Bruno Dubois, Nicolas Villain, Lon Schneider, Nick Fox, Noll Campbell, Douglas Galasko, Miia Kivipelto, Frank Jessen, Bernard Hanseeuw, Mercè Boada, Frederik Barkhof, Agneta Nordberg, Lutz Froelich, Gunhild Waldemar, Kristian Steen Frederiksen, Alessandro Padovani, Vincent Planche, Christopher Rowe, Alexandre Bejanin, Agustin Ibanez, Stefano Cappa, Paulo Caramelli, Ricardo Nitrini, Ricardo Allegri, Andrea Slachevsky, Leonardo Cruz de Souza, Andrea Bozoki, Eric Widera, Kaj Blennow, Craig Ritchie, Marc Agronin, Francisco Lopera, Lisa Delano-Wood, Stéphanie Bombois, Richard Levy, Madhav Thambisetty, Jean Georges, David T Jones, Helen Lavretsky, Jonathan Schott, Jennifer Gatchel, Sandra Swantek, Paul Newhouse, Howard H Feldman, Giovanni B Frisoni
{"title":"Alzheimer Disease as a Clinical-Biological Construct-An International Working Group Recommendation.","authors":"Bruno Dubois, Nicolas Villain, Lon Schneider, Nick Fox, Noll Campbell, Douglas Galasko, Miia Kivipelto, Frank Jessen, Bernard Hanseeuw, Mercè Boada, Frederik Barkhof, Agneta Nordberg, Lutz Froelich, Gunhild Waldemar, Kristian Steen Frederiksen, Alessandro Padovani, Vincent Planche, Christopher Rowe, Alexandre Bejanin, Agustin Ibanez, Stefano Cappa, Paulo Caramelli, Ricardo Nitrini, Ricardo Allegri, Andrea Slachevsky, Leonardo Cruz de Souza, Andrea Bozoki, Eric Widera, Kaj Blennow, Craig Ritchie, Marc Agronin, Francisco Lopera, Lisa Delano-Wood, Stéphanie Bombois, Richard Levy, Madhav Thambisetty, Jean Georges, David T Jones, Helen Lavretsky, Jonathan Schott, Jennifer Gatchel, Sandra Swantek, Paul Newhouse, Howard H Feldman, Giovanni B Frisoni","doi":"10.1001/jamaneurol.2024.3770","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Evidence review: </strong>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.</p><p><strong>Findings: </strong>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.</p><p><strong>Conclusions and relevance: </strong>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.</p>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":null,"pages":null},"PeriodicalIF":20.4000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAMA neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1001/jamaneurol.2024.3770","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
JAMA Neurology is an international peer-reviewed journal for physicians caring for people with neurologic disorders and those interested in the structure and function of the normal and diseased nervous system. The Archives of Neurology & Psychiatry began publication in 1919 and, in 1959, became 2 separate journals: Archives of Neurology and Archives of General Psychiatry. In 2013, their names changed to JAMA Neurology and JAMA Psychiatry, respectively. JAMA Neurology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications.