Journal of Alzheimer's Disease - Volume 90, issue 3

Authors: Rosen, Allyson C.

Article Type: Introduction

Abstract: Advances in biomarkers, genetics, and other data used as dementia risk evidence (DRE) are increasingly informing clinical diagnosis and management. The purpose of this Mini-Forum is to provide a solutions-based discussion of the ethical and legal gaps and practical questions about how to use and communicate these data. Investigators often use DRE in research. When participants ask for their personal results, investigators have concerns. Will data that was intended to study groups be valid for individuals? Will sharing data cause distress? Debates around sharing DRE became heated when blood-based amyloid tests and amyloid reducing drugs appeared poised to enable clinicians …easily to identify people with elevated brain amyloid and reduce it with a drug. Such an approach would transform the traditional role of DRE from investigational to foundational; however, then the high costs, uncertain clinical benefits and risks of the therapy led to an urgent need for education to support clinical decision making. Further complicating DRE use are direct to consumer genetic testing and increasingly available biomarker testing. Withholding DRE becomes less feasible and public education around responsible use and understanding become vital. A critical answer to these legal and ethical issues is supporting education that clearly delineates known risks, benefits, and gaps in knowledge, and communication to promote understanding among researchers, clinicians, patients, and all stakeholders. This paper provides an overview and identifies general concepts and resource documents that support more informed discussions for individuals and interdisciplinary groups. Show more

Keywords: Alzheimer’s disease, biomarkers, diagnosis, ethics, genetics, imaging, magnetic resonance imaging, positron emission tomography, risk, uncertainty

DOI: 10.3233/JAD-220722

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 933-944, 2022

Authors: Walter, Sarah | Taylor, Angela | Tyrone, Jamie | Langer, Sara | Pagan, John-Richard | Hummel, Cynthia Huling | Wheaton, Bonnie M. | Zallen, Doris T. | Rosen, Allyson C.

Article Type: Editorial

Abstract: This Study Participant’s Bill of Rights is a call to action for researchers in Alzheimer’s disease and related dementias (ADRD) to proactively design clinical studies that provide the option for research participants to learn their individual research results if they choose, and in a manner that ensures study integrity. This Bill of Rights was crafted by a committee of study participants, care partners, representatives of dementia advocacy organizations, and other stakeholders in dementia research for the Advisory Group on Risk Education for Dementia (AGREEDementia). The framework developed by the Multi-Regional Clinical Trials (MRCT) Return of Individual Research Results provides a …useful context for researchers to plan their studies and disclosure. Show more

Keywords: Biomarkers, communication, dementia, disclosure, ethics, genetics, patient rights

DOI: 10.3233/JAD-220810

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 945-952, 2022

Authors: Rosen, Allyson C. | Arias, Jalayne J. | Ashford, J. Wesson | Blacker, Deborah | Chhatwal, Jasmeer P. | Chin, Nathan A. | Clark, Lindsay | Denny, Sharon S. | Goldman, Jill S. | Gleason, Carey E. | Grill, Joshua D. | Heidebrink, Judith L. | Henderson, Victor W. | Lavacot, James A. | Lingler, Jennifer H. | Menon, Malavika | Nosheny, Rachel L. | Oliveira, Fabricio F. | Parker, Monica W. | Rahman-Filipiak, Annalise | Revoori, Anwita | Rumbaugh, Malia C. | Sanchez, Danurys L. | Schindler, Suzanne E. | Schwarz, Christopher G. | Toy, Leslie | Tyrone, Jamie | Walter, Sarah | Wang, Li-san | Wijsman, Ellen M. | Zallen, Doris T. | Aggarwal, Neelum T.

Article Type: Editorial

Abstract: The brain changes of Alzheimer’s disease and other degenerative dementias begin long before cognitive dysfunction develops, and in people with subtle cognitive complaints, clinicians often struggle to predict who will develop dementia. The public increasingly sees benefits to accessing dementia risk evidence (DRE) such as biomarkers, predictive algorithms, and genetic information, particularly as this information moves from research to demonstrated usefulness in guiding diagnosis and clinical management. For example, the knowledge that one has high levels of amyloid in the brain may lead one to seek amyloid reducing medications, plan for disability, or engage in health promoting behaviors to fight …cognitive decline. Researchers often hesitate to share DRE data, either because they are insufficiently validated or reliable for use in individuals, or there are concerns about assuring responsible use and ensuring adequate understanding of potential problems when one’s biomarker status is known. Concerns include warning people receiving DRE about situations in which they might be compelled to disclose their risk status potentially leading to discrimination or stigma. The Advisory Group on Risk Evidence Education for Dementia (AGREEDementia) welcomes all concerned with how best to share and use DRE. Supporting understanding in clinicians, stakeholders, and people with or at risk for dementia and clearly delineating risks, benefits, and gaps in knowledge is vital. This brief overview describes elements that made this group effective as a model for other health conditions where there is interest in unfettered collaboration to discuss diagnostic uncertainty and the appropriate use and communication of health-related risk information. Show more

Keywords: Alzheimer’s disease, amyloid, biomarkers, dementia, genetics

DOI: 10.3233/JAD-220458

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 953-962, 2022

Authors: Galasko, Douglas R. | Grill, Joshua D. | Lingler, Jennifer H. | Heidebrink, Judith L.

Article Type: Article Commentary

Abstract: A blood test for Alzheimer’s disease is now available for clinical use in persons with cognitive impairment. This is an extraordinary milestone, though the amyloid-based PrecivityAD™ test is not without limitations. Pre and post-test counseling are essential. Phosphorylated tau blood tests are likely to follow soon. When used in conjunction with an appropriate clinical evaluation, blood tests provide the opportunity for an early, accurate, and accessible diagnosis of Alzheimer’s disease. Standalone use, however, carries a significant risk of misinterpretation and is strongly discouraged. Now is the time to develop appropriate use criteria to guide the use of these promising assays.

Keywords: Alzheimer’s disease, biomarker, blood test, diagnosis

DOI: 10.3233/JAD-215490

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 963-966, 2022

Authors: Karikari, Thomas K.

Article Type: Research Article

Abstract: The recent academic and commercial development, and regulatory approvals, of blood-based Alzheimer’s disease (AD) biomarkers are breakthrough developments of immense potential. However, clinical validation studies and therapeutic trial applications are limited almost exclusively to non-Hispanic White cohorts often including highly-educated, high-earning participants. This commentary argues that the true benefits of blood tests for AD will be realized by active inclusion of diverse groups including minoritized populations, people of socioeconomic status different from those included in existing cohorts, and residents of low- and middle-income countries. The article discusses key factors that are critical for a successful implementation of diversity programs.

Keywords: Alzheimer’s disease, amyloid-β, blood biomarker, dementia, diagnostics, low- and middle-income countries, minoritized populations, neurofilament light, phosphorylated tau

DOI: 10.3233/JAD-215730

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 967-974, 2022

Authors: Schindler, Suzanne E.

Article Type: Article Commentary

Abstract: Predicting not just if but when cognitively normal individuals will develop the onset of Alzheimer’s disease (AD) dementia seems increasingly feasible, as evidenced by converging findings from several approaches and cohorts. These estimates may improve the efficiency of clinical trials by better identifying cognitively normal individuals at high risk of developing AD symptoms. As models are refined, the implications of disclosing estimates of the age of AD symptom onset must be examined, since telling a cognitively normal individual the age they are expected to develop AD symptoms may have different implications than disclosing increased risk for AD dementia.

Keywords: A4 study, Alzheimer’s disease, amyloid chronicity, amyloid clock, amyloid duration, amyloid PET, amyloid time, disclosure, symptom onset

DOI: 10.3233/JAD-215722

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 975-979, 2022

Authors: Parra, Mario A.

Article Type: Article Commentary

Abstract: Recently, Alzheimer’s Disease International (ADI) stressed that around 75% of people living with dementia globally are still not receiving a diagnosis. In this commentary, I reflect on how efforts towards better cognitive assessments, particularly of memory, can be aligned and harmonized to contribute to such needs. I highlight some barriers that ongoing collaborations and trials are facing and their potential drivers. I suggest some strategies that can help overcome them and in so doing, integrate research agendas. We need to ignite the debate towards strategies that can help level the playfield to tackle Alzheimer’s disease with true global solutions.

Keywords: Alzheimer’s disease, biomarkers, cognitive markers, early detection, neuropsychological assessment, prevention

DOI: 10.3233/JAD-215445

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 981-988, 2022

Authors: Daly, Timothy | Mastroleo, Ignacio | Migliaccio, Raffaella

Article Type: Article Commentary

Abstract: Given the unknown therapeutic value of targeting Alzheimer’s disease pathology and the discovery of robust risk factors for dementia, non-pharmacological risk reduction (RR) is increasingly offered as an alternative to targeting Alzheimer’s disease pathology. While RR will surely be a useful tool to make public health gains, we propose solutions to three possible issues with over-reliance on multi-domain interventions to achieve RR: limited individual impact, an exclusive focus on later life, and overlooking social determinants of dementia. We argue in favor of a broader debate within the research community and greater society about how different therapeutic avenues should be explored.

Keywords: Alzheimer’s disease, dementia, health inequities, multidomain interventions, public health, risk reduction, social determinants of health

DOI: 10.3233/JAD-215647

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 989-992, 2022

Authors: Lerner, Alan J.

Article Type: Research Article

Abstract: After years of anticipation, non-invasive tests for detecting cerebral amyloidosis and Alzheimer’s disease (AD) are entering clinical care. The PrecivityADtrademark test from C2N is a plasma-based test yielding an Amyloid Probability score with high sensitivity and specificity for brain amyloid accumulation, but some samples may have inconclusive results. The AGREEDementia consortium raised concerns that the field needs study of how best to use and communicate results of PrecivityADtrademark. Continued attention and mindfulness should be applied to the whole class of dementia biomarker tests and directed in light of FDA biomarker context of use framework. Unintended uses of biomarkers tests may …have unintended consequences, such as mislabeling patients. AD biomarker tests may efficiently stratify AD risk but will inevitably be included in electronic medical records and be subject to interpretation by medical personnel lacking proper knowledge or context to interpret results appropriately. Another way forward is mindful discussion and consensus among all stakeholders about the uses and limits of each specific test. Show more

Keywords: Alzheimer’s disease, amyloid, biomarkers, dementia, mindfulness, plasma, prediction

DOI: 10.3233/JAD-215592

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 993-996, 2022

Authors: Zallen, Doris T.

Article Type: Article Commentary

Abstract: Although the medical record is the centerpiece of modern medical care, its usefulness is diminished by the reluctance of people to disclose important health information, such as a higher risk for Alzheimer’s disease, to their doctors. Steps should be taken now to ensure that the medical record, the repository of one’s health information, can continue to serve the needs of the medical community and of patients.

Keywords: APOE, biomarkers, jurisprudence, medical records electronic

DOI: 10.3233/JAD-220584

Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 997-999, 2022