General analysis considerations
dementia, MCI
DISEASE PROGRESSION
Analyses were performed in accordance with a pre-specified statistical analysis plan (SAP). For the majority of the psychometric properties tested, screening/baseline and month 36 data were primarily used in the analyses; test–retest leveraged data from screening/baseline and month 6; responsiveness to change leveraged data from screening/baseline and month 36.The initial focus of the psychometric tests was baseline data, except for those tests that typically include follow-up data, such as test–retest or responsiveness analyses. However, initial analyses showed that the MCI population had limited functional impairments at baseline as reflected by low variability of the data and various ADCS-ADL-MCI items exhibiting ceiling effects. Further, some of the reference COA instruments were assessed at screening only (i.e., CDR-SB, ADAS-Cog, and MMSE), while the ADCS-ADL-MCI was assessed at baseline. Per protocol, the baseline was assessed between three and five weeks after the screening visit. While it is not expected that change occurred between these two assessments, ideally, data are evaluated on the same day to ensure that analyses, such as correlation analyses, are not affected by potential alternative effects such as different assessment time points. Therefore, for these two reasons the 36-month data were additionally included for all psychometric tests where applicable (e.g., due to increased variability of scores observed (due to progression over the 36 months in the study) and the fact that all COAs were assessed at the same time point). While evaluation of only placebo patients at month 36 was considered, the richness and real-world relevance of information contained in the full population was deemed more informative. Indeed, a heterogeneous cohort of patients was envisioned, with varying degrees of disease progression, which was considered helpful to evaluate the measurement properties. It is noted that patients at the 36-month timepoint do not include those who had progressed to dementia, and thus the sample only reflects those with slower disease progression.