Abstract
PurposeThe objective of this study is to investigate the hippocampal neurodegeneration and its associated aberrant functions in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) patients using simultaneous PET/MRI.MethodsForty-two cognitively normal controls (NC), 38 MCI, and 22 AD patients were enrolled in this study. All subjects underwent 18F-FDG PET/functional MRI (fMRI) and high-resolution T1-weighted MRI scans on a hybrid GE Signa PET/MRI scanner. Neurodegeneration in hippocampus and its subregions was quantified by regional gray matter volume and 18F-FDG standardized uptake value ratio (SUVR) relative to cerebellum. An iterative reblurred Van Cittert iteration method was used for voxelwise partial volume correction on 18F-FDG PET images. Regional gray matter volume was estimated from voxel-based morphometric analysis with MRI. fMRI data were analyzed after slice time correction and head motion correction using statistical parametric mapping (SPM12) with DPARSF toolbox. The regions of interest including hippocampus, cornu ammonis (CA1), CA2/3/dentate gyrus (DG), and subiculum were defined in the standard MNI space.ResultsPatient groups had reduced SUVR, gray matter volume, and functional connectivity compared to NC in CA1, CA2/3/DG, and subiculum (AD < MCI < NC). There was a linear correlation between the left CA2/3DG gray matter volume and 18F-FDG SUVR in AD patients (P < 0.001, r = 0.737). Significant correlation was also found between left CA2/3/DG-superior medial frontal gyrus functional connectivity and left CA2/3/DG hypometabolism in patients with AD. The functional connectivity of right CA1-precuneus in patients with MCI and right subiculum-superior frontal gyrus in patients with AD was positively correlated with mini mental status examination scores (P < 0.05).ConclusionOur findings demonstrate that the associations existed at subregional hippocampal level between the functional connectivity measured by fMRI and neurodegeneration measured by structural MRI and 18F-FDG PET. Our results may provide a basis for precision neuroimaging of hippocampus in AD.
Highlights
The hippocampus, as a structure playing a key role in cognitive processes, is known to remain central to the understanding of the Alzheimer’s disease (AD) pathophysiology with sensitivity to the neurofibrillary tangle development and a strong association with progression to AD [1,2,3]
We hypothesized that different subregions have various contributions to the functionalities of hippocampus, and we aimed to investigate the aberrant of hippocampal subregions in mild cognitive impairment (MCI) and AD patients regarding functional connectivity and metabolism using hybrid PET/MRI
Hybrid PET/MRI is capable of simultaneous evaluating resting-state intrinsic activity, glucose metabolism, and gray matter volume, which could provide evidence for better understanding the neurodegenerative mechanisms underlying AD
Summary
The hippocampus, as a structure playing a key role in cognitive processes, is known to remain central to the understanding of the Alzheimer’s disease (AD) pathophysiology with sensitivity to the neurofibrillary tangle development and a strong association with progression to AD [1,2,3]. Using in vivo MRI, the hippocampus can be divided into three subregions: cornu ammonis (CA1), CA2/3/dentate gyrus (CA2/3/DG), and subiculum [9]. Resting-state fMRI studies showed that the disrupted total hippocampal connectivity [10], right CA1 and left CA2 subregions connectivity [11], and subiculum network (functional connectivity with frontal and posterior cingulate cortex [PCC] regions) [12] in mild cognitive impairment (MCI) and AD patients were strongly associated with memory impairment [5, 13, 14]. In MCI patients, we found that the left hippocampal CA2 functional connectivity measured by resting-state fMRI was associated with decreased dorsal raphe nuclei binding potential measured by [11C]DASB PET [16]
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