Xu G, Christian BT, Wooten DW, Hillmer AT, Murali D, Barnhart T, Harding S, Cleary C, Kastman EK, Johnson SC.
The influence of amyloid burden on cerebral glucose metabolism and cognition in cognitively normal middle age subjects who have high risk for Alzheimer's disease.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
Background and objective: There is growing evidence that healthy middle-aged adults at risk for Alzheimer's
Disease (AD) experience preclinical brain changes, but the relationship between fibrillar amyoid burden, glucose
metabolism, and cognitive status in pre-disease states is not yet well understood. Here we present initial baseline
results from an ongoing longitudinal multimodal imaging study in people at risk for AD.
Method: A total of 60 subjects (age 51-75) participated including 7 MCI and 53 subjects from a unique registry
of adult children of AD affected individuals known as WRAP (Wisconsin Registry for Alzheimer's Prevention). All
subjects underwent imaging scans of [18F]FDG PET, [11C]PiB PET, MRI and neuropsychological battery tests
including the Rey auditory verbal learning test (RAVLT). All subjects' PIB distribution volume ratio (DVR) and FDG
SUVR images were coregistered and normalized to the MNI standard template for the voxel-based analyses.
An amyloid burden index (ABI) was measured by averaging the DVR values from the posterior cingluate cortex
(PCC), precuneus, superior parietal lobules (SPL), and frontal cortex. A multiple linear regression model was used
to estimate the relationship between cerebral glucose metabolism and cognitive function and whether the ABI
influenced that relationship.
Results: With or without adjusting for their brain amyloid burden, these subjectfs cognitive memory function
(RAVLT score) was found both tightly and positively correlated to the brain metabolism at bilateral parietal lobules,
PCC, anterior cingulate cortex and frontal lobes. A significant PiB-RAVLT by group interaction was also observed
(MCI vs preMCI-decliner and control), such that the relationship was more negative in the MCIs than people at risk
and preMCI stage. Additionally, across all subjects, the ABI was negatively correlated to glucose metabolism in
the bilateral mesial temporal lobe and this relationship influenced memory.
Discussion and conclusion: These are early baseline results from a longitudinal multi-model neuroimaging project
that represents a unique opportunity to comprehensively study high-risk patients from cognitively normal to pre-
MCI, and eventually to MCI and AD. Two conclusions are drawn thus far: 1) glucose metabolism tracks better with
cognitive function in preclinical and early AD; 2) the influence of amyloid on the metabolism-cognition relationship
was region specific (it was observed in the MTL region but not the medial and lateral parietal regions). Collection
of a larger sample and longitudinal imaging is underway to better elucidate the temporal relationships between
amyloid burden, glucose metabolism and cognition in people at risk for AD.