title: Randomized controlled trials in mild cognitive impairment: Sources of variability.
abstract: OBJECTIVE
  To examine the variability in performance among placebo groups in randomized controlled trials for mild cognitive impairment (MCI).
  
  
  METHODS
  Placebo group data were obtained from 2 National Institute on Aging (NIA) MCI randomized controlled trials, the Alzheimer's Disease Cooperative Study (ADCS) MCI trial and the Alzheimer's Disease Neuroimaging Initiative (ADNI), which is a simulated clinical trial, in addition to industry-sponsored clinical trials involving rivastigmine, galantamine, rofecoxib, and donepezil. The data were collated for common measurement instruments. The performance of the placebo participants from these studies was tracked on the Alzheimer's Disease Assessment Scale-cognitive subscale, Mini-Mental State Examination, and Clinical Dementia Rating-sum of boxes, and for progression on these measures to prespecified clinical study endpoints.APOEstatus, where available, was also analyzed for its effects.
  
  
  RESULTS
  The progression to clinical endpoints varied a great deal among the trials. The expected performances were seen for the participants in the 2 NIA trials, ADCS and ADNI, with generally worsening of performance over time; however, the industry-sponsored trials largely showed stable or improved performance in their placebo participants.APOE4 carrier status influenced results in an expected fashion on the study outcomes, including rates of progression and cognitive subscales.
  
  
  CONCLUSIONS
  In spite of apparently similar criteria for MCI being adopted by the 7 studies, the implementation of the criteria varied a great deal. Several explanations including instruments used to characterize participants and variability among study populations contributed to the findings.
authors.affiliation: From the Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Department of Neurosciences (R.G.T.), University of California, San Diego, La Jolla; University of Southern California (P.S.A.), Los Angeles; Eli Lilly and Company (R.C.M.), Indianapolis, IN; Division of Medical & Scientific Relations (M.C.C.), Alzheimer's Association, Chicago, IL; and Johns Hopkins School of Medicine (M.S.A.), Baltimore, MD. R.C.M. is currently with Global Alzheimer's Platform Foundation, Washington, DC. peter8@mayo.edu.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: From the Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Department of Neurosciences (R.G.T.), University of California, San Diego, La Jolla; University of Southern California (P.S.A.), Los Angeles; Eli Lilly and Company (R.C.M.), Indianapolis, IN; Division of Medical & Scientific Relations (M.C.C.), Alzheimer's Association, Chicago, IL; and Johns Hopkins School of Medicine (M.S.A.), Baltimore, MD. R.C.M. is currently with Global Alzheimer's Platform Foundation, Washington, DC.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Thomas
authors.affiliation: From the Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Department of Neurosciences (R.G.T.), University of California, San Diego, La Jolla; University of Southern California (P.S.A.), Los Angeles; Eli Lilly and Company (R.C.M.), Indianapolis, IN; Division of Medical & Scientific Relations (M.C.C.), Alzheimer's Association, Chicago, IL; and Johns Hopkins School of Medicine (M.S.A.), Baltimore, MD. R.C.M. is currently with Global Alzheimer's Platform Foundation, Washington, DC.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.affiliation: From the Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Department of Neurosciences (R.G.T.), University of California, San Diego, La Jolla; University of Southern California (P.S.A.), Los Angeles; Eli Lilly and Company (R.C.M.), Indianapolis, IN; Division of Medical & Scientific Relations (M.C.C.), Alzheimer's Association, Chicago, IL; and Johns Hopkins School of Medicine (M.S.A.), Baltimore, MD. R.C.M. is currently with Global Alzheimer's Platform Foundation, Washington, DC.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Mohs
authors.affiliation: From the Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Department of Neurosciences (R.G.T.), University of California, San Diego, La Jolla; University of Southern California (P.S.A.), Los Angeles; Eli Lilly and Company (R.C.M.), Indianapolis, IN; Division of Medical & Scientific Relations (M.C.C.), Alzheimer's Association, Chicago, IL; and Johns Hopkins School of Medicine (M.S.A.), Baltimore, MD. R.C.M. is currently with Global Alzheimer's Platform Foundation, Washington, DC.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Carrillo
authors.affiliation: From the Department of Neurology (R.C.P.), Mayo Clinic College of Medicine, Rochester, MN; Department of Neurosciences (R.G.T.), University of California, San Diego, La Jolla; University of Southern California (P.S.A.), Los Angeles; Eli Lilly and Company (R.C.M.), Indianapolis, IN; Division of Medical & Scientific Relations (M.C.C.), Alzheimer's Association, Chicago, IL; and Johns Hopkins School of Medicine (M.S.A.), Baltimore, MD. R.C.M. is currently with Global Alzheimer's Platform Foundation, Washington, DC.
authors.forename: Marilyn S
authors.initials: MS
authors.lastname: Albert
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D053327:Apolipoprotein E4 / Q000235:genetics; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D018697:Nootropic Agents / Q000627:therapeutic use; D018579:Patient Selection; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index
chemical_list: D053327:Apolipoprotein E4; D018697:Nootropic Agents; D010919:Placebos