Diagnostic Accuracy of Markers for Prodromal Alzheimer's Disease in Independent Clinical Series

Alzheimers Dement. 2013 Nov;9(6):677-86. doi: 10.1016/j.jalz.2012.09.016. Epub 2013 Jan 30.


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.

Keywords: Alzheimer's disease; Diagnostic accuracy; Diagnostic test assessment; MCI; MRI; PET.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / analysis*
  • Cognition Disorders / cerebrospinal fluid*
  • Cognition Disorders / complications
  • Cognition Disorders / diagnosis*
  • Databases, Factual / statistics & numerical data
  • Disease Progression
  • Female
  • Fluorodeoxyglucose F18
  • Hippocampus / diagnostic imaging
  • Hippocampus / pathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Positron-Emission Tomography
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Time Factors


  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Fluorodeoxyglucose F18