[O1–06–03]: EFFECTS OF TAU DEPOSITION ON CEREBRAL GLUCOSE METABOLISM IN NORMAL OLDER ADULTS VARY BY AMYLOID LEVEL

Relationships between brain β-amyloid and glucose metabolism in cognitively normal older adults (OA) have been weak and inconsistent. We examined associations between tau and glucose metabolism and whether relationships varied with global Aβ burden. 47 OA (Table) received 18F-AV-1451 (tau, 80–100 min SUVR), 11C-PiB (Aβ, 35–90 min DVR), and 18F-FDG (30–60 min SUVR) PET, which were coregistered to T1-weighted MRI. We processed native-space T1 (FreeSurfer v5.3) to delineate cerebellar gray matter (PiB and AV-1451 reference region) and brainstem (edited to derive FDG pons reference). For each subject we calculated a weighted cortical PiB average to characterize Aβ-positivity. We warped OA MRI to MNI space (ANTS) and applied transformations to AV-1451 and FDG images. A cortical testing mask was created by intersecting AAL ROIs with high-probability gray matter (GM) voxels (SPM12 probability map). MNI-space FDG and AV-1451 PET images were masked and smoothed (4mm). We used SPM12 VBM (10mm FWHM smoothing) on T1 images to generate voxelwise MNI-space GM concentration images, which were also masked. We used a newly-developed Spatially Varying Coefficient Model to examine associations between increased tau accumulation and reduced glucose metabolism (within Aβ status group, controlling for local GM). This method incorporates false discovery control, accounts for continuity among adjacent voxels, and has higher detection power than voxel-wise analysis. Reported clusters are significant at p<.0001 (>=20 voxels). Among Aβ- OA, increased AV-1451 uptake was significantly associated with reduced FDG metabolism (Figure) in clusters located in bilateral medial temporal lobes (MTL), with additional smaller clusters in inferior frontal cortex and temporo-occipital fusiform gyrus. Among Aβ+ OA, significant inverse AV-1451—FDG associations were located in right inferolateral temporal, and bilateral medial parietal and inferior medial frontal cortex. AV-1451—FDG associations by Aβ status. Clusters indicate significant negative associations between AV-1451 and FDG in Aβ- (left) and Aβ+ (right) older adults.