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Supporting evidence for using biomarkers in the diagnosis of MCI due to AD

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Abstract

The aim of this study is to support the use of biomarkers in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) according to the revised NIA-AA diagnostic criteria. We compared clinical features and conversion to AD and other dementias among groups of MCI patients with different abnormal biomarker profiles. In this study, we enrolled 58 patients with MCI, and for each of them AD biomarkers (CSF Abeta42 and tau, temporoparietal hypometabolism on 18F-FDG PET, and hippocampal volume) were collected. Patients were divided into three groups: (i) no abnormal biomarker, (ii) AD biomarker pattern (including three subgroups of early = only abnormal Abeta42, intermediate = abnormal Abeta42 and FDG PET or tau, and late = abnormal Abeta42, FDG PET or tau, and HV), and (iii) any other biomarker combination. MCI patients with AD biomarker pattern had lower behavioural disturbances than patients with any other biomarker combination (p < 0.0005). This group also showed lower performance on verbal and non-verbal memory than the other two groups (p = 0.07 and p = 0.004, respectively). Within the three subgroups with AD biomarker patterns we observed a significant trend toward a higher rate of conversion to dementia (p for trend = 0.006). With regard to dementia conversion, 100 % of patients with an AD biomarker pattern developed AD, but none of the patients with no abnormal biomarker and 27 % of patients with any other biomarker combination (p = 0.002) did so. We also described some clinical cases representative for each of these three groups. The results of this study provide evidence in favour of the use of biomarkers for the diagnosis of MCI due to AD, in line with recently published research criteria.

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Acknowledgments

We wish to thank Chiara Barattieri di San Pietro for editing the English language of the manuscript. This work was supported by the grants: sottoprogetto finalizzato Strategico 2006: ‘‘Strumenti e procedure diagnostiche per le demenze utilizzabili nella clinica ai fini della diagnosi precoce e differenziale, della individuazione delle forme a rapida o lenta progressione e delle forme con risposta ottimale alle attuali terapie’’; Programma Strategico 2006, Convenzione 71; Programma Strategico 2007, Convenzione PS39, Ricerca Corrente Italian Ministry of Health, and was also supported in part by a grant from the Associazione Fatebenefratelli per la Ricerca (AFaR): “Proteomica Clinica nelle Malattie Neurodegenerative ad esordio tardivo”. Some of the costs related to patient assessment and imaging and biomarker detection were paid by an ad hoc grant from the Fitness e Solidarietà 2006 and 2007 campaigns.

Conflicts of interest

Dr.S Galluzzi, Geroldi, Amicucci, Bocchio-Chiavetto, Bonetti, Bonvicini, Cotelli, Ghidoni, Paghera, report no disclosures. Dr. Zanetti has acted as a speaker for Pfizer, Novartis, Bracco, and Lunbeck. Dr. Frisoni has acted as a consultant for Lilly, BMS, Bayer, Lundbeck, Elan, Astra Zeneca, Pfizer, Taurx, Wyeth.

Ethical standard

All human studies must state that they have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Authors and Affiliations

  1. Laboratory of Epidemiology, Neuroimaging and Telemedicine (LENITEM), IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, via Pilastroni 4, 25125, Brescia, Italy

    Samantha Galluzzi & Giovanni B. Frisoni

  2. Alzheimer’s Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

    Cristina Geroldi & Orazio Zanetti

  3. Service of Anesthesiology, Azienda Ospedaliera Mellino Mellini di Chiari, Brescia, Italy

    Giovanni Amicucci

  4. Neuropsychopharmacology Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

    Luisella Bocchio-Chiavetto

  5. Neuroradiology Service, Istituto Clinico Città di Brescia, Brescia, Italy

    Matteo Bonetti

  6. Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

    Cristian Bonvicini

  7. Neuropsychology Unit, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

    Maria Cotelli

  8. Proteomics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

    Roberta Ghidoni

  9. Nuclear Medicine Service, Spedali Civili of Brescia, Brescia, Italy

    Barbara Paghera

Authors
  1. Samantha Galluzzi
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  2. Cristina Geroldi
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  4. Luisella Bocchio-Chiavetto
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  6. Cristian Bonvicini
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  7. Maria Cotelli
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  8. Roberta Ghidoni
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  9. Barbara Paghera
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  10. Orazio Zanetti
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  11. Giovanni B. Frisoni
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Consortia

Translational Outpatient Memory Clinic Working Group

Corresponding author

Correspondence to Giovanni B. Frisoni.

Additional information

The contributors of the Translational Outpatient Memory Clinic Working Group are listed in the appendix.

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Supplementary material 2 (DOC 28 kb)

Appendix

Appendix

Translational Outpatient Memory Clinic Working Group contributors: S Archetti, L Benussi, G Binetti, E Canu, F Caobelli, E Cavedo, E Chitò, D Costardi, M Gennarelli, R Giubbini, UP Guerra, G Kuffenschin, G Lussignoli, D Moretti, A Orlandini, M Parapini, D Paternicò, C Porteri, M Romano, S Rosini, C Scarpazza, I Villa, R Zanardini.

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Galluzzi, S., Geroldi, C., Amicucci, G. et al. Supporting evidence for using biomarkers in the diagnosis of MCI due to AD. J Neurol 260, 640–650 (2013). https://doi.org/10.1007/s00415-012-6694-0

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  • DOI: https://doi.org/10.1007/s00415-012-6694-0

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