title: Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials.
abstract: BACKGROUND
  Mild cognitive impairment (MCI) represents a transitional state between the cognitive changes of normal aging and very early dementia and is becoming increasingly recognized as a risk factor for Alzheimer disease (AD). The Memory Impairment Study (MIS) is a multicenter clinical trial in patients with MCI designed to evaluate whether vitamin E or donepezil is effective at delaying the time to a clinical diagnosis of AD.
  
  
  OBJECTIVE
  To describe the baseline characteristics of patients with MCI recruited for the MIS and compare them with those of elderly controls and patients with AD in another clinical trial.
  
  
  METHODS
  Descriptive and comparative study of patients with MCI participating in a multicenter clinical trial.
  
  
  METHODS
  Memory disorder centers in the United States and Canada.
  
  
  METHODS
  A total of 769 patients with MCI, 107 cognitively normal elderly controls, 122 patients with very mild AD (Clinical Dementia Rating [CDR] 0.5), and 183 patients with mild AD (CDR 1.0) were evaluated. Patients in the MIS met operational criteria for amnestic MCI. Controls were recruited in parallel with the MCI group, underwent the same assessments, and had a CDR of 0.
  
  
  METHODS
  Clinical, neuropsychologic, functional, neuroimaging, and genetic measures.
  
  
  RESULTS
  Mean +/- SD Alzheimer's Disease Assessment Scale-Cognitive Subscale scores were 5.6 +/- 3.3 for controls, 11.3 +/- 4.4 for patients with MCI, 18.0 +/- 6.2 for the AD CDR 0.5 group, and 25.2 +/- 8.8 for the AD CDR 1.0 group. Compared with controls, patients with MCI were most impaired on memory tasks, with less severe impairments in other cognitive domains. Patients with MCI were more likely than controls but less likely than patients with AD to carry the apolipoprotein E epsilon4 allele. Patients with MCI had hippocampal volumes that were intermediate between those of controls and patients with AD.
  
  
  CONCLUSIONS
  Patients with MCI had a predominant memory impairment with relative sparing of other cognitive domains and were intermediate between clinically normal individuals and patients with AD on cognitive and functional ratings. These results demonstrate the successful implementation of operational criteria for this unique group of at-risk patients in a multicenter clinical trial.
authors.affiliation: Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California-San Diego, 8950 Villa La Jolla Drive, Suite 227, La Jolla, CA 92037, USA. mgrundman@ucsd.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Grundman
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Steven H
authors.initials: SH
authors.lastname: Ferris
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Thomas
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.forename: Norman L
authors.initials: NL
authors.lastname: Foster
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Galasko
authors.forename: Rachelle
authors.initials: R
authors.lastname: Doody
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kaye
authors.forename: Mary
authors.initials: M
authors.lastname: Sano
authors.forename: Richard
authors.initials: R
authors.lastname: Mohs
authors.forename: Serge
authors.initials: S
authors.lastname: Gauthier
authors.forename: Hyun T
authors.initials: HT
authors.lastname: Kim
authors.forename: Shelia
authors.initials: S
authors.lastname: Jin
authors.forename: Arlan N
authors.initials: AN
authors.lastname: Schultz
authors.forename: Kimberly
authors.initials: K
authors.lastname: Schafer
authors.forename: Ruth
authors.initials: R
authors.lastname: Mulnard
authors.forename: Christopher H
authors.initials: CH
authors.lastname: van Dyck
authors.forename: Jacobo
authors.initials: J
authors.lastname: Mintzer
authors.forename: Edward Y
authors.initials: EY
authors.lastname: Zamrini
authors.forename: Deborah
authors.initials: D
authors.lastname: Cahn-Weiner
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Thal
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000503:physiopathology; D001921:Brain / Q000473:pathology; D002986:Clinical Trials as Topic / Q000379:methods; D003072:Cognition Disorders / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D012307:Risk Factors