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Diagnostic utility of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) in asymptomatic subjects at increased risk for Alzheimer’s disease

  • Alexander Drzezga
  • Daniele Altomare
  • Cristina Festari
  • Javier Arbizu
  • Stefania Orini
  • Karl Herholz
  • Peter Nestor
  • Federica Agosta
  • Femke Bouwman
  • Flavio Nobili
  • Zuzana Walker
  • Giovanni Battista Frisoni
  • Marina Boccardi
  • for the EANM-EAN Task Force for the Prescription of FDG-PET for Dementing Neurodegenerative Disorders
Review Article

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.

Keywords

FDG-PET Alzheimer’s disease SCD ADAD APOE PSEN1 Amyloidosis 

Notes

Acknowledgements

The procedure for assessing scientific evidence and defining consensual recommendations was funded by the European Association of Nuclear Medicine (EANM) and by the European Academy of Neurology (EAN). We thank the Guidelines working group of EAN, particularly Simona Arcuti and Maurizio Leone, for methodological advice.

Funding

This project was partially funded by the European Association of Nuclear Medicine (EANM) and the European Academy of Neurology (EAN).

Compliance with ethical standards

Conflict of interest

Flavio Nobili: received personal fees and non-financial support from GE Healthcare, non-financial support from Eli-Lilly, and grants from Chiesi Farmaceutici.

Cristina Festari: declares that she has no conflict of interest.

Daniele Altomare: was the recipient of the grant allocated by the European Academy of Neurology (EAN) for data extraction and evidence assessment for the present project.

Federica Agosta: is Section Editor of NeuroImage Clinical; has received speaker fees from Biogen Idec, Novartis, and Excellence in Medical Education; and receives or has received research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), and the European Research Council. She received personal fees from Elsevier INC.

Stefania Orini:: declares that she has no conflict of interest.

Federica Gandolfo: declares that she has no conflict of interest.

Javier Arbizu: received grants from Eli-Lilly & Co, Piramal and GE Healthcare.

Femke Bouwman: none.

Peter Nestor: none.

Alexander Drzezga: received grants and non-financial support from Eli-Lilly & Co, Siemens, and GE Healthcare; he also received non-financial support from Piramal.

Zuzana Walker: received from GE Healthcare grants and tracers, personal fees for consultancy, and speakers fee.

Marina Boccardi: has received funds from the European Association of Nuclear Medicine (EANM) to perform the evidence assessment and the global coordination of the present project. Moreover, she has received research grants from Piramal, and served as a paid member of advisory boards for Eli Lilly.

Giovanni B Frisoni: is principal investigator of industry-sponsored trials funded by AbbVie, Acadia, Altoida, Amoneta, Araclon, Biogen, Janssen, Novartis, Piramal; has received funding for investigator-initiated trials from GE, Piramal, and Avid-Lilly; has received speaker fees from a number of pharma and imaging companies.

Ethical approval

This is a review article that does not contain any original study with human participants performed by any of the authors. Ethical approval is shown in each of the quoted original paper.

Informed consent

Not applicable, this is a review article. Informed consent statement is declared in each of the revised paper.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Alexander Drzezga
    • 1
  • Daniele Altomare
    • 2
    • 3
  • Cristina Festari
    • 2
    • 3
  • Javier Arbizu
    • 4
  • Stefania Orini
    • 5
  • Karl Herholz
    • 6
  • Peter Nestor
    • 7
    • 8
  • Federica Agosta
    • 9
  • Femke Bouwman
    • 10
  • Flavio Nobili
    • 11
  • Zuzana Walker
    • 12
  • Giovanni Battista Frisoni
    • 2
    • 13
    • 14
  • Marina Boccardi
    • 2
    • 13
  • for the EANM-EAN Task Force for the Prescription of FDG-PET for Dementing Neurodegenerative Disorders
  1. 1.Department of Nuclear Medicine, University Hospital of CologneUniversity of Cologne and German Center for Neurodegenerative Diseases (DZNE)CologneGermany
  2. 2.LANE – Laboratory of Alzheimer’s Neuroimaging & EpidemiologyIRCCS S. Giovanni di Dio FatebenefratelliBresciaItaly
  3. 3.Department of Molecular and Translational MedicineUniversity of BresciaBresciaItaly
  4. 4.Department of Nuclear Medicine, Clinica Universidad de NavarraUniversity of NavarraPamplonaSpain
  5. 5.Alzheimer Operative UnitIRCCS S. Giovanni di Dio, FatebenefratelliBresciaItaly
  6. 6.Institute of Brain, Behaviour and Mental Health, Wolfson Molecular Imaging CentreThe University of ManchesterManchesterUK
  7. 7.German Center for Neurodegenerative Diseases (DZNE)MagdeburgGermany
  8. 8.Queensland Brain InstituteUniversity of Queensland and at the Mater Hospital BrisbaneBrisbaneAustralia
  9. 9.Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific InstituteVita-Salute San Raffaele UniversityMilanItaly
  10. 10.Department of Neurology & Alzheimer Center, Amsterdam NeuroscienceVU University Medical CenterAmsterdamthe Netherlands
  11. 11.Department of Neuroscience (DINOGMI)University of Genoa and Polyclinic IRCCS San Martino-ISTGenoaItaly
  12. 12.Division of Psychiatry & Essex Partnership University NHS Foundation TrustUniversity College LondonLondonUK
  13. 13.LANVIE (Laboratoire de Neuroimagerie du Vieillissement), Department of PsychiatryUniversity of GenevaGenevaSwitzerland
  14. 14.Memory ClinicUniversity HospitalsGenevaSwitzerland

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