Alzheimer Disease as a Clinical-Biological Construct—An International Working Group Recommendation
Journal
JAMA Neurology
ISSN
2168-6149
Date Issued
2024
Author(s)
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
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
Type
journal-article
Abstract
<jats:sec id="ab-nsc240001-1"><jats:title>Importance</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-nsc240001-2"><jats:title>Objective</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-nsc240001-3"><jats:title>Evidence Review</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-nsc240001-4"><jats:title>Findings</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-nsc240001-5"><jats:title>Conclusions and Relevance</jats:title><jats:p>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.</jats:p></jats:sec>
Subjects
biological marker
;
alzheimer disease
;
cerebrospinal fluid
;
clinical practice
;
dementia
;
diagnosis
;
human
;
nerve degeneration
;
positron emission tomography
;
review