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CSF p-tau/Aβ42 ratio and brain FDG-PET may reliably detect MCI “imminent” converters to AD

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Abstract

Purpose

To know whether mild cognitive impairment (MCI) patients will develop Alzheimer’s disease (AD) dementia in very short time or remain stable is of crucial importance, also considering new experimental drugs usually tested within very short time frames. Here we combined cerebrospinal fluid (CSF) AD biomarkers and a neurodegeneration marker such as brain FDG-PET to define an objective algorithm, suitable not only to reliably detect MCI converters to AD dementia but also to predict timing of conversion.

Methods

We included 77 consecutive MCI patients with neurological/neuropsychological assessment, brain 18F-FDG-PET and CSF analysis available at diagnosis and a neuropsychological/neurological evaluation every 6 months for a medium- to a long-term follow-up (at least 2 and up to 8 years). Binomial logistic regression models and Kaplan-Meier survival analyses were performed to determine the best biomarker (or combination of biomarkers) in detecting MCI converters to AD dementia and then, among the converters, those who converted in short time frames.

Results

Thirty-five out of 77 MCI patients (45%) converted to AD dementia, with an average conversion time since MCI diagnosis of 26.07 months. CSF p-tau/Aβ42 was the most accurate predictor of conversion from MCI to AD dementia (82.9% sensitivity; 90% specificity). CSF p-tau/Aβ42 and FDG-PET-positive MCIs converted to AD dementia significantly earlier than the CSF-positive-only MCIs (median conversion time, 17.1 vs 31.3 months).

Conclusions

CSF p-tau/Aβ42 ratio and brain FDG-PET may predict both occurrence and timing of MCI conversion to full-blown AD dementia. MCI patients with both biomarkers suggestive for AD will likely develop an AD dementia shortly, thus representing the ideal target for any new experimental drug requiring short periods to be tested for.

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Availability of data and material

The dataset used and analysed during the current study will be made available by the corresponding author upon request to qualified researchers (i.e. affiliated to a university or research institution/hospital).

Funding

This work was carried out within the framework of the Ivascomar project of the Italian Ministry of Research (CTN01_00177_165430), Cluster Tecnologico Nazionale Scienze della Vita “Alisei”, Italian Ministry of Research. The sponsor had no role in the study design; the collection, analysis and interpretation of data; the writing of the report; and the decision to submit the article for publication.

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Author notes

  1. Roberto Santangelo and Federico Masserini contributed equally to this work.

Authors and Affiliations

  1. Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Roberto Santangelo, Federico Masserini, Giordano Cecchetti, Francesca Caso, Vittorio Martinelli, Giuseppe Magnani & Massimo Filippi

  2. Vita-Salute San Raffaele University, Milan, Italy

    Roberto Santangelo, Federica Agosta, Arianna Sala, Silvia P. Caminiti, Daniela Perani & Massimo Filippi

  3. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Federica Agosta, Giordano Cecchetti & Massimo Filippi

  4. In vivo human molecular and structural neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Arianna Sala, Silvia P. Caminiti & Daniela Perani

  5. Department of Neurology, Papa Giovanni XXIII Hospital, Bergamo, Italy

    Patrizia Pinto

  6. Department of Laboratory Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Gabriella Passerini

  7. Nuclear Medicine Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Daniela Perani

  8. Neurophysiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Massimo Filippi

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  1. Roberto Santangelo
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  2. Federico Masserini
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  3. Federica Agosta
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  4. Arianna Sala
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  5. Silvia P. Caminiti
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  6. Giordano Cecchetti
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  7. Francesca Caso
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  8. Vittorio Martinelli
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  9. Patrizia Pinto
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  10. Gabriella Passerini
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  11. Daniela Perani
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  12. Giuseppe Magnani
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Corresponding author

Correspondence to Massimo Filippi.

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Conflict of interest

R Santangelo has received compensation for teaching courses from Roche.

F Masserini, A Sala, SP Caminiti, G Cecchetti, F Caso, V Martinelli, P Pinto, G Passerini, D Perani and G Magnani have nothing to disclose.

F Agosta is Section Editor of NeuroImage: Clinical; has received speaker honoraria from Biogen Idec, Novartis and Philips; 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.

M Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, Takeda and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and AriSLA (Fondazione Italiana di Ricerca per la SLA).

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Santangelo, R., Masserini, F., Agosta, F. et al. CSF p-tau/Aβ42 ratio and brain FDG-PET may reliably detect MCI “imminent” converters to AD. Eur J Nucl Med Mol Imaging 47, 3152–3164 (2020). https://doi.org/10.1007/s00259-020-04853-4

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