Impact of sex and APOE-ε4 genotype on regional brain metabolism in Alzheimer's Disease

Age, sex and APOE-ε4 genotype have been identified as the strongest predictors of the risk of developing Alzheimer's Disease (AD). This work models the pathological progression of regional brain hypometabolism, using mixed-effect models with latent time variable and longitudinal FDG-PET data. Statistical comparisons then disentangle the effects of sex and APOE-ε4 genotype on the onset age and pace of progression of hympometabolism in each brain region, while correcting for education level. They provide a brain map of the regions with earlier and/or faster alterations of the metabolism. We show that females are associated with faster hypometabolism in the caudate nuclei, the thalamus and right temporal and medial-occipital lobes, while APOE-ε4 is associated with earlier hypometabolism in the limbic system (hippocampus, parahippocampus and amygdala) and temporal lobe.