and colleagues whose cohort found that 40% of participants declined to learn their biomarker results. ² This was particularly true of individuals identifying as Black, and people with a parent with AD dementia, because “knowing would be a burden,” among other reasons. ² These findings are quite different from the following claims of Rico et al.'s study: “Although psychological distress is a concern, it can be managed with appropriate counseling and should not deter offering the option to receive results” ¹ and Delphi process consensus statement (which reached approximately 70% consensus): “Potential for psychological distress should not be the sole reason to withhold individual research results that can be shared with appropriate counseling and support to mitigate distress.” ¹

Why does this specific point on researchers and lay participants matter in light of Rico et al.'s other findings? Because the difference here rests on the intensive conceptual engineering of the AD concept of recent years, which has transformed the meaning of biomarkers and their interpretation. In expert discourse, AD increasingly means “biomarker-positivity” ³ as opposed to “AD = dementia.” ⁴ The growing gap between societal and researchers’ framings creates the possibility of confusion, whereby people referring to “AD” and interpreting the meaning of “AD biomarkers” may be talking about different things. ⁵ Rico and colleagues recognize the complexity of communicating biomarker status, due to their exploratory nature and the lack of scientific consensus regarding their interpretation.

I provide two more examples before generalizing my claim that contemporary AD research has been mostly investigator-driven, i.e., it has tended to happen to, rather than with, the public. First, community advisory boards (CABs), i.e., an advisory board consisting of representatives of the general public, who meet with and relay information to and from representatives of a clinical research institution. For other diseases like HIV/AIDS, CABs were instrumental in developing upstream research priorities and providing critical feedback on research methodologies and interpretations during the epidemic in the United States. ⁶ In AD/ADRD research, they tend to play a much more passive role: “in enhancing recruitment and retention” in AD/ADRD research, ⁷ for example, to improve “recruitment and retention of a globally diverse, well-phenotyped cohort.” ⁸ Recruitment and retention is of course one important role that CABs can play, and there are examples of CABs that play a more active role: e.g., The Stanford Alzheimer's Disease Research Center (ADRC) Community Advisory Board (CAB), whose members “Provide guidance to the Stanford ADRC on priorities related to Alzheimer's Disease services, education, and research.” ⁹ Nevertheless, the general rule is that CABs in AD/ADRD research are more passive than for other conditions.

Second, take heavily-commercialized blood biomarkers of AD/ADRD. There has been an explosion of scientific interest and publications, with 885 papers published between 2020–2024. ¹⁰ However, over 500 focused on their technical capacity; over 200 were secondary articles tending to promote them; a handful of papers have addressed their diagnostic accuracy, whereas “none of the studies … focused on the perspective of patients.” ¹⁰

This is a bleak diagnosis of the commercial, investigator-driven field of AD/ADRD research that fails to take other perspectives into consideration. Are there any alternatives? Jason Karlawish discusses a problematic one, focusing on deadline-driven mission-driven “moonshot initiatives” like Operation Warp Speed for COVID-19 vaccines, or getting a man to the moon and back within a decade ¹¹ :

^“we commit a moral hazard when we adopt deadline-driven rhetoric and methods used to solve big engineering problems to message and tell the narrative of how we’ll tackle big health problems such as … Alzheimer's disease. Vast normative differences exist between engineering problems and biomedical problems.”

He is right about the futility of deadlines, of course. But getting democratic society involved in priority setting does not necessarily mean establishing a deadline. It means assuring the democratic legitimacy of scientific decision-making. ¹² The process could start simply, using consensus building with CABs as a starting point, as they stand at the interface of AD science and society. The goal is trustworthy AD/ADRD research, ¹³ that is, research that withstands scientific scrutiny, and that is relevant to what people care about. ¹⁴ However, the inclusion of the AD/ADRD community requires voluntary engagement, which may not be of interest among specific sub-groups due to concerns over discrimination, medical mistrust, and epistemic injustice. ¹⁵ Overcoming such barriers is vital to achieve true diversity in more participatory AD/ADRD research. ¹⁶ This mention of social justice brings to mind the history of CABs in HIV/AIDS research, which stands as a reminder that academia and activism were not themselves an automatic match, but were achieved by persistent advocacy and required ongoing negotiations to overcome the various challenges the partnership faced. ⁶ There is much more scope for “activist research” in the AD/ADRD space that works up-close with disadvantaged communities to address their brain health needs. ¹⁷

In conclusion, AD/ADRD research needs to be oriented toward the perspective of the affected community and broader society, to ensure that what is being researched is what the community thinks is important.