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Variable Selection and Model Construction. Model Selection and Parameter Estimation. Regional Brain Atrophy Analysis. For regional mediation analysis, we employed the same methodology as explained above (Multivariate Analysis).

Code and Material Availability. ResultsMultivariate Analysis: Simvastatin Effect on Clinical Outcomes and Brain Atrophy Is Independent of Cholesterol. The Bayesian Analysis: Simvastatin Effects on Clinical Outcomes Are Independent of Cholesterol and Are Partially Mediated by Brain Atrophy.

The Effect of Simvastatin on Brain Atrophy Was Predominant on the Lateral Ventricles and Transverse Temporal Gyrus. DiscussionWe used multivariate structural equation models to explore and test hypothesized causal mechanisms that may explain the observed treatment effect of a potential neuroprotective drug using the simvastatin trial as a model.

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