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Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting

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

An Erratum to this article was published on 08 October 2015

Abstract

Purpose

The aim of this study was to evaluate the supportive role of molecular and structural biomarkers (CSF protein levels, FDG PET and MRI) in the early differential diagnosis of dementia in a large sample of patients with neurodegenerative dementia, and in determining the risk of disease progression in subjects with mild cognitive impairment (MCI).

Methods

We evaluated the supportive role of CSF Aβ42, t-Tau, p-Tau levels, conventional brain MRI and visual assessment of FDG PET SPM t-maps in the early diagnosis of dementia and the evaluation of MCI progression.

Results

Diagnosis based on molecular biomarkers showed the best fit with the final diagnosis at a long follow-up. FDG PET SPM t-maps had the highest diagnostic accuracy in Alzheimer’s disease and in the differential diagnosis of non-Alzheimer’s disease dementias. The p-tau/Aβ42 ratio was the only CSF biomarker providing a significant classification rate for Alzheimer’s disease. An Alzheimer’s disease-positive metabolic pattern as shown by FDG PET SPM in MCI was the best predictor of conversion to Alzheimer’s disease.

Conclusion

In this clinical setting, FDG PET SPM t-maps and the p-tau/Aβ42 ratio improved clinical diagnostic accuracy, supporting the importance of these biomarkers in the emerging diagnostic criteria for Alzheimer’s disease dementia. FDG PET using SPM t-maps had the highest predictive value by identifying hypometabolic patterns in different neurodegenerative dementias and normal brain metabolism in MCI, confirming its additional crucial exclusionary role.

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Compliance with ethical standards

Funding

This research was funded by EU FP7 INMIND Project (FP7-HEALTH-2013, grant agreement no. 278850), the Italian Ministry of Health (Ricerca Finalizzata Progetto Reti Nazionale AD NET-2011-02346784), and Fondazione Eli-Lilly (Eli-Lilly grant 2011 "Imaging of neuroinflammation and neurodegeneration in prodromal and presymptomatic Alzheimer's disease phases”).

Conflicts of interest

None.

Ethical approval

For this type of study formal consent is not required.

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Authors and Affiliations

  1. Vita-Salute San Raffaele University, Via Olgettina, 58, 20132, Milan, Italy

    Daniela Perani, Chiara Cerami, Silvia Paola Caminiti, Andrea Falini & Giancarlo Comi

  2. Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy

    Daniela Perani, Chiara Cerami, Silvia Paola Caminiti, Andrea Falini & Stefano Francesco Cappa

  3. Nuclear Medicine Unit, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy

    Daniela Perani & Luigi Gianolli

  4. Clinical Neuroscience Department, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy

    Chiara Cerami & Sandro Iannaccone

  5. Department of Neurology, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy

    Roberto Santangelo, Elisabetta Coppi, Laura Ferrari, Giancarlo Comi & Giuseppe Magnani

  6. Department of Neurology, Papa Giovanni XXIII Hospital, Piazza OMS, 1, 24127, Bergamo, Italy

    Patrizia Pinto

  7. Servizio di Medicina di Laboratorio OSR, Via Olgettina, 60, 20132, Milan, Italy

    Gabriella Passerini

  8. CERMAC – Department of Neuroradiology, San Raffaele Hospital, Via Olgettina, 60, 20132, Milan, Italy

    Andrea Falini

  9. IUSS Pavia, Piazza della Vittoria, 15, 27100, Pavia, Italy

    Stefano Francesco Cappa

Authors
  1. Daniela Perani
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  2. Chiara Cerami
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  3. Silvia Paola Caminiti
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  4. Roberto Santangelo
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  5. Elisabetta Coppi
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  6. Laura Ferrari
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  7. Patrizia Pinto
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  8. Gabriella Passerini
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  9. Andrea Falini
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  11. Stefano Francesco Cappa
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  12. Giancarlo Comi
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  13. Luigi Gianolli
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  14. Giuseppe Magnani
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Corresponding author

Correspondence to Daniela Perani.

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Perani, D., Cerami, C., Caminiti, S.P. et al. Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting. Eur J Nucl Med Mol Imaging 43, 499–508 (2016). https://doi.org/10.1007/s00259-015-3170-y

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  • DOI: https://doi.org/10.1007/s00259-015-3170-y

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