Resting-state Functional MRI Study On The Cognitive Impairment In Type 2 Diabetes Mellitus

Part Ⅰ. Subbands analysis of amplitude of low-frequency fluctuations in T2DM:A resting-state functional MRI studyBackgrounds and objective:An amount of researches indicate that type 2 diabetes mellitus(T2DM) has adverse impact on the cognitive function of central neural system by risk factors including insulin resistance, hyperglycemia, and advanced glycation endproducts. T2 DM patients showed abnormal amplitude of low-frequency fluctuations(ALFF) in lingual gyrus, middle occipital gyrus and anterior cingulate gyrus in resting-state functional MRI studies, accompanying with decreased cognition of memory, attention and execution. However, these conclusions were based on the low-frequency range from 0.01 Hz to 0.08 Hz, which may causes information loss for the confounding of physiological noise. Subband analysis of ALFF has the advantage of avoiding the confounding of physiological noise on other subbands and highlighting the pattern of brain activities distribution. And as a normalized ALFF, fractional ALFF(f ALFF) can suppress the signal of vascular pulsatility and cerebrospinal fluid, and provide a more specific measure of low-frequency oscillatory phenomena. Therefore, the aim of the present study is to investigate changes of spontaneous brain activities in T2 DM patients by f ALFF on subbands of slow-5(0.01-0.027 Hz) and slow-4(0.027-0.073 Hz) and its possible relationship with cognitive impairment.Material and methods:Twenty-two T2 DM patients(T2DM group) and 23 healthy control subjects(HC group) were involved in this study. Demographic data, fasting plasma glucose and Hb A1 c were obtained in all subjects. General cognition was assessed by Mini-Mental State Examination(MMSE) in all subjects. Memory performance was assessed by Auditory Verbal Learn Test(AVLT) in T2 DM group. Structural and functional MRI data were collected by 3.0 T MR scanner for the calculation of f ALFF value on slow-5(0.01-0.027 Hz) and slow-4(0.027-0.073 Hz) subbands. Inter group comparison of demographic and clinical data were conducted with SPSS 20 software. One-sample t test and two-sample t test of f ALFF map were conducted with REST 1.8 software(Alpha Sim correction, P<0.05, cluster size>85 voxels). Then f ALFF values were extracted from brain regions with significant differences for the correlation analyses with clinical data and cognitive performance.Results:T2DM group had higher fasting plasma glucose and Hb A1 c than HC subjects(both P<0.05). T2 DM group also showed increased f ALFF values in bilateral anterior cingulate gyrus and partial left cerebellum areas, and decreased f ALFF values in bilateral middle occipital gyrus and precuneus on subband slow-5. Moreover, f ALFF values of T2 DM patients increased in left inferior temporal gyrus, and decreased in right lingual gyrus on subband slow-4. There was positive correlation between f ALFF values of middle occipital gyrus and precuneus and AVLT immediate memory score(r=0.457, P=0.033).Conclusion:Aberrant spontaneous activities exhibited in brain regions associated with cognition of T2 DM patients. These brain regions were related to default mode network on subband slow-5 such as anterior cingulate gyrus and precuneus, and semantic cognition and visual information processing on subband slow-4 such as temporal and lingual gyrus. The present study confirmed that the spatial distribution of abnormal brain regions varied with the subbands of low-frequency fluctuations in T2 DM patients. Part Ⅱ. Regional homogeneity and fractional amplitude of low-frequency fluctuationalterations in T2 DM patients with mild cognitive impairment:a resting-state f MRI studyBackgrounds and objective:Patients with type 2 diabetes mellitus(T2DM) are at higher risk of developing into dementia. Mild cognitive impairment(MCI) is a state between normal aging and dementia, in which interventions may slow down the rate of progression to dementia. It has been demonstrated that T2 DM patients had aberrant functional connectivity between right temporal gyrus and posterior cingulate cortex, as well as between bilateral hippocampus and anterior cingulate gyrus. It also showed abnormal spontaneous brain activities in medial frontal gyrus, middle occipital gyrus, lingual gyrus and medial temporal lobe. There was association between these alterations and cognitive impairment in T2 DM patients. However, the previous studies involved T2 DM patients with cognitive impairment of different degrees. It is necessary to clarify the characteristic of brain activities in T2 DM patients who meet the diagnostic criteria of MCI. The present study calculated regional homogeneity(Re Ho) and fractional amplitude of low-frequency fluctuations(f ALFF) in T2 DM patients with MCI for the attempt of better understanding of the relationship between T2 DM and cognitive impairment. And it might contribute a new reference in assessing and intervening cognitive impairment of T2 DM patients.Materials and Methods:T2DM with MCI(D-MCI, n=21) and healthy control subjects(HC, n=25) were enrolled in this study. All subjects were group-matched in terms of age, gender and education. Demographic data, fasting plasma glucose and Hb A1 c were obtained in both groups. General cognition was assessed by Mini-Mental State Examination(MMSE) and Montreal Cognitive Assessment(Mo CA) in all subjects and memory performance was assessed by Auditory Verbal Learn Test(AVLT) in D-MCI group. Then all participants underwent 3.0T MR scanning for the data of T2 WI, FLAIR, 3D-T1 WI and resting-state f MRI. Intra-group and inter-group t-tests of Re Ho and f ALFF map were conducted with REST 1.8 software(Alpha Sim correction, P<0.05, cluster size>85 voxels). Correlation analyses were performed with SPSS 20 software to explore the relationship among clinical and neuropsychological data and Re Ho/f ALFF values extracted from brain areas with significant inter-group differences.Results:The demographic data and MMSE score showed no significant intra-group differences. Compared with HC group, D-MCI group has significant lower Mo CA score and higher fasting plasma glucose and Hb A1 c levels(all P<0.05). Re Ho values of D-MCI group increased in right superior frontal gyrus and partial right cerebellum area, and decreased in bilateral medial orbital part of superior frontal gyrus, right middle frontal gyrus, right inferior temporal gyrus, left middle occipital gyrus and right lingual gyrus. D-MCI patients’ f ALFF values increased in left inferior temporal gyrus and bilateral anterior cingulate gyrus, and decreased in right lingual gyrus. Hb A1 c was negatively related to f ALFF values of anterior cingulate gyrus(r=-0.482, P=0.027), Mo CA score was negatively related to f ALFF values of left inferior temporal gyrus(r=-0.547, P =0.010) in D-MCI group. Moreover, there was negative correlation between Re Ho values of right cerebellum area 8 and AVLT immediate memory score(r=-0.551,P=0.010). Re Ho values of right inferior temporal gyrus was positively related to AVLT immediate memory score(r=0.508, P=0.019) and AVLT total score(r=0.585, P=0.005).Conclusions:D-MCI patients developed aberrant brain functional activities among regions associated with cognitive control network, visual processing and semantic cognition, including superior frontal gyrus, middle occipital gyrus, lingual gyrus and inferior temporal gyrus. Control of blood glucose level may benefit T2 DM patients in putting off their decline of cognition.