title: Limited agreement between biomarkers of neuronal injury at different stages of Alzheimer's disease.
abstract: New diagnostic criteria for Alzheimer's disease (AD) treat different biomarkers of neuronal injury as equivalent. Here, we quantified the degree of agreement between hippocampal volume on structural magnetic resonance imaging, regional glucose metabolism on positron emission tomography, and levels of phosphorylated tau in cerebrospinal fluid (CSF) in 585 subjects from all phases of the AD Neuroimaging Initiative. The overall chance-corrected agreement was poor (Cohen κ, 0.24-0.34), in accord with a high rate of conflicting findings (26%-41%). Neither diagnosis nor APOE ε4 status significantly influenced the distribution of agreement between the biomarkers. The degree of agreement tended to be higher in individuals with abnormal versus normal CSF β-amyloid (Aβ1-42) levels. Prospective diagnostic criteria for AD should address the relative importance of markers of neuronal injury and elaborate a way of dealing with conflicting biomarker findings.
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany; Department of Psychiatry, University of Patras, Rion Patras, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Alexopoulos
authors.affiliation: Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Kriett
authors.affiliation: Institute of Medical Statistics and Epidemiology, Technische Universität München, Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Haller
authors.affiliation: Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Klupp
authors.affiliation: Biomedical Image Analysis Group, Department of Computing, Imperial College London, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Gray
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
authors.affiliation: Department of Informatics, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Laskaris
authors.affiliation: Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Förster
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany; Neuroepidemiology and Ageing Research Unit, School of Public Health, The Imperial College of Science, Technology and Medicine, London, UK; West London Cognitive Disorders Treatment and Research Unit, West London Mental Health Trust, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Perneczky
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurz
authors.affiliation: Department of Nuclear Medicine, University of Cologne, Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center of Mainz, Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fellgiebel
authors.affiliation: Department of Nuclear Medicine, Technische Universität München, Munich, Germany. Electronic address: igor.yakushev@lrz.tum.de.
authors.forename: Igor
authors.initials: I
authors.lastname: Yakushev
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics; D001284:Atrophy / Q000209:etiology; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D016009:Chi-Square Distribution; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000209:etiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D049268:Positron-Emission Tomography; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D016875:tau Proteins; D019788:Fluorodeoxyglucose F18
keywords: Agreement; Dementia; Diagnostic criteria; FDG-PET; Hippocampal atrophy; Tau