© 2015 American Academy of Neurology. Objective: We tested the a priori hypothesis that older participants differ in rates of decline on cognitive outcomes compared with younger participants, and examined the potential effect of age distributions on individual clinical trial outcomes. Methods: From a meta-database of 18 studies from the Alzheimer's Disease Cooperative Study and the Alzheimer's Disease Neuroimaging Initiative, we included a cohort of 2,793 participants for whom there were baseline demographic data and at least one postbaseline cognitive assessment on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Clinical Dementia Rating-Sum of Boxes (CDR-SB), or Mini-Mental State Examination (MMSE). We used mixed-effects models (random coefficient models) to estimate change on the outcomes across 7 age groups ranging from younger than 61 years to older than 85 years after adjusting for education. Results: Significant worsening occurred in all age groups on all outcomes over time. The 4 older groups, aged 71 years and older, showed slower rates of decline on the ADAS-cog than the younger groups (p 0.001). The older groups scored 2-3, 2-5, and 4-6 points better than the younger groups at 12, 18, and 24 months, respectively. There were similar differences across age groups for the MMSE, but not for the CDR-SB. Conclusions: The differences in change on the ADAS-cog between older and younger participants are substantially greater than differences expected between experimental drugs and placebo in current trials or differences between marketed cholinesterase inhibitors and placebo. The clinical interpretation of change on the ADAS-cog or MMSE differs depending on age. Until predictors of decline are better understood, considering effects of age on rates of change is particularly important regarding clinical practice and outcomes of trials.