Alexander Drzezga1, Daniele Altomare2,3, Cristina Festari2,3, Javier Arbizu4, Stefania Orini5, Karl Herholz6, Peter Nestor7,8, Federica Agosta9, Femke Bouwman10, Flavio Nobili11, Zuzana Walker12, Giovanni Battista Frisoni2,13,14, Marina Boccardi2,13. 1. Department of Nuclear Medicine, University Hospital of Cologne, University of Cologne and German Center for Neurodegenerative Diseases (DZNE), Kerpener Str. 62, 50937, Cologne, Germany. alexander.drzezga@uk-koeln.de. 2. LANE - Laboratory of Alzheimer's Neuroimaging & Epidemiology, IRCCS S. Giovanni di Dio Fatebenefratelli, Brescia, Italy. 3. Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. 4. Department of Nuclear Medicine, Clinica Universidad de Navarra, University of Navarra, Pamplona, Spain. 5. Alzheimer Operative Unit, IRCCS S. Giovanni di Dio, Fatebenefratelli, Brescia, Italy. 6. Institute of Brain, Behaviour and Mental Health, Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK. 7. German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany. 8. Queensland Brain Institute, University of Queensland and at the Mater Hospital Brisbane, Brisbane, Australia. 9. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy. 10. Department of Neurology & Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands. 11. Department of Neuroscience (DINOGMI), University of Genoa and Polyclinic IRCCS San Martino-IST, Genoa, Italy. flaviomariano.nobili@hsanmartino.it. 12. Division of Psychiatry & Essex Partnership University NHS Foundation Trust, University College London, London, UK. 13. LANVIE (Laboratoire de Neuroimagerie du Vieillissement), Department of Psychiatry, University of Geneva, Geneva, Switzerland. 14. Memory Clinic, University Hospitals, Geneva, Switzerland.
Abstract
PURPOSE: To assess the clinical utility of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) for detection of early signs of neurodegeneration in conditions of increased risk for Alzheimer's disease (AD) as defined by: subjective cognitive decline (SCD), evidence of cerebral amyloid-pathology, apolipoprotein E (APOE) ε4-positive genotype, or autosomal dominant forms of AD (ADAD) in asymptomatic stages. METHODS: A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted using the Delphi method on three different diagnostic scenarios. RESULTS: The level of empirical study evidence for the use of FDG-PET to detect meaningful early signs of neurodegeneration was considered to be poor for ADAD and lacking for SCD and asymptomatic persons at risk, based on APOE ε4-positive genotype or cerebral amyloid pathology. Consequently, and consistent with current diagnostic criteria, panelists decided not to recommend routine clinical use of FDG-PET in these situations and to currently mainly reserve it for research purposes. CONCLUSION: Currently, there is limited evidence on which to base recommendations regarding the clinical routine use of FDG-PET to detect diagnostically meaningful early signs of neurodegeneration in asymptomatic subjects with ADAD, with APOE ε4-positive genotype, or with cerebral amyloid pathology, and in subjects with SCD. Future prospective studies are warranted and in part already ongoing, aiming to assess the added value of FDG-PET in this context beyond research applications.
PURPOSE: To assess the clinical utility of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) for detection of early signs of neurodegeneration in conditions of increased risk for Alzheimer's disease (AD) as defined by: subjective cognitive decline (SCD), evidence of cerebral amyloid-pathology, apolipoprotein E (APOE) ε4-positive genotype, or autosomal dominant forms of AD (ADAD) in asymptomatic stages. METHODS: A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted using the Delphi method on three different diagnostic scenarios. RESULTS: The level of empirical study evidence for the use of FDG-PET to detect meaningful early signs of neurodegeneration was considered to be poor for ADAD and lacking for SCD and asymptomatic persons at risk, based on APOE ε4-positive genotype or cerebral amyloid pathology. Consequently, and consistent with current diagnostic criteria, panelists decided not to recommend routine clinical use of FDG-PET in these situations and to currently mainly reserve it for research purposes. CONCLUSION: Currently, there is limited evidence on which to base recommendations regarding the clinical routine use of FDG-PET to detect diagnostically meaningful early signs of neurodegeneration in asymptomatic subjects with ADAD, with APOE ε4-positive genotype, or with cerebral amyloid pathology, and in subjects with SCD. Future prospective studies are warranted and in part already ongoing, aiming to assess the added value of FDG-PET in this context beyond research applications.
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