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

Ying Wang, Zhihong Shi, Nan Zhang, Li Cai, Yansheng Li, Hailei Yang, Shaobo Yao, Xiling Xing, Yong Ji, Shuo Gao

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. 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 (BPND) of VOIs were generated by using PMOD software. In addition, statistical analysis of BPND among four types of AD in each specific network was calculated by SPSS software. 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 BPND showed that there were no significant differences (p > 0.05) among AD groups within the specific networks. The phenotypic diversity of AD correlates with specific functional network failure; however, Aβ plaques do not associate with specific network vulnerability.