Project description:Type 2 diabetes mellitus (T2DM) is closely linked to cognitive decline and alterations in brain structure and function. Resting-state functional magnetic resonance imaging (rs-fMRI) is used to diagnose neurodegenerative diseases, such as cognitive impairment (CI), Alzheimer's disease (AD), and vascular dementia (VaD). However, whether the functional connectivity (FC) of patients with T2DM and mild cognitive impairment (T2DM-MCI) is conducive to early diagnosis remains unclear. To answer this question, we analyzed the rs-fMRI data of 37 patients with T2DM and mild cognitive impairment (T2DM-MCI), 93 patients with T2DM but no cognitive impairment (T2DM-NCI), and 69 normal controls (NC). We achieved an accuracy of 87.91% in T2DM-MCI versus T2DM-NCI classification and 80% in T2DM-NCI versus NC classification using the XGBoost model. The thalamus, angular, caudate nucleus, and paracentral lobule contributed most to the classification outcome. Our findings provide valuable knowledge to classify and predict T2DM-related CI, can help with early clinical diagnosis of T2DM-MCI, and provide a basis for future studies.
Project description:BackgroundMild cognitive impairment and cognitive impairment, no dementia, are emerging terms that encompass the clinical state between normal cognition and dementia in elderly people. Controversy surrounds their characterization, definition and application in clinical practice. In this article, we provide physicians with practical guidance on the definition, diagnosis and treatment of mild cognitive impairment and cognitive impairment, no dementia, based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, held in March 2006.MethodsWe developed evidence-based guidelines using systematic literature searches, with specific criteria for study selection and quality assessment, and a clear and transparent decision-making process. We selected studies published from January 1996 to December 2005 that had mild cognitive impairment or cognitive impairment, no dementia, as the outcome. Subsequent to the conference, we searched for additional articles published between January 2006 and January 2008. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care.ResultsWe identified 2483 articles, of which 314 were considered to be relevant and of good or fair quality. From a synthesis of the evidence in these studies, we made 16 recommendations. In brief, family physicians should be aware that most types of dementia are preceded by a recognizable phase of mild cognitive decline. They should be familiar with the concepts of mild cognitive impairment and of cognitive impairment, no dementia. Patients with these conditions should be closely monitored because of their increased risk for dementia. Leisure activities, cognitive stimulation and physical activity could be promoted as part of a healthy lifestyle in elderly people and those with mild cognitive impairment. Vascular risk factors should be treated optimally. No other specific therapies can yet be recommended.InterpretationPhysicians will increasingly see elderly patients with mild memory loss, and learning an approach to diagnosing states such as mild cognitive impairment is now warranted. Close monitoring for progression to dementia, promotion of a healthy lifestyle and treatment of vascular risk factors are recommended for the management of patients with mild cognitive impairment.
Project description:ObjectivesTo assess the potential value of some miRNAs as diagnostic biomarkers for mild cognitive impairment (MCI) among patients with type2 diabetes mellitus (T2DM) and to identify other risk factors for MCI among them.MethodsThis study enrolled 163 adults with T2DM using face to face interview. Cognitive function with its domains was assessed using Adenbrooke's Cognitive Examination III (ACE III). Lipid profile, glycated hemoglobin, and miR-128, miR-132, miR- 874, miR-134, miR-323, and miR-382 expressions, using quantitative real-time PCR, were assessed.ResultsMCI was detected among 59/163 (36.2%) patients with T2DM. Plasma expression of miR-132 was significantly higher in T2DM patients with MCI compared to those without MCI and to normal cognitive healthy individuals (median = 2, 1.1 and 1.2 respectively, P < 0.05. Logistic regression analysis showed that higher miR-132 expression with adjusted odds ratio (AOR): 1.2 (95% CI 1.0-1.3), female gender (AOR:2.1; 95%CI 1.0-4.3), education below postgraduate (secondary and university education with AOR: 9.5 & 19.4 respectively) were the significant predicting factors for MCI among T2DM patients. Using ROC curve, miR-132 was the only assayed miRNA that significantly differentiates T2DM patients with MCI from those with normal cognition with 72.3% sensitivity, 56.2% specificity, and 63.8% accuracy (P < 0.05). Other studied miRNAs showed lower sensitivity and specificity for detecting MCI among studied T2DM participants.ConclusionMCI affects nearly one-third of adult patients with T2DM. A significantly over expression of miR-132 was detected among T2DM with MCI compared to those with normal cognition.
Project description:Background: Type 2 diabetes mellitus (T2DM)-related cognitive decline is associated with neuroimaging changes. However, only a few studies have focused on early functional alteration in T2DM prior to mild cognitive impairment (MCI). This study aimed to investigate the early changes of global connectivity patterns in T2DM by using a resting-state functional magnetic resonance imaging (rs-fMRI) technique. Methods: Thirty-four T2DM subjects and 38 age-, sex-, and education-matched healthy controls (HCs) underwent rs-fMRI in a 3T MRI scanner. Degree centrality (DC) was used to identify the functional hubs of the whole brain in T2DM without MCI. Then the functional connectivity (FC) between hubs and the rest of the brain was assessed by using the hub-based approach. Results: Compared with HCs, T2DM subjects showed increased DC in the right cerebellum lobules III-V. Hub-based FC analysis found that the right cerebellum lobules III-V of T2DM subjects had increased FC with the right cerebellum crus II and lobule VI, the right temporal inferior/middle gyrus, and the right hippocampus. Conclusions: Increased DC in the right cerebellum regions III-V, as well as increased FC within cerebellar regions and ipsilateral cerebrocerebellar regions, may indicate an important pathophysiological mechanism for compensation in T2DM without MCI.
Project description:Although disturbed functional connectivity is known to be a factor influencing cognitive impairment, the neuropathological mechanisms underlying the cognitive impairment caused by type 2 diabetes mellitus (T2DM) remain unclear. To characterize the neural mechanisms underlying T2DM-related brain damage, we explored the altered functional architecture patterns in different cognitive states in T2DM patients. Thirty-seven T2DM patients with normal cognitive function (DMCN), 40 T2DM patients with mild cognitive impairment (MCI) (DMCI), and 40 healthy controls underwent neuropsychological assessments and resting-state functional MRI examinations. Functional connectivity density (FCD) analysis was performed, and the relationship between abnormal FCD and clinical/cognitive variables was assessed. The regions showing abnormal FCD in T2DM patients were mainly located in the temporal lobe and cerebellum, but the abnormal functional architecture was more extensive in DMCI patients. Moreover, in comparison with the DMCN group, DMCI patients showed reduced long-range FCD in the left superior temporal gyrus (STG), which was correlated with the Rey auditory verbal learning test score in all T2DM patients. Thus, DMCI patients show functional architecture abnormalities in more brain regions involved in higher-level cognitive function (executive function and auditory memory function), and the left STG may be involved in the neuropathology of auditory memory in T2DM patients. These findings provide some new insights into understanding the neural mechanisms underlying T2DM-related cognitive impairment.
Project description:Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment in many domains. There are several pieces of evidence that changes in neuronal neuropathies and metabolism have been observed in T2DM. Structural and functional MRI shows that abnormal connections and synchronization occur in T2DM brain circuits and related networks. Neuroplasticity and energy metabolism appear to be principal effector systems, which may be related to amyloid beta (Aβ) deposition, although there is no unified explanation that includes the complex etiology of T2DM with cognitive impairment. Herein, we assume that cognitive impairment in diabetes may lead to abnormalities in neuroplasticity and energy metabolism in the brain, and those reflected to MRI structural connectivity and functional connectivity, respectively.
Project description: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.
Project description:Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder frequently accompanied by cognitive impairment. Contributing factors such as modern lifestyle, genetic predisposition, and gene environmental interactions have been postulated, but the pathogenesis remains unclear. In this study, we attempt to investigate the potential mechanisms and interventions underlying T2DM-induced cognitive deficits from the brain-gut axis perspective. A combined analysis of the brain transcriptome, plasma metabolome, and gut microbiota in db/db mice with cognitive decline was conducted. Transcriptome analysis identified 222 upregulated gene sets and 85 downregulated gene sets, mainly related to mitochondrial respiratory, glycolytic, and inflammation. In metabolomic analysis, a total of 75 significantly altered metabolites were identified, correlated with disturbances of glucose, lipid, bile acid, and steroid metabolism under disease state. Gut microbiota analysis suggested that the species abundance and diversity of db/db mice were significantly increased, with 23 significantly altered genus detected. Using the multi-omics integration, significant correlations among key genes (n = 33), metabolites (n = 41), and bacterial genera (n = 21) were identified. Our findings suggest that disturbed circulation and brain energy metabolism, especially mitochondrial-related disturbances, may contribute to cognitive impairment in db/db mice. This study provides novel insights into the functional interactions among the brain, circulating metabolites, and gut microbiota.