Altered Functional Hubs and Connectivity in Type 2 Diabetes Mellitus Without Mild Cognitive Impairment

Li, Yifan; Liang, Yi; Tan, Xin; Chen, Yuna; Yang, Jinquan; Zeng, Hui; Qin, Chunhong; Feng, Yue; Ma, Xiaomeng; Qiu, Shijun

doi:10.3389/fneur.2020.01016

Cited by 22 publications

(22 citation statements)

References 56 publications

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“…The MoCA assesses the cognitive ability of subjects from the perspective of overall cognitive function and is currently widely used in cognitive-related research. In our study, we found that T2DM patients has lower MoCA scores than HCs, which was consistent with our previous studies ( 35 ). In addition, we found that the AVLT (immediate) scores were lower in the T2DM patients, suggesting that T2DM patients had immediate memory impaired.…”

Section: Discussionsupporting

confidence: 93%

Altered Hippocampal Subfields Volumes Is Associated With Memory Function in Type 2 Diabetes Mellitus

Liu

et al. 2021

Front. Neurol.

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Objective: Cognitive impairment in type 2 diabetes mellitus (T2DM) patients is related to changes in hippocampal structure and function. However, the alternation of hippocampal subfields volumes and their relationship with cognitive function are unclear. This study explored morphological alterations in the hippocampus and its subfields in T2DM patients and their relationship with cognitive function.Methods: Thirty T2DM patients and 20 healthy controls (HCs) were recruited and underwent 3-dimensional, high-resolution T1-weighted sequence (3D-T1) and a battery of cognitive tests. Freesurfer 6.0 was performed to segment the hippocampus into 12 subregions automatically. Then relationships between hippocampal subfield volumes and neurocognitive scale scores in the T2DM group were evaluated.Results: Immediate memory scores on the auditory verbal learning test (AVLT) and Montreal Cognitive Assessment (MoCA) scores in T2DM patients were lower than in the HCs. T2DM patients showed that volumes of the bilateral hippocampus were significantly reduced, mainly in the bilateral molecular layer, granule cell and molecular layer of the dentate gyrus (GC-ML-DG), cornu ammonis 4 (CA4), fimbria, and left subiculum and the right hippocampus amygdala transition area (HATA) compared to HCs. In addition, T2DM patients showed the FINS was negatively correlated with volume of left GC-ML-DG (r = −0.415, P = 0.035) and left CA4 (r = −0.489, P = 0.011); the FBG was negatively correlated with volume of right fimbria (r = −0.460, P = 0.018); the HOMA-IR was negatively correlated with volume of left GC-ML-DG (r = −0.367, P = 0.046) and left CA4(r = 0.462, P = 0.010). Partial correlation analysis found that the volume of right HATA in T2DM group was positively correlated with AVLT (immediate) scores (r = 0.427, P = 0.03).Conclusion: This study showed the volumes of multiple hippocampal subfields decreased and they were correlated with FINS, FBG and HOMA-IR in T2DM patients. We hypothesized that decreased hippocampal subfields volumes in T2DM patients was related to insulin resistance and impaired vascular function. In addition, we also found that abnormal hippocampal subfields volumes were related to memory function in T2DM patients, suggesting that reduced volumes in specific hippocampal subfields may be the potential mechanism of memory dysfunction in these patients.

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Section: Discussionsupporting

confidence: 93%

Altered Hippocampal Subfields Volumes Is Associated With Memory Function in Type 2 Diabetes Mellitus

Liu

et al. 2021

Front. Neurol.

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“…Previous studies ( 15 , 18 ) have combined the DC and FC to explore the alteration of functional patterns in patients with neurological diseases. A recent study ( 13 ) reported increased DC of the right cerebellum and right fusiform gyrus among middle-aged patients with T2DM. Another study ( 18 ) with a similar population reported increased DC and FC value of the right anterior insula and dorsal anterior cingulate cortex.…”

Section: Introductionmentioning

confidence: 95%

“…Degree centrality (DC) is a method of measuring whole-brain connectivity based on the level of voxels, which effectively identifies the brain center. This method has been used in research related to diabetes ( 13 ), bipolar disorder ( 14 ), and Parkinson's disease ( 15 ). DC measures the connectivity of the whole brain to individual regions; this underlies the importance of the local region, termed the “brain hub” ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Altered Gray Matter Volume, Functional Connectivity, and Degree Centrality in Early-Onset Type 2 Diabetes Mellitus

Feng

Tan

et al. 2021

Front. Neurol.

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Background: Structural and functional brain alterations that underlie cognitive decline have been observed in elderly adults with type 2 diabetes mellitus (T2DM); however, whether these alterations can be observed in patients with early-onset T2DM remains unclear. Therefore, we aimed to describe the abnormalities in brain volume and functional patterns in patients with early-onset T2DM in the present study.Methods: We enrolled 20 patients with early-onset T2DM and 20 healthy controls (HCs). Changes in brain volume were assessed using voxel-based morphology (VBM), while changes in brain function were assessed using degree centrality (DC) and functional connectivity (FC).Results: Compared to HCs, patients with early-onset T2DM exhibited gray matter reductions in the left orbital superior, middle, and inferior frontal gyri as well as the right superior frontal gyrus. The gray matter reductions in the right superior frontal gyrus were negatively associated with the urine albumin to creatinine ratio. Furthermore, increased DC values were observed in the left superior temporal gyrus, left Heschl gyrus, and left hippocampus in patients with early-onset T2DM. An FC analysis of these regions revealed elevated connectivity in the right precuneus, left inferior parietal gyrus, left Heschl gyrus, bilateral post-central gyrus, bilateral insula, bilateral superior temporal gyrus, and bilateral medial and paracingulate gyrus. Furthermore, the FC of the hubs to the superior temporal gyrus, insula, and Heschl gyrus was increased and positively correlated with trail making test-B.Conclusion: Decreased local gray matter volume and increased DC and FC may represent the neurobiological mechanism underlying cognitive dysfunction in patients with early-onset T2DM.

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“…In recent years, resting‐state functional MRI (rs‐fMRI) has been used to investigate T2DM‐related changes in brain activity using amplitude of low‐frequency fluctuation (ALFF) of the blood oxygenation level‐dependent (BOLD) signal, and the changes in localized energy consumption using the regional homogeneity (ReHo) (Chen et al, 2014; Cui et al, 2014; Cui et al, 2015; Moheet, Mangia, & Seaquist, 2015; Xia et al, 2013). Other rs‐fMRI studies indicated that functional interactions of certain functional systems, measured by functional connectivity (FC) based on the temporal synchronizations of BOLD signals among distinct brain regions, could also be affected (Li et al, 2020). However, these studies mainly focused on the default mode network (DMN), a large‐scale resting‐state functional network mediating cognitive and emotional processes (Cui et al, 2014), and did not involve other functional systems, such as the attention (Xia et al, 2015), frontoparietal, and sensorimotor networks (SMNs) (Chen et al, 2015), in which the alterations were reported in the studies afterward.…”

Section: Introductionmentioning

confidence: 99%

Classification of type 2 diabetes mellitus with or without cognitive impairment from healthy controls using high‐order functional connectivity

Chen

Zhou

Liang

et al. 2021

Human Brain Mapping

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Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment and may progress to dementia. However, the brain functional mechanism of T2DM‐related dementia is still less understood. Recent resting‐state functional magnetic resonance imaging functional connectivity (FC) studies have proved its potential value in the study of T2DM with cognitive impairment (T2DM‐CI). However, they mainly used a mass‐univariate statistical analysis that was not suitable to reveal the altered FC “pattern” in T2DM‐CI, due to lower sensitivity. In this study, we proposed to use high‐order FC to reveal the abnormal connectomics pattern in T2DM‐CI with a multivariate, machine learning‐based strategy. We also investigated whether such patterns were different between T2DM‐CI and T2DM without cognitive impairment (T2DM‐noCI) to better understand T2DM‐induced cognitive impairment, on 23 T2DM‐CI and 27 T2DM‐noCI patients, as well as 50 healthy controls (HCs). We first built the large‐scale high‐order brain networks based on temporal synchronization of the dynamic FC time series among multiple brain region pairs and then used this information to classify the T2DM‐CI (as well as T2DM‐noCI) from the matched HC based on support vector machine. Our model achieved an accuracy of 79.17% in T2DM‐CI versus HC differentiation, but only 59.62% in T2DM‐noCI versus HC classification. We found abnormal high‐order FC patterns in T2DM‐CI compared to HC, which was different from that in T2DM‐noCI. Our study indicates that there could be widespread connectivity alterations underlying the T2DM‐induced cognitive impairment. The results help to better understand the changes in the central neural system due to T2DM.

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Altered Functional Hubs and Connectivity in Type 2 Diabetes Mellitus Without Mild Cognitive Impairment

Cited by 22 publications

References 56 publications

Altered Hippocampal Subfields Volumes Is Associated With Memory Function in Type 2 Diabetes Mellitus

Altered Hippocampal Subfields Volumes Is Associated With Memory Function in Type 2 Diabetes Mellitus

Altered Gray Matter Volume, Functional Connectivity, and Degree Centrality in Early-Onset Type 2 Diabetes Mellitus

Classification of type 2 diabetes mellitus with or without cognitive impairment from healthy controls using high‐order functional connectivity

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