It is generally recognized that more sensitive instruments for the earliest stages of Alzheimer’s disease (AD) are needed. The integrated Alzheimer’s Disease Rating Scale (iADRS) combines scores from 2 widely accepted measures, the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Alzheimer’s Disease Cooperative Study – instrumental Activities of Daily Living (ADCS-iADL). Disease progression and treatment differences as measured by the iADRS were analyzed using data from solanezumab EXPEDITION, EXPEDITION2, and EXPEDITION-EXT Studies; semagacestat IDENTITY Study; and donepezil ADCS – mild cognitive impairment (ADCS-MCI) Study. Psychometric properties of the iADRS were established through principal component analysis (PCA) and estimation of contributions of subscores and individual item scores to the iADRS total score. The iADRS performed better than most composites and scales in detecting disease progression and comparably or better than individual scales in detecting treatment differences. PCA demonstrated the iADRS can be divided into two principal components primarily representing cognitive items and instrumental ADLs. Dynamic ranges of the subscales were similar across all studies, reflecting approximately equal contributions from both subscales to the iADRS total score. In item analyses, every item contributed to the total score, with varying strength of contributions by item and across data sets. The iADRS demonstrated acceptable psychometric properties and was effective in capturing disease progression from MCI through moderate AD and treatment effects across the early disease spectrum. These findings suggest the iADRS can be used in studies of mixed populations, ensuring sensitivity to treatment effects as subjects progress during studies of putative disease-modifying agents