Title:Disrupted Balance of Gray Matter Volume and Directed Functional Connectivity
in Mild Cognitive Impairment and Alzheimer’s Disease
Volume: 20
Issue: 3
Author(s): Yu Xiong, Chenghui Ye, Ruxin Sun, Ying Chen, Xiaochun Zhong, Jiaqi Zhang, Zhanhua Zhong, Hongda Chen*Min Huang*
Affiliation:
- Department of Traditional Chinese Medicine, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen,
Guangdong 518107, China
- Department of Neurology, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107,
China
Keywords:
Granger causality density (GCD), volume-based morphometry (VBM), resting-state functional MRI (rs-fMRI), structural MRI, Alzheimer’s disease (AD), mild cognitive impairment (MCI), dementia.
Abstract:
Background: Alterations in functional connectivity have been demonstrated in Alzheimer’s
disease (AD), an age-progressive neurodegenerative disorder that affects cognitive function;
however, directional information flow has never been analyzed.
Objective: This study aimed to determine changes in resting-state directional functional connectivity
measured using a novel approach, granger causality density (GCD), in patients with AD, and mild
cognitive impairment (MCI) and explore novel neuroimaging biomarkers for cognitive decline detection.
Methods: In this study, structural MRI, resting-state functional magnetic resonance imaging, and neuropsychological
data of 48 Alzheimer’s Disease Neuroimaging Initiative participants were analyzed,
comprising 16 patients with AD, 16 with MCI, and 16 normal controls. Volume-based morphometry
(VBM) and GCD were used to calculate the voxel-based gray matter (GM) volumes and directed
functional connectivity of the brain. We made full use of voxel-based between-group comparisons of
VBM and GCD values to identify specific regions with significant alterations. In addition, Pearson’s
correlation analysis was conducted between directed functional connectivity and several clinical variables.
Furthermore, receiver operating characteristic (ROC) analysis related to classification was performed
in combination with VBM and GCD.
Results: In patients with cognitive decline, abnormal VBM and GCD (involving inflow and outflow
of GCD) were noted in default mode network (DMN)-related areas and the cerebellum. GCD in the
DMN midline core system, hippocampus, and cerebellum was closely correlated with the Mini-
Mental State Examination and Functional Activities Questionnaire scores. In the ROC analysis combining
VBM with GCD, the neuroimaging biomarker in the cerebellum was optimal for the early detection
of MCI, whereas the precuneus was the best in predicting cognitive decline progression and
AD diagnosis.
Conclusion: Changes in GM volume and directed functional connectivity may reflect the mechanism
of cognitive decline. This discovery could improve our understanding of the pathology of AD and
MCI and provide available neuroimaging markers for the early detection, progression, and diagnosis
of AD and MCI.
