Modeling Spatial and Temporal Patterns of APOE ε4 Mediated Glucose Uptake in Mild Cognitive Impairment and Normal Controls

Apolipoprotein E (APOE) ε4 allele is a risk factor for developing Alzheimer's disease. In this study, we analyzed longitudinal changes in fluorodeoxyglucose (FDG) uptake between APOE ε4 carriers and non-carriers in normal control (NC) and Mild Cognitive Impairment (MCI) subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We reported forebrain and limbic regions that exhibit APOE ε4-mediated declines in FDG uptake over a 96 month period in subjects with MCI but not NCs. Using voxel-based and ROI-based analysis, we compared the longitudinal changes in glucose uptake between APOE ε4 carriers and non-carriers from 34 NCs with no cognitive impairment and 48 subjects with MCI. Parietal, temporal and frontal regions had greater longitudinal decreases in FDG uptake in APOE ε4 carriers compared to non-carriers. The Superior parietal lobe, inferior temporal gyrus, thalamus, caudate, parahippocampal gyrus, fusiform gyrus and middle temporal gyrus showed greater longitudinal decreases in FDG uptake in APOE ε4 carriers compared to non-carriers in subjects with MCI but not NC. These findings suggest APOE ε4 genotype is associated with decline in glucose uptake over time and that specific limbic and forebrain structures exhibit APOE ε4-mediated FDG decline in MCI but not NCs. Our work in identifying the brain regions most associated with APOE ε4 related AD pathophysiology will improve quantitative FDG imaging as a biomarker in precision medicine.