title: Predicting Alzheimer's disease development: a comparison of cognitive criteria and associated neuroimaging biomarkers.
abstract: BACKGROUND
  The definition of "objective cognitive impairment" in current criteria for mild cognitive impairment (MCI) varies considerably between research groups and clinics. This study aims to compare different methods of defining memory impairment to improve prediction models for the development of Alzheimer's disease (AD) from baseline to 24 months.
  
  
  METHODS
  The sensitivity and specificity of six methods of defining episodic memory impairment (< -1, -1.5 or -2 standard deviations [SD] on one or two memory tests) were compared in 494 non-demented seniors from the Alzheimer's Disease Neuroimaging Initiative using the area under the curve (AUC) for receiver operating characteristic analysis. The added value of non-memory measures (language and executive function) and biomarkers (hippocampal and white-matter hyperintensity volume, brain parenchymal fraction [BPF], and APOEε4 status) was investigated using logistic regression.
  
  
  RESULTS
  Baseline scores < -1 SD on two memory tests predicted AD with 75.91 % accuracy (AUC = 0.80). Only APOE ε4 status further improved prediction (B = 1.10, SE = 0.45, p = .016). A < -1.5 SD cut-off on one test had 66.60 % accuracy (AUC = 0.77). Prediction was further improved using Trails B/A ratio (B = 0.27, SE = 0.13, p = .033), BPF (B = -15.97, SE = 7.58, p = .035), and APOEε4 status (B = 1.08, SE = 0.45, p = .017). A cut-off of < -2 SD on one memory test (AUC = 0.77, SE = 0.03, 95 % CI 0.72-0.82) had 76.52 % accuracy in predicting AD. Trails B/A ratio (B = 0.31, SE = 0.13, p = .017) and APOE ε4 status (B = 1.07, SE = 0.46, p = .019) improved predictive accuracy.
  
  
  CONCLUSIONS
  Episodic memory impairment in MCI should be defined as scores < -1 SD below normative references on at least two measures. Clinicians or researchers who administer a single test should opt for a more stringent cut-off and collect and analyze whole-brain volume. When feasible, ascertaining APOE ε4 status can further improve prediction.
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Rm A4 21, Toronto, Ontario, M4N 3 M5, Canada. brandy.callahan@sri.utoronto.ca.|Heart & Stroke Foundation Canadian Partnership in Stroke Recovery, Sunnybrook Health Sciences Centre, Toronto, Canada. brandy.callahan@sri.utoronto.ca.|Sunnybrook Health Sciences Centre, Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Canada. brandy.callahan@sri.utoronto.ca.|Université Laval, Faculté de médecine (Radiologie), Québec, Canada. brandy.callahan@sri.utoronto.ca.|Centre de recherche de l'Institut universitaire en santé mentale de Québec, Québec, Canada. brandy.callahan@sri.utoronto.ca.
authors.forename: Brandy L
authors.initials: BL
authors.lastname: Callahan
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Rm A4 21, Toronto, Ontario, M4N 3 M5, Canada. joelr@sri.utoronto.ca.|Heart & Stroke Foundation Canadian Partnership in Stroke Recovery, Sunnybrook Health Sciences Centre, Toronto, Canada. joelr@sri.utoronto.ca.|Sunnybrook Health Sciences Centre, Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Canada. joelr@sri.utoronto.ca.
authors.forename: Joel
authors.initials: J
authors.lastname: Ramirez
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Rm A4 21, Toronto, Ontario, M4N 3 M5, Canada. cberezuk@sri.utoronto.ca.|Heart & Stroke Foundation Canadian Partnership in Stroke Recovery, Sunnybrook Health Sciences Centre, Toronto, Canada. cberezuk@sri.utoronto.ca.|Sunnybrook Health Sciences Centre, Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Canada. cberezuk@sri.utoronto.ca.
authors.forename: Courtney
authors.initials: C
authors.lastname: Berezuk
authors.affiliation: Université Laval, Faculté de médecine (Radiologie), Québec, Canada. simon.duchesne@fmed.ulaval.ca.|Centre de recherche de l'Institut universitaire en santé mentale de Québec, Québec, Canada. simon.duchesne@fmed.ulaval.ca.
authors.forename: Simon
authors.initials: S
authors.lastname: Duchesne
authors.affiliation: LC Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Rm A4 21, Toronto, Ontario, M4N 3 M5, Canada. sandra.black@sunnybrook.ca.|Heart & Stroke Foundation Canadian Partnership in Stroke Recovery, Sunnybrook Health Sciences Centre, Toronto, Canada. sandra.black@sunnybrook.ca.|Sunnybrook Health Sciences Centre, Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Canada. sandra.black@sunnybrook.ca.|Department of Medicine (Neurology), University of Toronto, Institute of Medical Science, Québec, Canada. sandra.black@sunnybrook.ca.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics; D019540:Area Under Curve; D001921:Brain / Q000473:pathology*; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D061212:Memory, Episodic; D008875:Middle Aged; D009483:Neuropsychological Tests; D011379:Prognosis; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D053327:Apolipoprotein E4