Two studies investigated the effect of donepezil: an Alzheimer’s Disease Cooperative study on donepezil and vitamin E, which showed no treatment effects, but a trend towards slowing hippocampal atrophy in the APOE ε4 carriers [56]; and a substudy from another donepezil trial where no effects on hippocampal or entorhinal cortex atrophy were found [57]. This evidence concerns the gene APOE and Alzheimer disease.