Abnormal Resting-State Functional Connectivity Strength in Mild Cognitive Impairment and Its Conversion to Alzheimer's Disease

Yuxia Li, Xiaoni Wang, Yongqiu Li, Yu Sun, Can Sheng, Hongyan Li, Xuanyu Li, Yang Yu, Guanqun Chen, Xiaochen Hu, Bin Jing, Defeng Wang, Kuncheng Li, Frank Jessen, Mingrui Xia, Ying Han, Yuxia Li, Xiaoni Wang, Yongqiu Li, Yu Sun, Can Sheng, Hongyan Li, Xuanyu Li, Yang Yu, Guanqun Chen, Xiaochen Hu, Bin Jing, Defeng Wang, Kuncheng Li, Frank Jessen, Mingrui Xia, Ying Han

Abstract

Individuals diagnosed with mild cognitive impairment (MCI) are at high risk of transition to Alzheimer's disease (AD). However, little is known about functional characteristics of the conversion from MCI to AD. Resting-state functional magnetic resonance imaging was performed in 25 AD patients, 31 MCI patients, and 42 well-matched normal controls at baseline. Twenty-one of the 31 MCI patients converted to AD at approximately 24 months of follow-up. Functional connectivity strength (FCS) and seed-based functional connectivity analyses were used to assess the functional differences among the groups. Compared to controls, subjects with MCI and AD showed decreased FCS in the default-mode network and the occipital cortex. Importantly, the FCS of the left angular gyrus and middle occipital gyrus was significantly lower in MCI-converters as compared with MCI-nonconverters. Significantly decreased functional connectivity was found in MCI-converters compared to nonconverters between the left angular gyrus and bilateral inferior parietal lobules, dorsolateral prefrontal and lateral temporal cortices, and the left middle occipital gyrus and right middle occipital gyri. We demonstrated gradual but progressive functional changes during a median 2-year interval in patients converting from MCI to AD, which might serve as early indicators for the dysfunction and progression in the early stage of AD.

Figures

Figure 1
Figure 1
The FCS in AD, MCI, and control groups. (a) The images show the mean FCS in AD, MCI, and control groups. The color bar at the bottom of each picture represents the FCS value for each group. (b) The images demonstrated the significant differences among the three groups and within each pair of the groups at baseline. The color bar at the bottom of each picture represents either F values for ANOVA or T values for post hoc t-tests.
Figure 2
Figure 2
The FCS differences between MCI-c and MCI-nc groups. The FCS of the left angular gyrus and middle occipital gyrus were significantly lower in the MCI-c group compared with the MCI-nc group. The color bar represents the T values for the two-sample t-test between MCI-c and MCI-nc groups.
Figure 3
Figure 3
The seed-based RSFC analysis between MCI-c and MCI-nc. The left and middle column present the within group RSFC pattern for the left angular gyrus and the left middle occipital gyrus. Between-group comparison on the right column revealed that comparing to MCI-nc group the MCI-c group had significantly decreased functional connectivity between the left angular gyrus and bilateral dlPFC and lateral temporal cortices and between the left middle occipital gyrus and right central sulci and right middle occipital gyrus. The color bars at the bottom represent the T value for either the one-sample t-test or two-sample t-test.
Figure 4
Figure 4
The correlation between FCS and neuropsychological scores in patients. The color bar represents the r value. AVLT-I, auditory verbal learning test-immediate recall; AVLT-D, auditory verbal learning test-delayed recall; AVLT-R, auditory verbal learning test-recognition; MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment.

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