title: Neuropsychological Testing Predicts Cerebrospinal Fluid Amyloid-β in Mild Cognitive Impairment.
abstract: BACKGROUND
  Psychometric tests predict conversion of mild cognitive impairment (MCI) to probable Alzheimer's disease (AD). Because the definition of clinical AD relies on those same psychometric tests, the ability of these tests to identify underlying AD pathology remains unclear.
  
  
  OBJECTIVE
  To determine the degree to which psychometric testing predicts molecular evidence of AD amyloid pathology, as indicated by cerebrospinal fluid (CSF) amyloid-β (Aβ)1 - 42, in patients with MCI, as compared to neuroimaging biomarkers.
  
  
  METHODS
  We identified 408 MCI subjects with CSF Aβ levels, psychometric test data, FDG-PET scans, and acceptable volumetric MR scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We used psychometric tests and imaging biomarkers in univariate and multivariate models to predict Aβ status.
  
  
  RESULTS
  The 30-min delayed recall score of the Rey Auditory Verbal Learning Test was the best predictor of Aβ status among the psychometric tests, achieving an AUC of 0.67 ± 0.02 and odds ratio of 2.5 ± 0.4. FDG-PET was the best imaging-based biomarker (AUC 0.67 ± 0.03, OR 3.2 ± 1.2), followed by hippocampal volume (AUC 0.64 ± 0.02, OR 2.4 ± 0.3). A multivariate analysis based on the psychometric tests improved on the univariate predictors, achieving an AUC of 0.68 ± 0.03 (OR 3.38 ± 1.2). Adding imaging biomarkers to the multivariate analysis did not improve the AUC.
  
  
  CONCLUSIONS
  Psychometric tests perform as well as imaging biomarkers to predict presence of molecular markers of AD pathology in MCI patients and should be considered in the determination of the likelihood that MCI is due to AD.
authors.affiliation: Penn Image Computing and Science Laboratory and Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Kandel
authors.affiliation: Penn Image Computing and Science Laboratory and Department of Radiology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Avants
authors.affiliation: Penn Image Computing and Science Laboratory and Department of Radiology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Gee
authors.affiliation: Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.affiliation: Department of Neurology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Wolk
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E; D019540:Area Under Curve; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D014706:Verbal Learning
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D019788:Fluorodeoxyglucose F18
keywords: Alzheimer’s disease; magnetic resonance imaging; mild cognitive impairment; positron emission tomography