Spatial Patterns of Hypometabolism and Amyloid Deposition in Variants of Alzheimer's Disease Corresponding to Brain Networks: a Prospective Cohort Study

Abstract

Purpose: To identify the most vulnerable network among typical and three variants of Alzheimer's disease (AD) and to link amyloid-β (Aβ) deposition and downstream network dysfunction.

Procedures: In this study, 38 typical AD, 11 frontal variants, 8 logopenic variants, 6 posterior variants, and 20 normal controls were enrolled. 2-(4'-[¹¹C] Methylaminophenyl)-6-hydroxybenzothiazole ([¹¹C]PIB) and 2-deoxy-2-[¹⁸]fluoro-D-glucose ([¹⁸F]FDG) positron emission tomography (PET) imaging were performed. Voxel-wise statistical analysis was used for [¹⁸F]FDG analysis, whereas two-sample t test was performed between each AD group and control group. Moreover, the goodness of fit (GOF) of t-maps with brain functional network templates was assessed, and the most vulnerable network in each phenotypic of AD was chosen as volume of interests (VOIs). [¹¹C]PIB binding potential (BP_ND) of VOIs were generated by using PMOD software. In addition, statistical analysis of BP_ND among four types of AD in each specific network was calculated by SPSS software.

Results: The hypometabolism patterns indicated that in typical and frontal variants of AD, the most vulnerable network was the left executive control network (GOF score = 4.3, 5.0). For the logopenic variant, the highest GOF score (1.9) belonged to the auditory network. For the posterior variant, the higher visual network was the most vulnerable (GOF score = 6.0). The [¹¹C]PIB BP_ND showed that there were no significant differences (p > 0.05) among AD groups within the specific networks.

Conclusion: The phenotypic diversity of AD correlates with specific functional network failure; however, Aβ plaques do not associate with specific network vulnerability.

Keywords: Alzheimer’s disease; Amyloid-β; Positron-emission tomography; [11C]PIB; [18F]FDG.