APOE and early-onset autosomal dominant Alzheimer disease: For example, studies have reported hippocampal and cortical hyperactivation in individuals with SCD (Fig. 2C and D), while they performed various associative and item novelty memory tasks.27-29,31,152 As noted earlier, studies have also revealed higher fMRI activation in younger and cognitively normal OAs carrying an APOE4 allele25,26,153-156 This suggests that hyperactivation may antedate the onset of memory complaint in the setting of developmental factors predisposing to developing Alzheimer’s disease.