title: Diagnostic accuracy of markers for prodromal Alzheimer's disease in independent clinical series.
abstract: 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.
authors: Laboratory of Epidemiology Neuroimaging and Telemedicine, and Unit for the Clinical Translation of Research, IRCCS Centro San Giovanni di Dio FBF, Brescia, Italy.
authors: Annapaola
authors: A
authors: Prestia
authors: Anna
authors: A
authors: Caroli
authors: Karl
authors: K
authors: Herholz
authors: Eric
authors: E
authors: Reiman
authors: Kewei
authors: K
authors: Chen
authors: William J
authors: WJ
authors: Jagust
authors: Giovanni B
authors: GB
authors: Frisoni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000032:analysis*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000150:complications / Q000175:diagnosis*; D016208:Databases, Factual / Q000706:statistics & numerical data; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D049268:Positron-Emission Tomography; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D019788:Fluorodeoxyglucose F18
keywords: Alzheimer's disease; Diagnostic accuracy; Diagnostic test assessment; MCI; MRI; PET
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