Spatially Distributed Amyloid-β Reduces Glucose Metabolism in Mild Cognitive Impairment

Abstract

Background: Several positron emission tomography (PET) studies have explored the relationship between amyloid-β (Aβ), glucose metabolism, and the APOE ϵ4 genotype. It has been reported that APOE ϵ4, and not aggregated Aβ, contributes to glucose hypometabolism in pre-clinical stages of Alzheimer's disease (AD) pathology. Objective: We hypothesize that typical measurements of Aβ 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 Aβ 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 Aβ, 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 Aβ. Results: From an older population of CN and MCI subjects, we found that the SVD-based Aβ score was significantly correlated with glucose metabolism in several cortical regions. Additionally, the corresponding Aβ network has hubs that contribute to distributed glucose hypometabolism, which, in turn, are not necessarily foci of Aβ deposition. Conclusions: Our approach uncovered hidden patterns of the glucose metabolism-Aβ relationship. We showed that the SVD-based Aβ score produces a stronger relationship with decreasing glucose metabolism than either APOE ϵ4 genotype or global measures of Aβ burden.