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Review
. 2016 Mar;12(3):292-323.
doi: 10.1016/j.jalz.2016.02.002.

Preclinical Alzheimer's Disease: Definition, Natural History, and Diagnostic Criteria

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Free PMC article
Review

Preclinical Alzheimer's Disease: Definition, Natural History, and Diagnostic Criteria

Bruno Dubois et al. Alzheimers Dement. .
Free PMC article

Abstract

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.

Keywords: Alzheimer's disease; Amyloid PET; Asymptomatic; Biomarkers; Blood biomarkers; CSF biomarkers; Diagnostic criteria; Genetics; MRI; Pathophysiology; Preclinical; Tau PET.

Figures

Fig. 1.
Fig. 1.
Proposal for a unified lexicon for preclinical AD. Abbreviation: AD, Alzheimer’s disease.
Fig. 2.
Fig. 2.
The risk of clinical AD–hypothetical model. Abbreviation: AD, Alzheimer’s disease; BM, pathophysiological biomarkers.

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