Investigation of functional connectivity changes in Alzheimer's disease and amnestic mild cognitive impairment using Degree Centrality
Yong Zhang1, Naying He2, Hua-Wei Lin2, Ajit Shankaranarayanan3, Zhenyu Zhou1, and Fu-Hua Yan2

1MR Research China, GE Healthcare, Beijing, China, People's Republic of, 2Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, People's Republic of, 3GE Healthcare, Menlo Park, CA, United States

Synopsis

This preliminary study investigated functional connectivity changes in Alzheimer’s Disease (AD) and amnestic mild cognitive impairment (MCI) using degree centrality (DC), a novel resting-state fMRI parameter to provide voxel-wise whole brain functional connectivity measurement. Twelve AD patients, twelve MCI patients and fifteen healthy controls were recruited for comparison. As compared to normal controls, AD patients showed the deceased DC in the posterior cingulate cortex while MCI patients showed decreased DC in bilateral cuneus (visual processing) but increased DC in bilateral hippocampus (memory) and right angular gyrus (language). The different patterns of FC changes might provide insight into disease evolvement.

Purpose

Progressive cognitive decline in neurodegenerative disorders such as Alzheimer’s disease (AD) and amnestic mild cognitive impairment (MCI) may be caused by altered functional connectivity (FC) between various brain regions.1 The previous resting-state fMRI studies often used local parameters, for example, Amplitude of Low Frequency Fluctuation (ALFF) and Regional homogeneity (ReHo) to investigate local spontaneous brain activities, which might be incapable to reflect whole brain FC changes.2 Degree centrality (DC), a novel resting-state fMRI parameter has been developed to calculate the number of functional connectivity of each voxel with all the other voxels in the brain to avoid subjectivity associated with manual seed region definition from traditional FC methods.3 In this preliminary study, we used DC to perform a voxel-wise whole brain FC analysis for AD and MCI patients as compared to normal controls.

Methods

The study was approved by the local ethical committee and written informed consent was obtained from all the participants. Twelve AD patients (aged 72.6±10.1 years, five females) and twelve MCI patients (aged 76.3±12.7 years, six females) were recruited according to the criteria of NINCDS-ADRDA, PADCS and Mini-Mental State Examination (MMSE) scores. The MMSE scores were 15.4±5.84 for AD patients and 25.3±2.63 for MCI patients respectively. Fifteen age- and gender-matched NC subjects (aged 72.4±9.39 years, seven females) were selected for group comparison. All subjects were right-handed. Thirty-five axial slices covering the whole brain were acquired using a 3.0-T HDXT scanner (GE Healthcare, Milwaukee, WI) with an 8-channel phase array head coil (TR/TE 2000/30 ms, flip angle 90°, matrix 64 × 64, FOV 24 cm, thickness/gap 4/0 mm, total 210 volumes). Data preprocessing included slice timing and realignment for temporal and spatial adjustment using SPM8, followed by spatial normalization to warp all the images into the same stereotactic space for group comparison. An in-house software REST was used for DC analysis (http://www.restfmri.net). All the time series were de-trended and band-pass filtered (0.01-0.08Hz). DC was calculated as the weighted sum of correlation coefficients between each pair of voxels and standardized by the global mean within the whole brain. The statistical analysis was one-way ANOVA to make comparison among AD, MCI and control groups. The AlphaSim program implemented in AFNI was used for multiple comparison correction (corrected p<0.05).

Results

As compared to the AD group, the control group showed increased DC in the left orbitofrontal cortex and posterior cingulate cortex but decreased DC in the bilateral cerebellum and vermis (Fig. 1). For comparison between the MCI and control groups, the control group showed increased DC in bilateral cuneus and right middle occipital gyrus but decreased DC in left caudate nucleus, bilateral hippocampus and right angular gyrus (Fig. 2).

Discussion and Conclusion

In this preliminary study, we found deceased DC in the posterior cingulate cortex for AD patients, which was consistent with previous studies. The posterior cingulate cortex served as an important hub in default mode network, suggesting substantial FC changes in AD patients. MCI patients showed decreased DC in bilateral cuneus (visual processing) but increased DC in bilateral hippocampus (memory) and right angular gyrus (language). The different patterns of FC changes might provide interesting insight into the mechanism of disease evolvement.

Acknowledgements

No acknowledgement found.

References

1. Liu Y, Wang K, Yu C, et al. Regional homogeneity, functional connectivity and imaging markers of Alzheimer's disease: a review of resting-state fMRI studies. Neuropsychologia. 2008;46(6):1648-1656.

2. Zang Y, Jiang T, Lu Y, et al. Regional homogeneity approach to fMRI data analysis. NeuroImage. 2004;22(1):394– 400.

3. Buckner R, Sepulcre J, Talukdar T et al. Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer's disease. J Neurosci 2009;29(6):1860-1873.

Figures

Comparison of DC between AD patients and normal controls (Red: controls>AD, Blue: controls<AD, corrected p<0.05, left is right)

Comparison of DC between MCI patients and normal controls (Red: controls>MCI, Blue: controls<MCI, corrected p<0.05, left is right)



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
1684