Background: APOE4 carrier status in normal individuals has been associated with both altered glucose metabolism
and higher levels of amyloid deposition.
Objective: To evaluate the impact of APOE-ε4 carrier status on FDG metabolism considering the effects of PiB
retention, cortical thickness and age in cognitively normal (CN) older individuals.
Methods: Forty-three CN subjects, mean age ± SD = 75.6 ± 7.0 (11 ε4 carriers, mean age = 73.4 ± 7.6, and
32 ε4 non-carriers, mean age = 76.4 ± 6.8) underwent PiB (DVR, cerebellar cortex reference region) and FDG (SUV,
covariance adjusted for cerebellar cortex SUV) PET and MR imaging; image data was processed using Freesurfer.
FDG analyses were performed vertex-wise controlling for precuneus PiB retention, cortical thickness local to each
vertex, and age, in order to isolate APOE-ε4 effects on metabolism.
Results: Compared to non-carriers, ε4 carriers had similar precuneus, parietal, frontal and global amyloid deposition,
but exhibited hypometabolism in default network areas and hypermetabolism in prefrontal, inferomedial temporal
and caudal anterior cingulate regions (cluster-wise corrected p<0.001). In addition, compared to non-carriers, the relationship of FDG metabolism to age in ε4 carriers was significantly steeper: greater age was associated with
lower FDG metabolism (interaction term peak vertex p<0.005, right-hemisphere superior frontal cortex, Talairach
xyz = 16,54,16; cluster-wise p<0.043 corrected for multiple comparisons).
Conclusions: These preliminary results in 43 CN subjects suggest that certain frontal and anterior cingulate
regions of relative hypermetabolism may mark an important intermediate step along a trajectory of prodromal AD.
