While the
ApoE ε4 allele is a known risk factor for
mild cognitive impairment (MCI) and
Alzheimer's disease, brain region specific effects remain elusive. In this study, we investigate whether the
ApoE ε4 allele exhibits brain region specific effects in longitudinal
glucose uptake among patients with MCI from the
Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed FDG PET images, MRIs, and demographic information were downloaded from the ADNI database. An iterative reblurred Van Cittertiteration method was used for partial volume correction (
PVC) on all PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. Longitudinal changes in ROI FDG standardized uptake value ratio (SUVR) relative to cerebellum in 24
ApoE ε4 carriers and 24 age-matched
ApoE ε4 non-carriers were measured for up to 84-months (median 72 months, SD = 11.2 months) and compared using a generalized linear mixed effects model controlling for gender, education, baseline age, and follow-up period. Additionally, voxelwise analysis was performed by implementing a paired t-test comparing matched baseline and 72 month FDG SUVR images in
ApoE carriers and non-carriers separately. Results with
PVC were compared with ones from non-
PVC based analysis. After applying
PVC, the superior fontal, parietal, lateral temporal, medial temporal, caudate, thalamus, and post-cingulate, and amygdala regions had greater longitudinal decreases in FDG uptake in
ApoE ε4 carriers with MCI compared to non-carriers with MCI. Similar forebrain and limbic clusters were found through voxelwise analysis. Compared to the
PVC based analysis, fewer significant
ApoE-associated regions and clusters were found in the non-
PVC based PET analysis. Our findings suggest that the
ApoE ε4 genotype is associated with a longitudinal decline in
glucose uptake in 8 forebrain and limbic brain regions in the context of MCI. In conclusion, this 84-months longitudinal FDG PET study demonstrates a novel
ApoE ε4-associated brain-region specific
glucose metabolism pattern in patients with MCI. Partial volume correction improved FDG PET quantification.