Structural And Functional Changes In Subcortical Vascular Mild Cognitive Impairment: A Combined Voxel-based Morphometry And Resting-state FMRI Study

Mild cognitive impairment (MCI) refers to a transitional state between normalaging and dementia and is characterized by various symptom clusters. As a clinicallyheterogeneous syndrome, MCI can be classified into subtypes of amnestic andnon-amnestic phenotypes. Numerous previous studies have primarily focused onamnestic MCI (aMCI), due to the relatively high incidence and straightforwardclinical diagnosis of this type of MCI. In recent years, the non-amnestic MCI,particularly the subcortical vascular MCI (svMCI) subtype, has begun to attractattention. Also, svMCI has been proposed as a prodromal stage of subcortical vasculardementia (SVaD), which is one of the most common types of vascular dementia.Recent evidences suggest that svMCI is potentially reversible; therefore,characterizing the structural and functional brain abnormalities in the atypicalpopulation with svMCI can provide insights into understanding thepathophysiological mechanism of svMCI.Previous studies have shown that human brain structure and function can beexplored in vivo by neuroimaging techniques, such as structural MRI (sMRI) andresting-state functional MRI (R-fMRI). Importantly, sMRI provides richmorphological information of brain tissues and has been extensively used to revealcortical atrophy, thinning and deformation in response to pathological attacks.Recently, R-fMRI has emerged as an effective, noninvasive imaging technique that is used to study the intrinsic functional architecture of the human brain when subjectsare not engaged in external tasks. R-fMRI measures the spontaneous neural activity aslow-frequency (typically <0.1Hz) oscillations (LFO) of BOLD signals that arecrucial for the understanding of the intrinsic functional organization of the humanbrain. Moreover, R-fMRI provides a promising avenue for exploring changes in thespontaneous neural activity that are associated with various brain disorders. In thecurrent study, we performed a multimodal imaging analysis by combining sMRI andR-fMRI to explore both structural and functional brain abnormalities in patients withsvMCI. Functionally, we utilized a test-retest reliable, regional measure of theamplitude of low-frequency fluctuation (ALFF) to characterize local amplitude ofspontaneous LFO. LFO amplitude reflects the intensity of the regional spontaneousbrain activity and is sensitive to disease states, such as aMCI, Alzheimer’s disease,schizophrenia and mesial temporal lobe epilepsy. Structurally, we used a voxel-basedmorphometry (VBM) approach to perform an unbiased whole-brain analysis of GMvolume. Additionally, we also tested whether and to what extent the functionalabnormalities in the svMCI patients could be influenced by structural changes.Structural and resting-sate functional MRI data were collected from26svMCIpatients and28age-and gender-matched healthy controls. Functionally, LFOamplitude changes were predominantly found in the default mode network (DMN) inthe svMCI patients. Compared with the healthy controls, the svMCI patients exhibiteddecreased LFO amplitudes in the anterior part of the DMN (e.g., the medial prefrontalcortex), whereas increased LFO amplitudes in the posterior part of the DMN (e.g., theposterior cingulate/precuneus and inferior parietal lobule). Structurally, widespreadGM atrophy was found in the svMCI patients that resided primarily in frontal (e.g.,the superior and inferior frontal gyri and medial prefrontal cortex) and temporal (thesuperior and middle temporal gyri and the hippocampal gyrus) brain regions. GMvolume reductions were also found in several subcortical brain sites (e.g., thethalamus and the caudate). No brain regions showed increased GM volume in thesvMCI patients. Finally, the functional alterations of LFO amplitudes remainedminimally changed after controlling for structural GM volume losses, which suggests that functional abnormalities can be only partly explained by morphological GMvolume changes. Together, our results indicate that svMCI patients exhibitwidespread abnormalities in both structural GM volume and functional intrinsic brainactivity, which have important implications in understanding the pathophysiologicalmechanism of svMCI.