title: Age and rate of cognitive decline in Alzheimer disease: implications for clinical trials.
abstract: BACKGROUND
  Factors that affect the rate of progression of Alzheimer disease (AD) need to be considered in the clinical trial designs of potential disease-modifying therapies.
  
  
  OBJECTIVE
  To determine the influence of age on AD course in a clinical trial setting.
  
  
  METHODS
  Pooled cohort study from 3 AD clinical trials of 18-month duration conducted by the Alzheimer Disease Cooperative Study group.
  
  
  METHODS
  Alzheimer disease research centers from across the United States.
  
  
  METHODS
  Four hundred seventy-one subjects with mild to moderate AD assigned to the placebo arm of 3 clinical trials.
  
  
  METHODS
  The relationships between baseline age and rate of change in the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog) 11, Mini-Mental State Examination, Clinical Dementia Rating scale Sum of Boxes score, Alzheimer Disease Cooperative Study–activities of daily living scale, and Neuropsychiatric Inventory were analyzed using a mixed-effect regression model. Sample size calculation for possible future AD clinical trials lasting 18 months using the results of the change in ADAS-cog 11 by tertiles of age groups.
  
  
  RESULTS
  Older age at baseline was associated with a slower rate of decline in the ADAS-cog 11 and the Mini-Mental State Examination scores. Almost twice as many subjects aged 80 years and older compared with those aged younger than 70 years would be required to demonstrate a 30% treatment effect on the ADAS-cog 11 in an 18-month AD trial.
  
  
  CONCLUSIONS
  Subject age is an important factor to consider when defining the study population in and analyzing data from AD trials of potential disease-modifying therapies.
authors.affiliation: Lou Ruvo Center for Brain Health, Cleveland Clinic, Las Vegas, Nevada 89106, USA. bernicc@ccf.org
authors.forename: Charles
authors.initials: C
authors.lastname: Bernick
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cummings
authors.forename: Rema
authors.initials: R
authors.lastname: Raman
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Sun
authors.forename: Paul
authors.initials: P
authors.lastname: Aisen
mesh_terms: D000203:Activities of Daily Living; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000150:complications* / Q000188:drug therapy / Q000523:psychology; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D015337:Multicenter Studies as Topic; D009483:Neuropsychological Tests; D017063:Outcome Assessment, Health Care; D011569:Psychiatric Status Rating Scales; D014481:United States
chemical_list: D014150:Antipsychotic Agents