Abstract
Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment. We investigated whether alterations of intranetwork and internetwork functional connectivity with T2DM progression exist, by using resting-state functional MRI. MRI data were analysed from 19 T2DM patients with normal cognition (DMCN) and 19 T2DM patients with cognitive impairment (DMCI), 19 healthy controls (HC). Functional connectivity among 36 previously well-defined brain regions which consisted of 5 resting-state network (RSN) systems [default mode network (DMN), dorsal attention network (DAN), control network (CON), salience network (SAL) and sensorimotor network (SMN)] was investigated at 3 levels (integrity, network and connectivity). Impaired intranetwork and internetwork connectivity were found in T2DM, especially in DMCI, on the basis of the three levels of analysis. The bilateral posterior cerebellum, the right insula, the DMN and the CON were mainly involved in these changes. The functional connectivity strength of specific brain architectures in T2DM was found to be associated with haemoglobin A1c (HbA1c), cognitive score and illness duration. These network alterations in intergroup differences, which were associated with brain functional impairment due to T2DM, indicate that network organizations might be potential biomarkers for predicting the clinical progression, evaluating the cognitive impairment, and further understanding the pathophysiology of T2DM.
Highlights
Microstructural white matter abnormalities[11], cerebral white matter network disruption[11,12], and impaired spontaneous brain activity[13,14]
We evaluated the functional connectivity patterns at three levels within five key restingstate network (RSN): the default mode network (DMN), the dorsal attention network (DAN), the control network (CON), the salience network (SAL) and the sensorimotor network (SMN), on the basis of the resting-fMRI data acquired from 19 Type 2 diabetes mellitus (T2DM) patients with cognitive impairment (DMCI), 19 T2DM patients with normal cognition (DMCN) and 19 well matched healthy controls (HC) with normal cognition
The results indicated that the T2DM patients had higher haemoglobin A1c (HbA1c) and fasting glucose levels than the HC group, especially the DMCI patients
Summary
Microstructural white matter abnormalities[11], cerebral white matter network disruption[11,12], and impaired spontaneous brain activity[13,14] These abnormalities are not correlated with distinct features, they are clearly associated with cognitive performance in patients with T2DM5,6,15. From the earlier findings in people at risk for AD25–27, we hypothesized that, compared with normal control subjects, T2DM patients especially those with cognitive impairment, would be associated with impaired functional connectivity in the five key networks; this impaired functional connectivity would be associated with cognitive ability. We investigated the relationships between the clinical scores (the Mini Mental State Examination (MMSE), haemoglobin A1c (HbA1c) and the duration of T2DM) and the strength of functional connectivity at each scale using Pearson’s correlations after controlling for age, gender and education effects in the patient groups (Fig. 1)
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