Age and Rate of Cognitive Decline in Alzheimer Disease Implications for Clinical Trials

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. Design: Pooled cohort study from 3 AD clinical trials of 18-month duration conducted by the Alzheimer Disease Cooperative Study group. Setting: Alzheimer disease research centers from across the United States. Patients: Four hundred seventy-one subjects with mild to moderate AD assigned to the placebo arm of 3 clinical trials. Main Outcome Measures: 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. Conclusion: 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.