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

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Résumé

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's 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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La notice

Revue

JAMA Neurology

Thématique

Dementia and Cognitive Impairment Research

Domaine

Medicine

Établissements canadiens

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Organismes subventionnaires

CilagJane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los AngelesNational Institute on AgingSahlgrenska AkademinInstituto de Salud Carlos IIIGeriatric Research Education and Clinical CenterFondo de Financiamiento de Centros de Investigación en Áreas PrioritariasUniversity of North Carolina at Chapel HillFogarty International CenterNational Institutes of HealthUniversity College LondonGrifolsClínica Alemana de SantiagoSiemens HealthineersServierUniversitat Autònoma de BarcelonaMassachusetts General HospitalUniversidade Federal de Minas GeraisUniversidad de ChileNIH Clinical CenterFleniAssociation de soutien à la Paralysie Supranucléaire ProgressiveGöteborgs UniversitetSahlgrenska UniversitetssjukhusetUniversidade de São PauloEli Lilly and CompanyUniversity of St AndrewsFundação de Amparo à Pesquisa do Estado de Minas GeraisSanofiUniversidad de AntioquiaNovo NordiskEisaiFonds De La Recherche Scientifique - FNRSConselho Nacional de Desenvolvimento Científico e TecnológicoAlzheimer's AssociationGlobal Brain Health InstituteAgencia Nacional de Investigación y DesarrolloUniversité de GenèveTrinity College DublinCerveau TechnologiesVeterans Affairs San Diego Healthcare SystemUniversity of California, Los AngelesProthenaJulius ClinicalVanderbilt University Medical CenterFondation pour la Recherche sur AlzheimerEuropean CommissionMcLean HospitalVanderbilt UniversityBiogenTauRx PharmaceuticalsUniversity of California, San FranciscoAlzheimer SocietyBristol-Myers SquibbUniversity of California, San DiegoU.S. Department of Veterans Affairs

Mots-clés

Construct (python library)DiseaseAlzheimer's diseaseGroup (periodic table)MedicinePsychologyNeuroscienceInternal medicineComputer science

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