Migraine versus tension-type headache in automatic emotional processing: A visual mismatch negativity study.

OBJECTIVE: It is important to discriminate different headaches in clinical practice, and neurocognitive biomarkers may serve as objective tools. Several reports have suggested potential cognitive impairment for primary headaches, whereas cognitions within specific domains remain elusive, e.g., emotional processing. In this study, we aimed to characterize processing of facial expressions in migraine and tension-type headache (TTH) by analyzing expression-related visual mismatch negativity (EMMN) and explored whether their processing patterns were distinct. METHODS: Altogether, 73 headache patients (20 migraine with aura (MA), 28 migraine without aura (MwoA), 25 TTH) and 27 age-matched healthy controls were recruited. After a battery of mood/neuropsychological evaluations, an expression-related oddball paradigm containing multiple models of neutral, happy and sad faces was used to investigate automatic emotional processing. RESULTS: We observed cognitive impairment in all headache patients, especially in attention/execution subdomains, but no discrepancy existed among different headaches. Although analyses of P1/N170 did not reach significant levels, amplitude of early and late EMMN was markedly diminished in MA and MwoA compared with controls and TTH, regardless of happy or sad expression. Moreover, sad EMMN was larger (more negative) than happy EMMN only in controls, while not in all headache groups. CONCLUSIONS: Our findings implied that migraine, rather than TTH, might lead to more severe impairment of automatic emotional processing, which was manifested as no observable EMMN elicitation and disappearance of negative bias effect. The EMMN component could assist in discrimination of migraine from TTH and diagnosis of undefined headaches, and its availability needed further validations.

Dysfunction of processing task-irrelevant emotional faces in primary insomnia patients: an evidence from expression-related visual MMN.

PURPOSE: According to the cognitive processing perspectives, patients with insomnia have insufficient neural management of expressional information. In this study, we compared the pre-attentive processing function of task-irrelevant facial expressions in patients with primary insomnia (PI) and matched healthy controls, with expression-related mismatch negativity (EMMN) elicited by emotional faces as the indicator. METHODS: Using three schematic facial expressions (neutral, happy, and sad) as task-irrelevant stimuli, we investigated the visual processing of PI patients (n = 22) and healthy subjects (n = 22) in an expression-related oddball paradigm designed to elicit the visual N170 and EMMN component. After recording and analyzing the electroencephalogram of all participants, amplitude analysis of N170 and EMMN was eventually conducted under corresponding time window. RESULTS: Compared with control group, the amplitude of sad-EMMN component was significantly attenuated in patients with PI, while no remarkable difference was observed under the happy condition. In addition, negative cognitive bias was further validated in the control group, but not presented in the PI group. CONCLUSION: The current data suggest dysfunctional expressional information processing in PI patients, accompanied by the disorganization of high level perceptual strategy of processing facial emotional expression.

Lycopene-Loaded Microemulsion Regulates Neurogenesis in Rats with Aß-Induced Alzheimer's Disease Rats Based on the Wnt/ß-catenin Pathway.

Objective: To investigate the effects of lycopene-loaded microemulsion (LME) on the cognitive function and neurogenesis in the dentate gyrus (DG) of the hippocampus and subventricular (SVZ) region of rats with amyloid ß- (Aß-) induced Alzheimer's disease (AD) and its mechanism based on the Wnt/ß-catenin pathway. Methods: Healthy Wistar rats were divided into four groups: the blank control (CON), AD control, traditional lycopene (LOO), and LME groups. The CON and AD groups were fed with normal saline, while the LOO group was fed with traditional lycopene, and the LME group was fed with lycopene-loaded microemulsion. Behavioral tests were performed after three weeks of gastric administration. Immunofluorescence-labeled cells were used to observe the differentiation and maturation of new nerve cells in the DG of the hippocampus and SVZ region. qRT-PCR and Western blotting detected the expression of neurogenesis genes and Wnt/ß-catenin pathway-related proteins, respectively. Results: On the Morris water maze test, LME rats had significantly shortened movement trajectory on the searching platform, reduced escape latency time, and increased residence time on the original platform quadrant. In addition, more LME rats crossed the platform when it was removed. Thus, LME can improve the spatial learning and memory of Aß-induced AD rats. On qRT-PCR, LME significantly increased Reelin, Nestin, and Pax6 gene expressions, which regulate neurogenesis. Immunofluorescence showed that LME could significantly increase BrdU+, Dcx+, BrdU+/Neun+, BrdU+/Dcx+ cells in the DG and SVZ regions, thus promoting neurogenesis. LME also reduced the number of Iba1+ and Iba1+/BrdU+ cells, thus reducing the neuroinflammatory response. On Western blot, LME upregulated the Wnt/ß-catenin pathway by upregulating Wnt3a, ß-catenin, Disheveled (Dvl), and p-GSK3ß and downregulating p-ß-catenin and GSK3ß. Conclusion: LME attenuates cognitive impairment in Aß-induced AD rats by promoting neurogenesis in the hippocampus and SVZ region through upregulating the Wnt/ß-catenin pathway.

Brachial-Ankle Pulse Wave Velocity is Related to the Total Cerebral Small-Vessel Disease Score in an Apparently Healthy Asymptomatic Population.

INTRODUCTION: Cerebral small-vessel disease (CSVD) is an extensive cerebrovascular disease associated with many poor outcomes. Previous studies have shown that brachial-ankle pulse wave velocity (baPWV) is related to various neuroimaging signatures, but its association with the total CSVD burden remains unknown. We aimed to explore whether baPWV is related to the total CSVD score and to establish a cutoff for detecting the presence and severity of CSVD, which may guide clinical preventive measures. METHODS: We retrospectively selected 684 neurologically healthy participants to explore correlations between baPWV and the total CSVD score and each of its components (lacunes, white matter hyperintensity (WMH), perivascular space (PVS), and cerebral microbleeds (CMBs)). Subsequently, we established two receiver operating characteristic (ROC) curves to study the effectiveness of baPWV in predicting CSVD (scores 1-4) and severe CSVD (scores 3-4). RESULTS: The median baPWV was 13.16 m/s, which increased significantly with increasing scores (0-4). BaPWV was significantly higher among persons with each component of the total CSVD score than among those without any components. Multivariable ordinal logistic regression analyses showed that a one-unit (m/s) change in baPWV significantly increased the total CSVD score by 0.012. The optimal baPWV cutoffs for detecting CSVD and severe CSVD were 13.12 m/s and 15.63 m/s, respectively. CONCLUSIONS: BaPWV was positively correlated with the total CSVD score, suggesting that baPWV measurement is a useful method for early diagnosis of CSVD, which may contribute to preventing and controlling CSVD progression in the general population of China.

The impact of attack frequency and duration on neurocognitive processing in migraine sufferers: evidence from event-related potentials using a modified oddball paradigm.

BACKGROUND: Several studies have suggested that migraineurs suffer from neurocognitive abnormalities, but this phenomenon and exact mechanisms remain controversial. In this study, we aimed to reevaluate visual spatial attention via event-related potential (ERP) examinations and explore further correlations between ERP data and migraine characteristics. METHODS: Altogether, 25 migraine patients (9 males, 16 females; mean age 35.240 years) in the interictal period and 21 age-matched healthy controls (8 males, 13 females; mean age 35.286 years) were recruited. A modified visual oddball paradigm which contained standard, target and novel stimuli was used in the test, and amplitudes and latencies of corresponding original/difference ERP components were measured and analyzed independently. RESULTS: We found that P3 amplitude was markedly reduced in migraineurs. This phenomenon was further validated in analysis of difference P3 components (target minus standard and novel minus standard). Additionally, the N1 and N2 latencies elicited by novel stimulus were both delayed in patients compared with controls. Furthermore, these deviant cognitive ERPs were correlated with frequency and duration of migraine attacks. CONCLUSIONS: These results indicated impaired visual spatial attention in migraine patients, which could be related to frequency and duration of attacks.

Contingent negative variation for the periodicity of migraine attacks without aura.

Migraine is a primary neuropsychological disorder, although its etiology and pathogenesis are unknown. It has been reported that using contingent negative variation, the periodicity of migraine attacks is three days in adults. However, there is still a lack of relevant reports about the periodicity of migraine without aura in adults. Therefore, we investigated the changes of contingent negative variation in adults with migraine without aura from three to seven days after migraine attacks in order to provide the basis for exploring the circulation periodicity of migraine without aura. This prospective, observational study involved a group of 34 individuals with migraine without aura, who were screened during the three to seven days after a migraine attack without aura. A healthy group (31 individuals) was used as controls to assess the amplitudes of contingent negative variation and habituation of early contingent negative variation. Indices of the amplitudes included overall contingent negative variation, initial contingent negative variation, terminal contingent negative variation, and postoperative negative contingent variation. Differences between these indicators were analyzed. No significant difference was found between the patient and control groups for either the amplitudes of these measures of contingent negative variation or habituation of the early contingent negative variation for three to seven days after a migraine attack without aura (all P > 0.05). Thus, the study reported here found that the periodicity of migraine attacks without aura in adults is more than three days.

Activation of Nrf2 signaling by sitagliptin and quercetin combination against ß-amyloid induced Alzheimer's disease in rats.

The objective of this study was to evaluate the neuroprotective effect of sitagliptin (Sita), quercetin (QCR) and its combination in ß-amyloid (Aß) induced Alzheimer's disease (AD). Male Sprague-Dawley rats, weighing between 220 and 280 g were used for experiment. Rats were divided into 5 groups (n = 10) and the groups were as follows: (a) Sham control; (b) Aß injected; (c) Aß injected + Sita 100; (d) Aß injected + QCR 100; and (e) Aß injected + Sita 100 + QCR 100. Cognitive performance was observed by the Morris water maze (MWM), biochemical markers, for example, MDA, SOD, CAT, GSH, Aß1-42 level, Nrf2/HO-1 expression and histopathological study of rat brain were estimated. Pretreatment with Sita, QCR and their combination showed a significant increase in escape latency in particular MWM cognitive model. Further co-administration of sita and QCR significantly reduced Aß1-42 level when compared with individual treatment. Biochemical markers, for example, increased SOD, CAT and GSH, decreased MDA were seen, and histopathological studies revealed the reversal of neuronal damage in the treatment group. Additionally, Nrf2/HO-1 pathway in rat's brain was significantly increased by Sita, QCR and their combination. Pretreatment with QCR potentiates the action of Sita in Aß induced AD in rats. The improved cognitive memory could be because of the synergistic effect of the drugs by decreasing Aß1-42 level, antioxidant activity and increased expression of Nrf2/HO-1 in rat brain.

Female versus male migraine: an event-related potential study of visual neurocognitive processing.

BACKGROUND: Several studies have suggested cognitive deficits in migraineurs, and sex differences have also been observed in migraine, such as a higher prevalence in females. Nevertheless, little is known about gender-related differences in cognitive processing. In this study, we aimed to investigate the effect of gender on neurocognitive processing in migraineurs. METHODS: Altogether, 46 migraine patients without aura (23 females; mean age 32.848 years) during the interictal period and 46 age-matched healthy controls (23 females; mean age 32.652 years) were recruited. The emotional characteristics of participants were evaluated, and attentive processing was analyzed via event-related potential examinations using a three-stimulus visual oddball paradigm. RESULTS: We found that migraineurs suffered from emotional and visual cognitive processing abnormalities compared with healthy controls, including higher levels of anxiety and reduced P3 amplitude. These parameters were modulated by gender in migraine patients, but not in healthy participants. Our findings indicated that female patients seemed to be more anxious and have more severe impairment in attentive processing of visual stimuli than their male counterparts. The gender-related differences in migraineurs were further validated using event-related potential difference waveforms. CONCLUSIONS: These results suggested that migraine might have an additional influence on females and lead to more dysfunction in their interictal neurocognitive processing. Our findings provide evidence that a gender effect exists in migraineurs, which should be considered when designing experiments and exploring treatment approaches. The gender-related differences and underlying mechanisms deserve further investigation for patients with migraine.

Selective Impairment of Attentional Networks of Executive Control in Middle-Aged Subjects with Type 2 Diabetes Mellitus.

BACKGROUND The influence of type 2 diabetes mellitus (T2DM) on attention has been elusive. The Attention Network Test (ANT) was developed to evaluate the functioning of 3 individual attentional networks: orienting, alerting, and executive control. The purpose of this study was to use the ANT to assess attentional function and its sub-components in T2DM patients ages 40-60 years. MATERIAL AND METHODS Thirty T2DM patients and 30 healthy controls ages 40-60 years were recruited in this investigation. The ANT was used to statistically compare the efficiency among 3 sub-components of the attention networks between middle-aged T2DM patients (n=30) and gender-, age-, and education-matched healthy controls (n=30). RESULTS The ANT demonstrated a significant difference in executive control network between the T2DM patients and healthy controls (t=3.242, P=0.002), whereas no significant difference was observed regarding the domains of alerting (t=0.515, P=0.609) and orienting control (t=0.078, P=0.938) between the T2DM patient group and the healthy control group. Moreover, the mean reaction time in the ANT in the T2DM patients was significantly longer compared with that in the healthy controls (t=3.561, P=0.001). CONCLUSIONS The ANT reveals significant impairment in the executive control of middle-aged patients diagnosed with T2DM, whereas no significant impairment was observed in the domains of alerting and orienting.

RAGE-Specific Inhibitor FPS-ZM1 Attenuates AGEs-Induced Neuroinflammation and Oxidative Stress in Rat Primary Microglia.

Advanced glycation end products (AGEs) enhance microglial activation and intensify the inflammatory response and oxidative stress in the brain. This process may occur due to direct cytotoxicity or interacting with AGEs receptors (RAGE), which are expressed on the surface of microglia. FPS-ZM1 is a high-affinity but nontoxic RAGE-specific inhibitor that has been recently shown to attenuate the Aß-induced inflammatory response by blocking the ligation of Aß to RAGE. In this study, we further investigated the effect of FPS-ZM1 on the AGEs/RAGE interaction and downstream elevation of neuroinflammation and oxidative stress in primary microglia cells. The results suggested that FPS-ZM1 significantly suppressed AGEs-induced RAGE overexpression, RAGE-dependent microglial activation, nuclear translocation of nuclear factor kappaB p65 (NF-κB p65), and the expression of downstream inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) and inducible nitric oxide synthase (iNOS)/nitric oxide (NO). Furthermore, FPS-ZM1 attenuated AGEs-stimulated NADPH oxidase (NOX) activation and reactive oxygen species (ROS) expression. Finally, FPS-ZM1 elevated the levels of transcription factors nuclear-factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1), as well as decreased antioxidant capacity and increased production of oxidative species. Our results suggest that FPS-ZM1 may be neuroprotective through attenuating microglial activation, oxidative stress and inflammation by blocking RAGE.

Brain-targeted lycopene-loaded microemulsion modulates neuroinflammation, oxidative stress, apoptosis and synaptic plasticity in ß-amyloid-induced Alzheimer's disease mice.

OBJECTIVES: ß-Amyloid protein (Aß) plays pivotal roles in pathogenesis of Alzheimer's disease (AD) and triggers various pathophysiological events. Lycopene is a promising neuroprotector with multiple bioactivities, while its bioavailability is limited. Lycopene-loaded microemulsion (LME) possessing superior bioavailability and brain-targeting efficiency was developed in our previous study. In this investigation, we aimed to comprehensively evaluate its neuroprotective effects and underlying mechanisms using intracerebroventricular (ICV) Aß1-42 injection mice. METHODS: Mice were assigned to the Sham, Aß, Aß + LME and Aß + lycopene dissolved in olive oil (LOO) groups. ICV Aß1-42 administration was performed, followed by oral gavage of brain-targeted LME or conventional LOO formulation for 3 weeks. Brain samples were harvested for immunohistochemistry, biochemical assays and western blotting analyses. RESULTS: Our findings verified Aß-induced neurotoxicity on neuroinflammation, oxidative stress, apoptosis, Aß metabolisms and synaptic plasticity. LME supplementation dramatically attenuated astrocytosis and microgliosis, decreased malondialdehyde production and rescued antioxidant capacities, normalized apoptotic parameters and alleviated neuronal loss, inhibited amyloidogenic processing and activated non-amyloidogenic pathway, together with upregulating synaptic protein expressions and restoring synaptic plasticity. Nevertheless, most of these phenomena were not observed for mice treated with LOO, implying that LME showed significantly higher therapeutic efficacy against Aß injury. DISCUSSION: In summary, brain-targeted LME could exert neuroprotective function via suppressing a series of cascades triggered by Aß aggregates, thus ameliorating Aß neurotoxicity and associated abnormalities. Given this, LME may serve as an attractive candidate for AD prevention and treatment, and superiority of brain-targeting delivery is highlighted.

AGEs induce cell death via oxidative and endoplasmic reticulum stresses in both human SH-SY5Y neuroblastoma cells and rat cortical neurons.

Advanced glycation endproducts (AGEs) are elevated in aging and neurodegenerative diseases such as Alzheimer's disease (AD), and they can stimulate the generation of reactive oxygen species (ROSs) via NADPH oxidase, induce oxidative stress that lead to cell death. In the current study, we investigated the molecular events underlying the process that AGEs induce cell death in SH-SY5Y cells and rat cortical neurons. We found: (1) AGEs increase intracellular ROSs; (2) AGEs cause cell death after ROSs increase; (3) oxidative stress-induced cell death is inhibited via the blockage of AGEs receptor (RAGE), the down-regulation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and the increase of scavenging by anti-oxidant alpha-lipoic acid (ALA); (4) endoplasmic reticulum (ER) stress was triggered by AGE-induced oxidative stress, resulting in the activation of C/EBP homologous protein (CHOP) and caspase-12 that consequently initiates cell death, taurine-conjugated ursodeoxycholic acid (TUDCA) inhibited AGE-induced ER stress and cell death. Blocking RAGE-NADPH oxidase, and RAGE-NADPH oxidase-ROSs and ER stress scavenging pathways could efficiently prevent the oxidative and ER stresses, and consequently inhibited cell death. Our results suggest a new prevention and or therapeutic approach in AGE-induced cell death.

Insidious Attentional Deficits in Patients With Cerebral Small Vessel Disease Revealed by Attention Network Test.

Background: Several reports have indicated potential cognitive decline for cerebral small vessel disease (CSVD), especially in attention domain, whereas the attentional function at network level is still elusive. In this study, we used the attention network test (ANT) paradigm to characterize the efficiency of the alerting, orienting, and executive control networks in patients with CSVD and explore possible correlations between attention network efficiencies and obtained CSVD total score. Methods: A total of 31 patients with CSVD and 30 healthy controls matched for age, gender, and education level were recruited. After neuropsychological and anxiety/depression/somatization assessments, an original version of ANT containing different cue conditions and target stimuli was used to investigate independent attentional components, and then, behavioral performance (accuracy and reaction time) and network efficacy were recorded and analyzed. Results: Assessed by traditional neuropsychological scale (MoCA), we did not find difference between groups on general cognition. Nevertheless, the overall reaction time to targets of ANT was markedly prolonged in patients with CSVD, and similar phenomenon was observed for overall accuracy on ANT. Moreover, patients showed significantly lower orienting and executive control network efficiencies compared with controls, while not for alerting network. These impairments were correlated with total CSVD burdens, but not with anxiety, depression, or somatization. Conclusions: Although general and almost all individual cognitive function evaluated by MoCA seemed to remain intact, the orienting and executive control function was impaired in individuals with CSVD, which was modulated by lesion grades. Our observations implied insidious attentional deficits regarding CSVD. Given this, considering its simplicity and sensitivity, ANT could serve as an attractive tool for early diagnosis of cognitive dysfunction. Further investigations on the availability of ANT detection for CSVD are warranted.

Preliminary Findings on Visual Event-Related Potential P3 in Asymptomatic Patients with Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease is the primary cause of cognitive impairment. Therefore, early recognition is of great significance. Some studies have shown that asymptomatic cerebral small vessel disease (aCSVD) patients have abnormal neurocognitive function, but this is not readily apparent at the initial stage. The objective of this paper was to assess visual spatial attention by event-related potential (ERP) examination and to analyze the relationship between ERP data and clinical characteristics in patients with aCSVD. METHODS: We selected 25 aCSVD patients and enrolled 23 age-matched normal subjects as the control group. We measured the latency and amplitude of original/corresponding differential ERP components using the modified visual oddball paradigm, which included a standard stimulus, target stimulus, and new stimulus. Additionally, we selected aberrant ERP components to study the correlations between the ERP data and clinical characteristics of the patients with aCSVD. RESULTS: We found not only lower amplitude but also significantly longer P3 latency in the aCSVD patients. The above results were further verified by analyzing the different components (target minus standard and novel minus standard) of P3. Furthermore, abnormal ERPs in the aCSVD patients were closely related to the changes observed with imaging. CONCLUSION: It was demonstrated that the speed and capability of processing visual spatial information was impaired in aCSVD patients compared with healthy controls. Thus, ERP examination could detect the presence of attentional deficits and might become a rapid and sensitive method for the early diagnosis of aCSVD. However, its availability needs further investigation.

Selective Impairment of Processing Task-Irrelevant Emotional Faces in Cerebral Small Vessel Disease Patients.

BACKGROUND: Few reports have implied electrophysiological alterations and neurocognitive abnormalities in patients with cerebral small vessel disease (CSVD), while no investigation is available regarding emotional processing. In the present study, pre-attentive processing of facial expressions was compared between CSVD sufferers and healthy controls using expression-related visual mismatch negativity (EMMN) as the indicator. METHODS: A total of 22 CSVD patients (12 males) and 21 age-matched healthy controls (12 males) were recruited for neuropsychological and emotional assessments, as well as electroencephalogram recording and analysis. We employed an expression-related oddball paradigm to investigate automatic emotional processing, and a series of schematic emotional faces (neutral, happy, sad) unrelated to subject's task were present in the test to avoid low-level processing of facial features. RESULTS: Although the distinctions of neuropsychological (MoCA and MMSE), emotional (GAD-7 and PHQ-9) and behavioral parameters (reaction time to target stimuli and response accuracy) did not reach significant levels, mean amplitudes of sad EMMN in time intervals of 150-250 ms and 250-350 ms were remarkably reduced in CSVD patients compared with healthy controls, but not for happy EMMN. Furthermore, in the control group, sad EMMN was demonstrated to be larger (more negative) than happy EMMN, while this interesting phenomenon disappeared in the CSVD group. CONCLUSION: Our findings confirmed selective impairment of processing expressions which were task-irrelevant in CSVD patients, without the existence of negative bias (sad superiority) effect. The efficacy of EMMN as an electrophysiological evaluation marker of CSVD should be taken into account in future investigations.

Prevalence of mild cognitive impairment in type 2 diabetes mellitus is associated with serum galectin-3 level.

AIMS/INTRODUCTION: Galectin-3 (Gal3) contributes to insulin resistance, inflammation and obesity, the three risk factors for mild cognitive impairment (MCI) in type 2 diabetes mellitus patients. MATERIALS AND METHODS: A total of 134 hospitalized type 2 diabetes mellitus patients were assessed by the Montreal Cognitive Assessment method, and divided into 65 MCI and 69 controls. Levels of variables, Gal3 and Aß42, were investigated in relation with cognitive function in both type 2 diabetes mellitus patients with MCI and high-fat diet/streptozotocin induced type 2 diabetes mellitus rats. RESULTS: Significantly higher levels of serum Gal3 and lower levels of plasma Aß42 (all P < 0.05) were found in the MCI type 2 diabetes mellitus group as compared with the non-MCI type 2 diabetes mellitus control. Partial correlation analysis showed that Gal3 is negatively correlated with both MMSE score (r = -0.51, P < 0.01) and Montreal Cognitive Assessment score (r = -0.47, P < 0.001) after adjustment for glycated hemoglobin, homoeostasis model assessment of insulin resistance and Aß42 in all type 2 diabetes mellitus patients, with a stronger effect seen in the MCI type 2 diabetes mellitus group after further analysis with MCI strata. A simple logistic regression model showed that Gal3 and Aß42 are significantly associated with MCI type 2 diabetes mellitus patients after adjustment with the covariates sex, age, body mass index, glycated hemoglobin, homoeostasis model assessment of insulin resistance and antidiabetic drugs. Serum and brain Gal3 levels were significantly increased in high-fat diet/streptozotocin diabetic rats, which correlate to the impairment of learning and memory ability. Gal3 inhibitor modified citrus pectin decreased serum and brain Gal3 levels in diabetic rats, accompanied by the amelioration of learning and memory impairment. CONCLUSIONS: Gal3 might be associated with cognitive impairment in type 2 diabetes mellitus, and serum Gal3 level might be a new risk factor of MCI in type 2 diabetes mellitus patients.

Pharmacological Inhibition of Galectin-3 Ameliorates Diabetes-Associated Cognitive Impairment, Oxidative Stress and Neuroinflammation in vivo and in vitro.

BACKGROUND: In diabetes, cognitive impairment is linked with oxidative stress and neuroinflammation. As the only chimeric member of the galectin family, galectin-3 (Gal3) induces neuroinflammation and cognitive impairment in models of Alzheimer's disease (AD); however, its role in diabetes-associated cognitive impairment is not established. METHODOLOGY: Here, we investigated the effects of Gal3 inhibition on cognitive impairment and the possible underlying molecular events in diabetes. We investigated the effects of the Gal3 inhibitor modified citrus pectin (MCP; 100 mg/kg/day oral for 6 weeks) in vivo in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Additionally, the effects of MCP on high glucose (HG)-stimulated BV-2 microglial cells were investigated in vitro. RESULTS: We found that MCP attenuated memory impairment in diabetic rats in the Morris water maze test and reduced insulin resistance, oxidative stress, and neuroinflammation. In HG-stimulated BV-2 microglial cells, MCP increased cell viability and decreased oxidative stress and the production of proinflammatory cytokines. CONCLUSION: The results of this study indicate that the inhibition of Gal3 by MCP ameliorates diabetes-associated cognitive impairment, oxidative stress, and neuroinflammation, suggesting that Gal3 could be a potential new target for therapeutic intervention to prevent cognitive impairment in diabetes.

Performance of facial expression classification tasks in patients with obstructive sleep apnea.

STUDY OBJECTIVES: People show a facial recognition speed advantage, termed positive classification advantage (PCA), when judging whether a facial expression is happy compared to angry or sad. This study investigated emotional face recognition by patients with obstructive sleep apnea (OSA) with impaired neurocognition. METHODS: Thirty-four patients with OSA and 26 healthy control patients who underwent 1 night of polysomnographic evaluation before recruitment were asked to complete an emotion recognition task. Accuracy rates and reaction times were recorded and analyzed using repeated-measures analysis of variance. RESULTS: When participants were asked to classify positive (happy) versus negative (sad) emotional expressions, the phenomenon of PCA disappeared. Importantly, however, compared with the control patients who showed PCA, patients with OSA identified sad faces faster but were similar in processing happy faces. CONCLUSIONS: In accordance with previous studies that showed depressive emotion in patients with OSA, our results indicate that patients with OSA show negative bias in facial expression recognition, which might lead to decline in ability of social communication.

Targetting Exosomes as a New Biomarker and Therapeutic Approach for Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease that mainly occurs in old age and involves progressive cognitive impairment. AD has become a major global issue for public health, with approximately 24 million people currently affected by the disease. Estimates indicted that this number will quadruple by 2050. Because of the high incidence of AD, there is an urgent need to develop new strategies to diagnose and treat AD. Many recent studies have indicated the multiple, yet somewhat controversial, roles of exosomes in AD. Although the underlying mechanisms by which exosomes play a role in AD are still unknown, current evidence suggests that exosomes can carry and spread toxic amyloid-beta, and hyperphosphorylated tau, between cells, and then induce apoptosis, thus contributing to the loss of neurons. In addition, exosomes appear to possess the ability to reduce brain amyloid-beta, and tau hyperphosphorylation, and transfer neuroprotective substances between neural cells. The accumulating data brings hope that the application of exosomes may be helpful for early diagnostics and the identification of new therapeutic targets for AD. Here, we summarized the various roles of exosomes, and how they might relate to the pathogenesis of AD. We also highlight the potential application of exosomes as a therapeutic option in AD therapy.