Assessing FDG-PET diagnostic accuracy studies to develop recommendations for clinical use in dementia

  • Marina BoccardiEmail author
  • Cristina Festari
  • Daniele Altomare
  • Federica Gandolfo
  • Stefania Orini
  • Flavio Nobili
  • Giovanni B. Frisoni
  • for the EANM-EAN Task Force for the Prescription of FDG-PET for Dementing Neurodegenerative Disorders
Review Article



FDG-PET is frequently used as a marker of synaptic damage to diagnose dementing neurodegenerative disorders. We aimed to adapt the items of evidence quality to FDG-PET diagnostic studies, and assess the evidence available in current literature to assist Delphi decisions for European recommendations for clinical use.


Based on acknowledged methodological guidance, we defined the domains, specific to FDG-PET, required to assess the quality of evidence in 21 literature searches addressing as many Population Intervention Comparison Outcome (PICO) questions. We ranked findings for each PICO and fed experts making Delphi decisions for recommending clinical use.


Among the 1435 retrieved studies, most lacked validated measures of test performance, an adequate gold standard, and head-to-head comparison of FDG-PET and clinical diagnosis, and only 58 entered detailed assessment. Only two studies assessed the accuracy of the comparator (clinical diagnosis) versus any kind of gold−/reference-standard. As to the index-test (FDG-PET-based diagnosis), an independent gold-standard was available in 24% of the examined papers; 38% used an acceptable reference-standard (clinical follow-up); and 38% compared FDG-PET-based diagnosis only to baseline clinical diagnosis. These methodological limitations did not allow for deriving recommendations from evidence.


An incremental diagnostic value of FDG-PET versus clinical diagnosis or lack thereof cannot be derived from the current literature. Many of the observed limitations may easily be overcome, and we outlined them as research priorities to improve the quality of current evidence. Such improvement is necessary to outline evidence-based guidelines. The available data were anyway provided to expert clinicians who defined interim recommendations.


FDG-PET Positron emission tomography Fluorodeoxyglucose metabolism 18F-FDG PET Evidence assessment Quality of evidence Recommendations Validation Biomarker Alzheimer Dementia Diagnosis 



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.

Collaborators for this paper are: Federica Agosta7, Javier Arbizu8, Femke Bouwman9, Alexander Drzezga10, Peter Nestor11, Zuzana Walker12.

7Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

8Department of Nuclear Medicine. Clinica Universidad de Navarra. University of Navarra. Pamplona, Spain.

9Department of Neurology & Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.

10Department of Nuclear Medicine, University Hospital of Cologne, University of Cologne and German Center for Neurodegenerative Diseases (DZNE), Germany.

11German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany; Queensland Brain Institute, University of Queensland and at the Mater Hospital Brisbane.

12University College London, Division of Psychiatry & Essex Partnership University NHS Foundation Trust, UK.


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

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.

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 Gandolfo: declares that she has no conflict of interest.

Stefania Orini: declares that she has no 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.

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; and 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 papers.

Informed consent

Not applicable to this review article. Informed consent statement is declared in each of the revised papers.


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Copyright information

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

Authors and Affiliations

  • Marina Boccardi
    • 1
    • 2
    Email author
  • Cristina Festari
    • 2
    • 3
  • Daniele Altomare
    • 2
    • 3
  • Federica Gandolfo
    • 4
  • Stefania Orini
    • 4
  • Flavio Nobili
    • 5
  • Giovanni B. Frisoni
    • 1
    • 2
    • 6
  • for the EANM-EAN Task Force for the Prescription of FDG-PET for Dementing Neurodegenerative Disorders
  1. 1.LANVIE (Laboratoire de Neuroimagerie du Vieillissement), Department of PsychiatryUniversity of GenevaChene-BourgSwitzerland
  2. 2.LANE – Laboratory of Alzheimer Neuroimaging & EpidemiologyIRCCS S. Giovanni di Dio, FatebenefratelliBresciaItaly
  3. 3.Department of Molecular and Translational MedicineUniversity of BresciaBresciaItaly
  4. 4.Alzheimer Operative Unit; IRCCS Centro S. Giovanni di Dio, FatebenefratelliBresciaItaly
  5. 5.DINOGMI – Department of Neuroscience, University of Genoa and IRCCS Polyclinic San Martino HospitalGenoaItaly
  6. 6.HUG Hopitaux Universitaires de GenèveGenevaSwitzerland

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