Abstract
Type 2 diabetes mellitus (T2DM) affects a vast population and is closely associated with cognitive impairment. However, the mechanisms of cognitive impairment in T2DM patients have not been unraveled. Research on the basic units (nodes or hubs and edges) of the brain functional network on the basis of neuroimaging may advance our understanding of the network change pattern in T2DM patients. This study investigated the change patterns of brain functional hubs using degree centrality (DC) analysis and the connectivity among these hubs using functional connectivity and Granger causality analysis. Compared to healthy controls, the DC values were higher in the left anterior cingulate gyrus (ACG) and lower in the bilateral lateral occipital cortices (LOC) and right precentral gyrus (PreCG) in T2DM patients. The functional connectivity between the left ACG and the right PreCG was stronger in T2DM patients, whereas the functional connectivity among the right PreCG and bilateral LOC was weaker. A negative causal effect from the left ACG to left LOC and a positive effect from the left ACG to right LOC were observed in T2DM patients, while in healthy controls, the opposite occurred. Additionally, the reserve of normal brain function in T2DM patients was negatively associated with the elevated glycemic parameters. This study demonstrates that there are brain functional hubs and connectivity alterations that may reflect the aberrant information communication in the brain of T2DM patients. The findings may advance our understanding of the mechanisms of T2DM-related cognitive impairment.
Highlights
Type 2 diabetes mellitus (T2DM) affects 415 million individuals and is predicted to increase to 642 million in 2040, according to the Diabetes Atlas 7th Edition published by the International Diabetes Federation
No significant inter-group differences were found in terms of age, sex, education, body mass index (BMI), blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, blood urea nitrogen, cystatin C, uric acid and thyroid-stimulating hormone (TSH)
The brain regions where identified hubs are located have been reported to be abnormal in previous studies using other neuroimaging metrics in T2DM patients, which suggests that these brain regions are susceptible to T2DM
Summary
Type 2 diabetes mellitus (T2DM) affects 415 million individuals and is predicted to increase to 642 million in 2040, according to the Diabetes Atlas 7th Edition published by the International Diabetes Federation (http://www.idf.org/about-diabetes/factsfigures). The abnormal amplitude of low-frequency fluctuation, regional homogeneity, and functional connectivity (FC) in T2DM patients have been associated with poor performance in cognitive tests (Xia et al, 2013; Chen et al, 2014; Cui et al, 2014, 2015; Moheet et al, 2015). These studies have focused on local spontaneous brain activity or have analyzed the FC or network within the selected brain regions based on a priori assumption. The aforementioned fMRI findings provide a clue to explore T2DM-related brain dysfunction from the perspective of macroscopic nodes and connectivity at the whole brain level, which may share universal laws of network
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