title: Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease.
abstract: OBJECTIVE
  Recommendations for the diagnosis of preclinical Alzheimer disease (AD) have been formulated by a workgroup of the National Institute on Aging and Alzheimer's Association. Three stages of preclinical AD were described. Stage 1 is characterized by abnormal levels of β-amyloid. Stage 2 represents abnormal levels of β-amyloid and evidence of brain neurodegeneration. Stage 3 includes the features of stage 2 plus subtle cognitive changes. Stage 0, not explicitly defined in the criteria, represents subjects with normal biomarkers and normal cognition. The ability of the recommended criteria to predict progression to cognitive impairment is the crux of their validity.
  
  
  METHODS
  Using previously developed operational definitions of the 3 stages of preclinical AD, we examined the outcomes of subjects from the Mayo Clinic Study of Aging diagnosed as cognitively normal who underwent brain MRI or [(18)F]fluorodeoxyglucose and Pittsburgh compound B PET, had global cognitive test scores, and were followed for at least 1 year.
  
  
  RESULTS
  Of the 296 initially normal subjects, 31 (10%) progressed to a diagnosis of mild cognitive impairment (MCI) or dementia (27 amnestic MCI, 2 nonamnestic MCI, and 2 non-AD dementias) within 1 year. The proportion of subjects who progressed to MCI or dementia increased with advancing stage (stage 0, 5%; stage 1, 11%; stage 2, 21%; stage 3, 43%; test for trend, p < 0.001).
  
  
  CONCLUSIONS
  Despite the short follow-up period, our operationalization of the new preclinical AD recommendations confirmed that advancing preclinical stage led to higher proportions of subjects who progressed to MCI or dementia.
authors.affiliation: Department of Neurology, Mayo Clinic Alzheimer’s Disease Research Center, Rochester, MN, USA. knopman@mayo.edu
authors.forename: D S
authors.initials: DS
authors.lastname: Knopman
authors.forename: C R
authors.initials: CR
authors.lastname: Jack
authors.forename: H J
authors.initials: HJ
authors.lastname: Wiste
authors.forename: S D
authors.initials: SD
authors.lastname: Weigand
authors.forename: P
authors.initials: P
authors.lastname: Vemuri
authors.forename: V
authors.initials: V
authors.lastname: Lowe
authors.forename: K
authors.initials: K
authors.lastname: Kantarci
authors.forename: J L
authors.initials: JL
authors.lastname: Gunter
authors.forename: M L
authors.initials: ML
authors.lastname: Senjem
authors.forename: R J
authors.initials: RJ
authors.lastname: Ivnik
authors.forename: R O
authors.initials: RO
authors.lastname: Roberts
authors.forename: B F
authors.initials: BF
authors.lastname: Boeve
authors.forename: R C
authors.initials: RC
authors.lastname: Petersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology*; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D054561:National Institute on Aging (U.S.); D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D013844:Thiazoles; D014481:United States
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18