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mixed model for repeated measures) was used in the majority of the included comparator trials, which further supports the use of the trial product estimand from the PIONEER 8 trial

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Therefore, a decrease in Cu transport in the brain could lead to an increase in oxidative stress as a consequence of increased release of ions that contribute to the formation of free radicals, a decrease in endogenous antioxidant systems (CU/Zn-SOD), and an increase in iron accumulation by decreasing the ferroxidase activity of ceruloplasmin [344]