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.
Background: Type 2 diabetes mellitus (T2DM)-related cognitive decline is associated with neuroimaging changes. However, only a few studies have focused on early functional alteration in T2DM prior to mild cognitive impairment (MCI). This study aimed to investigate the early changes of global connectivity patterns in T2DM by using a resting-state functional magnetic resonance imaging (rs-fMRI) technique. Methods: Thirty-four T2DM subjects and 38 age-, sex-, and education-matched healthy controls (HCs) underwent rs-fMRI in a 3T MRI scanner. Degree centrality (DC) was used to identify the functional hubs of the whole brain in T2DM without MCI. Then the functional connectivity (FC) between hubs and the rest of the brain was assessed by using the hub-based approach. Results: Compared with HCs, T2DM subjects showed increased DC in the right cerebellum lobules III-V. Hub-based FC analysis found that the right cerebellum lobules III-V of T2DM subjects had increased FC with the right cerebellum crus II and lobule VI, the right temporal inferior/middle gyrus, and the right hippocampus. Conclusions: Increased DC in the right cerebellum regions III-V, as well as increased FC within cerebellar regions and ipsilateral cerebrocerebellar regions, may indicate an important pathophysiological mechanism for compensation in T2DM without MCI.
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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