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.
Highlights
The amnestic mild cognitive impairment represents an intermediate stage between normal aging and Alzheimer’s disease (AD) (Petersen et al, 2014)
Regarding the general cognitive ability, we found that three groups exhibited the significant differences in the score of Mini-Mental State Examination (MMSE) and ADAS-cog, with mean diffusivity (MD)-amnestic mild cognitive impairment (aMCI) displaying the worst performance
MDaMCI group presented a trend of the increased level of t-tau and p-tau181 as well as decreased Aβ1−42, no significant differences existed among groups (p > 0.05)
Summary
The amnestic mild cognitive impairment (aMCI) represents an intermediate stage between normal aging and Alzheimer’s disease (AD) (Petersen et al, 2014). Neuroimaging studies pointed out that the MD-aMCI displays more diffuse gray matter atrophy (Haller et al, 2010; Zhang et al, 2012) and lower brain activity than the SD-aMCI, mainly involving default mode network (DMN) and frontoparietal regions (Li et al, 2014). Despite these studies shedding light into the aMCI pathological mechanism to some extent, it remains unclear whether SD-aMCI and MD-aMCI have different inter-hemispheric connection pattern. Few studies investigated whether SD-aMCI and MD-aMCI have different inter-hemispheric connectivity pattern
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