Abstract
Cognitive impairment in type 2 diabetes mellitus (T2DM) is associated with functional and structural abnormalities in the intrinsic brain network. The salience network (SN) is a neurocognitive network that maintains normal cognitive function, but it has received little attention in T2DM. We explored SN changes in patients with T2DM with normal cognitive function (DMCN) and in patients with T2DM with mild cognitive impairment (DMCI). Sixty-five T2DM patients and 31 healthy controls (HCs) underwent a neuropsychological assessment, independent component analysis (ICA), and voxel-based morphometry (VBM) analysis. The ICA extracted the SN for VBM to compare SN functional connectivity (FC) and gray matter (GM) volume (GMV) between groups. A correlation analysis examined the relationship between abnormal FC and GMV and clinical/cognitive variables. Compared with HCs, DMCN patients demonstrated increased FC in the left frontoinsular cortex (FIC), right anterior insula, and putamen, while DMCI patients demonstrated decreased right middle/inferior frontal gyrus FC. Compared with DMCN patients, DMCI patients showed decreased right FIC FC. There was no significant difference in SN GMV in DMCN and DMCI patients compared with HCs. FIC GMV was decreased in the DMCI patients compared with DMCN patients. In addition, right FIC FC and SN GMV positively correlated with Montreal Cognitive Assessment and Mini-Mental State Examination (MMSE) scores. These findings indicate that changes in SN FC, and GMV are complex non-linear processes accompanied by increased cognitive dysfunction in patients with T2DM. The right FIC may be a useful imaging biomarker for supplementary assessment of early cognitive dysfunction in patients with T2DM.
Highlights
Diabetes is becoming increasingly common worldwide and is considered a global chronic illness burden in aging societies (Sinclair et al, 2020)
In terms of cognitive performance, Type 2 diabetes mellitus (T2DM) with mild cognitive impairment (DMCI) patients had poorer Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores and higher Trail-Making Test A (TMT-A) scores compared with T2DM with normal cognitive function (DMCN) patients and healthy controls (HC) (P < 0.05)
A between-group analysis demonstrated that the DMCN group displayed increased functional connectivity (FC) in the left frontoinsular cortex (FIC), as well as in the right anterior insula and putamen compared with HCs (Table 2, Figure 1B)
Summary
Diabetes is becoming increasingly common worldwide and is considered a global chronic illness burden in aging societies (Sinclair et al, 2020). T2DM leads to multiple chronic complications, such as cardiovascular disease, nephropathy, and retinopathy, but it increases the risk of dementia, as well as the proportion of patients who convert from mild cognitive impairment to dementia (Koekkoek et al, 2015). It is believed that the neuropathological basis of cognitive impairment in patients with T2DM is related to increased levels of advanced glycation end-products (AGEs) caused by chronic hyperglycemia. T2DM-related cognitive impairment is concealed, mainly affecting executive function, including memory, attention, and visuospatial ability (Palta et al, 2014). Exploration of biomarkers that can evaluate cognitive decline in patients with T2DM would guide early clinical diagnosis and treatment, as well as prevent or delay cognitive dysfunction and dementia
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