Identifying the Alteration Patterns of Brain Functional Connectivity in Progressive Mild Cognitive Impairment Patients: A Longitudinal Whole-Brain Voxel-Wise Degree Analysis.

Yanjia Deng,Lin Shi,Yi Lei,Winnie C W Chu,Kuncheng Li,Defeng Wang,Peipeng Liang,Kai Liu

doi:10.3389/fnagi.2016.00195

Abstract

Patients with mild cognitive impairment (MCI) are at high risk for developing Alzheimer’s disease (AD), while some of them may remain stable over decades. The underlying mechanism is still not fully understood. In this study, we aimed to explore the connectivity differences between progressive MCI (PMCI) and stable MCI (SMCI) individuals on a whole-brain scale and on a voxel-wise basis, and we also aimed to reveal the differential dynamic alteration patterns between these two disease subtypes. The resting-state functional magnetic resonance images of PMCI and SMCI patients at baseline and year-one were obtained from the Alzheimer’s Disease Neuroimaging Initiative dataset, and the progression was determined based on a 3-year follow-up. A whole-brain voxel-wise degree map that was calculated based on graph-theory was constructed for each subject, and then the cross-sectional and longitudinal analyses on the degree maps were performed between PMCI and SMCI patients. In longitudinal analyses, compared with SMCI group, PMCI group showed decreased long-range degree in the left middle occipital/supramarginal gyrus, while the short-range degree was increased in the left supplementary motor area and middle frontal gyrus and decreased in the right middle temporal pole. A significant longitudinal alteration of decreased short-range degree in the right middle occipital was found in PMCI group. Taken together with previous evidence, our current findings may suggest that PMCI, compared with SMCI, might be a “severe” presentation of disease along the AD continuum, and the rapidly reduced degree in the right middle occipital gyrus may have indicative value for the disease progression. Moreover, the cross-sectional comparison results and corresponding receiver-operator characteristic-curves analyses may indicate that the baseline degree difference is not a good predictor of disease progression in MCI patients. Overall, these findings may provide objective evidence and an indicator to characterize the progression-related brain connectivity changes in MCI patients.

Highlights

Mild cognitive impairment (MCI) causes slight but measurable cognitive impairment that does not influence the activities of an individual’s daily life (Gauthier et al, 2006; Brooks and Loewenstein, 2010)
The age, gender, and education level were matched between progressive MCI (PMCI) and stable MCI (SMCI) groups (Table 1; Supplementary Table 1)
At 3 years of followup, the mean Mini-Mental State Exam (MMSE) scores of PMCI and SMCI groups were decreased by 2.9 points and increased by 0.2 points, respectively (Table 1)

Summary

Introduction

Mild cognitive impairment (MCI) causes slight but measurable cognitive impairment that does not influence the activities of an individual’s daily life (Gauthier et al, 2006; Brooks and Loewenstein, 2010). Significant hypometabolism and altered functional connectivity (FC) have been discovered in the tempo-parietal region and precuneus/posterior cingulate gyrus in PMCI patients by comparing with stable MCI (SMCI) patients using positron emission tomography imaging and magnetoencephalography analysis (Lopez et al, 2014; Cerami et al, 2015). Overall, these findings confirm that PMCI and SMCI are able to be distinguished and characterized at the neurobiological level

Objectives

Methods

Results

Conclusion