Objective: To relate cortical FDG metabolism, PiB retention and APOE-ε4 carrier status in cognitively normal (CN) older individuals.

Methods: Fifty-six CN subjects mean age} sd = 74.7} 7.7 (43 ε4 non-carriers, mean age = 76.1} 7.0, and 13 carriers, mean age = 70.3} 8.5) underwent PiB (DVR, cerebellar reference region) and FDG (SUV, covariance adjusted for cerebellar SUV) PET, and MR imaging. Analyses performed at each cortical vertex (Freesurfer) included linear regressions (in carriers and non-carriers separately) of FDG metabolism on PiB retention covarying local cortical thickness and age, and ANCOVA of PiB retention and FDG metabolism by ε4 status with the same covariates. Local cortical thickness was included to control for partial volume error.

Results: Compared to non-carriers, ε4 carriers had higher PiB retention in precuneus/posterior cingulate, inferior parietal lobule (IPL), and lateral and inferior temporal regions (p <0.001). ε4 carriers had lower FDG metabolism in precuneus but higher metabolism in frontal regions (p <0.001). Among ε4 carriers, FDG metabolism was inversely related to PiB retention in precuneus and IPL (p <0.001), but in non-carriers was positively correlated with PiB in prefrontal regions.

Conclusions: These results suggest that ε4 carrier status modulates the relationship of FDG metabolism and PiB retention differentially across the cortex, with carriers exhibiting significant decline in metabolism with increasing amyloid burden. They confirm previously reported increased amyloid burden in CN carriers compared to noncarriers, but suggest that there may be regions of FDG hypermetabolism in CN ε4 carriers relative to non-carriers.