Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria

Bruno Dubois*, Harald Hampel, Howard H. Feldman, Philip Scheltens, Paul Aisen, Sandrine Andrieu, Hovagim Bakardjian, Habib Benali, Lars Bertram, Kaj Blennow, Karl Broich, Enrica Cavedo, Sebastian Crutch, Jean François Dartigues, Charles Duyckaerts, Stéphane Epelbaum, Giovanni B. Frisoni, Serge Gauthier, Remy Genthon, Alida A. GouwMarie Odile Habert, David M. Holtzman, Miia Kivipelto, Simone Lista, José Luis Molinuevo, Sid E. O'Bryant, Gil D. Rabinovici, Christopher Rowe, Stephen Salloway, Lon S. Schneider, Reisa Sperling, Marc Teichmann, Maria C. Carrillo, Jeffrey Cummings, Cliff R. Jack

*Corresponding author for this work
160 Citations (Scopus)


During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.

Original languageEnglish
JournalAlzheimer's and Dementia
Issue number3
Pages (from-to)292-323
Number of pages32
Publication statusPublished - 01.03.2016


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