Statistical Analysis.
NAWM, AMRF
ALZHEIMER
Group 1 received treatment from baseline through 3 mo and group 2 from 3 mo to 5 mo post-baseline. Given the structural change induced by the treatment, a delayed treatment analysis was undertaken to evaluate the effect of treatment on the MRI outcomes. Mixed-effects linear models were used to compare the changes from baseline at each time point between the two groups in the NAWM and lesions of the CC, OR, and CST. More specifically, the model specified the categorical time point, the treatment indicator (1 for months 3 and 5 in group 1 and 1 for month 5 in group 2), and the interaction of these as fixed effects and included a random intercept for each subject to account for intrasubject correlation of the longitudinal measurements.To examine the supplementary dedicated reliability dataset (based on the MWF values within the VOIs of the seven healthy subjects), we calculated the median MWF from each VOI for each subject and time point. We performed an ANOVA for the three time points and computed coefficient of variation for each subject. We report the average coefficient of variation across subjects for each VOI.The correlation between CC and OR MWF and VEP change was assessed using a hierarchical linear model with random intercepts and slopes, accounting for within-subjects and within-eye correlations.To consider planning for future trials we performed a power analysis for the different tracts we used the SD within groups at baseline and expected difference in mean change from baseline, ranging from 0.005 to 0.01 (similar to the differences in mean change from baseline observed in the trial in the different VOIs).This study was funded by generous support from The Rachleff Family Westridge Foundation, Janet Lustgarten and the Lustgarten Family Whitney Fund, and the Adelson Medical Research Foundation. C.C. reports support from Merck Serono outside the submitted work. R.G.H. reports personal fees from Sanofi-Genzyme, Novartis, Roche, QIA, Boston Pharma, and Neurona Therapeutic outside the submitted work. J.R.C. reports support from Pipeline Therapeutics outside the submitted work. A.J.G. reports support from Pipeline Therapeutics, Neurona, Synthon, Bionure, Amneal, and JAMA Neurology outside the submitted work. R.G.H. reports grants from Roche-Genentech, Atara, and Medday outside the submitted work. N.P. reports research support outside the submitted work from the Race to Erase MS Foundation and from the National Center for Advancing Translational Sciences, NIH, through a UCSF-CTSI grant. J.R.C. reports grants from NIH, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and Mead Johnson outside the submitted work outside the submitted work. A.J.G. reports grants from the National MS Society, US NIH, AMRF, C. Light Technologies, along with the Alzheimer's Drug Discovery Foundation.