title: Preclinical Alzheimer's disease: A systematic review of the cohorts underlying the concept.
abstract: Preclinical Alzheimer's disease (AD) is a relatively recent concept describing an entity characterized by the presence of a pathophysiological biomarker signature characteristic for AD in the absence of specific clinical symptoms. There is rising interest in the scientific community to define such an early target population mainly because of failures of all recent clinical trials despite evidence of biological effects on brain amyloidosis for some compounds. A conceptual framework has recently been proposed for this preclinical phase of AD. However, few data exist on this silent stage of AD. We performed a systematic review to investigate how the concept is defined across studies. The review highlights the substantial heterogeneity concerning the three main determinants of preclinical AD: "normal cognition," "cognitive decline," and "AD pathophysiological signature." We emphasize the need for a harmonized nomenclature of the preclinical AD concept and standardized population-based and case-control studies using unified operationalized criteria.
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Neurologie, Institut de la mémoire et de la maladie d'Alzheimer, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; ICM, CNRS UMR 7225, Inserm U 1127, UPMC-P6 UMR S 1127, GH Pitié-Salpêtrière, Paris, France. Electronic address: stephane.epelbaum@aphp.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Epelbaum
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Neurologie, Institut de la mémoire et de la maladie d'Alzheimer, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Genthon
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Neurologie, Institut de la mémoire et de la maladie d'Alzheimer, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Enrica
authors.initials: E
authors.lastname: Cavedo
authors.affiliation: ICM, CNRS UMR 7225, Inserm U 1127, UPMC-P6 UMR S 1127, GH Pitié-Salpêtrière, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de médecine nucléaire, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Marie Odile
authors.initials: MO
authors.lastname: Habert
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire de Biochimie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Foudil
authors.initials: F
authors.lastname: Lamari
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Neurologie, Institut de la mémoire et de la maladie d'Alzheimer, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; ICM, CNRS UMR 7225, Inserm U 1127, UPMC-P6 UMR S 1127, GH Pitié-Salpêtrière, Paris, France.
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Gagliardi
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Neurologie, Institut de la mémoire et de la maladie d'Alzheimer, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; IHU-A-ICM, Paris Institute of Translational Neurosciences, Hôpital de la Pitié-Salpêtrière, Paris, France; AXA Research Fund & UPMC Chair, Paris, France.
authors.forename: Simone
authors.initials: S
authors.lastname: Lista
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Neurologie, Institut de la mémoire et de la maladie d'Alzheimer, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; ICM, CNRS UMR 7225, Inserm U 1127, UPMC-P6 UMR S 1127, GH Pitié-Salpêtrière, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Teichmann
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Neurologie, Institut de la mémoire et de la maladie d'Alzheimer, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; IHU-A-ICM, Paris Institute of Translational Neurosciences, Hôpital de la Pitié-Salpêtrière, Paris, France; AXA Research Fund & UPMC Chair, Paris, France.
authors.forename: Hovagim
authors.initials: H
authors.lastname: Bakardjian
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Neurologie, Institut de la mémoire et de la maladie d'Alzheimer, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; ICM, CNRS UMR 7225, Inserm U 1127, UPMC-P6 UMR S 1127, GH Pitié-Salpêtrière, Paris, France; AXA Research Fund & UPMC Chair, Paris, France.
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Neurologie, Institut de la mémoire et de la maladie d'Alzheimer, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; ICM, CNRS UMR 7225, Inserm U 1127, UPMC-P6 UMR S 1127, GH Pitié-Salpêtrière, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dubois
mesh_terms: D000544:Alzheimer Disease / Q000145:classification / Q000175:diagnosis / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D062706:Prodromal Symptoms; D009626:Terminology as Topic
chemical_list: D015415:Biomarkers
keywords: Biomarker; Clinical trial; Cognition; Cohort; Cross-sectional; Familial Alzheimer's disease; Longitudinal; Neuropathology; Preclinical Alzheimer's disease; Systematic review