In this retrospective study, we investigate the presence of anxiety and depression in a well-characterized sample of AD patients and analyzed the influence of APOE variants and CYP2D6, CYP2C19, and CYP2C9 geno-phenotypes on the frequency and severity of anxiety and depression as well as the effect that different APOE single nucleotide polymorphisms (SNPs) and CYP phenotypes exert on the evolution of mood disorders after treatment with multifactorial therapy. The gene discussed is APOE; the disease is major depressive disorder.