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Incremental value of amyloid-PET versus CSF in the diagnosis of Alzheimer’s disease

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

To compare the incremental diagnostic value of amyloid-PET and CSF (Aβ42, tau, and phospho-tau) in AD diagnosis in patients with mild cognitive impairment (MCI) or mild dementia, in order to improve the definition of diagnostic algorithm.

Methods

Two independent dementia experts provided etiological diagnosis and relative diagnostic confidence in 71 patients on 3 rounds, based on (1) clinical, neuropsychological, and structural MRI information alone; (2) adding one biomarker (CSF amyloid and tau levels or amyloid-PET with a balanced randomized design); and (3) adding the other biomarker.

Results

Among patients with a pre-biomarker diagnosis of AD, negative PET induced significantly more diagnostic changes than amyloid-negative CSF at both rounds 2 (CSF 67%, PET 100%, P = 0.028) and 3 (CSF 0%; PET 78%, P < 0.001); PET induced a diagnostic confidence increase significantly higher than CSF on both rounds 2 and 3.

Conclusions

Amyloid-PET should be prioritized over CSF biomarkers in the diagnostic workup of patients investigated for suspected AD, as it provides greater changes in diagnosis and diagnostic confidence.

Trial registration

EudraCT no.: 2014-005389-31

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Abbreviations

AD:

Alzheimer’s disease

MCI:

Mild cognitive impairment

PET:

Positron emission tomography

CSF:

Cerebrospinal fluid

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Acknowledgments

The study (EudraCT no. 2014-005389-31) sponsor was the Hôpitaux Universitaires de Genève (HUG). The study was financially supported by Piramal Imaging (now Life Molecular Imaging) that provided 18F-florbetaben at no cost, by the EU-EFPIA Innovative Medicines Initiative 2 Joint Undertaking grant no. 115952 (AMYPAD) and by the Swiss National Science Foundation under grant SNF 320030_169876. Piramal Imaging had no role in the design and conduct of the study: collection, management, analysis, and interpretation of the data.

Funding

This study was supported by Hôpitaux Universitaires de Genève (HUG); Piramal Imaging [grant number 115952]; and the Swiss National Science Foundation [grant number SNF 320030_169876].

Author information

Author notes

  1. Matteo Cotta Ramusino and Valentina Garibotto contributed equally to this work.

Authors and Affiliations

  1. Memory Clinic and LANVIE -Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Chemin du Petit Bel-Air 2, Bâtiment Voirons, CH1225, Geneva, Switzerland

    Matteo Cotta Ramusino, Ruggero Bacchin, Daniele Altomare, Frederic Assal, Aline Mendes, Maura Parapini, Marina Boccardi & Giovanni B Frisoni

  2. Center for Cognitive and Behavioral Disorders, IRCCS Mondino Foundation and Dept of Brain and Behavior, University of Pavia, 27100, Pavia, Italy

    Matteo Cotta Ramusino & Alfredo Costa

  3. NIMTlab, Neuroimaging and Innovative Molecular Tracers Laboratory, University of Geneva, CH1205, Geneva, Switzerland

    Valentina Garibotto & Alessandra Dodich

  4. Division of Nuclear Medicine, Geneva University Hospitals, CH1205, Geneva, Switzerland

    Valentina Garibotto

  5. Dept of Neurosciences, Biomedicine and Movement Sciences, Section of Neurology, University of Verona, 34134, Verona, Italy

    Ruggero Bacchin & Michele Tinazzi

  6. Nuclear Medicine, Dept of Health Sciences (DISSAL), University of Genoa and IRCCS AOU San Martino-IST, 16132, Genoa, Italy

    Silvia D. Morbelli & Matteo Bauckneht

  7. Clinical Neurology, Dept. of Neuroscience (DINOGMI), University of Genoa, 16126, Genoa, Italy

    Agnese Picco & Flavio Nobili

  8. Nuclear Medicine Division, “S. Maria della Misericordia” Hospital, 06129, Perugia, Italy

    Massimo E. Dottorini & Cristina Tranfaglia

  9. Center for Memory Disturbances, Laboratory of Clinical Neurochemistry, University of Perugia, 06123, Perugia, Italy

    Lucia Farotti & Nicola Salvadori

  10. Alzheimer‘s Disease Operative Unit, IRCCS S, Giovanni di Dio Fatebenefratelli, 25125, Brescia, Italy

    Davide Moretti

  11. Nuclear Medicine Division, Fondazione Poliambulanza Istituto Ospedaliero, 25124, Brescia, Italy

    Giordano Savelli

  12. LANE-Laboratory of Alzheimer’s Neuroimaging and Epidemiology, IRCCS San Giovanni di Dio Fatebenefratelli, 25125, Brescia, Italy

    Anna Tarallo & Marina Boccardi

  13. IRCCS Ospedale Policlinico San Martino, 16132, Genoa, Italy

    Flavio Nobili

  14. IRCCS SDN, 80143, Naples, Italy

    Carlo Cavaliere & Marco Salvatore

  15. University of Naples “Federico II”, 80131, Naples, Italy

    Elena Salvatore

Authors
  1. Matteo Cotta Ramusino
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  2. Valentina Garibotto
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  3. Ruggero Bacchin
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  4. Daniele Altomare
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  5. Alessandra Dodich
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  6. Frederic Assal
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  7. Aline Mendes
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  8. Alfredo Costa
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  10. Silvia D. Morbelli
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  15. Lucia Farotti
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  26. Giovanni B Frisoni
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Contributions

Study concept and design: Frisoni, Parapini.

Clinical consultant and data collection: Assal, Mendes, Picco, Nobili, Fattori, Salvadori, Costa, Tinazzi, Farotti, Moretti, E. Salvatore, M. Salvatore, Tarallo, Cotta Ramusino, Bacchin.

Amyloid PET scan reading: Morbelli, Bauckneht, Dottorini, Tranfaglia, Savelli, Cavaliere.

Statistical analysis and interpretation of data: Cotta Ramusino, Altomare, Garibotto, Boccardi, Frisoni.

Drafting of the manuscript: Cotta Ramusino, Altomare, Bacchin.

Critical revision of the manuscript for important intellectual continent: Garibotto, Dodich, Boccardi, Frisoni.

Obtained funding: Frisoni.

Study supervision: Cotta Ramusino, Frisoni.

Corresponding author

Correspondence to Matteo Cotta Ramusino.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval and consent to participate

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee (ethics committee of the University of Geneva) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

All subjects participating in this study have signed an informed consent form.

Data policy

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Consent for publication

The manuscript has been seen and approved by all authors for submission to EJNMMI.

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Ramusino, M.C., Garibotto, V., Bacchin, R. et al. Incremental value of amyloid-PET versus CSF in the diagnosis of Alzheimer’s disease. Eur J Nucl Med Mol Imaging 47, 270–280 (2020). https://doi.org/10.1007/s00259-019-04466-6

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