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Plasma microRNAs biomarkers in mild cognitive impairment among patients with type 2 diabetes mellitus.

ABSTRACT: OBJECTIVES:To 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. METHODS:This 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. RESULTS:MCI 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. CONCLUSION:MCI 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.

SUBMITTER: Salama II

PROVIDER: S-EPMC7390351 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Plasma microRNAs biomarkers in mild cognitive impairment among patients with type 2 diabetes mellitus.

Salama Iman I II Sami Samia M SM Abdellatif Ghada A GA Mohsen Amira A Rasmy Hanaa H Kamel Solaf Ahmed SA Ibrahim Mona Hamed MH Mostafa Mona M Fouad Walaa A WA Raslan Hala M HM

PloS one 20200729 7

<h4>Objectives</h4>To 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.<h4>Methods</h4>This 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, m ...[more]

PMID: 32726329

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Project description:Plasma-based biomarkers present a promising approach in the research and clinical practice of Alzheimer's disease as they are inexpensive, accessible and minimally invasive. In particular, prognostic biomarkers of cognitive decline may aid in planning and management of clinical care. Although recent studies have demonstrated the prognostic utility of plasma biomarkers of Alzheimer pathology or neurodegeneration, such as pTau-181 and NF-L, whether other plasma biomarkers can further improve prediction of cognitive decline is undetermined. We conducted an observational cohort study to determine the prognostic utility of plasma biomarkers in predicting progression to dementia for individuals presenting with mild cognitive impairment due to probable Alzheimer's disease. We used the Olink™ Proximity Extension Assay technology to measure the level of 460 circulating proteins in banked plasma samples of all participants. We used a discovery data set comprised 60 individuals with mild cognitive impairment (30 progressors and 30 stable) and a validation data set consisting of 21 stable and 21 progressors. We developed a machine learning model to distinguish progressors from stable and used 44 proteins with significantly different plasma levels in progressors versus stable along with age, sex, education and baseline cognition as candidate features. A model with age, education, APOE genotype, baseline cognition, plasma pTau-181 and 12 plasma Olink protein biomarker levels was able to distinguish progressors from stable with 86.7% accuracy (mean area under the curve = 0.88). In the validation data set, the model accuracy was 78.6%. The Olink proteins selected by the model included those associated with vascular injury and neuroinflammation (e.g. IL-8, IL-17A, TIMP-4, MMP7). In addition, to compare these prognostic biomarkers to those that are altered in Alzheimer's disease or other types of dementia relative to controls, we analyzed samples from 20 individuals with Alzheimer, 30 with non-Alzheimer dementias and 34 with normal cognition. The proteins NF-L and PTP-1B were significantly higher in both Alzheimer and non-Alzheimer dementias compared with cognitively normal individuals. Interestingly, the prognostic markers of decline at the mild cognitive impairment stage did not overlap with those that differed between dementia and control cases. In summary, our findings suggest that plasma biomarkers of inflammation and vascular injury are associated with cognitive decline. Developing a plasma biomarker profile could aid in prognostic deliberations and identify individuals at higher risk of dementia in clinical practice.

Project description:Both type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are common age-associated disorders and T2DM patients show an increased risk to suffer from AD, however, there is currently no marker to identify who in T2DM populations will develop AD. Since glycogen synthase kinase-3? (GSK-3?) activity, ApoE genotypes and olfactory function are involved in both T2DM and AD pathogenesis, we investigate whether alterations of these factors can identify cognitive impairment in T2DM patients.The cognitive ability was evaluated using Minimum Mental State Examination (MMSE) and Clinical Dementia Rating (CDR), and the mild cognitive impairment (MCI) was diagnosed by Petersen's criteria. GSK-3? activity in platelet, ApoE genotypes in leucocytes and the olfactory function were detected by Western/dot blotting, the amplification refractory mutation system (ARMS) PCR and the Connecticut Chemosensory Clinical Research Center (CCCRC) test, respectively. The odds ratio (OR) and 95% confidence intervals (95% CI) of the biomarkers for MCI diagnosis were calculated by logistic regression. The diagnostic capability of the biomarkers was evaluated by receiver operating characteristics (ROC) analyses.We recruited 694 T2DM patients from Jan. 2012 to May. 2015 in 5 hospitals (Wuhan), and 646 of them met the inclusion criteria and were included in this study. 345 patients in 2 hospitals were assigned to the training set, and 301 patients in another 3 hospitals assigned to the validation set. Patients in each set were randomly divided into two groups: T2DM without MCI (termed T2DM-nMCI) or with MCI (termed T2DM-MCI). There were no significant differences for sex, T2DM years, hypertension, hyperlipidemia, coronary disease, complications, insulin treatment, HbA1c, ApoE ?2, ApoE ?3, tGSK3? and pS9GSK3? between the two groups. Compared with the T2DM-nMCI group, T2DM-MCI group showed lower MMSE score with older age, ApoE ?4 allele, higher olfactory score and higher rGSK-3? (ratio of total GSK-3? to Ser9-phosphorylated GSK-3?) in the training set and the validation set. The OR values of age, ApoE ?4 gene, olfactory score and rGSK-3? were 1.09, 2.09, 1.51, 10.08 in the training set, and 1.06, 2.67, 1.47, 7.19 in the validation set, respectively. The diagnostic accuracy of age, ApoE ?4 gene, olfactory score and rGSK-3? were 0.76, 0.72, 0.66, 0.79 in the training set, and 0.70, 0.68, 0.73, 0.79 in the validation set, respectively. These four combined biomarkers had the area under the curve (AUC) of 82% and 86%, diagnostic accuracy of 83% and 81% in the training set and the validation set, respectively.Aging, activation of peripheral circulating GSK-3?, expression of ApoE ?4 and increase of olfactory score are diagnostic for the mild cognitive impairment in T2DM patients, and combination of these biomarkers can improve the diagnostic accuracy.

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Plasma microRNAs biomarkers in mild cognitive impairment among patients with type 2 diabetes mellitus.

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Plasma microRNAs biomarkers in mild cognitive impairment among patients with type 2 diabetes mellitus.

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