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Diagnostic performance of molecular imaging methods in predicting the progression from mild cognitive impairment to dementia: an updated systematic review

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

Abstract

Purpose

Epidemiological and logistical reasons are slowing the clinical validation of the molecular imaging biomarkers in the initial stages of neurocognitive disorders. We provide an updated systematic review of the recent advances (2017–2022), highlighting methodological shortcomings.

Methods

Studies reporting the diagnostic accuracy values of the molecular imaging techniques (i.e., amyloid-, tau-, [18F]FDG-PETs, DaT-SPECT, and cardiac [123I]-MIBG scintigraphy) in predicting progression from mild cognitive impairment (MCI) to dementia were selected according to the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) method and evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Main eligibility criteria were as follows: (1) ≥ 50 subjects with MCI, (2) follow-up ≥ 3 years, (3) gold standard: progression to dementia or diagnosis on pathology, and (4) measures of prospective accuracy.

Results

Sensitivity (SE) and specificity (SP) in predicting progression to dementia, mainly to Alzheimer’s dementia were 43–100% and 63–94% for [18F]FDG-PET and 64–94% and 48–93% for amyloid-PET. Longitudinal studies were lacking for less common disorders (Dementia with Lewy bodies-DLB and Frontotemporal lobe degeneration-FTLD) and for tau-PET, DaT-SPECT, and [123I]-MIBG scintigraphy. Therefore, the accuracy values from cross-sectional studies in a smaller sample of subjects (n > 20, also including mild dementia stage) were chosen as surrogate outcomes. DaT-SPECT showed 47–100% SE and 71–100% SP in differentiating Lewy body disease (LBD) from non-LBD conditions; tau-PET: 88% SE and 100% SP in differentiating DLB from Posterior Cortical Atrophy. [123I]-MIBG scintigraphy differentiated LBD from non-LBD conditions with 47–100% SE and 71–100% SP.

Conclusion

Molecular imaging has a moderate-to-good accuracy in predicting the progression of MCI to Alzheimer’s dementia. Longitudinal studies are sparse in non-AD conditions, requiring additional efforts in these settings.

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Data availability

The datasets generated during and/or analyzed during the current study are all included in the present manuscript and in the supplementary materials.

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Acknowledgements

The literature review was performed in the context of the European Intersocietal Consensus for the diagnosis of MCI and mild dementia [20] to assist the expert panel in determining the priority of biomarkers in the clinical workup of neurocognitive disorders. Co-authors SM and VG are the representatives of the European Association of Nuclear Medicine (EANM) for that effort. We thank EANM for the conceptual contribution to this work.

Funding

This work was supported by an unrestricted grant from F. Hoffmann-La Roche Ltd., Biogen International GmbH, Eisai Europe Limited, Life Molecular Imaging GmbH, and OM Pharma Suisse SA. Funders had no role in data collection, data analysis, and discussion of the results. FM is supported by NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006) – A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022). MCR was supported by the Italian Ministry of Health “Ricerca Corrente 2022-2024” granted to IRCCS Mondino Foundation.

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Author notes

  1. Silvia Morbelli and Valentina Garibotto contributed equally to this work, on behalf of the European Association of Nuclear Medicine (EANM).

Authors and Affiliations

  1. Unit of Behavior Neurology and Dementia Research Center, IRCCS Mondino Foundation, via Mondino 2, 27100, Pavia, Italy

    Matteo Cotta Ramusino

  2. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy

    Federico Massa

  3. IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Federico Massa, Flavio Nobili & Silvia Morbelli

  4. Laboratory of Alzheimer’s Neuroimaging and Epidemiology, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, Italy

    Cristina Festari

  5. Department of Geriatric Care, Orthogeriatrics and Rehabilitation, E.O. Galliera Hospital, Genoa, Italy

    Federica Gandolfo

  6. UOC Neurologia Ospedale Magalini Di Villafranca Di Verona (VR) ULSS 9, Verona, Italy

    Valentina Nicolosi

  7. Alzheimer’s Unit-Memory Clinic, IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli, Brescia, Italy

    Stefania Orini

  8. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

    Stefania Orini

  9. Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland

    Giovanni B. Frisoni

  10. Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University and University Hospitals, Geneva, Switzerland

    Giovanni B. Frisoni

  11. Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy

    Silvia Morbelli

  12. Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, University Hospitals of Geneva, Geneva, Switzerland

    Valentina Garibotto

  13. NIMTLab, Department of Radiology and Medical Informatics, Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Valentina Garibotto

  14. CIBM Center for Biomedical Imaging, Geneva, Switzerland

    Valentina Garibotto

Authors
  1. Matteo Cotta Ramusino
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  2. Federico Massa
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  3. Cristina Festari
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  4. Federica Gandolfo
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  7. Flavio Nobili
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  8. Giovanni B. Frisoni
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  9. Silvia Morbelli
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Consortia

for the European Inter-Societal Consensus on the Biomarker-Based Diagnosis of Dementia

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Matteo Cotta Ramusino, Federico Massa, Cristina Festari, Federica Gandolfo, Valentina Nicolosi, and Stefania Orini. The first draft of the manuscript was written by Matteo Cotta Ramusino, Federico Massa, and Cristina Festari, and all authors commented on previous versions of the manuscript. Giovanni Frisoni, Flavio Nobili, Silvia Morbelli, and Valentina Garibotto revised the final draft critically for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Matteo Cotta Ramusino.

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Ethics approval

This is a systematic literature review and therefore no ethical approval is required.

Competing interests

SM received speaker honoraria from GE Healthcare, Life Molecular Imaging, and Eli Lilly. VG received speaker honoraria (through her institution) from GE Healthcare, Siemens Healthineers, and Novo Nordisk. CF has acquired research support (for the institution) from the Italian Ministry of Health (RC).

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Cotta Ramusino, M., Massa, F., Festari, C. et al. Diagnostic performance of molecular imaging methods in predicting the progression from mild cognitive impairment to dementia: an updated systematic review. Eur J Nucl Med Mol Imaging (2024). https://doi.org/10.1007/s00259-024-06631-y

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