Improvement Of Cognitive Impairment Research Articles

Experimental study on improvement of cognitive impairment in Alzheimer's disease by different degrees of steaming and sunning of Polygoni Multiflori Radix based on fecal metabolomics

The fecal metabolomics method was employed to investigate the cognitive improvement mechanism of Polygoni Multiflori Radix in Alzheimer's disease(AD) and examine the effects of different degrees of steaming and sunning on cognitive function in AD model mice. Additionally, the processing principle of Polygoni Multiflori Radix was discussed. Forty-eight 5-month-old APP/PS1 mice were randomly assigned to the following groups: model group, positive group, raw product group, three-steaming and three-sunning product group, six-steaming and six-sunning product group, and nine-steaming and nine-sunning product group. Seven negative control mice from the same litter were included as the blank group. After 150 days of intragastric administration, the learning and memory abilities of mice in each group were assessed by using the Barnes maze and dark avoidance tests. Fecal samples were collected for extensive targeted metabolomics testing. Principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and other multivariate statistical methods were utilized to analyze metabolites in mouse feces. Comparison of behavioral results between the model group and different product groups demonstrated that the six-steaming and six-sunning product group exhibited significantly reduced latency in the Barnes maze positioning and navigation test(P<0.05), as well as a notable decrease in the number of errors in the space exploration experiment(P<0.05). Moreover, the latency of mice entering the dark box for the first time in the dark avoidance experiment was significantly prolonged(P<0.05), indicating the best overall improvement in the learning and memory ability of AD model mice. Metabolomics results revealed that compared with the model group, the differential metabolites in other groups in descending order were as follows: six-steaming and six-sunning product group > nine-steaming and nine-sunning product group > raw product group > three-steaming and three-sunning product group, encompassing 146, 120, 95, and 81 potential biomarkers, respectively. Among them, 16 differential metabolites were related to AD disease. Further comparisons based on the degree of processing indicated that the six-steaming and six-sunning product group exhibited the most significant adjustments in total metabolic pathways, particularly regulating the interconversion of pentose and glucuronic acid, as well as amino acid anabolism and other pathways. In summary, the mechanism of Polygoni Multiflori Radix after processing in enhancing the learning and memory ability of APP/PS1 mice may be associated with improved amino acid metabolism and increased energy metabolism in the body. The six-steaming and six-sunning yielded the best outcomes.

Immediate effect of Bhastrika Pranayama on cerebral hemodynamics in patient with depression: A case report

BackgroundDepression is a common mental disorder with increasing prevalence in India, which involves cognitive impairment as well. Pharmacological management of depression has many adverse effects, which provides symptomatic relief to the patients, with little to no improvement in cognitive impairment or cerebral hemodynamics. This necessitates the exploration of complementary and alternative treatment modalities. Yoga, in particular Bhastrika pranyama, has been utilized as a complementary practice for various conditions, but evidence of its impact on depression and cerebral hemodynamics is limited. Case detailsA 66-year-old male, previously diagnosed with depression, was admitted to our inpatient hospital for a holistic approach to his condition, combining yoga and naturopathy as part of his treatment. During his stay, he participated in a ten-minute Bhastrika pranayama intervention, conducted under supervision. To evaluate cerebral hemodynamics, a 16-channel functional near-infrared spectroscopy (fNIRS) device was used and changes in oxygenated hemoglobin (oxyHb), deoxygenated hemoglobin (deoxyHb), and total hemoglobin (Total Hb) was recorded. ResultsFollowing the practice of Bhastrika Pranayama, the results indicated a rise in bilateral oxygenated hemoglobin (OxyHb) levels during and immediately after the practice, particularly in the prefrontal cortex region. Simultaneously, a decrease in deoxygenated hemoglobin (DeoxyHb) was observed during the practice, with a slight subsequent increase after the Bhastrika Pranayama session. ConclusionThese preliminary findings indicate that Bhastrika pranayama may have an immediate positive impact on cerebral hemodynamics in patients with depression. Further research with larger sample sizes and controlled studies is needed to confirm and generalize these observations.

Efficacy of virtual reality-based training programs and games on the improvement of cognitive disorders in patients: a systematic review and meta-analysis

IntroductionCognitive impairments present challenges for patients, impacting memory, attention, and problem-solving abilities. Virtual reality (VR) offers innovative ways to enhance cognitive function and well-being. This study explores the effects of VR-based training programs and games on improving cognitive disorders.MethodsPubMed, Scopus, and Web of Science were systematically searched until May 20, 2023. Two researchers selected and extracted data based on inclusion and exclusion criteria, resolving disagreements through consultation with two other authors. Inclusion criteria required studies of individuals with any cognitive disorder engaged in at least one VR-based training session, reporting cognitive impairment data via scales like the MMSE. Only English-published RCTs were considered, while exclusion criteria included materials not primarily focused on the intersection of VR and cognitive disorders. The risk of bias in the included studies was assessed using the MMAT tool. Publication bias was assessed using funnel plots and Egger’s test. The collected data were utilized to calculate the standardized mean differences (Hedges’s g) between the treatment and control groups. The heterogeneity variance was estimated using the Q test and I2 statistic. The analysis was conducted using Stata version 17.0.ResultsTen studies were included in the analysis out of a total of 3,157 retrieved articles. VR had a statistically significant improvement in cognitive impairments among patients (Hedges’s g = 0.42, 95% CI: 0.15, 0.68; p_value = 0.05). games (Hedges’s g = 0.61, 95% CI: 0.30, 0.39; p_value = 0.20) had a more significant impact on cognitive impairment improvement compared to cognitive training programs (Hedges’s g = 0.29, 95% CI: -0.11, 0.69; p_value = 0.24). The type of VR intervention was a significant moderator of the heterogeneity between studies.ConclusionVR-based interventions have demonstrated promise in enhancing cognitive function and addressing cognitive impairment, highlighting their potential as valuable tools in improving care for individuals with cognitive disorders. The findings underscore the relevance of incorporating virtual reality into therapeutic approaches for cognitive disorders.

The effect of atomoxetine on cognitive function in patients with multiple sclerosis.

Background: Recent research shows that most of the patients with multiple sclerosis (MS) have cognitive-like disorders. Due to the beneficial effects of atomoxetine on improving cognition in limited animal and human surveys, the aim of the present study was to investigate the effect of the atomoxetine on improving cognitive disorders of MS. Methods: This study was a parallel, randomized clinical trial, designed to investigate the effect of atomoxetine drug on the improvement of cognitive impairment (CI) in MS, from April 2021 to March 2022. According to the inclusion and exclusion criteria, a total of 52 participants were involved in the study and then randomly divided in two groups of 26. Experimental group was treated with atomoxetine and the control group was treated with placebo. The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) test was performed for assessment at the beginning and after 3 months. The California Verbal Learning Test (CVLT), the CVLT-delay, the Brief Visuospatial Memory Test-Revised (BVMT-R), and the Symbol Digit Modalities Test (SDMT) were used to evaluate the CI and changes following medication. Finally, data were analyzed by SPSS software at significance level of 0.05. Results: The mean age of patients in the experimental group was 37.7 ± 8.5 and in the placebo group was 37.8 ± 7.6 (P = 0.32). The results showed significant changes in cognitive levels before and after the use of atomoxetine and also in comparison to the placebo group (P < 0.05). Conclusion: This study showed that atomoxetine improved the cognitive domains after administration compared to placebo.

Individuals with depression exhibiting a pro-inflammatory phenotype receiving omega-3 polyunsaturated fatty acids experience improved motivation-related cognitive function: Preliminary results from a randomized controlled trial

Cognitive impairment related to major depressive disorder (MDD) is highly prevalent, debilitating and is lacking in effective treatments; dysregulated inflammatory physiology is a putative mechanism and may represent a therapeutic target. In depressed individuals exhibiting a pro-inflammatory phenotype who were enrolled in a 12-week randomized placebo-controlled trial of 3 doses of omega-3 polyunsaturated fatty acids (ω-3-FA), we examined: (i) the relationship between dysregulated inflammatory physiology and baseline cognitive impairment; (ii) improvement in cognitive impairment following treatment; and (iii) the association between baseline inflammatory biomarkers and change in cognitive impairment for those receiving treatment. We randomized 61 unmedicated adults aged 45.50 years (75% female) with DSM-5 MDD, body mass index >25 kg/m2, and C-reactive protein (CRP) ≥3.0 mg/L to three doses of ω-3-FA (1, 2, or 4 g daily) or matching placebo. Analyses focused on 45 study completers who had inflammatory biomarkers assessed [circulating CRP, interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) as well as lipopolysaccharide (LPS)-stimulated concentrations of IL-6 and TNFα in peripheral blood mononuclear cells (PBMC)] and on the highest dose ω-3-FA (4 g daily; n = 11) compared to placebo (n = 10). Impairment in motivational symptoms (e.g., alertness, energy, enthusiasm) and higher-order cognitive functions (e.g., word-finding, memory) were assessed by a validated self-report measure. Among all 45 participants at baseline, lower concentrations of IL-6 in LPS-stimulated PBMC were associated with greater impairment in higher-order cognitive functions (r = −0.35, p = .02). Based on hierarchical linear modeling, individuals receiving 4 g/day of ω-3-FA reported significant improvement in motivational symptoms compared to placebo (B = −0.07, p = .03); in the 4 g/day group, lower baseline concentrations of TNFα in LPS-stimulated PBMC were associated with significant improvement in motivational symptoms (Ρ = .71, p = .02) following treatment. In this exploratory clinical trial, daily supplementation with 4 g of ω-3-FA improves motivational symptoms in depressed individuals exhibiting an inflammatory phenotype.

Gut Microbiota and Aging: Traditional Chinese Medicine and Modern Medicine.

The changing composition of gut microbiota, much like aging, accompanies people throughout their lives, and the inextricable relationship between both has recently attracted extensive attention as well. Modern medical research has revealed that a series of changes in gut microbiota are involved in the aging process of organisms, which may be because gut microbiota modulates aging-related changes related to innate immunity and cognitive function. At present, there is no definite and effective method to delay aging. However, Nobel laureate Tu Youyou's research on artemisinin has inspired researchers to study the importance of Traditional Chinese Medicine (TCM). TCM, as an ancient alternative medicine, has unique advantages in preventive health care and in treating diseases as it already has formed an independent understanding of the aging system. TCM practitioners believe that the mechanism of aging is mainly deficiency, and pathological states such as blood stasis, qi stagnation and phlegm coagulation can exacerbate the process of aging, which involves a series of organs, including the brain, kidney, heart, liver and spleen. Our current understanding of aging has led us to realise that TCM can indeed make some beneficial changes, such as the improvement of cognitive impairment. However, due to the multi-component and multi-target nature of TCM, the exploration of its mechanism of action has become extremely complex. While analysing the relationship between gut microbiota and aging, this review explores the similarities and differences in treatment methods and mechanisms between TCM and Modern Medicine, in order to explore a new approach that combines TCM and Modern Medicine to regulate gut microbiota, improve immunity and delay aging.

Effect of famotidine on cognitive and behavioral dysfunctions induced in post-COVID-19 infection: A randomized, double-blind, and placebo-controlled study

ObjectivesThis is an investigation of the efficacy and safety of famotidine, a selective histamine H2 receptor antagonist, on improvement of cognitive impairment, depression and anxiety symptoms developing post-COVID-19, in a 12-week, randomized controlled trial. MethodsA total of 50 patients with a confirmed diagnosis of COVID-19 and a score ≤ 23 on the Mini-Mental State Examination (MMSE) test or a score ≤ 22 on the Montreal Cognitive Assessment (MoCA) were randomly assigned to either the famotidine (40 mg twice daily) or the placebo group. Changes in MMSE scores at weeks 6 and 12 were the primary outcome, while changes in other scales were the secondary outcomes. Participants and evaluators were blinded. ResultsAt weeks 6 and 12, patients in the famotidine group had significantly higher MMSE scores (p = 0.014, p < 0.001, respectively). Regarding the MoCA scale, the famotidine group had a significantly higher score at weeks 6 and 12 (p = 0.001, p < 0.001, respectively). Considering the HAM-D scale (Hamilton Depression Rating Scale), at weeks 6 and 12, the famotidine group experienced a larger reduction (p = 0.009, p = 0.02, respectively). Additionally, comparison of the HAM-A scale scores (Hamilton Anxiety Rating Scale) at weeks 6 and 12 showed a statistically significant larger reduction in the famotidine group (p = 0.04, p = 0.02, respectively). The two groups did not differ in the frequency of adverse effects. ConclusionOur study supports safety and efficacy of famotidine in treating cognitive impairment, depression and anxiety symptoms induced by COVID-19. Trial registrationThis trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir; registration number: IRCT20090117001556N138).

Effects of Dl-3-n-butylphthalide on cognitive functions and blood–brain barrier in chronic cerebral hypoperfusion rats

Vascular cognitive impairment (VCI) has been one of the major types of cognitive impairment. Blood–brain barrier damage plays an essential part in the pathogenesis of VCI. At present, the treatment of VCI is mainly focused on prevention, with no drug clinically approved for the treatment of VCI. This study aimed to investigate the effects of DL-3-n-butylphthalide (NBP) on VCI rats. A modified bilateral common carotid artery occlusion (mBCCAO) model was applied to mimic VCI. The feasibility of the mBCCAO model was verified by laser Doppler, 13N-Ammonia-Positron Emission Computed Tomography (PET), and Morris Water Maze. Subsequently, the Morris water maze experiment, Evans blue staining, and western blot of tight junction protein were performed to evaluate the effect of different doses of NBP (40 mg/kg, 80 mg/kg) on the improvement of cognitive impairment and BBB disruption induced by mBCCAO. Immunofluorescence was employed to examine the changes in pericyte coverage in the mBCCAO model and the effect of NBP on pericyte coverage was preliminarily explored. mBCCAO surgery led to obvious cognitive impairment and the decrease of whole cerebral blood flow, among which the blood flow in the cortex, hippocampus and thalamus brain regions decreased more significantly. High-dose NBP (80 mg/kg) improved long-term cognitive function in mBCCAO rats, alleviated Evans blue leakage and reduced the loss of tight junction proteins (ZO-1, Claudin-5) in the early course of the disease, thereby exerting a protective effect on the blood–brain barrier. No significant changes in pericyte coverage were observed after mBCCAO. High-dose NBP improved cognitive function in mBCCAO rats. High-dose NBP protected the integrity of BBB by upregulating TJ protein expression, rather than regulating pericyte coverage ratio. NBP could be a potential drug for the treatment of VCI.

Astrocyte-derived exosome-transported GJA1-20k attenuates traumatic brain injury in rats.

Astrocyte-derived exosome-transported GJA1-20k attenuates traumatic brain injury in rats.

Efficacy of Artemisia annua Linné in improving cognitive impairment in a chronic cerebral hypoperfusion-induced vascular dementia animal model

BackgroundVascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. Currently, no FDA-approved drugs are available for the treatment of VaD. Artemisia annua Linné (AA) is known to have antioxidant properties, but its effects and mechanisms of action on cognitive impairment are still unknown. PurposeIn this study, the improvement in cognitive impairment by AA in terms of protection against oxidative stress, neuroinflammation, and preservation of the integrity of the neurovascular unit (NVU) was assessed in an animal model of VaD with bilateral common carotid artery occlusion (BCCAO). MethodsEight-week-old male Wistar rats were allowed to adapt for four weeks, and BCCAO was induced at 12 weeks of age. The rats were randomly assigned into four groups, with seven rats in each group: sham group without BCCAO, VaD group that received oral administration of distilled water after BCCAO surgery, and two AA groups that received oral administration of 150 mg/kg or 750 mg/kg AA after BCCAO surgery for 8 weeks. Nine weeks after BCCAO surgery, the cognitive function of the rats was evaluated and accumulated oxidative stress was assessed by immunohistochemistry, immunofluorescence, and western blotting. Damage to the components of the NVU was evaluated, and sirtuin (Sirt) 1 and 2 expression and nuclear factor-erythrocyte 2-associated factor 2 (Nrf2)/Kelch-like ECH-associated protein1 (Keap1) activation were investigated to assess the reduction in cell signaling and antioxidant pathways. ResultsBCCAO-induced cerebral perfusion decreased memory function and induced neuroinflammation and oxidative stress. But AA treatment mitigated cognitive impairment and reduced neuroinflammation and oxidative stress caused by chronic cerebral hypoperfusion. AA extracts activated the Nrf2/Keap1/activating antioxidant response elements pathway and maintained Sirt 1 and 2, subsequently leading to the maintenance of neurons, improved construct of microvessels, increased platelet-derived growth factor receptor beta, and platelet-endothelial cell adhesion molecule-1 associated with the blood-brain barrier integrity. ConclusionAA is effective in alleviating BCCAO-induced cognitive decline and its administration may be a useful therapeutic approach for VaD.

Relationship between glycemic control and cognitive impairment: A systematic review and meta-analysis.

Diabetes mellitus, or hyperglycemia, is an independent risk factor for cognitive impairment. Here we systematically analyzed whether glycemic control could improve cognitive impairment in patients with diabetes mellitus (DM), hyperglycemia, or insulin resistance. Three databases (PubMed, EMBASE, and Cochrane Library) and ClinicalTrials.gov were searched for randomized controlled trials analyzing the relationship between glycemic control and cognitive function assessments, published from database inception to June 2022. Patients in experimental groups were treated with antidiabetic drugs, while control groups were treated with a placebo or alternative antidiabetic drugs. Data analysis was conducted using RevMan 5.3 and StataSE-64, and standardized mean difference (SMD) and 95% confidence intervals (CIs) were calculated. Thirteen studies comprising 19,314 participants were included. Analysis revealed that glycemic control significantly attenuated the degree of decline in cognitive function assessment scores (SMD = 0.15; 95% CI 0.05, 0.26; p < 0.00001), and funnel plots confirmed no publication bias. Seven studies used Mini-Mental State Examination as the primary cognitive function assessment, showing that glycemic control significantly delayed the degree of decline in cognitive function assessment scores (SMD = 0.18; 95% CI 0.03, 0.34; p = 0.02). Similar results were seen in two studies using the Montreal Cognitive Assessment scale, but without significant difference (SMD = 0.05; 95% CI-0.10, 0.21; p = 0.51). One study using Auditory Word Learning Test (AVLT) showed that glycemic control significantly delayed the decline in cognitive function assessment scores (SMD = 0.52; 95% CI 0.11,0.93; p = 0.01), and another used Wechsler Memory Scale Revised, showing similar results (SMD = 1.45; 95% CI 0.86, 2.04; p < 0.00001). Likewise, a study that used Modified Mini-Mental State scale showed that glycemic control significantly delayed the decline in cognitive function assessment scores (SMD = -0.10; 95% CI-0.16, -0.03; p = 0.005). Lastly, one study used AVLT subtests to show that glycemic control delayed the decline in cognitive function assessment scores, although not statistically significant (SMD = 0.09; 95% CI-0.53, 0.71; p = 0.78). Glycemic control through antidiabetic treatment correlates with the improvement of cognitive impairment in patients with DM, hyperglycemia or insulin resistance. However, further studies are needed to validate the results of this study. PROSPERO, identifier CRD42022342260.

Compound Danshen Dripping Pills moderate intestinal flora and the TLR4/MyD88/NF-κB signaling pathway in alleviating cognitive dysfunction in type 2 diabetic KK-Ay mice

BackgroudBidirectional communications between the gut microbiota and the brain may play a critical role in diabetes-related cognitive impairment. Compound Danshen Dripping Pills (CDDP) treatment has shown remarkable improvement in cognitive impairment in people with type 2 diabetes mellitus (T2DM) in clinical settings, but the underlying mechanisms remain unknown. PurposeAn extensive detailed strategy via in vivo functional experiments, transcriptomics, metabolomics, and network pharmacology was adopted to investigate the CDDP-treatment mechanism in diabetic cognitive dysfunction. MethodsFor 12 weeks, KK-Ay mice, a spontaneous T2DM model, were intragastrically administered various doses of CDDP solution or an equivalent volume of water, and the nootropic drug piracetam was orally administered as a positive control. At the 12th week, cognition was assessed using Morris water maze tests and brain magnetic resonance imaging (MRI). Furthermore, transcriptomics, metabolomics, and network pharmacology analyses were applied to reveal novel molecular mechanisms of CDDP-treatment in diabetic cognitive dysfunction of KK-Ay mice, which were then validated using quantitative real-time polymerase chain reaction and Western blot. ResultsHere we verified that CDDP can suppress inflammatory response and alleviate the cognitive dysfunction in KK-Ay mice. Also, as demonstrated by 16S rRNA sequencing and short-chain fatty acids (SCFAs) analysis, CDDP attenuated intestinal flora disorder as well as increases of metabolites including butyric acid, hexanoic acid, and isohexic acid. Given the integrated analyses of network pharmacology, transcriptomic, metabolomic data, and molecular biology, the TLR4/MyD88/NF-κB signaling pathway was activated in diabetes, which could be reversed by CDDP. ConclusionsOur findings demonstrate that CDDP restructures the gut microbiota composition and increased the intestinal SCFAs in KK-Ay mice, which might inhibit neuroinflammation, and thus improve diabetic mice cognitive disorder.

Sarcopenia and impairment in global cognitive, delayed memory, and olfactory function, among community-dwelling adults, in Jakarta, Indonesia: Active aging study.

This study aimed to investigate the association of sarcopenia among community-dwelling older adults with chronic conditions, lipid profiles, and cognitive ability measured by multiple assessment tools. This cross-sectional study involved 398 older adults aged 60 years and older who resided in Jakarta, Indonesia. The study participants were visited and interviewed by trained interviewers in the subdistrict office. Participants were clinically examined using a standardized protocol, which included the participants' medical history, general physical examination, cognitive assessment, and blood test for lipid profile. Sarcopenia was measured using three components that were muscle strength (measured by handgrip strength), physical performance (measured by 6-m walk speed), and appendicular skeletal mass (measured using bioelectrical impedance analysis). Association was tested using multivariate logistic regression and reported as an odds ratio. Sarcopenia was significantly associated with older age (adjusted odd ratio [AOR]: 2.91, 95% confidence interval [CI]: 1.22-3.95) and smoking (AOR: 6.53, 95% CI: 2.89-14.73). Global cognitive impairment, word list recall impairment, and olfactory dysfunction have 191% (95% CI: 1.28-6.66), 141% (95% CI: 1.12-5.2), and 100% (95% CI: 1.11-3.61) increase of odds of having sarcopenia, respectively. Global cognitive impairment, word list recall impairment, and olfactory dysfunction could be the predictors of sarcopenia. Strategies and implementations directed more toward the improvement of cognitive impairment might improve or prevent sarcopenia. However, the exact causality between both variables still needs to be explored further.

Zunyimycin C enhances immunity and improves cognitive impairment and its mechanism.

This study aimed to explore the efficacy of zunyimycin C in the immunological enhancement of hypoimmune mice and improvement of cognitive impairment in a mice model of Alzheimer's disease (AD). Zunyimycin C was administered intranasally to interfere with AD mouse models or gavage to hypoimmune animals. Results of the Morris water maze (MWM) showed that zunyimycin may improve the learning and memory abilities of the AD mice model. The results of differential expression analysis of mRNA levels of inflammatory factors and pathways in brain tissues of the AD mouse model suggested that differential expression was more obvious under Zun-Int L. Western blot revealed that the relative expression of glial fibrillary acidic protein in the brain tissue of the AD mouse model in the Zun-Pre group was significantly higher than that in the other groups, and the difference was statistically significant. The relative expression of interleukin (IL)-6 protein in the brain tissue of mice in the low-dose intervention group was significantly lower than that in the other groups, and the difference was statistically significant. As for hypoimmune animals, short chain fatty acids (SCFAs) assay and intestinal flora assay results showed that zunyimycin C may change intestinal flora diversity and SCFA biosynthesis. The prophylactic administration of zunyimycin C could not inhibit acute neuroinflammation in AD mice. Zunyimycin C may participate in the immune response by activating the Ras-Raf-MEK-ERK signaling pathway to stimulate microglia to produce more inflammatory factors. Zunyimycin C may inhibit autophagy by activating the PI3K-AKT-mTOR signaling pathway, promote cell survival, mediate neuroprotective effects of reactive microglia and reactive astrocytes, and reduce IL-1β in brain tissue and IL-6 secretion, thereby attenuating neuroinflammation in AD mice and achieving the effect of improving learning and memory impairment. Zunyimycin C may play a role in immunological enhancement by changing intestinal flora diversity and SCFAs.

Carob Seed Peels Effect on Cognitive Impairment and Oxidative Stress Status in Methionine-Induced Mice Models of Schizophrenia.

Background:Ceratonia siliqua L. (Carob tree) is a Mediterranean evergreen, well known for its medicinal properties. The different parts of Carob were proven to exert antidiabetic, antibacterial, antifungal, and antiproliferative effects. Hence, the present paper aims to validate the positive correlation between the high antioxidant activity of carob seed peels and the improvement of negative symptoms of schizophrenia. Materials & Methods: The antioxidant activity was carried out using the β-carotene test. Methionine and carob seed peels (CSP) extracts (50 and 100 mg/kg) were orally administrated to mice for a week. After administration, behavioral tests were assessed using the Y-maze, elevated plus maze, and forced swimming tests, as well as the novel object recognition task. Furthermore, the oxidative stress status was evaluated by analyzing the levels of the antioxidant enzymes: Superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde levels (MDA). Results: Both extracts exhibited remarkable antioxidant activity and showed antibacterial effect against Gram-positive bacteria tested (Bacillus subtilis and Staphylococcus aureus) and against Pseudomonas aeruginosa (Gram-negative). Therefore, Escherichia coli was very resistant. The behavioral tests proved the efficacy of CSP in enhancing the cognitive impairment of animal models of schizophrenia. Hence, the stated correlation between oxidative stress and schizophrenia was confirmed by the increased SOD and GPx activities and the decreased MDA level. Conclusions: The present study gave further confirmation of the potential correlation between oxidative stress and the development of psychiatric disorders and highlighted the use of natural antioxidants, especially Ceratonia siliqua L. in the improvement of cognitive impairment in the dementia of schizophrenia.

Pharmaceutical Potential of Casein-Derived Tripeptide Met-Lys-Pro: Improvement in Cognitive Impairments and Suppression of Inflammation in APP/PS1 Mice.

Background:Tripeptide Met-Lys-Pro (MKP), a component of casein hydrolysates, has effective angiotensin-converting enzyme (ACE) inhibitory activity. Brain angiotensin II enzyme activates the NADPH oxidase complex via angiotensin II receptor type 1 (AT1) and enhances oxidative stress injury. ACE inhibitors improved cognitive function in Alzheimer’s disease (AD) mouse models and previous clinical trials. Thus, although undetermined, MKP may be effective against pathological amyloid-β (Aβ) accumulation-induced cognitive impairment.Objective:The current study aimed to investigate the potential of MKP as a pharmaceutical against AD by examining MKP’s effect on cognitive function and molecular changes in the brain using double transgenic (APP/PS1) mice.Methods:Experimental procedures were conducted in APP/PS1 mice (n = 38) with a C57BL/6 background. A novel object recognition test was used to evaluate recognition memory. ELISA was used to measure insoluble Aβ40, Aβ42, and TNF-α levels in brain tissue. Immunohistochemical analysis allowed the assessment of glial cell activation in MKP-treated APP/PS1 mice.Results:The novel object recognition test revealed that MKP-treated APP/PS1 mice showed significant improvement in recognition memory. ELISA of brain tissue showed that MKP significantly reduced insoluble Aβ40, Aβ42, and TNF-α levels. Immunohistochemical analysis indicated the suppression of the marker for microglia and reactive astrocytes in MKP-treated APP/PS1 mice.Conclusion:Based on these results, we consider that MKP could ameliorate pathological Aβ accumulation-induced cognitive impairment in APP/PS1 mice. Furthermore, our findings suggest that MKP potentially contributes to preventing cognitive decline in AD.

Pharmacological activation of the C5a receptor leads to stimulation of the β-adrenergic receptor and alleviates cognitive impairment in a murine model of familial Alzheimer's disease.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease of the brain causing either familial or sporadic dementia. We have previously administered the modified C5a receptor agonist (EP67) for a short period to a transgenic mouse model of AD (5XFAD) and have observed not only reduction in β-amyloid deposition and gliosis but also improvement in cognitive impairment. Inquiring, however, on the effects of EP67 in an already heavily burdened animal, thus representing a more realistic scenario, we treated 6-month-old 5XFAD mice for a period of 14 weeks. We recorded a significant decrease in both fibrillar and pre-fibrillar β-amyloid as well as remarkable amelioration of cognitive impairment. Following proteomic analysis and pathway association, we postulate that these events are triggered through the upregulation of β-adrenergic and GABAergic signaling. In summary, our results reveal how inflammatory responses can be employed in inducing tangible phenotype improvements even in advanced stages of AD.

The Effect of Non-immersive Virtual Reality Exergames Versus Band Stretching on Cardiovascular and Cerebral Hemodynamic Response: A Functional Near-Infrared Spectroscopy Study

BackgroundExercise is one of the effective ways to improve cognition. Different forms of exercises, such as aerobic exercise, resistance exercise, and coordination exercise, have different effects on the improvement of cognitive impairment. In recent years, exergames based on Non-Immersive Virtual Reality (NIVR-Exergames) have been widely used in entertainment and have gradually been applied to clinical rehabilitation. However, the mechanism of NIVR-Exergames on improving motor cognition has not been clarified. Therefore, the aim of this study is to find whether NIVR-Exergames result in a better neural response mechanism to improve the area of the cerebral cortex related to motor cognition under functional near-infrared spectroscopy (fNIRS) dynamic monitoring in comparison with resistance exercise (resistance band stretching).MethodsA cross-over study design was adopted in this study, and 15 healthy young subjects (18–24 years old) were randomly divided into group A (n = 8) and group B (n = 7) according to a computerized digital table method. Task 1 was an NIVR-Exergame task, and Task 2 was resistance band stretching. Group A first performed Task 1, rested for 30 min (i.e., a washout period), and then performed Task 2. Group B had the reverse order. The fNIRS test was synchronized in real time during exercise tasks, and heart rate measurements, blood pressure measurements, and 2-back task synchronization fNIRS tests were performed at baseline, Post-task 1, and Post-task 2. The primary outcomes were beta values from the general linear model (GLM) in different regions of interest (ROIs), and the secondary outcomes were heart rate, blood pressure, reaction time of 2-back, and accuracy rate of 2-back.ResultsThe activation differences of Task 1 and Task 2 in the right premotor cortex (PMC) (P = 0.025) and the left PMC (P = 0.011) were statistically significant. There were statistically significant differences in the activation of the right supplementary motor area (SMA) (P = 0.007), left dorsolateral prefrontal cortex (DLPFC) (P = 0.031), left and right PMC (P = 0.005; P = 0.002) between baseline and Post-task 1. The differences in systolic pressure (SBP) between the two groups at three time points among women were statistically significant (P1 = 0.009, P2 < 0.001, P3 = 0.044).ConclusionIn this study, we found that NIVR-Exergames combined with motor and challenging cognitive tasks can promote the activation of SMA, PMC and DLPFC in healthy young people compared with resistance exercise alone, providing compelling preliminary evidence of the power for the rehabilitation of motor and cognitive function in patients with central nervous system diseases.

Influence of Daily Dark Sweet Cherry (DSC) Juice Consumption for 4 Weeks in Obesity-Associated Inflammation and Cognitive Decline: A Randomized Controlled Trial

Abstract Objectives To assess the effects of DSC juice consumption in biomarkers of inflammation and cognitive function in adults with obesity Methods Eligible participants (&amp;gt;18 years, body-mass index (BMI) = 30–40 kg/m2, no history of chronic disease and/or antibiotics), were allocated to cherry or placebo groups following a single-blind randomized design after a 2-week run-in period. Participants were instructed to drink 200 mL of DSC juice supplemented with 3 g of DSC powder (n = 19) or placebo drink (n = 21) twice a day for 4 weeks. Levels of biomarkers for inflammation and cognitive function were assessed on fasting blood samples collected at week 0 and week 4 by the multiplex bead assay using the Human Cytokine/Chemokine/Growth Factor and Human Neuropeptide Magnetic bead panel, respectively, (Millipore; Billerica, MA) following the manufacturers’ protocol. Results were expressed as mean ± SEM. Results Results showed that 4 weeks of DSC supplementation lowered the levels of monocyte chemoattractant protein 1 (MCP-1) and RANTES (MCP-1 = 316.07 ± 26.81 vs. 281.45 ± 19.93, RANTES = 175.13 ± 56.91 vs. 100.54 ± 17.92), although these changes were not significant. In contrast, the levels of MCP-1 and RANTES showed no improvement in week 4 (MCP-1 = 261.04 ± 18.75 vs. 298.99 ± 28.91, RANTES = 101.7 ± 28.14 vs. 96.79 ± 20.59) in the placebo group. Since MCP-1 is critical for the development of cardiovascular diseases, its downregulation accompanied by lowering RANTES may contribute to lessen obesity-associated inflammation and heart disease. These results were accompanied by improvements in cognitive impairment observed in DSC group. The levels of neurotensin which is altered in obesity was significantly higher in the placebo group at week 4 (103.70 ± 24.29 vs 127.57 ± 30.96, p = 0.006) compared to the DSC group (105.81 ± 25.85 vs. 122.41 ± 28.05, p = 0.07). Likewise, the levels of substance-P which promotes an inflammatory environment in obesity, was significantly elevated in placebo group (21.36 ± 7.29 vs. 27.59 ± 7.65, p = 0.04) when compared to DSC group (21.89 ± 7.53 vs. 28.65 ± 4.32, p = 0.52). Conclusions These findings suggest that consumption of DSC juice over 4 weeks may decrease obesity-associated low-grade inflammation and cognitive decline. Funding Sources Northwest Cherry Growers.

Effect of low-level laser therapy (LLLT) on cognitive impairment among patients with chronic schizophrenia: a double-blind randomized placebo-controlled clinical trial.

Low-level laser therapy (LLLT) is a noninvasive technique used in different medical fields. It has been applied in different medical areas such as wound healing, traumatic brain injuries, neurological disorders, cognitive disorders, Alzheimer's disease, pain, and arthritis, with different results. We studied the effectiveness of LLLT on cognitive impairment in patients with chronic schizophrenia. A randomized controlled double-blind clinical trial was performed in a men's chronic treatment center, in Razi Psychiatric Hospital, in Tehran, Iran. We screened the cognitive impairment by Mini-Mental State Examination (MMSE). Positive And Negative Syndrome Scale (PANSS) was also used to assess the patients' positive and negative symptoms. Seventeen consenting patients were randomly allocated to the treatment arm, and 15 to the sham treatment control arm. The mean age of the control and treated patients was 49.47 ± 6.99 and 50.24 ± 7.69, respectively. No significant difference in PANSS and MMSE test scores was detected in both groups after the 6th session and after 2months of follow-up after laser therapy. The positive and negative scales and agitation and excitement levels did not change significantly in either group. Nevertheless, the depression/anxiety subscale in the PANSS test showed a significant reduction after 6 sessions but did not persist after 2months. No improvement in cognitive impairment or the positive and negative symptoms was detected after LLLT in patients with chronic schizophrenia. Trial registration: IRCT 20210520051349N1.