Alzheimer’s disease (AD) patients and those with high-risk mild cognitive impairment are increasingly considered to have dysfunction syndromes. Large-scale network studies based on neuroimaging techniques may provide additional insight into AD pathophysiology. The aim of the present study is to evaluate the impaired network functional connectivity with the disease progression. For this purpose, we explored altered functional connectivities based on previously well-defined brain areas that comprise the five key functional systems [the default mode network (DMN), dorsal attention network (DAN), control network (CON), salience network (SAL), sensorimotor network (SMN)] in 35 with AD and 27 with mild cognitive impairment (MCI) subjects, compared with 27 normal cognitive subjects. Based on three levels of analysis, we found that intra- and inter-network connectivity were impaired in AD. Importantly, the interaction between the sensorimotor and attention functions was first attacked at the MCI stage and then extended to the key functional systems in the AD individuals. Lower cognitive ability (lower MMSE scores) was significantly associated with greater reductions in intra- and inter-network connectivity across all patient groups. These profiles indicate that aberrant intra- and inter-network dysfunctions might be potential biomarkers or predictors of AD progression and provide new insight into AD pathophysiology.

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.

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