Differentiated Effective Connectivity Patterns of the Executive Control Network in Progressive MCI: A Potential Biomarker for Predicting AD.

OBJECTIVE: Mild cognitive impairment (MCI) is often a transitional state between normal aging and Alzheimer's disease (AD). When observed longitudinally, some MCI patients convert to AD, while a considerable portion either remains MCI or revert to a normal functioning state. This divergence has provided some enlightenment on a potential biomarker to be represented in the resting state brain activities of MCI patients with different post-hoc labels. Recent studies have shown impaired executive functions, other than typically explicated memory impairment with AD/MCI patients. This observation raises the question that whether or not the executive control network (ECN) was impaired, which pivotally supports the central executive functions. Given the fact that effective connectivity is a sufficient index in detecting resting brain abnormalities in AD/MCI, the current study specifically asks a question whether the effective connectivity patterns are differentiated in MCI patients with different post-hoc labels. METHODS: We divided the MCI subjects into three groups depending on their progressive state obtained longitudinally: 1) 15 MCI-R subjects: MCI reverted to the normal functioning state and stabilized to the normal state in 24 months; 2) 35 MCI-S subjects: MCI patients maintained this disease in a stable state for 24 months; 3) 22 MCI-P subjects: MCI progressed to AD and stabilized to AD in 24 months, and 4) 39 age-matched normal control subjects (NC). We conducted a Granger causality analysis after identifying the core nodes of ECN in all of the subjects using Independent Component Analysis. Our findings revealed that different MCI groups presented different effective connectivity patterns within the ECN compared to the NC group. Specifically, (1) dorsolateral prefrontal cortex (dLPFC) and medial prefrontal cortex (mPFC) were the core nodes in the ECN network that exhibited different connecting patterns; (2) an effective connection circuit "R.dLPFC→ right caudate→ left thalamus→R.dLPFC" in the ECN showed different levels of damage; and (3) there were four pathways between the R.dLPFC and L.LP, and these four pathways were also different. RESULTS: Our results would help to understand the potential central mechanism of MCI patients. The differentiated effective connectivity of ECN may serve as a potential biomarker for early detection of AD, which may also provide a reference for clinical researchers to manipulate active but distinctive interventions for MCI patients who have different risks.

Altered functional brain networks in amnestic mild cognitive impairment: a resting-state fMRI study.

Amnestic mild cognitive impairment MCI (aMCI) has a high progression to Alzheimer's disease (AD). Recently, resting-state functional MRI (RS-fMRI) has been increasingly utilized in studying the pathogenesis of aMCI, especially in resting-state networks (RSNs). In the current study, we aimed to explore abnormal RSNs related to memory deficits in aMCI patients compared to the aged-matched healthy control group using RS-fMRI techniques. Firstly, we used ALFF (amplitude of low-frequency fluctuation) method to define the regions of interest (ROIs) which exhibited significant changes in aMCI compared with the control group. Then, we divided these ROIs into different networks in line with prior studies. The aim of this study is to explore the functional connectivity between these ROIs within networks and also to investigate the connectivity between networks. Comparing aMCI to the control group, our results showed that 1) the hippocampus (HIPP) had decreased FC with the medial prefrontal cortex (mPFC) and inferior parietal lobe (IPL), and the mPFC showed increased connectivity to IPL in the default mode network; 2) the thalamus showed decreased FC with the putamen and HIPP, and the HIPP showed increased connectivity to the putamen in the limbic system; 3) the supplementary motor area had decreased FC with the middle temporal gyrus and increased FC with the superior parietal lobe in the sensorimotor network; 4) increased connectivity between the lingual gyrus and middle occipital gyrus in the visual network; and 5) the DMN has reduced inter-network connectivities with the SMN and VN. These findings indicated that functional brain networks involved in cognition such as episodic memory, sensorimotor and visual cognition in aMCI were altered, and provided a new sight in understanding the important subtype of aMCI.