Cognitive Decline In Type Research Articles

Association of systolic blood pressure variability with cognitive decline in type 2 diabetes: A post hoc analysis of a randomized clinical trial.

We aimed to explore the association between visit-to-visit systolic blood pressure variability (BPV) and cognitive function in individuals with type 2 diabetes. We performed a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORD-MIND) substudy. A total of 2867 diabetes patients with ≥3 BP measurements between the 4- and 20-month visits were included. Visit-to-visit systolic BPV was calculated. Cognitive decline was defined as a Mini-Mental State Exam (MMSE), Digit Symbol Substitution Test (DSST), or Rey Auditory Verbal Learning Test (RAVLT) score greater than 1 standard deviation (SD) below the baseline mean, or a Stroop test score more than 1 SD above the baseline mean. The associations of systolic BPV with risks of cognitive decline were examined using Cox proportional hazards models, and with changes in brain magnetic resonance imaging parameters were evaluated using mixed models. The risk of cognitive decline defined by the DSST score (but not by other scores) increased significantly with systolic BPV quartiles (p for trend = 0.008), and there was a 55% increased risk for BPV quartile 4 versus quartile 1 (hazard ratio = 1.55, 95% confidence interval 1.10-2.19). Furthermore, a positive correlation was observed between systolic BPV and change in white matter lesion volume (β = 0.07, 95% CI 0.01-0.13). A greater visit-to-visit systolic BPV was significantly associated with an increased risk of cognitive decline measured by DSST and an increase in white matter lesion volume in patients with type 2 diabetes.

Association of glycogen synthase kinase-3β with cognitive impairment in type 2 diabetes patients: a six-year follow-up study.

Our previous multicenter case-control study showed that aging, up-regulation of platelet glycogen synthase kinase-3β (GSK-3β), impaired olfactory function, and ApoE ϵ4 genotype were associated with cognitive decline in type 2 diabetes mellitus (T2DM) patients. However, the causal relationship between these biomarkers and the development of cognitive decline in T2DM patients remains unclear. To further investigate this potential relationship, we designed a 6-year follow-up study in 273 T2DM patients with normal cognitive in our previous study. Baseline characteristics of the study population were compared between T2DM patients with and without incident mild cognitive impairment (MCI). We utilized Cox proportional hazard regression models to assess the risk of cognitive impairment associated with various baseline biomarkers. Receiver operating characteristic curves (ROC) were performed to evaluate the diagnostic accuracy of these biomarkers in predicting cognitive impairment. During a median follow-up time of 6 years (with a range of 4 to 9 years), 40 patients (16.13%) with T2DM developed MCI. Participants who developed incident MCI were more likely to be older, have a lower education level, have more diabetic complications, a higher percentage of ApoE ϵ4 allele and a higher level of platelet GSK-3β activity (rGSK-3β) at baseline (P<0.05). In the longitudinal follow-up, individuals with higher levels of rGSK-3β were more likely to develop incident MCI, with an adjusted hazard ratio (HR) of 1.60 (95% confidence interval [CI] 1.05, 2.46), even after controlling for potential confounders. The AUC of the combination of age, rGSK-3β and ApoEϵ4 allele predicted for incident MCI was 0.71. Platelet GSK-3β activity could be a useful biomarker to predict cognitive decline, suggesting the feasibility of identifying vulnerable population and implementing early prevention for dementia.

Cognitive decline in type II diabetes mellitus among post-menopausal women: A cross-sectional study in South India

This study was contemplated to ascertain the occurrence of cognitive impairment and explore the relationship between cognition and diabetes mellitus type 2 (T2DM) in post-menopausal women. The present cross-sectional study was conducted in the community setting in and around Anaicut Panchayat, Vellore, over 6 months (July 2023 to Dec 2023). Post-menopausal women with T2DM in the age group of above 35 years were included. The Montreal Cognitive Assessment (MoCA) scale was utilized to evaluate the cognitive function. Glycated hemoglobin (HbA1c) was also measured. The acquired data were analyzed using IBM Statistical Package for the Social Sciences (SPSS) software version 23. The inclusion criteria were met by 188 subjects. The diabetic women who were involved in the study have an average age of 57 years. The current study population evinced a mean MoCA score of 20.91 ± 3.99 and a mean HbA1c level of 9.27 ± 2.45 suggesting a strong link between cognitive dysfunction and hyperglycemia. 67% of the study subjects exhibited mild cognitive impairment (MCI). A noticeable inverse relationship was found between MoCA score and duration of T2DM (r = −0.744) as well as between MoCA score and HbA1c (r = −0.769). This study suggested that the duration of T2DM and the level of HbA1c have an antithetical influence on cognitive function. Due to the higher prevalence exists for MCI in diabetic patients, it is recommended that healthcare professionals should assess cognitive function in diabetic patients in their routine clinical practice to prevent the progression of dementia.

Relationship between acute glucose variability and cognitive decline in type 2 diabetes: A systematic review and meta-analysis.

Cognitive decline is one of the most widespread chronic complications of diabetes, which occurs in more than half of the patients with type 2 diabetes (T2DM). Emerging evidences have suggested that glucose variability (GV) is associated with the pathogenesis of diabetic complications. However, the influence of acute GV on cognitive dysfunction in T2DM is still controversial. The aim of the study was to evaluate the association between acute GV and cognitive defect in T2DM, and provide a most recent and comprehensive summary of the evidences in this research field. PubMed, Cochrane library, EMBASE, Web of science, Sinomed, China National Knowledge Infrastructure (CNKI), and Wanfang were searched for articles that reported on the association between acute GV and cognitive impairment in T2DM. 9 eligible studies were included, with a total of 1263 patients with T2DM involved. Results showed that summary Fisher's z value was -0.23 [95%CI (-0.39, -0.06)], suggesting statistical significance (P = 0.006). Summary r value was -0.22 [95%CI (-0.37, -0.06)]. A lower cognitive performance was found in the subjects with greater glucose variation, which has statistical significance. Mean amplitude of glycemic excursions (MAGE) was associated with a higher risk of poor functional outcomes. Fisher's z value was -0.35 [95%CI (-0.43, -0.25)], indicating statistical significance (P = 0.011). Sensitivity analyses by omitting individual studies showed stability of the results. Overall, higher acute GV is associated with an increased risk of cognitive impairment in patients with T2DM. Further studies should be required to determine whether targeted intervention of reducing acute GV could prevent cognitive decline.

Chronic hyperglycaemia increases the vulnerability of the hippocampus to oxidative damage induced during post-hypoglycaemic hyperglycaemia in a mouse model of chemically induced type 1 diabetes

Aims/hypothesisChronic hyperglycaemia and recurrent hypoglycaemia are independently associated with accelerated cognitive decline in type 1 diabetes. Recurrent hypoglycaemia in rodent models of chemically induced (streptozotocin [STZ]) diabetes leads to cognitive impairment in memory-related tasks associated with hippocampal oxidative damage. This study examined the hypothesis that post-hypoglycaemic hyperglycaemia in STZ-diabetes exacerbates hippocampal oxidative stress and explored potential contributory mechanisms.MethodsThe hyperinsulinaemic glucose clamp technique was used to induce equivalent hypoglycaemia and to control post-hypoglycaemic glucose levels in mice with and without STZ-diabetes and Nrf2−/− mice (lacking Nrf2 [also known as Nfe2l2]). Subsequently, quantitative proteomics based on stable isotope labelling by amino acids in cell culture and biochemical approaches were used to assess oxidative damage and explore contributory pathways.ResultsEvidence of hippocampal oxidative damage was most marked in mice with STZ-diabetes exposed to post-hypoglycaemic hyperglycaemia; these mice also showed induction of Nrf2 and the Nrf2 transcriptional targets Sod2 and Hmox-1. In this group, hypoglycaemia induced a significant upregulation of proteins involved in alternative fuel provision, reductive biosynthesis and degradation of damaged proteins, and a significant downregulation of proteins mediating the stress response. Key differences emerged between mice with and without STZ-diabetes following recovery from hypoglycaemia in proteins mediating the stress response and reductive biosynthesis.Conclusions/interpretationThere is a disruption of the cellular response to a hypoglycaemic challenge in mice with STZ-induced diabetes that is not seen in wild-type non-diabetic animals. The chronic hyperglycaemia of diabetes and post-hypoglycaemic hyperglycaemia act synergistically to induce oxidative stress and damage in the hippocampus, possibly leading to irreversible damage/modification to proteins or synapses between cells. In conclusion, recurrent hypoglycaemia in sub-optimally controlled diabetes may contribute, at least in part, to accelerated cognitive decline through amplifying oxidative damage in key brain regions, such as the hippocampus.Data availabilityThe datasets generated during and/or analysed during the current study are available in ProteomeXchange, accession no. 1-20220824-173727 (www.proteomexchange.org). Additional datasets generated during and/or analysed during the present study are available from the corresponding author upon reasonable request.Graphical abstract

Regional high iron deposition on quantitative susceptibility mapping correlates with cognitive decline in type 2 diabetes mellitus.

To quantitatively evaluate the iron deposition and volume changes in deep gray nuclei according to threshold-method of quantitative susceptibility mapping (QSM) acquired by strategically acquired gradient echo (STAGE) sequence, and to analyze the correlation between the magnetic susceptibility values (MSV) and cognitive scores in type 2 diabetes mellitus (T2DM) patients. Twenty-nine patients with T2DM and 24 healthy controls (HC) matched by age and gender were recruited in this prospective study. QSM images were used to evaluate whole-structural volumes (Vwh), regional magnetic susceptibility values (MSVRII), and volumes (VRII) in high-iron regions in nine gray nuclei. All QSM data were compared between groups. Receiver operating characteristic (ROC) analysis was used to assess the discriminating ability between groups. The predictive model from single and combined QSM parameters was also established using logistic regression analysis. The correlation between MSVRII and cognitive scores was further analyzed. Multiple comparisons of all statistical values were corrected by false discovery rate (FDR). A statistically significant P-value was set at 0.05. Compared with HC group, the MSVRII of all gray matter nuclei in T2DM were increased by 5.1-14.8%, with significant differences found in bilateral head of caudate nucleus (HCN), right putamen (PUT), right globus pallidus (GP), and left dentate nucleus (DN) (P < 0.05). The Vwh of most gray nucleus in T2DM group were decreased by 1.5-16.9% except bilateral subthalamic nucleus (STN). Significant differences were found in bilateral HCN, bilateral red nucleus (RN), and bilateral substantia nigra (SN) (P < 0.05). VRII was increased in bilateral GP, bilateral PUT (P < 0.05). VRII/Vwh was also increased in bilateral GP, bilateral PUT, bilateral SN, left HCN and right STN (P < 0.05). Compared with the single QSM parameter, the combined parameter showed the largest area under curve (AUC) of 0.86, with a sensitivity of 87.5% and specificity of 75.9%. The MSVRII in the right GP was strongly associated with List A Long-delay free recall (List A LDFR) scores (r = -0.590, P = 0.009). In T2DM patients, excessive and heterogeneous iron deposition as well as volume loss occurs in deep gray nuclei. The MSV in high iron regions can better evaluate the distribution of iron, which is related to the decline of cognitive function.

Discovering new peripheral plasma biomarkers to identify cognitive decline in type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is an independent risk factor of Alzheimer's disease (AD), and thus identifying who among the increasing T2DM populations may develop into AD is important for early intervention. By using TMT-labeling coupled high-throughput mass spectrometry, we conducted a comprehensive plasma proteomic analysis in none-T2DM people (Ctrl, n = 30), and the age-/sex-matched T2DM patients with mild cognitive impairment (T2DM-MCI, n = 30) or T2DM without MCI (T2DM-nMCI, n = 25). The candidate biomarkers identified by proteomics and bioinformatics analyses were verified by ELISA, and their diagnostic capabilities were evaluated with machine learning. A total of 53 differentially expressed proteins (DEPs) were identified in T2DM-MCI compared with T2DM-nMCI patients. These DEPs were significantly enriched in multiple biological processes, such as amyloid neuropathies, CNS disorders, and metabolic acidosis. Among the DEPs, alpha-1-antitrypsin (SERPINA1), major viral protein (PRNP), and valosin-containing protein (VCP) showed strong correlation with AD high-risk genes APP, MAPT, APOE, PSEN1, and PSEN2. Also, the levels of PP2A cancer inhibitor (CIP2A), PRNP, corticotropin-releasing factor-binding protein (CRHBP) were significantly increased, while the level of VCP was decreased in T2DM-MCI patients compared with that of the T2DM-nMCI, and these changes were correlated with the Mini-Mental State Examination (MMSE) score. Further machine learning data showed that increases in PRNP, CRHBP, VCP, and rGSK-3β(T/S9) (ratio of total to serine-9-phosphorylated glycogen synthase kinase-3β) had the greatest power to identify mild cognitive decline in T2DM patients.

Clinical and psychopathological analysis of emotional and cognitive disorders in patients with type II diabetes

The psycho-emotional state has the most significant effect on the clinical picture and course of diabetes of any type. According to many researchers, it is known that patients with diabetes suffer from depression almost three times more often than patients without it. When the patient has symptoms of depression, his emotional state is disturbed, which quite often leads to the patient's refusal of the prescribed necessary treatment, and eventually decompensation of the somatic state occurs. In turn, it causes new episodes of depression, which requires the use of psychotropic drugs and psychotherapy. A comprehensive clinical-psychopathological and psychodiagnostic examination of 82 patients with type II diabetes of moderate and severe forms was conducted. The average duration of diabetes was (7.9±5.2) years. Emotional disorders are represented by anxious, depressive, astheno-hypochondriac, hysteroform variants of psychopathological symptoms. Cognitive dysfunction is a frequent complication of type II diabetes. It is associated with both the age-related aspect of the disease and the pathological dysmetabolic cascade that forms basis of the pathogenesis of diabetic encephalopathy development. Cognitive decline in type II diabetes has a mixed (vascular-degenerative) nature and is characterized by complaints of decreased working capacity, and is marked by a decrease in memory, auditory-speech and visual modalities, slowing of thinking, decreased concentration of attention, absent-mindedness, inability to focus on performance of a certain task for a long time. The analysis of cognitive functions using the MMSE method showed that the examined patients had mild or moderate cognitive impairments in the form of a decrease in verbal memory, a decrease in the speed of calculation operations, difficulty in orientation, and a decrease in indicators of the perceptual-gnostic sphere. Keywords: cognitive disorders, emotional disorders, metabolic disorders, depression.

Chronic kidney disease and cognitive decline in patients with type 2 diabetes at elevated cardiovascular risk

AimsWe addressed the question whether chronic kidney disease (CKD) may contribute to cognitive decline in type 2 diabetes. MethodsParticipants with type 2 diabetes with elevated cardiovascular risk or CKD from cognition substudies of two large trials were studied prospectively (CARMELINA: n = 2666, mean ± SD age 68.1 ± 8.7 years, CAROLINA: n = 4296; 64.7 ± 9.4 years). Estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) at baseline were related to cognitive performance (Mini-Mental State Examination (MMSE) and attention and executive functioning score (A&E)) in linear regression analyses, adjusted for demographics, cardiovascular risk factors and treatment, at baseline and follow-up. ResultsCKD at baseline was more common in CARMELINA than CAROLINA (eGFR<60 in 72.6 % and 19.6 %, macroalbuminuria in 35.0 % and 4.1 %, respectively). Baseline eGFR was related to A&E in CARMELINA (b = 0.02 per 10 ml/min/1.73m2, 95%CI [0.01,0.03]). Baseline UACR was related to A&E in CAROLINA (b = −0.01 per doubling of UACR mg/g, 95%CI [−0.02,−0.002]). Baseline UACR predicted decline in A&E in CAROLINA (median 6.1 years follow-up; b = −0.01, 95%CI [−0.03,−0.0001] per doubling of UACR mg/g). ConclusionseGFR and UACR were associated with A&E in two cohorts with type 2 diabetes, enriched for CKD and cardiovascular disease. The small effect size estimates indicate limited impact of kidney dysfunction on cognition in this setting. ClinicalTrials.gov identifiersNCT01897532NCT01243424

Risk factors for cognitive decline in type 2 diabetes mellitus patients in Brazil: a prospective observational study

BackgroundType 2 Diabetes Mellitus (T2DM) patients are twice as likely to develop dementia. The study’s goal was to evaluate cognitive performance and risk factors for cognitive decline in this population.MethodsProspective observational study was conducted with 400 T2DM adults, of whom, during routine baseline and follow-up appointments, had socio-demographic, clinical, and laboratory data collected, and underwent physical examination, screening for depression symptoms (Patient Health Questionaire-9-PHQ-9), and cognitive tests: Mini-Mental State Examination (MMSE), Semantic Verbal Fluency Test, Trail Making Test A/B, and Word Memory Tests. Each cognitive test score was converted to a z-score and its average resulted in a new variable called Global Cognitive z-Score [GCS(z)]. Averages of the cognitive test scores and GCS(z) at both moments were compared by the Student’s T-Test for paired samples. Multivariate binary logistic regression models were built to assess the association of GCS(z) < zero with risk factors for cognitive decline at the baseline and follow-up.ResultsAfter exclusions, 251 patients were eligible, being 56.6% female, mean age of 61.1 (± 9.8) years, 12.6 (± 8.9) years of DM duration, and 7.6 (± 4.2) years of school education. Follow-up had 134 patients reevaluated and took place after a mean of 18.4(± 5.0) months. Eleven (14%) patients with a GCS(z) ≥ 0 at baseline turned into a GCS(z) < 0 at follow-up. There were no significant differences between the means of cognitive test scores and GCS(z) at the two evaluation moments. At the baseline, the multivariate logistic regression model identified five risk factors associated with GCS(z) < zero: age ≥ 65 years, schooling ≤ 6 years, arterial hypertension, depression symptoms, and diabetic retinopathy (DR), with odds ratio (OR) and 95% confidence interval (CI95%) respectively: 5.46 (2.42–12.34); 12.19 (5.62–26.46); 2.55 (0.88–7.39); 3.53 (1.55–8.07) e 2.50 (1.18–5.34). At follow-up, the risk factors for GCS(z) < zero were: schooling ≤ 6 years, DM duration ≥ 10 years, depression symptoms, arterial hypertension, and cardiovascular disease (CVD), OR and CI95% respectively: 10.15 (3.68–28.01); 2.68 (0.96–7.48); 4.92 (1.77–13.70); 7.21 (1.38–35.71) e 5.76 (1.93–17.18).ConclusionsBased on our results, cognitive evaluation and follow-up should be incorporated on the routine of T2DM patients, especially for those with advanced age, low education level, prolonged DM duration, arterial hypertension, depression symptoms, CVD, and DR.

Decline in skeletal muscle mass is associated with cognitive decline in type 2 diabetes mellitus

AimsTo examine the longitudinal association between skeletal muscle mass (SMM) loss and cognitive decline over time in type 2 diabetes mellitus (T2DM). MethodsWe conducted a prospective cohort study of 453 patients from SMART2D cohort with follow-up intervals of 1.6 to 6.4 years. Baseline and follow-up measurements included bio-impedance analysis (BIA) measure of skeletal muscle mass index (SMI) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) measure of cognitive function. We examined the association between annual rate of SMI and RBANS scores using linear regression, adjusting for demographics, education, depression, clinical co-variables and presence of apolipoprotein E4 (APOE) Ɛ4 allele. ResultsThe mean age of participants was 60.3 ± 7.4 years. Compared to patients with Tertile 1 SMI change, the group with greater SMI decline (Tertile 3 SMI change) experienced 0.30 decline in RBANS total score (95%CI −0.57 to −0.03; p = 0.030) in the adjusted analysis. RBANS scores for subdomains in immediate memory and visuo-spatial/construction were lower in Tertile 3 SMI change group with corresponding coefficients −0.54 (95%CI −1.01 to −0.06; p = 0.026), and −0.71 (95%CI −1.30 to −0.12; p = 0.019) respectively. ConclusionIn patients with T2DM, BIA measure of muscle mass loss over time was independently associated with cognitive decline globally and in the domains of memory and visuo-spatial/construction.

ASSESSMENT OF COGNITIVE FUNCTION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.

Type 2 DM is a complex metabolic disorder which can have detrimental affect on all the system of the body. This is often associated with accelerated risk of dementia.Objective of the study is to assess the cognitive function in individuals with type 2 diabetes. Twenty ve type 2 diabetics attending the endocrinology outpatient department of MS Ramaiah Medical College and Hospital were recruited for the study. Twenty ve age, sex and education matched normal subjects were enrolled for the study. Detailed history was taken. A thorough general physical examination and systemic examination was done. The subjects were divided into the two groups based on their serum HbA1C level. Cognitive function was assessed using Critical Flicker Frequency (CFF) and a validated questionnaire Adenbrooke's Cognitive Examination-III (ACE-III). Statistically signicant reduction was found in CFF values between controls and type 2 diabetics. ACE III scores were also signicantly lower in type 2 diabetics compared to controls. Decrease in CFF value and ACE-III score indicates reduction in cognitive function in type 2 diabetics. Our study shows an early onset of cognitive decline in type 2 diabetics compared to normal subjects.

Effects of Subcortical Atrophy and Alzheimer's Pathology on Cognition in Elderly Type 2 Diabetes: The Alzheimer's Disease Neuroimaging Initiative Study.

BackgroundSubcortical atrophy and increased cerebral β-amyloid and tau deposition are linked to cognitive decline in type 2 diabetes. However, whether and how subcortical atrophy is related to Alzheimer’s pathology in diabetes remains unclear. This study therefore aimed to investigate subcortical structural alterations induced by diabetes and the relationship between subcortical alteration, Alzheimer’s pathology and cognition.MethodsParticipants were 150 patients with type 2 diabetes and 598 propensity score-matched controls without diabetes from the Alzheimer’s Disease Neuroimaging Initiative. All subjects underwent cognitive assessments, magnetic resonance imaging (MRI), and apolipoprotein E (ApoE) genotyping, with a subset that underwent amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) assays to determine cerebral β-amyloid deposition (n = 337) and CSF p-tau (n = 433). Subcortical structures were clustered into five modules based on Pearson’s correlation coefficients of volumes across all subjects: the ventricular system, the corpus callosum, the limbic system, the diencephalon, and the striatum. Using structural equation modeling (SEM), we investigated the relationships among type 2 diabetes, subcortical structural alterations, and AD pathology.ResultsCompared with the controls, the diabetic patients had significant reductions in the diencephalon and limbic system volumes; moreover, patients with longer disease duration (>6 years) had more severe volume deficit in the diencephalon. SEM suggested that type 2 diabetes, age, and the ApoE ε4 allele (ApoE-ε4) can affect cognition via reduced subcortical structure volumes (total effect: age > ApoE-ε4 > type 2 diabetes). Among them, age and ApoE-ε4 strongly contributed to AD pathology, while type 2 diabetes neither directly nor indirectly affected AD biomarkers.ConclusionOur study suggested the subcortical atrophy mediated the association of type 2 diabetes and cognitive decline. Although both type 2 diabetes and AD are correlated with subcortical neurodegeneration, type 2 diabetes have no direct or indirect effect on the cerebral amyloid deposition and CSF p-tau.

Insulin resistance is associated with cognitive decline in type 1 diabetes mellitus.

Insulin resistance is associated with cognitive decline in type 1 diabetes mellitus.

Gum Arabic supplementation prevents loss of learning and memory through stimulation of mitochondrial function in the hippocampus of type 2 diabetic rats

The aim was to determine whether gum Arabic (GA) supplementation prevents cognitive decline in type 2 diabetes, through stimulation of mitochondrial function in the hippocampus. Type 2 diabetic rats and controls were assigned to following groups for 16 weeks: Control + Water; Control + GA 10% w/v; Diabetes + Water; Diabetes + GA 10% w/v. Latency in water maze was shorter for Diabetes + GA compared to Diabetes + Water (P < 0.05). Diabetes + GA group had a higher expression density per cell of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) compared to Diabetes + Water (P < 0.05). A similar trend was observed for ATP synthase β-subunit expression (ATPB). Number of PGC-1α positive cells was higher in diabetes compared to control groups (p < 0.05). The GA prevented learning and memory loss in type 2 diabetes. This was associated with greater expression of PGC-1a and a trend for greater ATBP protein expression in the hippocampus.

Periphery Biomarkers for Objective Diagnosis of Cognitive Decline in Type 2 Diabetes Patients.

Introduction: Type 2 diabetes mellitus (T2DM) is an independent risk factor of Alzheimer’s disease (AD), and populations with mild cognitive impairment (MCI) have high incidence to suffer from AD. Therefore, discerning who may be more vulnerable to MCI, among the increasing T2DM populations, is important for early intervention and eventually decreasing the prevalence rate of AD. This study was to explore whether the change of plasma β-amyloid (Aβ) could be a biomarker to distinguish MCI (T2DM-MCI) from non-MCI (T2DM-nMCI) in T2DM patients.Methods: Eight hundred fifty-two T2DM patients collected from five medical centers were assigned randomly to training and validation cohorts. Plasma Aβ, platelet glycogen synthase kinase-3β (GSK-3β), apolipoprotein E (ApoE) genotypes, and olfactory and cognitive functions were measured by ELISA, dot blot, RT-PCR, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test based on the diluted butanol, and Minimum Mental State Examination (MMSE) test, respectively, and multivariate logistic regression analyses were applied.Results: Elevation of plasma Aβ1-42/Aβ1-40 is an independent risk factor of MCI in T2DM patients. Although using Aβ1-42/Aβ1-40 alone only reached an AUC of 0.631 for MCI diagnosis, addition of the elevated Aβ1-42/Aβ1-40 to our previous model (i.e., activated platelet GSK-3β, ApoE ε4 genotype, olfactory decline, and aging) significantly increased the discriminating efficiency of T2DM-MCI from T2DM-nMCI, with an AUC of 0.846 (95% CI: 0.794–0.897) to 0.869 (95% CI: 0.822–0.916) in the training cohort and an AUC of 0.848 (95% CI: 0.815–0.882) to 0.867 (95% CI: 0.835–0.899) in the validation cohort, respectively.Conclusion: A combination of the elevated plasma Aβ1-42/Aβ1-40 with activated platelet GSK-3β, ApoE ε4 genotype, olfactory decline, and aging could efficiently diagnose MCI in T2DM patients. Further longitudinal studies may consummate the model for early prediction of AD.

Inhibition of soluble epoxide hydrolase (sEH) protects hippocampal neurons and reduces cognitive decline in type 2 diabetic mice.

Diabetes mellitus is a metabolic disorder that can lead to cognitive dysfunction. The hippocampus plays an important role in the cognitive function. Research has identified correlations between hippocampal impairment and diabetes, yet their intermediate remains unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects by suppressing inflammation, apoptosis and oxidative stress. In this study, under diabetic conditions both hippocampal injury and cognitive decline are accompanied by upregulation of sEH. Moreover, the sEH inhibitor trans-4-[4-(3-adamantan-1-y1-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) prevents cognitive dysfunction and decreased ROS accumulation and apoptosis in the diabetic hippocampus. t-AUCB treatment restored neuronal synaptic plasticity by restoring the expression of the postsynaptic proteins Postsynaptic density protein-95 (PSD95) and N-methyl-d-aspartate receptor subunit 2B (NR2B), the levels of which were positively correlated with Proline-rich tyrosine kinase 2 (Pyk2) levels under diabetic conditions. Thus, we suggest that hippocampal protection via sEH inhibition might be a potential therapeutic approach to attenuate the progression of cognitive decline in diabetes.

On the physiology of cognitive decline in type 1 diabetes

ObjectivesType 1 diabetes mellitus (T1DM) may be associated with cognitive impairment and notably a decline in psychomotor speed, information processing speed and attention. The mechanism for this decline is uncertain. Previous studies by our group and others have demonstrated a decline in EEG-power and event-related potential amplitude in T1DM. The objectives of the present study were to explore whether 1) the association between event-related potential (N100) amplitude and psychomotor speed is different between T1DM and healthy subjects, and 2) the decline in N100 amplitude depends on duration of diabetes. MethodsPatients with T1DM (N = 204) and healthy control subjects (N = 358) were included in a cross-sectional study. Event-related brain potentials were recorded with auditory reaction tasks. Psychomotor speed was evaluated with the Grooved Pegboard test in a subset of the patients (N = 70) and the healthy control subjects (N = 89). ResultsPatients with T1DM had a decrease in the N100 amplitude that correlated with a decline in psychomotor speed, longer duration of diabetes and increasing age. In healthy controls, the N100 amplitude did not decrease with age and the association between psychomotor speed and N100 amplitude was absent. ConclusionThe association between psychomotor speed and N100 amplitude is likely to be a specific trait for T1DM since it was not found in healthy controls and was dependent on diabetes duration. Our findings indicate that the pathogenesis of cognitive decline in T1DM may involve a disease-related factor with a long-term influence on the N100 amplitude.

Clinical observation on therapeutic effect of moxibustion on cognitive decline in type 2 diabetes mellitus

To observe the effect of moxibustion on cognitive function in patients with cognitive decline of type 2 diabetes mellitus (T2DM). A total of 47 patients with cognitive decline of T2DM were randomized into an observation group (24 cases, 4 cases dropped off ) and a control group (23 cases, 3 cases dropped off ). Conventional hypoglycemic intervention was adopted in the control group. On the basis of the treatment in the control group, Huayu Tongluo moxibustion (moxibustion for removing stasis and clearing collaterals) was applied at Baihui (GV 20), Dazhui (GV 14), Shenting (GV 24), once every 2 days, 4 weeks were as one course, totally 3 courses were required. Before and after treatment, scores of auditory verbal learning test (AVLT), complex figure test (CFT), Montreal cognitive assessment (MoCA) and trail making test-A (TMT-A) were observed in the both groups, and the clinical effective rates were compared. After treatment, the scores of immediate memory and delayed memory of AVLT in the observation group were higher than those before treatment and those in the control group (P<0.05). After treatment, the scores of visual space and executive function, delayed memory, attention and orientation of MoCA in the observation group were higher than those before treatment and those in the control group (P<0.05). The effective rate was 85.0% (17/20) in the observation group, which was superior to 10.0% (2/20) in the control group (P<0.05). Huayu Tongluo moxibustion has a definite effect on cognitive decline of type 2 diabetes mellitus.

Western Diet Accelerates the Impairment of Odor-Related Learning and Olfactory Memory in the Mouse.

Olfactory dysfunction could be an early indicator of cognitive decline in type 2 diabetes (T2D). However, whether obesity affects olfaction in people with T2D is unclear. This question needs to be addressed, because most people with T2D are obese. Importantly, whether different contributing factors leading to obesity (e.g., different components of diet or gain in weight) affect specific olfactory functions and underlying mechanisms is unknown. We examined whether two T2D-inducing obesogenic diets, one containing a high proportion of fat (HFD) and one with moderate fat and high sugar (Western diet, WD), affect odor detection/discrimination, odor-related learning, and olfactory memory in the mouse. We also investigated whether the diets impair adult neurogenesis, GABAergic interneurons, and neuroblasts in the olfactory system. Here, we further assessed olfactory cortex volume and cFos expression-based neuronal activity. The WD-fed mice showed declined odor-related learning and olfactory memory already after 3 months of diet intake (p = 0.046), although both diets induced similar hyperglycemia and weight gain compared to those of standard diet-fed mice (p = 0.0001 and p < 0.0001, respectively) at this time point. Eight months of HFD and WD diminished odor detection (p = 0.016 and p = 0.045, respectively), odor-related learning (p = 0.015 and p = 0.049, respectively), and olfactory memory. We observed no changes in the investigated cellular mechanisms. We show that the early deterioration of olfactory parameters related to learning and memory is associated with a high content of sugar in the diet rather than with hyperglycemia or weight gain. This finding could be exploited for understanding, and potentially preventing, cognitive decline/dementia in people with T2D. The mechanisms behind this finding remain to be elucidated.