title: An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease.
abstract: OBJECTIVE
  A workgroup commissioned by the Alzheimer's Association (AA) and the National Institute on Aging (NIA) recently published research criteria for preclinical Alzheimer disease (AD). We performed a preliminary assessment of these guidelines.
  
  
  METHODS
  We employed Pittsburgh compound B positron emission tomography (PET) imaging as our biomarker of cerebral amyloidosis, and (18) fluorodeoxyglucose PET imaging and hippocampal volume as biomarkers of neurodegeneration. A group of 42 clinically diagnosed AD subjects was used to create imaging biomarker cutpoints. A group of 450 cognitively normal (CN) subjects from a population-based sample was used to develop cognitive cutpoints and to assess population frequencies of the different preclinical AD stages using different cutpoint criteria.
  
  
  RESULTS
  The new criteria subdivide the preclinical phase of AD into stages 1 to 3. To classify our CN subjects, 2 additional categories were needed. Stage 0 denotes subjects with normal AD biomarkers and no evidence of subtle cognitive impairment. Suspected non-AD pathophysiology (SNAP) denotes subjects with normal amyloid PET imaging, but abnormal neurodegeneration biomarker studies. At fixed cutpoints corresponding to 90% sensitivity for diagnosing AD and the 10th percentile of CN cognitive scores, 43% of our sample was classified as stage 0, 16% stage 1, 12 % stage 2, 3% stage 3, and 23% SNAP.
  
  
  CONCLUSIONS
  This cross-sectional evaluation of the NIA-AA criteria for preclinical AD indicates that the 1-3 staging criteria coupled with stage 0 and SNAP categories classify 97% of CN subjects from a population-based sample, leaving only 3% unclassified. Future longitudinal validation of the criteria will be important.
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA. jack.clifford@mayo.edu
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Weigand
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Wiste
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
authors.forename: Val
authors.initials: V
authors.lastname: Lowe
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ivnik
authors.forename: Rosebud O
authors.initials: RO
authors.lastname: Roberts
authors.forename: Walter A
authors.initials: WA
authors.lastname: Rocca
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis*; D000814:Aniline Compounds / Q000592:standards; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging*; D003072:Cognition Disorders / Q000175:diagnosis*; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000592:standards; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D054561:National Institute on Aging (U.S.) / Q000592:standards*; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D013844:Thiazoles / Q000592:standards; D014481:United States
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D015415:Biomarkers; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18