title: Susceptibility of the conventional criteria for mild cognitive impairment to false-positive diagnostic errors.
abstract: BACKGROUND
  We assessed whether mild cognitive impairment (MCI) subtypes could be empirically derived within the Alzheimer's Disease Neuroimaging Initiative (ADNI) MCI cohort and examined associated biomarkers and clinical outcomes.
  
  
  METHODS
  Cluster analysis was performed on neuropsychological data from 825 MCI ADNI participants.
  
  
  RESULTS
  Four subtypes emerged: (1) dysnomic (n = 153), (2) dysexecutive (n = 102), (3) amnestic (n = 288), and (4) cluster-derived normal (n = 282) who performed within normal limits on cognitive testing. The cluster-derived normal group had significantly fewer APOE ε4 carriers and fewer who progressed to dementia compared with the other subtypes; they also evidenced cerebrospinal fluid Alzheimer's disease biomarker profiles that did not differ from the normative reference group.
  
  
  CONCLUSIONS
  Identification of empirically derived MCI subtypes demonstrates heterogeneity in MCI cognitive profiles that is not captured by conventional criteria. The large cluster-derived normal group suggests that conventional diagnostic criteria are susceptible to false-positive errors, with the result that prior MCI studies may be diluting important biomarker relationships.
authors.affiliation: Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Edmonds
authors.affiliation: Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Delano-Wood
authors.affiliation: San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.
authors.forename: Lindsay R
authors.initials: LR
authors.lastname: Clark
authors.affiliation: Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Jak
authors.affiliation: Department of Psychology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nation
authors.affiliation: Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
authors.forename: Carrie R
authors.initials: CR
authors.lastname: McDonald
authors.affiliation: Department of Neurology, Drexel University, College of Medicine, Philadelphia, PA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Libon
authors.affiliation: Department of Neurology, Boston University, School of Medicine, Boston, MA, USA; Framingham Heart Study, Boston University, School of Medicine, Boston, MA, USA.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
authors.affiliation: Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Galasko
authors.affiliation: Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Salmon
authors.affiliation: Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA. Electronic address: mbondi@ucsd.edu.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Bondi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016000:Cluster Analysis; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D016208:Databases, Factual / Q000706:statistics & numerical data; D003951:Diagnostic Errors; D018450:Disease Progression; D004198:Disease Susceptibility / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule / Q000592:standards; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000592:standards*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer's disease; Cluster analysis; Dementia; MCI; Mild cognitive impairment; Misclassification; Misdiagnosis; Neuropsychology