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The new Alzheimer’s criteria in a naturalistic series of patients with mild cognitive impairment

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Abstract

To test the validity of the new diagnostic criteria for Alzheimer’s disease (AD) in a naturalistic series of patients with mild cognitive impairment (MCI). Ninety consecutive MCI patients were enrolled in a longitudinal study on the natural history of cognitive impairment. Medial temporal (MT) atrophy on MRI was defined as hippocampal volume below the fifth percentile of the distribution in healthy elders, abnormal CSF was based on Sjogren’s cutoffs for Abeta42 and tau, and temporoparietal hypometabolism on 18F-FDG PET based on Herholz’s t sum score. Patients were followed clinically to detect conversion to AD (MCI-AD), non-AD dementia (MCI-nAD), or no conversion (MCI-NC). The 24 MCI-AD and 15 MCI-nAD patients had sociodemographic, clinical, and neuropsychological baseline features similar to the 51 MCI-NC patients. All MCI patients with MT atrophy converted to AD, as did all those with abnormal CSF, but only 48 and 35% of those without MT atrophy or abnormal CSF converted (p on logrank test = 0.0007 and 0.001). Prediction of AD conversion was enhanced when positivity to either MT atrophy or abnormal CSF was considered, with only 15% of those MCI patients negative on both converting to AD (p < 0.0005). Markers were not predictive of non-AD dementia conversion. The accuracy of either MT atrophy or abnormal CSF in discriminating MCI-AD from MCI-NC was good (AUC 0.82, 95% CI 0.70–0.95). MT atrophy and abnormal CSF are the single most robust predictors of conversion to AD in MCI patients, and their combination enhances prediction. AD markers are not predictive of conversion to non-AD dementia.

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Acknowledgments

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 agreement from the Italian Ministry of Health: “Analisi dei Fattori di Rischio e di Potenziali Elementi Predittivi di Danno Neurodegenerativo Nelle Sindromi Parkinsoniane number 502/92”. Some of the costs related to patient assessment and imaging and biomarker detection were paid by an ad hoc grant from the Fitness e Solidarieta` 2006 and 2007 campaigns.

Conflict of interest statement

Authors have not competing interests to declare.

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Authors and Affiliations

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

    S. Galluzzi, C. Geroldi & G. B. Frisoni

  2. Psychogeriatric Ward, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

    C. Geroldi & G. B. Frisoni

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

    R. Ghidoni

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

    B. Paghera

  5. Service of Anesthesiology, S. Orsola-Fatebenefratelli Hospital, Brescia, Italy

    G. Amicucci

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

    M. Bonetti

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

    O. Zanetti

  8. Laboratory of the Neuropsychology Cognitive Neuroscience Unit, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

    M. Cotelli

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

    M. Gennarelli

  10. Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia, Italy

    M. Gennarelli

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  1. S. Galluzzi
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  2. C. Geroldi
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  3. R. Ghidoni
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  4. B. Paghera
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  10. G. B. Frisoni
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Translational Outpatient Memory Clinic Working Group

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Correspondence to G. B. Frisoni.

Additional information

Translational Outpatient Memory Clinic Working Group contributors: M Romano, A Prestia, A Caroli, R Ganzola, L Frassine, E Canu, D Costardi, C Scarpazza, S Rosini, L Bocchio-Chiavetto, R Zanardini, L Benussi, G Binetti, R Giubbini, F Caobelli.

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Galluzzi, S., Geroldi, C., Ghidoni, R. et al. The new Alzheimer’s criteria in a naturalistic series of patients with mild cognitive impairment. J Neurol 257, 2004–2014 (2010). https://doi.org/10.1007/s00415-010-5650-0

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  • DOI: https://doi.org/10.1007/s00415-010-5650-0

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