APOE and Alzheimer disease: In addition, several studies have indicated a reduction in CMRglc early in the time course of AD pathology (Mosconi, 2005; Jack et al., 2013), with such changes evident in both asymptomatic, cognitively normal carriers of the APOE4 allele (Reiman et al., 2001, 2004, 2005; Protas et al., 2013; Riedel et al., 2016) and in midlife men and women at risk for AD (Mosconi et al., 2007, 2010, 2017, 2018a,b, 2021; Rahman et al., 2020; Schelbaum et al., 2021).