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Front Neurosci. 2019 Jul 24;13:738. doi: 10.3389/fnins.2019.00738. eCollection 2019.

Disrupted Regional Cerebral Blood Flow, Functional Activity and Connectivity in Alzheimer's Disease: A Combined ASL Perfusion and Resting State fMRI Study.

Zheng W1, Cui B1, Han Y2, Song H2, Li K3,4, He Y5,6,7, Wang Z1.

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Department of Radiology, Aerospace Center Hospital, Beijing, China.
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, China.
State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
Beijing Key Laboratory of Brain Imaging and Connectomics, Beijing Normal University, Beijing, China.
IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.


Recent studies have demonstrated a close relationship between regional cerebral blood flow (rCBF) and resting state functional connectivity changes in normal healthy people. However, little is known about the parameter changes in the most vulnerable regions in Alzheimer's disease (AD). Forty AD patients and 30 healthy controls participated in this study. The data of resting-state perfusion and functional magnetic resonance imaging (fMRI) was collected. By using voxel-wise arterial spin labeling (ASL) perfusion, we identified several regions of altered rCBF in AD patients. Then, by using resting state fMRI analysis, including amplitude low frequency fluctuation (ALFF) and seed-based functional connectivity, we investigated the changes of functional activity and connectivity among the identified rCBF regions. We extracted cognition-related parameters and searched for a sensitive biomarker to differentiate the AD patients from the normal controls (NC). Compared with controls, AD patients showed special disruptions in rCBF, which were mainly located in the left posterior cingulate cortex (PCC), the left and right dorsolateral prefrontal cortex (DLPFC), the left inferior parietal lobule (IPL), the right middle temporal gyrus (MTG), the left middle occipital gyrus (MOG), and the left precuneus (PCu). ALFF was performed based on the seven regions identified by the ASL method, and AD patients presented significantly decreased ALFF in the left PCC, left IPL, right MTG, left MOG, and left PCu and increased ALFF in the bilateral DLPFC. We constituted the network based on the seven regions and found that there was decreased connectivity among the identified regions in the AD patients, which predicted a disruption in the default mode network (DMN), executive control network (ECN) and visual network (VN). Furthermore, these abnormal parameters are closely associated with cognitive performances in AD patients. We combined the rCBF and ALFF value of PCC/PCu as a biomarker to differentiate the two groups and reached a sensitivity of 85.3% and a specificity of 88.5%. Our findings suggested that there was disrupted rCBF, functional activity and connectivity in specific cognition-related regions in Alzheimer's disease, which can be used as a valuable imaging biomarker for the diagnosis of AD.


Alzheimer’s disease; amplitude low frequency fluctuation; arterial spin labeling; functional connectivity; regional cerebral blood flow; resting state fMRI

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