Alzheimer Disease as a Clinical-Biological Construct—An International Working Group Recommendation

Importance: Since 2018, a movement has emerged to define Alzheimer disease (AD) as a purely biological entity based on biomarker findings. The recent revision of the Alzheimer Association (AA) criteria for AD furthers this direction. However, concerns about a purely biological definition of AD being applied clinically, the understanding of AD by society at large, and the translation of blood-based biomarkers into clinical practice prompt these International Working Group (IWG) updated recommendations. Objective: To consider the revised AA criteria and to offer an alternative definitional view of AD as a clinical-biological construct for clinical use. The recommendations of the 2021 IWG diagnostic criteria are updated for further elaborating at-risk and presymptomatic states. Evidence Review: PubMed was searched for articles published between July 1, 2020, and March 1, 2024, using the terms "biomarker" OR "amyloid" OR "tau" OR "neurodegeneration" OR "preclinical" OR "CSF" OR "PET" OR "plasma" AND "Alzheimer's disease." The references of relevant articles were also searched. Findings: In the new AA diagnostic criteria, AD can be defined clinically as encompassing cognitively normal people having a core 1 AD biomarker. However, recent literature shows that the majority of biomarker-positive cognitively normal individuals will not become symptomatic along a proximate timeline. In the clinical setting, disclosing a diagnosis of AD to cognitively normal people with only core 1 AD biomarkers represents the most problematic implication of a purely biological definition of the disease. Conclusions and Relevance: The ultimate aim of the field was to foster effective AD treatments, including preventing symptoms and dementia. The approach of diagnosing AD without a clinical and biological construct would be unwarranted and potentially concerning without a clear knowledge of when or whether symptoms will ever develop. It is recommended that those who are amyloid-positive only and, more generally, most biomarker-positive cognitively normal individuals, should not be labeled as having AD. Rather, they should be considered as being at risk for AD. The expansion of presymptomatic AD is viewed as a better diagnostic construct for those with a specific pattern of biomarkers, indicating that they are proximate to the expression of symptoms in the near future.

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UNC Libraries
Published
2024-11-07
DOI
https://doi.org/10.17615/pxky-1x56
Primary Topic
Cancer Research and Treatment
Type
article
Field-Weighted Citation Impact
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article

Alzheimer Disease as a Clinical-Biological Construct—An International Working Group Recommendation

Lisa Delano‐Wood, Gunhild Waldemar, Eric Widera, Agustín M. Ibáñez et al.
UNC Libraries
Cancer Research and Treatment
article

Alzheimer Disease as a Clinical-Biological Construct—An International Working Group Recommendation

Lisa Delano‐Wood, Gunhild Waldemar, Eric Widera, Agustín M. Ibáñez, Nick C. Fox, Stefano Francesco Cappa, Christopher C. Rowe, Marc Agronin, Noll L. Campbell, Kaj Blennow, Sandra Swantek, Craig Ritchie, Nicolas Villain, Kristian Steen Frederiksen, Howard Feldman, Leonardo Cruz de Souza, Jonathan M. Schott, Bernard Hanseeuw, Jennifer R. Gatchel, Paulo Caramelli, Lutz Froelich, Merçé Boada, PAUL A. NEWHOUSE, Douglas Galasko, Ricardo Nitríni, David Thomas Jones, Frederik Barkhof, Frank Jessen, Andrea Slachevsky, Andrea Bozoki, Ricardo Allegri, Madhav Thambisetty, Helen Lavretsky, Stéphanie Bombois, Vincent Planche, Alexandre Bejanin, Agneta Nordberg, Alessandro Padovani, Miia Kivipelto, Jean Georges, Lon S. Schneider, Giovanni B. Frisoni, Bruno Dubois, Richard Lévy
article en

Abstract

Importance: Since 2018, a movement has emerged to define Alzheimer disease (AD) as a purely biological entity based on biomarker findings. The recent revision of the Alzheimer Association (AA) criteria for AD furthers this direction. However, concerns about a purely biological definition of AD being applied clinically, the understanding of AD by society at large, and the translation of blood-based biomarkers into clinical practice prompt these International Working Group (IWG) updated recommendations. Objective: To consider the revised AA criteria and to offer an alternative definitional view of AD as a clinical-biological construct for clinical use. The recommendations of the 2021 IWG diagnostic criteria are updated for further elaborating at-risk and presymptomatic states. Evidence Review: PubMed was searched for articles published between July 1, 2020, and March 1, 2024, using the terms "biomarker" OR "amyloid" OR "tau" OR "neurodegeneration" OR "preclinical" OR "CSF" OR "PET" OR "plasma" AND "Alzheimer's disease." The references of relevant articles were also searched. Findings: In the new AA diagnostic criteria, AD can be defined clinically as encompassing cognitively normal people having a core 1 AD biomarker. However, recent literature shows that the majority of biomarker-positive cognitively normal individuals will not become symptomatic along a proximate timeline. In the clinical setting, disclosing a diagnosis of AD to cognitively normal people with only core 1 AD biomarkers represents the most problematic implication of a purely biological definition of the disease. Conclusions and Relevance: The ultimate aim of the field was to foster effective AD treatments, including preventing symptoms and dementia. The approach of diagnosing AD without a clinical and biological construct would be unwarranted and potentially concerning without a clear knowledge of when or whether symptoms will ever develop. It is recommended that those who are amyloid-positive only and, more generally, most biomarker-positive cognitively normal individuals, should not be labeled as having AD. Rather, they should be considered as being at risk for AD. The expansion of presymptomatic AD is viewed as a better diagnostic construct for those with a specific pattern of biomarkers, indicating that they are proximate to the expression of symptoms in the near future.

UNC Libraries
University of North Carolina at Chapel Hill (US)
U.S. Department of Veterans Affairs, Massachusetts General Hospital, Vanderbilt University, McLean Hospital, Vanderbilt University Medical Center, University of St Andrews, University College London, Trinity College Dublin, University of Melbourne, Centre National de la Recherche Scientifique, Universidad de Antioquia, Universidade de São Paulo, Sahlgrenska Universitetssjukhuset, Göteborgs Universitet, Universidad de Chile, Université de Genève, Università degli Studi di Brescia, Universidade Federal de Minas Gerais, Centre Hospitalier Universitaire de Bordeaux, Universitat Autònoma de Barcelona, Clínica Alemana de Santiago, Fleni, National Institutes of Health, University of California, Los Angeles, University of North Carolina at Chapel Hill, University of California, San Diego, University of California, San Francisco, Veterans Affairs San Diego Healthcare System, Geriatric Research Education and Clinical Center, Sahlgrenska Akademin, NIH Clinical Center, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles
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