Spatially Distributed Amyloid-? Reduces Glucose Metabolism in Mild Cognitive Impairment.

ABSTRACT:

Background

Several positron emission tomography (PET) studies have explored the relationship between amyloid-? (A?), glucose metabolism, and the APOE?4 genotype. It has been reported that APOE?4, and not aggregated A?, contributes to glucose hypometabolism in pre-clinical stages of Alzheimer's disease (AD) pathology.

Objective

We hypothesize that typical measurements of A? taken either from composite regions-of-interest with relatively high burden actually cover significant patterns of the relationship with glucose metabolism. In contrast, spatially weighted measures of A? are more related to glucose metabolism in cognitively normal (CN) aging and mild cognitive impairment (MCI).

Methods

We have generated a score of amyloid burden based on a joint singular value decomposition (SVD) of the cross-correlation structure between glucose metabolism, as measured by [18F]2-fluoro-2-deoxyglucose (FDG) PET, and A?, as measured by [18F]florbetapir PET, from the Alzheimer's Disease Neuroimaging Initiative study. This SVD-based score reveals cortical regions where a reduced glucose metabolism is maximally correlated with distributed patterns of A?.

Results

From an older population of CN and MCI subjects, we found that the SVD-based A? score was significantly correlated with glucose metabolism in several cortical regions. Additionally, the corresponding A? network has hubs that contribute to distributed glucose hypometabolism, which, in turn, are not necessarily foci of A? deposition.

Conclusions

Our approach uncovered hidden patterns of the glucose metabolism-A? relationship. We showed that the SVD-based A? score produces a stronger relationship with decreasing glucose metabolism than either APOE?4 genotype or global measures of A? burden.

SUBMITTER: Carbonell F 

PROVIDER: S-EPMC7029335 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature