Diagnostic accuracy of markers for prodromal Alzheimer's disease in independent clinical series

Annapaola Prestia, Anna Caroli, Karl Herholz, Eric Reiman, Kewei Chen, William J. Jagust, Giovanni B. Frisoni, G. Amicucci, S. Archetti, L. Benussi, G. Binetti, L. Bocchio-Chiavetto, M. Bonetti, E. Canu, F. Caobelli, E. Cavedo, E. Chittò, D. Costardi, M. Cotelli, S. GalluzziM. Gennarelli, C. Geroldi, R. Ghidoni, R. Giubbini, U. P. Guerra, G. Kuffenschin, G. Lussignoli, D. Moretti, A. Orlandini, B. Paghera, M. Parapini, D. Paternicò, C. Porteri, M. Romano, S. Rosini, C. Scarpazza, I. Villa, R. Zanardini, O. Zanetti

Research output: Contribution to journalArticlepeer-review


Objective: To capitalize on data from different clinical series to compare sensitivity and specificity of individual biomarkers for predicting mild cognitive impairment (MCI) progression to Alzheimer's disease (AD). Methods: Medial temporal atrophy, cortical hypometabolism, and cerebrospinal fluid biomarkers were assessed in 18 patients with mild cognitive impairment (MCI) with prodromal AD (pAD; conversion time, 26 ± 12 months) and 18 stable MCI (sMCI) patients from the Translational Outpatient Memory Clinic cohort, as well as in 24 pAD patients (conversion time, 36 ± 12 months) and 33 sMCI patients from the Alzheimer's Disease Neuroimaging Initiative cohort. Medial temporal atrophy was measured by manual, semi-automated, and automated hippocampal volumetry; cortical hypometabolism was measured using several indices of AD-related hypometabolism pattern; and cerebrospinal fluid markers were amyloid β (Aβ)42 and total tau protein concentrations. For each biomarker, sensitivity for pAD, specificity for sMCI, and diagnostic accuracy were computed. Results: Sensitivity to predict MCI conversion to AD in the Alzheimer's Disease Neuroimaging Initiative and Translational Outpatient Memory Clinic cohorts was 79% and 94% based on Aβ42, 46% and 28% based on hippocampal volumes, 33% to 66% and 56% to 78% based on different hypometabolism indices, and 46% and 61% based on total tau levels, respectively. Specificity to exclude sMCI was 27% and 50% based on Aβ42, 76% and 94% based on hippocampal volumes, 58% to 67% and 55% to 83% based on different hypometabolism indices, and 61% and 83% based on total tau levels, respectively. Conclusions: Current findings suggest that Aβ42 concentrations and hippocampal volumes may be used in combination to best identify pAD.

Original languageEnglish
Pages (from-to)677-686
Number of pages10
JournalAlzheimer's and Dementia
Issue number6
Publication statusPublished - 2013


  • Alzheimer's disease
  • Diagnostic accuracy
  • Diagnostic test assessment
  • MCI
  • MRI
  • PET

ASJC Scopus subject areas

  • Clinical Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Epidemiology
  • Health Policy
  • Medicine(all)


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