Resting-state FMRI And Its Relationships With Clinical Characteristics In T2DM Patients

Part 1:Altered baseline brain activity in type 2 diabetes and its relationships with clinical variablesPurpose:This study aims to investigate whether altered baseline brain activity exists in type 2 diabetes mellitus (T2DM) patients using resting-state functional magnetic resonance imaging (rs-fMRI) and whether abnormal neural activity is correlated with cognitive function.Methods:T2DM patients (n=28) were compared with nondiabetic age-, sex-, and education-matched control subjects (n=29) using rs-fMRI. We computed the amplitude of low-frequency fluctuations (ALFF) of fMRI signals to measure spontaneous neuronal activity and detect the relationship between rs-fMRI information and clinical data.Results:Compared with healthy controls, T2DM patients had significantly decreased ALFF values in the bilateral middle temporal gyrus, left fusiform gyrus, left middle occipital gyrus, right inferior occipital gyrus; and increased ALFF values in both the bilateral cerebellum posterior lobe and right cerebellum culmen. Moreover, we found an inverse correlation between the ALFF values in the MTG and both the HbAlc (r=-0.451,p= 0.016) and the score of Trail Making Test-B (r=-0.420, p=0.026) in the patient group. On the other hand, C-peptide level and pancreatic β-cell function had a positive correlation (r=0.429, p=0.023; r=0.453,p= 0.016, respectively) with the ALFF value in the middle temporal gyrus.Conclusion:The present study confirms that T2DM patients have altered ALFF in many brain regions, which is associated with poor neurocognitive performances, severity of consistent hyperglycemic state and impaired β-cell function. ALFF disturbance in MTG may play a central role in cognitive decline associated with T2DM and serve as reference for future clinical diagnosis.Part 2:Disrupted resting-state attentional networks in T2DM patients and its relationships with clinical variablesPurpose:Although Type 2 diabetes mellitus (T2DM) is a well-recognized risk factor for dementia, the neural mechanisms that underlie cognitive impairment in T2DM remain unclear. This study uses resting-state functional magnetic resonance imaging (fMRI) to examine attention network alterations in T2DM and their relationships to impaired cognitive performance.Methods:Data-driven independent component analysis was applied to resting-state fMRI data from 38 T2DM patients and 32 healthy controls to identify the dorsal attention network (DAN) and ventral attention network (VAN). Correlations were then determined among the resting-state functional connectivity (rsFC), clinical data, and neuropsychological scores.Results:The T2DM patients exhibited decreased rsFC in the left middle frontal gyrus (MFG) and bilateral inferior parietal lobe (IPL) of the DAN, as well as the left IPL and right MFG/IFG of the VAN. In addition, the rsFC of the left MFG was inversely correlated with the Trail Making Test-B scores; the rsFC of the left IPL was positively correlated with the Digit Span Test scores but negatively correlated with HbAlc; and the rsFC in the right precuneus was positively associated with cognitive performance.Conclusion:T2DM affects resting-state attentional networks, which may be related to reduced attention and a hyperglycemic state.Part 3:Insulin resistance-associated interhemispheric functional connectivity alterations in T2DMPurpose:We aim to investigate whether decreased interhemispheric functional connectivity exists in patients with type 2 diabetes mellitus (T2DM) by using resting-state functional magnetic resonance imaging (rs-fMRI). In addition, we sought to determine whether interhemispheric functional connectivity deficits associated with cognition and insulin resistance (IR) among T2DM patients.Methods:We compared the interhemispheric resting state functional connectivity of 32 T2DM patients and 30 healthy controls using rs-fMRI. Partial correlation coefficients were used to detect the relationship between rs-fMRI information and cognitive or clinical data. Compared with healthy controls, T2DM patients showed bidirectional alteration of functional connectivity in several brain regions. Functional connectivity values in the middle temporal gyrus (MTG) and in the superior frontal gyrus were inversely correlated with Trail Making Test-B score of patients. Notably, insulin resistance (log homeostasis model assessment-IR) negatively correlated with functional connectivity in the MTG of patients.Conclusion:T2DM patients exhibit abnormal interhemispheric functional connectivity in several default mode network regions, particularly in the MTG, and such alteration is associated with IR. Alterations in interhemispheric functional connectivity might contribute to cognitive dysfunction in T2DM patients.Part 4:Cholesterol-associated functional connectivity alterations in T2DMPurpose:Debate remains on whether hypercholesteremia is associated with cognitive impairment. We aim to investigate whether poor controlled cholesterol impairs functional connectivity among patients with type 2 diabetes mellitus (T2DM).Methods:Resting-state functional connectivity infers to an interregional cooperation which can be characterized by synchronous and low-frequency (<0.08 Hz) fluctuations on blood oxygen level-dependent functional magnetic resonance imaging (fMRI). We used resting-state fMRI to investigate the functional connectivity of 25 T2DM patients with poor controlled cholesterol,22 patients with target cholesterol and 26 healthy controls. Further correlation analysis was conducted between functional connectivity and clinical data as well as neuropsychological tests. Results:The three groups did not statistically differ in age, sex, education level, Body Mass Index, blood pressure, fasting C-peptides, and triglyceride. Compared with target cholesterol patients, patients with poor controlled cholesterol had significantly higher serum cholesterol levels, low-density lipoproteins, low-density lipoproteins/high-density lipoproteins (LDL/HDL) ratio and worse performance in Trail Making Test-B (TMT-B) (p<0.05). Disordered functional connectivity of bilateral hippocampus-middle frontal gyrus (MFG) in the poor controlled group had been consistently shown when compared with the other two groups. Besides, the aberrant functional connectivity was associated with TMT-B scores as well as the LDL/HDL index in T2DM patients with poor controlled cholesterol.Conclusions:T2DM patients with poor controlled cholesterol show impaired attention and executive function. Resting-state connectivity disturbance of the hippocampus-MFG may be involved in this process. Lowering the LDL/HDL ratio might be taken precaution against cognitive decrements.