title: Longitudinal decline in mild-to-moderate Alzheimer's disease: Analyses of placebo data from clinical trials.
abstract: Accurate estimates of cognitive and clinical decline rates are essential to the design of clinical trials in Alzheimer's disease (AD) dementia.
  
  
  
  To investigate the trajectories of individuals enrolled in therapeutic trials in mild-to-moderate AD, we analyzed the placebo arm data from 20 clinical trials including over 4500 subjects. We analyzed decline as measured by two cognitive instruments, the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAScog) and the Mini-Mental State Examination, and one clinical rating scale, the Clinical Dementia Rating Sum of Boxes.
  
  
  
  Trajectories were generally similar across trials and nearly linear. Greater cognitive impairment at baseline, younger age, and greater education were associated with increased rate of cognitive decline. Effect sizes for the ADAScog were generated as a function of population characteristics.
  
  
  
  These data will inform the design of future studies of potential disease-modifying therapies for mild-to-moderate AD dementia.
authors.affiliation: Department of Neurosciences, University of California San Diego, San Diego, CA, USA.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Thomas
authors.affiliation: Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Albert
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA. Electronic address: paisen@ucsd.edu.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000453:epidemiology; D002986:Clinical Trials as Topic; D003072:Cognition Disorders / Q000453:epidemiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010919:Placebos; D013997:Time Factors
chemical_list: D010919:Placebos
keywords: Alzheimer's dementia; Cognitive assessment; Therapeutic trials