Investigating CR1 as an indicated Gene for mild cognitive impairment in type 2 diabetes mellitus
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ABSTRACT:
SUBMITTER: Zhou X
PROVIDER: S-EPMC11344402 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Here, we performed platelet proteomics in T2DM patients with MCI (T2DM-MCI) and without MCI (T2DM-nMCI)
2022-02-16 | PXD023316 | Pride
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.
| S-EPMC7390351 | biostudies-literature
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.
| S-EPMC7533640 | biostudies-literature
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.
| S-EPMC9856282 | biostudies-literature
Project description:Background: Accumulated evidence suggests that adverse lipid changes are risk factors for type 2 diabetes mellitus (T2DM) and neurodegenerative disorders. The ATP-binding cassette A1 transporter (ABCA1) gene contributes to both lipid processing and amyloid-β formation and thus shows promise as a biological target in the pathology of mild cognitive impairment (MCI) in T2DM. Objective: This study aimed to investigate the interactions among lipids, ABCA1 R219K polymorphism, and cognitive function in T2DM. Methods: Clinical parameters, including lipids, were measured. The testing scores of different cognitive domains were recorded, and the ABCA1 R219K polymorphisms were analyzed. Results: A total of 226 patients, including 124 MCI patients and 102 controls, were enrolled in this study. T2DM patients with MCI showed lower cognitive functions, serum high-density lipoprotein (HDL-c), and apolipoprotein A1 (apoA-I) levels; and higher total cholesterol level than the controls. Serum HDL-c (P = 0.001) and apoA-I (P = 0.016) were positively associated with the MoCA score in MCI patients. Further stratification analyses revealed that the subjects with higher HDL-c concentration showed better attention and memory for verbal, visual, and logical functions than the group with lower HDL-c concentration (P < 0.05). No significant differences were observed among the distributions of ABCA1 R219K variants between MCI patients and controls; however, the KK genotype carriers presented higher apoA-I levels than those with RR genotype in MCI individuals. Conclusion: This study does not support the association between R219K polymorphism and T2DM-related MCI. However, our data suggested that the serum HDL-c level might positively influence cognition, especially memory function, in T2DM patients. Further studies are needed to determine the interaction between lipids and ABCA1 genotype and its effect on cognition in T2DM patients. Trial registration: Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060; http://www.chictr.org.cn/showproj.aspx?proj=10536.
| S-EPMC5540897 | biostudies-literature
Project description:Studies have suggested that insulin resistance plays a role in cognitive impairment in individuals with type 2 diabetes. We aimed to determine whether an improvement in insulin resistance could explain cognitive performance variations over 36 weeks in older individuals with mild cognitive impairment (MCI) and type 2 diabetes.A total of 97 older individuals (mean +/- SD age 76 +/- 6 years) who had recently (<2 months) started an antidiabetes treatment of metformin (500 mg twice a day) (n = 30) or metformin (500 mg/day)+rosiglitazone (4 mg/day) (n = 32) or diet (n = 35) volunteered. The neuropsychological test battery consisted of the Mini-Mental State Examination (MMSE), Rey Verbal Auditory Learning Test (RAVLT) total recall, and Trail Making Tests (TMT-A and TMT-B) performed at baseline and every 12 weeks for 36 weeks along with clinical testing.At baseline, no significant differences were found between groups in clinical or neuropsychological parameters. Mean +/- SD values in the entire population were as follows: A1C 7.5 +/- 0.5%, fasting plasma glucose (FPG) 8.6 +/- 1.3 mmol/l, fasting plasma insulin (FPI) 148 +/- 74 pmol/l, MMSE 24.9 +/- 2.4, TMT-A 61.6 +/- 42.0, TMT-B 162.8 +/- 78.7, the difference between TMT-B and TMT-A [DIFFBA] 101.2 +/- 58.1, and RAVLT 24.3 +/- 2.1. At follow-up, ANOVA models tested changes in metabolic control parameters (FPI, FPG, and A1C). Such parameters improved in the metformin and metformin/rosiglitazone groups (P(trend) < 0.05 in both groups). ANCOVA repeated models showed that results for the metformin/rosiglitazone group remained stable for all neuropsychological tests, and results for the diet group remained stable for the MMSE and TMT-A and declined for the TMT-B (P(trend) = 0.024), executive efficiency (DIFFBA) (P(trend) = 0.026), and RAVLT memory test (P(trend) = 0.011). Results for the metformin group remained stable for the MMSE and TMTs but declined for the RAVLT (P(trend) = 0.011). With use of linear mixed-effects models, the interaction term, FPI x time, correlated with cognitive stability on the RAVLT in the metformin/rosiglitazone group (beta = -1.899; P = 0.009).Rosiglitazone may protect against cognitive decline in older individuals with type 2 diabetes and MCI.
| S-EPMC2909046 | biostudies-other
Project description:Type 2 diabetes mellitus (T2DM) is an independent risk factor of Alzheimer's disease (AD). Therefore, identifying periphery biomarkers correlated with mild cognitive impairment (MCI) is of importance for early diagnosis of AD. Here, we performed platelet proteomics in T2DM patients with MCI (T2DM-MCI) and without MCI (T2DM-nMCI). Pearson analysis of the omics data with MMSE (mini-mental state examination), Aβ1-42/Aβ1-40 (β-amyloid), and rGSK-3β(T/S9) (total to Serine-9-phosphorylated glycogen synthase kinase-3β) revealed that mitophagy/autophagy-, insulin signaling-, and glycolysis/gluconeogenesis pathways-related proteins were most significantly involved. Among them, only the increase of optineurin, an autophagy-related protein, was simultaneously correlated with the reduced MMSE score, and the increased Aβ1-42/Aβ1-40 and rGSK-3β(T/S9), and the optineurin alone could discriminate T2DM-MCI from T2DM-nMCI. Combination of the elevated platelet optineurin and rGSK-3β(T/S9) enhanced the MCI-discriminating efficiency with AUC of 0.927, specificity of 86.7%, sensitivity of 85.3%, and accuracy of 0.859, which is promising for predicting cognitive decline in T2DM patients.
| S-EPMC8520722 | biostudies-literature
Project description:BackgroundIron is one of the most important elements in brain that may has a direct impact on the stability of central nervous system. The current study devoted to explore the alterations of iron distribution across the whole brain in type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI).MethodsThe quantitative susceptibility mapping (QSM) technique was used to quantify the intracranial iron content of 74 T2DM patients with MCI and 86 T2DM patients with normal cognition (NC). The group comparison was performed by a voxel-based analysis. Then we evaluated the relationships between cognitive indicators and magnetic susceptibility value (MSV) measured by QSM of the significant brain areas, which were set as the regions of interest (ROIs). In addition, we analyzed the moderation effects of grey matter volume (GMV) of the related brain areas and several metabolic and cerebrovascular factors on the associations between MSV of ROIs and cognitive characteristics.ResultsT2DM patients with MCI exhibited a lower MSV in the right middle temporal gyrus (MTG) compared to NC group. And in the MCI group, there were significantly negative correlations between MSV of the right MTG and several memory indexes. Furthermore, the moderation effects of GMV of the whole brain and the bilateral MTG on the relationship between MSV of the right MTG and scores of list recognition were significant.ConclusionsT2DM patients with MCI had a temporary decreased iron content in the right MTG, which may partially compensate for cognitive impairment.Trial registrationThe study was registered at Clinicaltrials.gov (NCT02738671).
| S-EPMC11753919 | biostudies-literature
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.
| S-EPMC9998866 | biostudies-literature
Project description:Diabetes mellitus is a risk factor for mild cognitive impairment (MCI) and dementia. However, how the clinical characteristics of MCI patients with type 2 diabetes mellitus are linked to sarcopenia and/or its criteria remain to be elucidated. Japanese patients with type 2 diabetes mellitus were categorized into the MCI group for MoCA-J (the Japanese version of the Montreal cognitive assessment) score <26, and into the non-MCI group for MoCA-J ≥26. Sarcopenia was defined by a low skeletal mass index along with low muscle strength (handgrip strength) or low physical performance (walking speed <1.0 m/s). Univariate and multivariate-adjusted odds ratio models were used to determine the independent contributors for MoCA-J <26. Among 438 participants, 221 (50.5%) and 217 (49.5%) comprised the non-MCI and MCI groups, respectively. In the MCI group, age (61 ± 12 vs. 71 ± 10 years, p < 0.01) and duration of diabetes mellitus (14 ± 9 vs. 17 ± 9 years, p < 0.01) were higher than those in the non-MCI group. Patients in the MCI group exhibited lower hand grip strength, walking speed, and skeletal mass index, but higher prevalence of sarcopenia. Only walking speed (rather than muscle loss or muscle weakness) was found to be an independent determinant of MCI after adjusting for multiple factors, such as age, gender, body mass index (BMI), duration of diabetes mellitus, hypertension, dyslipidemia, smoking, drinking, estimated glomerular filtration rate (eGFR), HbA1c, and history of coronary heart diseases and stroke. In subgroup analysis, a group consisting of male patients aged ≥65 years, with BMI <25, showed a significant OR for walking speed. This study showed that slow walking speed is a sole determinant criterion of sarcopenia of MCI in patients with type 2 diabetes mellitus. It was suggested that walking speed is an important factor in the prediction and prevention of MCI development in patients with diabetes mellitus.
| S-EPMC7408848 | biostudies-literature