Decreased Bilateral FDG-PET Uptake and Inter-Hemispheric Connectivity in Multi-Domain Amnestic Mild Cognitive Impairment Patients: A Preliminary Study

Abstract

Background: Amnestic mild cognitive impairment (aMCI) is a heterogeneous condition. Based on clinical symptoms, aMCI could be categorized into single-domain aMCI (SD-aMCI, only memory deficit) and multi-domain aMCI (MD-aMCI, one or more cognitive domain deficit). As core intrinsic functional architecture, inter-hemispheric connectivity maintains many cognitive abilities. However, few studies investigated whether SD-aMCI and MD-aMCI have different inter-hemispheric connectivity pattern.Methods: We evaluated inter-hemispheric connection pattern using fluorine-18 positron emission tomography – fluorodeoxyglucose (18F PET-FDG), resting-state functional MRI and structural T1 in 49 controls, 32 SD-aMCI, and 32 MD-aMCI patients. Specifically, we analyzed the 18F PET-FDG (intensity normalized by cerebellar vermis) in a voxel-wise manner. Then, we estimated inter-hemispheric functional and structural connectivity by calculating the voxel-mirrored homotopic connectivity (VMHC) and corpus callosum (CC) subregions volume. Further, we correlated inter-hemispheric indices with the behavioral score and pathological biomarkers.Results: We found that MD-aMCI exhibited more several inter-hemispheric connectivity damages than SD-aMCI. Specifically, MD-aMCI displayed hypometabolism in the bilateral middle temporal gyrus (MTG), inferior parietal lobe, and left precuneus (PCu) (p < 0.001, corrected). Correspondingly, MD-aMCI showed decreased VMHC in MTG, PCu, calcarine gyrus, and postcentral gyrus, as well as smaller mid-posterior CC than the SD-aMCI and controls (p < 0.05, corrected). Contrary to MD-aMCI, there were no neuroimaging indices with significant differences between SD-aMCI and controls, except reduced hypometabolism in bilateral MTG. Within aMCI patients, hypometabolism and reduced inter-hemispheric connectivity correlated with worse executive ability. Moreover, hypometabolism indices correlated to increased amyloid deposition.Conclusion: In conclusion, patients with MD-aMCI exhibited the more severe deficit in inter-hemispheric communication than SD-aMCI. This long-range connectivity deficit may contribute to cognitive profiles and potentially serve as a biomarker to estimate disease progression of aMCI patients.

Gray matter structural covariance networks changes along the Alzheimer's disease continuum

“…Regarding the DMN, subjects at the early stage of AD showed increased structural association while decreased association in subjects at the late stage. This result is in line with previous studies which reported the early involvement of DMN in AD (Seeley et al, 2009; He et al, 2007; Luo et al, 2018a; Luo et al, 2018b; Gili et al, 2011), and the progressive SCN DMN score decline through the AD progression (Spreng and Turner, 2013). The mechanism may be the activity-dependent or metabolism-dependent pathology hypothesis: the DMN's continuous activity may lead to the early formation and diffusion of the AD neuropathological hallmarks (Palmqvist et al, 2017; Buckner et al, 2005; Buckner et al, 2009).…”

Functional Integration Between the Two Brain Hemispheres: Evidence From the Homotopic Functional Connectivity Under Resting State

“…Compared to healthy controls, some studies have demonstrated increased HoFC in patient groups, such as idiopathic generalized epilepsy ( Yang et al, 2014 ) and paroxysmal kinesigenic dyskinesia ( Ren et al, 2015 ), while others reported decreased HoFC, ranging from cocaine addiction ( Kelly et al, 2011 ), schizophrenia ( Hoptman et al, 2012 ), Parkinson’s disease ( Luo et al, 2015 ), major depressive disorder (MDD) ( Hermesdorf et al, 2016 ), to amnestic mild cognitive impairment ( Luo et al, 2018 ). Some brain diseases, including HBV-related cirrhosis ( Ye et al, 2020 ) and subacute stroke ( Chen et al, 2020 ), showed both increases and decreases of HoFC in different brain regions.…”

Mapping the patterns of cortical thickness in single- and multiple-domain amnestic mild cognitive impairment patients: a pilot study

“…Also, fractional anisotropy (FA) and mean diffusivity (MD) alteration were compared using diffusion tensor imaging (DTI) [10]. Connectivity damage difference was discussed between aMCI-m and aMCI-s using positron emission tomography (PET) [11]. As for the structural neuroimaging analysis for the two subtypes of aMCI, atrophy and volume of the cortical gray matter or manually defined regions of interest (ROIs) have been discussed [12, 13].…”