Abstract
Background and PurposePrevious neuroimaging studies have demonstrated type 2 diabetes (T2D)-related brain structural and functional changes are partly associated with cognitive decline. However, less is known about the underlying mechanisms. Chronic hyperglycemia and microvascular complications are the two of most important risk factors related to cognitive decline in diabetes. Cerebral small vessel diseases (CSVDs), such as those defined by lacunar infarcts, white matter hyperintensities (WMHs) and microhemorrhages, are also associated with an increased risk of cognitive decline and dementia. In this study, we examined brain magnetic resonance imaging (MRI) changes in patients in the early stages of T2D without CSVDs to focus on glucose metabolism factors and to avoid the interference of vascular risk factors on T2D-related brain damage.MethodsT2D patients with disease durations of less than 5 years and without any signs of CSVDs (n = 34) were compared with healthy control subjects (n = 24). Whole-brain region-based functional connectivity was analyzed with network-based statistics (NBS), and brain surface morphology was examined. In addition, the Montreal Cognitive Assessment (MoCA) was conducted for all subjects.ResultsAt the whole-brain region-based functional connectivity level, thirty-three functional connectivities were changed in T2D patients relative to those in controls, mostly manifested as pathological between-network positive connectivity and located mainly between the sensory-motor network and auditory network. Some of the connectivities were positively correlated with blood glucose level, insulin resistance, and MoCA scores in the T2D group. The network-level analysis showed between-network hyperconnectivity in T2D patients, but no significant changes in within-network connectivity. In addition, there were no significant differences in MoCA scores or brain morphology measures, including cortical thickness, surface area, mean curvature, and gray/white matter volume, between the two groups.ConclusionThe findings indicate that pathological between-network positive connectivity occurs in the early stages of T2D without CSVDs. The abnormal connectivity may indicate that the original balance of mutual antagonistic/cooperative relationships between the networks is broken, which may be a neuroimaging basis for predicting cognitive decline in early T2D patients.
Highlights
Previous neuroimaging studies have demonstrated type 2 diabetes (T2D)-related brain structural (de Bresser et al, 2010; Moran et al, 2013) and functional changes (Chen et al, 2015; Wood et al, 2016), which are partly associated with cognitive decline
All of the subjects were selected according to the following criteria: (1) all T2D patients met the diagnostic criteria proposed by the American Diabetes Association (Expert Committee on the Diagnosis, and Classification of Diabetes Mellitus, 2002) for a duration of 1–5 years before enrollment; (2) there were no abnormal findings in conventional magnetic resonance imaging (MRI) sequences including T1WI, T2WI, T2-fluid attenuated inversion recovery (T2-FLAIR), and susceptibilityweighted imaging (SWI); (3) participants were 30 70 years of age; and (4) participants were right-handed
No significant difference was found in fasting C-peptide and fasting insulin between the two groups, and there was no significant difference in the montreal cognitive assessment (MoCA) scores between the two groups (P = 0.058)
Summary
Previous neuroimaging studies have demonstrated T2D-related brain structural (de Bresser et al, 2010; Moran et al, 2013) and functional changes (Chen et al, 2015; Wood et al, 2016), which are partly associated with cognitive decline. CSVDs, such as those defined by lacunar infarcts, WMHs and microhemorrhages, are associated with an increased risk of cognitive decline and dementia (Brickman et al, 2012; Kitagawa et al, 2015; Akoudad et al, 2016). We explored brain structural and functional changes in the early stages of T2D patients without CSVDs. Previous neuroimaging studies have demonstrated type 2 diabetes (T2D)-related brain structural and functional changes are partly associated with cognitive decline. Cerebral small vessel diseases (CSVDs), such as those defined by lacunar infarcts, white matter hyperintensities (WMHs) and microhemorrhages, are associated with an increased risk of cognitive decline and dementia. We examined brain magnetic resonance imaging (MRI) changes in patients in the early stages of T2D without CSVDs to focus on glucose metabolism factors and to avoid the interference of vascular risk factors on T2D-related brain damage
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