title: Emergence of mild cognitive impairment in late middle-aged adults in the wisconsin registry for Alzheimer's prevention.
abstract: OBJECTIVE
  It is difficult to reliably detect the earliest signs of Alzheimer's disease (AD)-associated cognitive impairment. Our aim was to compare 3 psychometric methods of identifying amnestic mild cognitive impairment (aMCI) in a middle-aged longitudinal cohort enriched for AD risk.
  
  
  METHODS
  Wisconsin Registry for Alzheimer's Prevention (WRAP) participants with 3 waves of cognitive assessment over approximately 6 years were coded as meeting each of 3 psychometric aMCI definitions: (a) 'aMCI standard-baseline' used published norms to establish cutoffs for baseline performance; (b) 'aMCI robust-baseline' applied WRAP-specific robust norms to baseline, and (c) 'aMCI robust-multiwave' applied these robust norms across 3 waves of assessment. Each group was compared to a cognitively healthy subset.
  
  
  RESULTS
  Half the aMCI standard-baseline and one third of the aMCI robust-baseline group reverted to normal ranges at follow-up. Only the aMCI robust-multiwave method had an aMCI × age interaction showing significantly worse age-related memory declines in the aMCI group compared to the cognitively healthy group over 6 years of follow-up.
  
  
  CONCLUSIONS
  Both cross-sectional methods showed instability over time, with many reverting to normal performance after baseline. The multiwave approach identified a group who showed progressive memory declines over 3 visits. Being able to detect progressive decline in late middle age is a critical step in improving prevention efforts.
authors.affiliation: Department of Medicine, Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wis., USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Koscik
authors.forename: Asenath
authors.initials: A
authors.lastname: La Rue
authors.forename: Erin M
authors.initials: EM
authors.lastname: Jonaitis
authors.forename: Ozioma C
authors.initials: OC
authors.lastname: Okonkwo
authors.forename: Sterling C
authors.initials: SC
authors.lastname: Johnson
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Bendlin
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Hermann
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sager
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000517:prevention & control*; D003071:Cognition; D060825:Cognitive Dysfunction / Q000150:complications / Q000175:diagnosis / Q000523:psychology; D057186:Comparative Effectiveness Research; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis* / Q000209:etiology / Q000523:psychology; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000592:standards; D011594:Psychometrics / Q000379:methods / Q000592:standards; D012042:Registries; D013997:Time Factors; D014922:Wisconsin