Link between regional neuronal metabolism impairment and aberrant inter-regional functional connectivity in patients with MCI or AD

1. BackgroundAlzheimers disease(AD) is the most prevalent neurodegenerative disorder being characterized by both decreasing regional neuronal activity and increasing inter-regional dysconnectivity. However, the relationship between them is poorly understood. Of note, FDG-metabolism is a proxy of regional neuronal activity, degree centrality (DC) is a proxy for global inter-regional functional connectivity (FC), and clustering coefficient(CC) is a proxy for local inter-regional FC. The purpose of this study was to investigate the link between FDG-metabolism and DC/CC using simultaneous FDG-PET and rs-fMRI measurements in patients with mild cognitive impairment (MCI) or AD, as well as healthy controls.2. Method Thirty-three patients with mild AD, 20 patients with MCI, and 26 healthy controls underwent simultaneous PET/MRI measurements on an integrated PET/MR scanner. Firstly, FDG-metabolism and DC/CC data was extracted from 112 regions that were defined by anatomical parcellation of the whole brain using Harvard- Oxford atlas. Then, we performed three sets of analysis of variance (ANOVA) across groups to definebrain regions that revealed FDG-metabolism and global/local inter-regional dysconnectivity alterations in patients with MCI or AD compared to controls. All the results were corrected for false positive correction for N-region statistical comparison which was applied using 1 / (amount of regions) = 1 / 112 = 0.009 as significance threshold. Afterwards, post-hoc analyses were conducted to identify the group differences in FDG-metabolism, DC, and CC. Finally, to assess the link between aberrant changes in local neuronal activity and inter-regional FC across groups, we performed partial correlation analysis between FDG-metabolism and DC/CC, while we controlled for covariates of no-interest including age and gender. 3. ResultsRegional FDG-metabolism analysis demonstrated hypo-metabolism in several regions in the parietal and temporal cortices. Hyper-metabolism was also observed in the frontal, temporal, and occipital lobes, as well as the brain stem. Regional topological metrics analysis demonstrated that CC is decreased in a several cortical regions and DC is also decreased in a several cortical regions but increased in the bilateral temporal fusiform,right brain stem and left pallidum. Partial correlation analysis identified significant positive association between FDG-metabolism and CC in the right angular gyrus (rCC&FDG = 0.317, p = 0.005) and right lateral occipital cortex (rCC&FDG = 0.252, p = 0.028). However FDG-metabolism and CC were negatively correlated in the right temporal occipital fusiform cortex (rCC&FDG = - 0.248, p = 0.031), and right sup- plementary motorcortex (rCC&FDG = - 0.230, p = 0.046). In addition, FDG-metabolism and DC of left and right precentral gyrus were negatively correlated (rDC&FDG (left precentral gyrus) = - 0.268, p = 0.019; rDC&FDG (right precentral gyrus) = - 0.282, p = 0.014). 4. Conclusions Results provide evidence that in patients with MCI or AD impairment of neural metabolism within the right angular gyrus, right lateral occipital cortex, right temporal occipital fusiform cortex, right supplementary motor cortex, and left and right precentral gyrus are linked with global and local inter-regional FC dysconnectivity.