Reactions of clinical neuropsychologists to the Alzheimer's Association workgroup's draft diagnostic and staging criteria for Alzheimer's disease

Abstract

Background

An Alzheimer's Association (AA) workgroup published criteria for the diagnosis and staging of Alzheimer's disease (AD). To date, there have not been empirical investigations of professionals’ opinions regarding the AA criteria for AD.

Objective

Our goal was to survey clinical neuropsychologists with expertise in dementia about these criteria.

Methods

Participants were recruited from a professional interest group of neuropsychologists focused on dementia. They rated their agreement with 15 statements about the AA draft criteria for AD prior to publication of the final version. The 15 statements were rated on a 4-point Likert scale ranging from 1 = Strongly Disagree to 4 = Strongly Agree.

Results

Sixty-one respondents provided analyzable data. When all 15 statements were coded such that higher values suggested more concern about the recommendations, the mean rating was 3.12 (SD = 0.36), suggesting that overall respondents had modest concerns about the recommendations. The statements that yielded the most concern focused on barriers to the implementation of the recommendations, including a lack of healthcare resources and costs of biomarker testing. Conversely, participants were equivocal about the criteria being a positive step forward and had mixed opinions about the applicability of these criteria to diverse groups.

Conclusions

Opinions of neuropsychologists suggest the need for important revisions or additions to the AA criteria for AD, including a clearer statement of purpose and more guidance on practical implementation.

Keywords

Alzheimer's disease biomarkers clinical syndrome diagnostic criteria neuropsychology staging

In 2023, an Alzheimer's Association (AA) workgroup sought to address advances in biomarker technology and innovations in Alzheimer's disease (AD) treatment, releasing draft criteria for the diagnosis and staging of AD: https://aaic.alz.org/diagnostic-criteria.asp. This update defined the disease by the presence of in vivo biomarkers. The revision followed a long history of diagnostic frameworks being updated in response to advances in our understanding of the pathology, neurobiology, and natural history of AD.^1–6 Until recently, the field conceptualized AD as a clinical-biological construct, requiring the integration of biomarkers anchored by clinical evidence of cognitive change.² In its current iteration, the revised diagnostic framework places sole emphasis on the use of in vivo biomarkers to identify and diagnose AD, independent of clinical presentation.

The release of the draft criteria was met with mixed reactions, as noted in the publicly posted commentary on the AA webpage: https://aaic.alz.org/diagnostic-criteria.asp. On the one hand, the criteria were praised as meeting a longstanding need for better incorporation of biomarkers into the AD diagnostic process. On the other hand, professional organizations, like the American Geriatrics Society, raised several concerns about potential harms of a diagnostic shift towards biomarkers, including that there is insufficient evidence to support their use in routine clinical care.⁷

To our knowledge, there have been no peer-reviewed research studies (either qualitative or quantitative) to assess reactions to the draft diagnostic criteria. Recognizing the absence of scholarly inquiry in this area, officers of the International Neuropsychological Society's (INS) Dementia Special Interest Group (SIG) sought to assess opinions of clinical neuropsychologists on the draft AD diagnostic and staging criteria. Examining the opinions of neuropsychologists with expertise in dementia is important because they have historically played a central role in the application of such criteria.⁸ Further, neuropsychologists have critical expertise in cognition, brain-behavior relationships, and psychosocial impacts of neurodegenerative disease that are core to creating patient-centered, clinically useful diagnostic and staging systems.

Subsequent to our data collection, the draft criteria for AD were finalized in a published manuscript,⁹ along with commentaries on the criteria from the workgroup authors.^10,11 Accordingly, the results from our survey afforded an opportunity to assess the extent to which the finalized criteria were responsive to comments and concerns raised by neuropsychologists. In addition, the findings can inform research directions, challenges, and opportunities related to the criteria moving forward.

Methods

Survey development and distribution

The officers of the International Neuropsychological Society Dementia Special Interest Group (INS Dementia SIG) discussed the AA draft criteria for AD (https://aaic.alz.org/diagnostic-criteria.asp) in late 2023. In January 2024, members of the officer team (KD, KA, AK) generated initial statements reflecting potential opinions about the draft criteria and distributed these statements to the INS dementia SIG officers’ group. Officers provided feedback, and a final survey draft was generated (see Table 1). The survey consisted of demographic questions and 15 statements related to the draft criteria (e.g., the purpose of the recommendations, applicability to diverse groups in and outside of the United States, access to biomarker testing), which respondents rated on a 4-point Likert-type scale (1 = Strongly Disagree, 2 = Disagree, 3 = Agree, 4 = Strongly Agree). Six statements were reverse scored. There was an additional open-ended response option for participants to provide qualitative feedback on the AA criteria. The survey was created in Qualtrics and approved by the Institutional Review Board at the University of Missouri on January 26, 2024 (IRB #2100329). The survey was advertised in person at the 2024 INS Annual Meeting (February 2024) during the Dementia SIG business meeting. It was also advertised to all INS Dementia SIG members via email. The final survey response was recorded on March 18, 2024 before the survey was closed.

Table 1.

Survey statements and responses.

Statement	M (SD)range
1. The purpose of the new Alzheimer's Association Criteria remains unclear. Whereas the title identifies them as “Criteria for Diagnosis and Staging of Alzheimer's Disease”, the authors also state that they do not represent “specific clinical practice guidelines.”	2.97 (0.66) 1–4
2. A lack of available healthcare resources (e.g., PET scanning facilities, CSF collection sites) would seriously hamper implementation of the Alzheimer's Association Criteria.	3.61 (0.56) 2–4
*3. Sufficient data on biomarkers and clinical staging among patients from diverse groups will allow for equitable implementation of the Alzheimer's Association Criteria.	2.93 (1.02) 1–4
*4. The relevance and application of these criteria in countries where access to biomarker technologies is limited or non-existent is adequately addressed.	1.95 (1.09) 1–4
5. The benefit of a clinical diagnosis in the absence of cognitive or functional impairment is inadequately justified.	3.12 (0.87) 1–4
6. There are potential adverse outcomes of an Alzheimer's disease diagnosis (e.g., losing one's driver's license, reduced insurability) that may occur in the absence of cognitive symptoms or functional impairment.	3.41 (0.59) 2–4
7. The costs associated with implementing the Alzheimer's Association Criteria will not* present a barrier for most patients and healthcare systems.	1.48 (0.75) 1–4
8. Invested parties (e.g., patients, care partners) may not want a diagnosis in the absence of symptoms.	3.38 (0.61) 2–4
*9. The provision of a diagnosis of Alzheimer's disease without clinical symptoms is ethically sound.	1.92 (0.77) 1–4
*10. The Alzheimer's Association Criteria represent a positive step forward in standardizing the diagnosis and staging of Alzheimer's disease in the era of biomarkers.	2.57 (0.75) 1–4
11. It remains unclear how indeterminate cases will be handled. For example, there may be discrepancies between biomarkers (e.g., some “positive” and others “negative”) or individuals whose biomarkers hover at the cutoffs.	3.34 (0.57) 2–4
12. The Alzheimer's Association Criteria do not sufficiently account for other symptom presentations in Alzheimer's disease, like mild behavioral impairment, which can be useful for diagnosis, prognosis, and treatment recommendations.	3.00 (0.75) 1–4
13. Neuropsychological test results may be more sensitive in identifying and tracking changes in pre-dementia and dementia phases than biomarkers.	3.21 (0.73) 1–4
*14. Biomarkers should be the primary way to certify a diagnosis of Alzheimer's disease across the world.	2.10 (0.82) 1–4
15. The Alzheimer's Association Criteria will create a divide between the way Alzheimer's disease is diagnosed in the US versus how it is diagnosed in the rest of the world.	3.25 (0.63) 2–4

Note. Response options were: 1 = Strongly Disagree, 2 = Disagree, 3 = Agree, 4 = Strongly Agree. Data presented are in raw form. Statements denoted by * were reverse scored for further analysis, as presented in the Results section.

Statistical analyses and interpretation

Responses to all statements were collated, and descriptive statistics were generated. Reverse coded statements were recoded (i.e., 1 coded as 4, 4 coded as 1, etc.), such that higher values reflected greater concern with the AA draft criteria. Twenty-five participants responded to the open-ended prompt. The qualitative feedback provided was brief and heterogeneous, making it unsuitable for thematic analysis.¹² However, a de-identified summary of the responses can be provided to any interested readers by reasonable request to the first author.

Results

Participant characteristics

Survey respondents included 61 members from the INS Dementia SIG, reflecting 30.7% of registered members. A majority of the respondents identified as women (67%), White (79%), not Hispanic, Latino/a, or of Spanish origin (84%), and currently working in the United States (75%). Items regarding primary areas of work allowed participants to choose more than one option, with 82% of the sample involved in clinical research, 67% of the sample involved in clinical practice, 11% in basic/translational science, and 3% in industry. The INS Dementia SIG has members from all levels of training, and this distribution was reflected in the career stage of survey respondents: 18% of respondents were trainees (graduate/postgraduate students, predoctoral interns, postdoctoral fellows), 16% were assistant professors, 20% were associate professors, 20% were full professors, 25% were clinical neuropsychologists (clinical practice), and 1% chose “other” (no designation given).

Survey responses

For 67% of statements, the full range of responses (i.e., 1–4) were observed (see Figure 1). The mean rating was 3.12 (SD = 0.36), suggesting that, overall, respondents had modest concerns about the recommendations (see Table 1). The statements that yielded the most concern focused on barriers to implementing the recommendations, including a lack of healthcare resources (Statement #2: M = 3.61, SD = 0.56) and costs of biomarker testing (Statement #7 when score was reversed: M = 3.52, SD = 0.75). Conversely, participants were equivocal about the criteria being a positive step forward (Statement #10 when score was reversed: M = 2.43, SD = 0.75) and had mixed opinions about the applicability of these criteria to diverse groups (Statement #3 when score was reversed: M = 2.07, SD = 1.02)

Figure 1.

Response frequencies per statement. Please see Table 1 for statements.

Discussion

New criteria for AD may better capture ongoing scientific developments

A small majority (55%) of respondents agreed that the AA diagnostic and staging criteria for AD represented a positive development (Statement 10). The ability to measure AD neuropathological markers in vivo has led to multiple field-advancing studies on the association between clinical symptoms and biomarkers, which should inform clinical diagnosis and practice. For example, higher levels of amyloid and tau, as measured through positron emission tomography (PET), have been associated with memory decline in older age,¹³ implicating these neuropathological biomarkers in the clinical syndrome typically associated with AD. Contrary evidence has also been observed. For example, the presence of elevated levels of amyloid in vivo can be found in cognitively unimpaired individuals¹⁴ and in the brains of deceased older adults who did not have mild cognitive impairment or a dementia syndrome.¹⁵ These findings raise concerns about the potential for mislabeling healthy individuals as diseased (i.e., amyloid positive cases that remain asymptomatic throughout life). They also highlight ongoing debate about the relative importance of amyloid biomarkers as the defining feature of an AD diagnosis.

Ambiguity surrounding the purpose of the AA draft criteria

There was consensus among respondents that the AA draft criteria were ambiguous in their purpose. Indeed, 83% of participants agreed or strongly agreed with the statement, “The purpose of the new Alzheimer's Association Criteria remains unclear” (Statement 1). This ambiguity is illustrated by conflicting wording in the document. The title of the final manuscript is, “Revised Criteria for Diagnosis and Staging of Alzheimer's Disease,” which carries a strong connotation that the manuscript includes prescriptive diagnostic and staging criteria for use in clinical practice. Conversely, in the abstract of the paper, the authors note, “These [criteria] are not intended to be step-by-step clinical practice guidelines.” As such, it may be unclear to audiences whether the criteria are meant to be applied as clinical diagnostic criteria or not. Perhaps this ambiguity reflects the transitional state of the field at this time, and the AA workgroup did note in the abstract that the manuscript is meant “to serve as a bridge between research and clinical care”. Other scholars have argued that the purpose of the revised AD criteria may not be directly stated in the manuscript at all. They called attention to the composition of the working group and raised concern for underlying financial interests as motivators of a shift towards biomarker-based diagnosis.¹⁶

Current healthcare resources may be inadequate to implement these criteria, particularly outside the United States

Many neuropsychologists in our sample (77–97%) had concerns about the feasibility of implementing the guidelines with currently available healthcare resources (Statements 2, 4, 7, and 15). Diagnostic criteria solely contingent on biomarker positivity present a significant challenge to healthcare facilities within and outside of the United States that do not have amyloid PET or magnetic resonance imaging capabilities, or lumbar punctures for cerebrospinal fluid (CSF) study. Despite the relative availability of amyloid PET scanning in the United States, both cost and tracer availability limit its utilization in clinical care.¹⁷ The advent of new plasma measures of AD neuropathology may greatly improve biomarker access; however, these tests also present technical and real-world challenges that are far from settled.¹⁸ Present issues include difficulties with sample storage, sample analysis, and access to healthcare providers with sufficient training for interpretation and appropriate explanation of results.

The shift towards biomarkers could also exacerbate healthcare systemic inequities already entrenched within the field of AD research and treatment. These changes may disadvantage under-resourced countries and clinics and the patients they serve due to poor access to the technological resources for AD biomarker measurements. In the published manuscript, the AA workgroup acknowledged, “The criteria we describe are presently operationalizable at some but by no means all centers even among major medical institutions in high-income countries” (p. 3). Nonetheless, it would be helpful for additional guidance to be developed for situations in which biomarker technologies are unavailable.

Unequal access to biomarkers may also exacerbate known racial/ethnic healthcare disparities for persons living with AD,¹⁹ and concerns have been raised about the applicability of biomarker findings across diverse groups.²⁰ One item (Statement 3) on our survey gathered responses regarding the ability of the AA draft criteria for AD to be implemented equitably. Sixty-nine percent of participants agreed that sufficient biomarker data would allow the criteria to be applied across individuals from diverse backgrounds. This result was surprising because the AA workgroup pointed out the lack of available data in diverse groups as a challenge for using the criteria. This unexpected finding may reflect ambiguity of the wording of the statement. Specifically, it was unclear whether readers were interpreting the statement as conveying that there are currently enough data to support equitable implementation in diverse groups versus the statement conveying that when we have enough data in diverse groups, equitable implementation will follow.

Unclear value of a biomarker-based diagnosis in the absence of clinical symptoms

Historically, clinical criteria for AD have only been applied in the context of an observable clinical syndrome.^1–5 The AA criteria will shift this landscape, whereby people who are asymptomatic with positive biomarkers may be diagnosed with AD. The workgroup was careful to note in the final manuscript, “The clinical use of AD biomarkers is presently intended for the evaluation of symptomatic individuals, not cognitively unimpaired individuals” (p. 10). They then highlighted a “distinction between can and should. AD can be diagnosed in asymptomatic individuals, but we do not believe this should be done for clinical purposes at this time” (p. 10). Nonetheless, they also noted that biomarkers “can identify the presence of AD in both symptomatic and asymptomatic individuals” (p. 4). Additionally, in a subsequent commentary, two of the workgroup authors suggested, “Some clinicians might consider performing biomarker testing in certain patients at clinical stage 2” (p. 2),¹¹ the preclinical stage of AD with subjective cognitive decline but no objective evidence of cognitive impairment.

Regardless of their real-world application, these criteria clearly represent a conceptual shift in AD diagnosis, wherein asymptomatic individuals with positive amyloid biomarkers could be diagnosed with AD when they previously could not have been given this label. Four statements in our survey asked participants to reflect on this change. Most (71–95%) respondents expressed a negative sentiment about the provision of a diagnosis based on biomarkers in the absence of clinical symptoms (Statements 5, 6, 8, 9, 14).

Indeed, there are deterministic genetic disorders, such as Huntington's disease, wherein the presence of a definitive genetic marker is not used to give a disease label to a patient.²¹ Rather, the term disease is only applied once symptoms emerge. A similar approach to AD was favored by the International Working Group on the clinical diagnosis of AD.²² Such a system applied to the AD population may allay concerns with inappropriate disclosures, inaccurate descriptions of healthy patients as diseased, stigmatization associated with the disease label, and patient confusion surrounding the lack of a 1:1 relationship between biomarker positivity and symptom development.

In the published manuscript, the AA workgroup argued that there should be a “distinction between a disease and an illness. A disease is a pathogenic condition, while the term illness denotes signs and symptoms that result from the disease” (p. 6). In contrast, others have advocated for asymptomatic persons with positive AD biomarkers to be labeled as being at-risk for the development of the disease syndrome.⁵ In its commentary on the new criteria, the AA workgroup eschewed this possibility and added that the public would be able to understand the distinction between preclinical AD as a biological entity versus AD as a degenerative syndrome “with the proper educational effort” (p. 2). Whether such a public education effort would be successful is an empirical question. And an important conceptual one is whether it would be easier for a smaller group of scientists and clinicians to avoid the term AD for asymptomatic individuals, especially given that this term is still associated with a devastating, often stigmatized condition in the public consciousness.²³

Important unanswered conceptual and scientific questions regarding AD diagnosis

Despite potential advances, the AA criteria raise important conceptual and scientific issues associated with the diagnosis and staging of AD. We covered three such questions in our survey and summarize more in Text Box 1. First, survey participants overwhelmingly (95%) expressed concern about the diagnosis of people who fall within an indeterminate range (e.g., some biomarkers above cutoffs but others below cutoffs, multiple biomarkers falling just below cutoffs; Statement 11). Recent models employing p-Tau217 blood tests provide one potential framework for classifying these cases.²⁴ For these tests, reference ranges are provided for positive cases, negative cases, and indeterminate cases; indeterminate cases are referred for confirmatory CSF or PET testing. We are pleased to note that the AA workgroup introduced a section (3.5: Conservative treatment of values near a cutpoint; the indeterminate zone) recommending the use of such a framework in the final version of the manuscript.

Text Box 1.

Unanswered Questions Regarding the Alzheimer's Association Revised Criteria for the Diagnosis and Staging of Alzheimer's Disease.

Are the criteria meant to be applied in routine clinical practice?

How can the criteria be applied in cases where biomarker testing is unavailable?

Can the criteria be equitably applied in diverse groups?

How do patients and their families understand the term Alzheimer's disease when given information about biomarkers?

Would an Alzheimer's disease diagnosis cause harm to an asymptomatic person?

How will indeterminate biomarker results be handled?

What is the relative importance of neurobehavioral symptom presentations to clinical staging in Alzheimer's disease?

Which tests or combination of tests best predict clinical outcomes in Alzheimer's disease?

What parties will benefit most from incorporating biomarkers in Alzheimer's disease diagnostic criteria?

Second, 82% of surveyed neuropsychologists expressed concern that alternative symptom presentations of AD, such as mild behavioral impairment (MBI), were inadequately addressed in the AA criteria (Statement 12). MBI consists of neuropsychiatric symptoms, like depression, apathy, and sleep disturbance, and is increasingly recognized as an early manifestation of AD.²⁵ MBI criteria will be added to the Uniform Data Set version 4 forms used across U.S.-based Alzheimer's Disease Research Centers.²⁶ In the prior research framework for AD, behavioral changes were a central feature of all stages of the proposed AD clinical continuum.²⁷ However, the current criteria state that individuals cannot be considered to have progressed to clinical stage 3 unless cognitive impairment is also present. There was not a clear rationale presented for this choice. Responses to this survey suggest that many neuropsychologists believe behavioral symptoms should be retained as independent markers of severity across the clinical stages of AD progression.

Third, it is perhaps unsurprising that neuropsychologists think that neuropsychological tools might more sensitively identify and track AD symptoms than biomarkers (Statement 13). In the survey, most respondents endorsed a statement to this effect (86%). This opinion is supported by research suggesting that cognitive test results are more closely tied to cognitive and functional prognosis than biomarkers (e.g.,²⁸) or at the very least provide incremental predictive utility to biomarkers in predicting incident clinical conversion (e.g.,²⁹). Similarly, baseline cognition and short-term practice effects separated groups of typical aging, mild cognitive impairment, and mild AD participants better than commonly used biomarkers in AD.³⁰ Finally, neuropsychological measures may be more tightly associated with ecologically relevant outcomes (e.g., driving cessation³¹) than biomarkers.

By exclusively focusing on biomarkers with the new criteria, there is a risk of stifling advancements in non-biomarker measures of AD that are potentially more clinically relevant. Nonetheless, the AA workgroup did note the potential of digital cognitive assessments “to reliably detect the subtle cognitive alterations characteristic of stage 2” (p. 15), and two of the authors noted in a commentary that “cognitive testing must be done to correctly stage the individual clinically before biomarker testing is performed” (p. 2).¹¹ Further, neuropsychologists may still play a role in determining the relative contributions of co-pathologies to the clinical presentation of a given patient, which the AA workgroup highlighted as an ongoing challenge even with the advent of biomarker technologies. Thus, neuropsychological expertise still appears to be critical for an AD diagnostic workup even if working under these revised criteria.

Limitations

This work should be interpreted in light of certain limitations. First, we assessed the opinions of a fairly narrow group of professionals regarding the AA draft criteria for AD; namely, neuropsychologists and neuropsychology trainees with expertise and interest in dementia who were willing to read the criteria and respond to our survey. In particular, it will be important to gather feedback on the criteria from more neuropsychologists outside the U.S., as well individuals from other invested parties (i.e., physicians, ethicists, legal experts, and patients living with AD and their support networks).

A second limitation concerns possible bias in the construction of survey statements. We endeavored to avoid bias by including both positively and negatively phrased statements regarding the AA draft criteria, and we observed the full range of response options on every statement. Nonetheless, it is possible that sentiment regarding the AA draft criteria for AD may have skewed responses due to the way the survey was constructed.

A third, related caveat is that there are guild issues at play for neuropsychologists involved in the diagnosis of AD. There is a possibility that the shift towards biomarkers may lead to a diminished role for neuropsychologists in the AD diagnostic process. Concern over such diminishment may be a factor underlying neuropsychologists’ opinions regarding the AA criteria for AD. This question and the future role of neuropsychology in the diagnostic process could be evaluated empirically in future research.

Conclusion

Diagnostic and staging criteria are routinely updated across medical fields, and the AA workgroup took on the formidable task of integrating recent findings on biomarkers and new AD treatments to publish revised criteria for the diagnosis and staging of AD. Neuropsychologists in our sample expressed concerns with the criteria surrounding ambiguity of purpose and potential difficulties with implementation given currently available resources and the state of the science. This data could be used to revise the criteria and improve them prior to implementation. Such ongoing scientific inquiry and dialogue will cultivate a responsive approach, ensuring that criteria continue to adapt to the evolving landscape of AD science and treatment.

Footnotes

Acknowledgments

Contributing Neuropsychologists (listed alphabetically by last name): John Bellone, Kaiser Permanente, Department of Behavioral Health, San Bernardino, CA, USA; Joseph Bascarino, James A. Haley Veterans’ Hospital, Tampa, FL, USA; Timothy Brearly, Department of Neurology, Penn State College of Medicine, Hershey, PA, USA; Davde Bruno, Liverpool John Moores University, Liverpool, UK; Molly Mather, Mesulam Center for Cognitive Neurology and Alzheimer's Disease and Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Kerryn Pike, Griffith Centre for Mental Health and School of Applied Psychology, Griffith University, Gold Coast, Australia; Sarah Prieto, Warren Alpert Medical School of Brown University, Providence, RI, United States; Danielle Shaked, Mount Auburn Hospital, Cambridge, MA, USA; Ryan Van Patten, VA Providence Healthcare System, Center for Neurorestoration & Neurotechnology, Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA.

The content of this manuscript is solely the responsibility of the co-authors and does not represent the views and opinions of the International Neuropsychological Society (INS). However, we acknowledge the INS for creating the Dementia Special Interest Group, which facilitated collaboration among the members.

ORCID iDs

Andrew M Kiselica

S Duke Han

Unai Diaz-Orueta

Marissa A Gogniat

Alberto Blanco-Campal

Kevin Duff

Author contributions

Andrew Kiselica (Conceptualization; Data curation; Methodology; Project administration; Writing – original draft; Writing – review & editing); Kelly Atkins (Conceptualization; Formal analysis; Methodology; Visualization; Writing – original draft; Writing – review & editing); S Duke Han (Conceptualization; Methodology; Writing – original draft; Writing – review & editing); Unai Diaz-Orueta (Conceptualization; Methodology; Writing – original draft; Writing – review & editing); Marissa Gogniat (Conceptualization; Methodology; Writing – original draft; Writing – review & editing); Alberto Blanco-Campal (Writing – original draft; Writing – review & editing); Greta Hermann (Data curation; Writing – original draft; Writing – review & editing); Kevin Duff (Conceptualization; Data curation; Formal analysis; Methodology; Writing – original draft; Writing – review & editing)

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Dr. Kiselica is supported by a career development award from the National Institute of Aging (NIA) of the National Institutes of Health (NIH), Award Number: U54AG063546. This award funds the NIA Imbedded Pragmatic Alzheimer's Disease and AD-Related Dementias Clinical Trials Collaboratory (NIA IMPACT Collaboratory). Dr Kiselica is further supported by National Institute on Aging (NIA) of the National Institutes of Health under Award Number U24AG073094, which funds the NIA a2Collective. Dr Han is supported by NIA grants R01AG068166, R01AG055430, K24AG081325, and P30AG066530. Dr Duff is supported by NIA grants: R01AG073261and P30AG66518. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data availability

Data will be shared by reasonable request to the lead author with appropriate IRB oversight.

The data supporting the findings of this study are available on request to the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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