Cognitive impairment in a Colombian cohort of patients with systemic lupus erythematosus: A cross-sectional study.

CONTEXT: Cognitive deficits are neuropsychiatric syndromes associated with systemic lupus erythematosus. In our context, there are no data on the frequency of cognitive deficit as a manifestation of neuropsychiatric SLE or the associated conditions. OBJECTIVE: To define determinants of cognitive deficit in a cohort of Colombian patients with SLE attending a third-level hospital. METHODS AND PATIENTS: This descriptive cross-sectional study included patients with SLE, explored the presence of cognitive impairment through screening testing using the Montreal Cognitive Assessment (MoCA test), and diagnostic confirmation with a specific neuropsychological test battery recommended by the American College of Rheumatology. Quality of life was assessed using the LupusCol questionnaire and depression using the Beck Depression Inventory. RESULTS: Most patients were women, with a median age of 37 years (IQR, 28.0 - 46.7). Most patients had a level of higher education or technical education. Fifty-nine (62.9%) patients presented with a normal MoCA test result ≥26 points, and 35 (37.1%) patients with a score <26 points that were considered abnormal. The comprehensive neuropsychological test battery was applied to 31 patients (33.0%) with an abnormal MoCA test. Forty-one patients (48.8%) had some degree of depression. The median loss of quality of life was 21.03% (IQR 10.2 - 40.3). 19 patients (20%) presented some degree of cognitive deficit, 15 (15.95% of the total sample) had cognitive impairment, and 4 (4.25%) had cognitive decline. In a logistic regression analysis using data from patients undergoing specific tests, variables related to cognitive deterioration were found to be associated with a lower quality of life, showing an adjusted odds ratio of 1.05 (CI 1.01-0.09). No association was demonstrated with SLEDAI, prednisolone use, cyclophosphamide use, and the presence of depression. CONCLUSION: In this study, it was found in 16% of patients evaluated with the complete neuropsychological test battery and in 37% with the MoCA screening test. Our results suggest that it is crucial to implement strategies to assess cognitive deficit, depression, and quality of life in the consultation of patients with SLE and to raise awareness among health providers who care for patients with lupus about their presence and impact.

Dose-Dependent Attenuation of the Efficacy of Clitoria ternatea by Cobalt Oxide Nanoparticles Against Diabetes-Induced Cognitive Impairment.

Diabetes mellitus is a metabolic disorder caused by insulin deficiency, insulin resistance, genetic alterations, and oxidative stress. The high glucose levels may impair the functioning of nerve cells, leading to neurodegenerative diseases, including cognitive impairment. Clitoria ternatea has various pharmacological activities, including antioxidant, anti-inflammatory, antidiabetic, and neuroprotective effects. The present study evaluates the efficacy of fresh flower aqueous extract of Clitoria ternatea against diabetes-induced cognitive impairment. The challenges in delivering drugs targeting the brain possess the limitations of crossing the blood-brain barrier. Metal nanoparticles are considered the most reliable brain drug delivery systems. Considering the neurotoxicity of cobalt oxide, whether it can be used to improve brain delivery is also evaluated. Cobalt oxide nanoparticles (Co3O4 NPs) of fresh flower aqueous extract of Clitoria ternatea are prepared by green synthesis and characterized. The effect of these nanoparticles is compared with Clitoria ternatea extract against Streptozotocin (STZ)-induced cognitive impairment. The behavioral, biochemical, in vivo antioxidant, total thiol content, estimation of proinflammatory cytokines, acetylcholine esterase, and nitrite levels in the brain of STZ-induced diabetic rats revealed that cobalt oxide nanoparticles showed neurotoxicity, whereas C. ternatea showed neuroprotective effect and also improved the cognitive function. The lower dose of cobalt oxide nanoparticles of C. ternatea (2 mg/kg) exhibited a neuroprotective and cognition improvement effect. However, the higher dose (4 mg/kg) of cobalt oxide nanoparticles of C. ternatea showed a neurotoxic effect. Since Co3O4 NPs are neuroprotective at low doses, they can be used for neuroprotective actions. However, dose optimization studies are required.

[Efficiency of computerized cognitive training for prevention of cognitive impairments and stimulation of neuroplasticity.]

Computerized cognitive training (CCT) is a rapidly developing area of cognitive rehabilitation at the intersection of information technology and healthcare, the constantly updated results of which can be successfully translated into practical application in clinical medicine and in particular in gerontology. The basis of CCT, as a non-invasive method of influencing the functional activity of the brain and the processes of neuroplasticity, is software for stimulating cognitive functions in order to improve their productivity. The level of scientific and practical interest in CCP technology is growing rapidly. The article reports on the current state of research on the use of CCT aimed at correcting cognitive impairment. The purpose of this work is to systematize the available scientific data in this area, as well as to promote further integration of research in the field of information technology into clinical practice, in particular, to study the potential of CCT as a promising therapeutic tool in the paradigm of successful aging and prevention of the progression of cognitive impairment. This noninvasive intervention may improve global cognitive function in patients with clinically defined impairments and during normal aging in cognitively healthy older adults. However, new studies with fully comparable protocols are needed to evaluate in more detail the duration of the effect and the effectiveness of CCT in preventing cognitive decline in the long term.

Dissociable effects of mild COVID-19 on short- and long-term memories.

Recent studies have highlighted the presence of cognitive deficits following COVID-19 that persist beyond acute infection, regardless of the initial disease severity. Impairments in short- and long-term memory are among the core deficits reported by patients and observed in objective tests of memory performance. We aimed to extend previous studies by examining performance in a task that allows us to directly compare and contrast memories at different timescales. More specifically, we assessed both short- and long-term memories for contextual-spatial associations encoded during a common session and probed at different durations using an equivalent task in non-hospitalized individuals recovering from mild COVID-19 compared to healthy controls. The approach equated all aspects of memory materials and response demands, isolating performance changes resulting only from memory timescales and thus allowing us to quantify the impact of COVID-19 on cognition. In addition to providing measures of accuracy and response times, the task also provided a sensitive continuous readout of the precision of memory representations, specifically by examining the resolution with which spatial locations were retained in memory. The results demonstrated selective impairment of long-term memory performance in individuals recovering from mild COVID-19 infection. Short-term memory performance remained comparable to healthy controls. Specifically, poor precision of long-term memory representations was demonstrated, which improved with days since diagnosis. No such relationship was observed for short-term memory performance. Our findings reveal a specific impairment to the precision of spatial-contextual long-term memory representations in individuals recovering from mild COVID-19 and demonstrate evidence of recovery in long-term memory over time. Further, the experimental design provides a carefully controlled and sensitive framework to assess memory across different durations with the potential to provide more detailed phenotyping of memory deficits associated with COVID-19 in general.

Chronic Alcohol Exposure Alters the Levels and Assembly of the Actin Cytoskeleton and Microtubules in the Adult Mouse Hippocampus.

BACKGROUND: Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus. METHODS: Mice were provided ad libitum access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis. RESULTS: Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice. CONCLUSIONS: Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.

Rethinking the role of trazodone in the different depressive dimensions.

INTRODUCTION: The efficacy of trazodone for several psychopathologic dimensions of depression has been shown in the literature. Trazodone has been widely used in some clinical contexts (e.g. for insomnia and depression in the elderly). However, the role of trazodone in several aspects of depression is not well known. AREA COVERED: Eight experts from academic and medical centers across Italy met to identify the difficulties and barriers faced in daily clinical practice in the assessment and management of major depressive disorder and how the use of trazodone could address some unmet needs. The objective of the expert meetings and the present document was to increase knowledge of particular areas of treatment with trazodone. EXPERT OPINION: Evidence of the role of trazodone in patients affected by major depressive disorder with anxiety symptoms, insomnia, agitation, cognitive deficits, alcohol use disorders, physical comorbidities, and suicide risk has been identified, showing the effectiveness of trazodone in different presentations of major depressive disorder. The main characteristics of patients with depression for whom trazodone seems to be most effective have been identified, providing clinicians with information on possible uses of this drug in such population of patients.

The association between neuropsychological impairment, self-perceived cognitive deficit, symptoms, and health related quality of life in newly diagnosed ovarian cancer patients.

Objective: To assess cognitive function in patients newly diagnosed with ovarian cancer (OC) before treatment and explore the relationship between neuropsychological impairment, self-perceived cognitive deficit, symptoms, and health-related quality of life in them. Methods: From May 2021 to February 2022, 105 women newly diagnosed with OC were enrolled in the Cancer Center of Fudan University, Shanghai, China. Objective and subjective cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) scale and Perceptual Deficits Questionnaire (PDQ). Symptoms and quality of life were evaluated using the Memorial Symptom Assessment Scale (MSAS) and Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O), respectively. Results: This study included 105 newly diagnosed OC patients, with an average age of 49.73 (±8.48) years. Of these, 72.38% had impaired neuropsychological test scores, especially in delayed recall, abstraction, and visuospatial/executive function. Retrospective, and prospective memory were the most serious perceived deficits. The results of the MoCA test were not associated with PDQ (Rs = -0.180, P = 0.067) and significantly correlated with the distress index, physiological and total scores of the MSAS, and emotional well- being of the FACT-O. The PDQ positively correlated with all MSAS dimensions but not with the FACT-O. Conclusion: The incidence of neuropsychological impairment in patients newly diagnosed with OC was high, with no association with self-perceived cognitive deficits. It is recommended that healthcare providers include cognitive impairment in symptom management in this population, who may benefit from early assessment, prevention, and intervention.

Neurological Consequences of Cardiac Arrhythmias: Relationship Between Stroke, Cognitive Decline, and Heart Rhythm Disorders.

Cardiac arrhythmias are one of the most common disorders with high morbidity and mortality. The effect of cardiac arrhythmias on the brain is very pronounced due to the high sensitivity of the brain to oxygen and blood supply. This mortality is preventable by early diagnosis and treatment which improves the patient's quality of life. Intervening at the right time, post arrhythmia is significant in preventing deaths and improving patient outcomes. Multiple pathophysiological mechanisms are studied for the brain-axis implications, that have the potential to be targeted by novel therapies. In this review, we describe the pathophysiological mechanisms and recent advances in detail to understand the functional aspects of the brain-heart axis and neurological implications post-stroke, caused by cardiac disorders.  This paper aims to discuss the current literature on the neurological consequences of cardiac arrhythmias and delve into a deeper understanding of the brain-heart axis, imbalances, and decline, with the aim of summarizing everything and all about the neurological consequences of cardiac arrhythmias.

The Impact of Long COVID on Cognitive Performance and Sleep Quality: An Analysis of the Rancagua Chilean Study (RACHIS).

Background Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to prolonged symptoms post-recovery, commonly known as long-term coronavirus disease 2019 (COVID-19) or "long COVID." Neuropsychiatric consequences of long COVID include cognitive dysfunction and sleep disturbances, which significantly impair daily living. This study aimed to explore the impact of long COVID on cognitive performance and sleep quality in patients receiving outpatient care. Material and methods This study involved a random sample of 138 of 363 patients, corresponding to 38% of the cohort, who tested positive for SARS-CoV-2 via polymerase chain reaction (PCR) between May 2020 and April 2021. These unvaccinated, non-hospitalized individuals, predominantly exhibiting mild disease symptoms, were prospectively assessed 11 months post-positive PCR test. After informed consent, demographic data, memory, and concentration impairment levels were collected through interviews. Participants reporting cognitive symptoms underwent the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MOCA), and the Pittsburgh Sleep Quality Index. Statistical analyses were conducted, including Student's t-test, Chi-square, Fisher's test, Kruskal-Wallis test, and Pearson correlation coefficient, with a significance threshold set at p<0.05. Results Of the 138 participants, 76 (55.1%) were female and 62 (44.9%) were male. The mean age was 45.9 years (± 13.0), with an average educational attainment of 10.4 years (± 3.7). Roughly 50% of the patients reported significant memory and concentration issues (p<0.001). Thirty-three participants underwent detailed cognitive assessments, revealing a 2:1 female-to-male ratio and a significantly higher prevalence of depression in female participants. Cognitive deficits were diagnosed in five (15.2%) participants via the MMSE and in 26 (78.8%) via the MOCA test, with notable deficits in visuospatial/executive functions, language repeat, and deferred recall (p<0.001). A lower educational level was correlated with higher cognitive deficits (p=0.03). Conclusion The study findings reveal that cognitive impairments, as a consequence of COVID-19, can persist up to 11 months post-infection. The MOCA test proved more effective in diagnosing these deficits and requires adjustments based on educational background. Sleep parameters remained largely unaffected in this cohort, likely attributed to the mild nature of the initial symptoms and the outpatient management of the disease.

Exploring the Effects of Major Depressive Disorder on Daily Occupations and the Impact of Psychotherapy: A Literature Review.

Major depressive disorder (MDD) is a prevalent psychological mood disorder that can disrupt one's functioning and result in decreased engagement in daily activities. Psychotherapy, in different approaches, is a common approach for individuals experiencing MDD. Nevertheless, a literature review of the research supporting the effectiveness of psychotherapeutic interventions in patients with MDD-impacted areas of their daily occupations, such as back to work, cognitive deficits, and well-being, has not been conducted. A literature review was carried out to evaluate the effectiveness of psychotherapy on daily occupations for individuals diagnosed with MDD. Due to variations in study design and outcome measures, a best evidence synthesis was carried out instead of a meta-analysis. Forty-one identified articles were fully assessed in total. These studies were conducted in various countries so that a global approach could be considered comprehensive. The findings showed strong evidence supporting the effectiveness of psychotherapy on return-to-work interventions in improving depressive symptoms. There was limited evidence for the effectiveness of psychotherapy on lifestyle interventions in reducing anxiety and suicidal ideation, as well as limited evidence for enhancing work participation. Notably, there were no studies evaluating individualized client-centered psychotherapy interactions with occupations, revealing a research gap. Challenges such as incomplete reporting within studies and study heterogeneity prevented a meta-analysis. While the overall evidence base for the effectiveness of psychotherapy for MDD in treating functionality is limited, the findings provide strong support for the efficacy of occupational therapy return-to-work interventions. This is particularly important given the economic costs associated with mental health issues and work-related absences. Further research is required to strengthen the existing evidence base.

Development of chitosan lipid nanoparticles to alleviate the pharmacological activity of piperine in the management of cognitive deficit in diabetic rats.

The aim of the present study was to prepare and evaluate Piperine (PP) loaded chitosan lipid nanoparticles (PP-CLNPs) to evaluate its biological activity alone or in combination with the antidiabetic drug Metformin (MET) in the management of cognitive deficit in diabetic rats. Piperine was successfully loaded on CLNPs prepared using chitosan, stearic acid, Tween 80 and Tripolyphosphate (TPP) at different concentrations. The developed CLNPs exhibited high entrapment efficiency that ranged from 85.12 to 97.41%, a particle size in the range of 59.56-414 nm and a negatively charged zeta potential values (- 20.1 to - 43.9 mV). In vitro release study revealed enhanced PP release from CLNPs compared to that from free PP suspensions for up to 24 h. In vivo studies revealed that treatment with the optimized PP-CLNPs formulation (F2) exerted a cognitive enhancing effect and ameliorated the oxidative stress associated with diabetes. PP-CLNPs acted as an effective bio-enhancer which increased the potency of metformin in protecting brain tissue from diabetes-induced neuroinflammation and memory deterioration. These results suggested that CLNPs could be a promising drug delivery system for encapsulating PP and thus can be used as an adjuvant therapy in the management of high-risk diabetic cognitive impairment conditions.

Disruptions of Gut Microbiota are Associated with Cognitive Deficit of Preclinical Alzheimer's Disease: A Cross-Sectional Study.

BACKGROUND: Alzheimer's Disease (AD) is the most prevalent type of dementia. The early change of gut microbiota is a potential biomarker for preclinical AD patients. OBJECTIVE: The study aimed to explore changes in gut microbiota characteristics in preclinical AD patients, including those with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI), and detect the correlation between gut microbiota characteristics and cognitive performances. METHODS: This study included 117 participants [33 MCI, 54 SCD, and 30 Healthy Controls (HC)]. We collected fresh fecal samples and blood samples from all participants and evaluated their cognitive performance. We analyzed the diversity and structure of gut microbiota in all participants through qPCR, screened characteristic microbial species through machine learning models, and explored the correlations between these species and cognitive performances and serum indicators. RESULTS: Compared to the healthy controls, the structure of gut microbiota in MCI and SCD patients was significantly different. The three characteristic microorganisms, including Bacteroides ovatus, Bifidobacterium adolescentis, and Roseburia inulinivorans, were screened based on the best classification model (HC and MCI) having intergroup differences. Bifidobacterium adolescentis is associated with better performance in multiple cognitive scores and several serum indicators. Roseburia inulinivorans showed negative correlations with the scores of the Functional Activities Questionnaire (FAQ). CONCLUSION: The gut microbiota in patients with preclinical AD has significantly changed in terms of composition and richness. Correlations have been discovered between changes in characteristic species and cognitive performances. Gut microbiota alterations have shown promise in affecting AD pathology and cognitive deficit.

Artemisinin ameliorates cognitive decline by inhibiting hippocampal neuronal ferroptosis via Nrf2 activation in T2DM mice.

BACKGROUND: Neuronal ferroptosis plays a critical role in the pathogenesis of cognitive deficits. The present study explored whether artemisinin protected type 2 diabetes mellitus (T2DM) mice from cognitive impairments by attenuating neuronal ferroptosis in the hippocampal CA1 region. METHODS: STZ-induced T2DM mice were treated with artemisinin (40 mg/kg, i.p.), or cotreated with artemisinin and Nrf2 inhibitor MEL385 or ferroptosis inducer erastin for 4 weeks. Cognitive performance was determined by the Morris water maze and Y maze tests. Hippocampal ROS, MDA, GSH, and Fe2+ contents were detected by assay kits. Nrf2, p-Nrf2, HO-1, and GPX4 proteins in hippocampal CA1 were assessed by Western blotting. Hippocampal neuron injury and mitochondrial morphology were observed using H&E staining and a transmission electron microscope, respectively. RESULTS: Artemisinin reversed diabetic cognitive impairments, decreased the concentrations of ROS, MDA and Fe2+, and increased the levels of p-Nr2, HO-1, GPX4 and GSH. Moreover, artemisinin alleviated neuronal loss and ferroptosis in the hippocampal CA1 region. However, these neuroprotective effects of artemisinin were abolished by Nrf2 inhibitor ML385 and ferroptosis inducer erastin. CONCLUSION: Artemisinin effectively ameliorates neuropathological changes and learning and memory decline in T2DM mice; the underlying mechanism involves the activation of Nrf2 to inhibit neuronal ferroptosis in the hippocampus.

Effect of pranayama on sympatho-vagal imbalance and cognitive deficit in premenstrual syndrome.

Context: Premenstrual syndrome (PMS) is a prevalent and often neglected condition that affects around 80% of women of reproductive age. In PMS, abnormal fluctuations in gonadal hormones cause altered homeostasis, resulting in sympatho-vagal imbalance and poor cognition. Aim: To compare autonomic function parameters and cognitive performance between PMS and control groups, and to study the effect of pranayama on the above parameters in PMS women. Settings and Design: It was a randomized control trial. Materials and Methods: We recruited 40 women of reproductive age who fit the inclusion criteria. They were asked to complete the Premenstrual Syndrome Screening Tool (PSST) questionnaire and were categorized as having PMS (n = 20) or not having PMS (n = 20). All study participants had their baseline CAFT, HRV, BRS, P300, and MOCA values recorded. Following that, participants in the PMS group were divided into two groups of ten at random. For 8 weeks, one group received pranayama training. Following that, all baseline data were recorded again in both the pranayama and no-intervention groups. Statistical Analysis Used: SPSS version 20 was used to analyze the data. For parametric data, the unpaired t test was used to compare between the PMS and no PMS groups, whereas the Mann-Whitney U test was employed for non-parametric data. To compare the parameters before and after intervention, the Students paired 't' test for parametric data and the Wilcoxan-signed rank test for non-parametric data were used. Results: According to the findings, autonomic function and cognition were considerably affected in the PMS group and improved significantly in the PMS group following pranayama intervention. Conclusion: Pranayama is an effective and safe non-pharmacological method for treating PMS and improving women's quality of life.

Neurological, Metabolic, and Psychopathological Correlates of Lifetime Suicidal Behaviour in Major Depressive Disorder without Current Suicide Ideation.

INTRODUCTION: Suicidal behaviour (SB) has a complex aetiology. Although suicidal ideation (SI) is considered the most important risk factor for future attempts, many people who engage in SB do not report it. METHODS: We investigated neurological, metabolic, and psychopathological correlates of lifetime SB in two independent groups of patients with major depression (sample 1: n = 230; age: 18-65 years; sample 2: n = 258; age >60 years) who did not report SI during an index episode. RESULTS: Among adults (sample 1), SB was reported by 141 subjects (58.7%) and severe SB by 33 (15%). After controlling for interactions, four risk factors for SB emerged: male gender (OR 2.55; 95% CI: 1.06-6.12), negative self-perception (OR 1.76; 95% CI: 1.08-2.87), subthreshold hypomania (OR 4.50; 95% CI: 1.57-12.85), and sexual abuse (OR 3.09; 95% CI: 1.28-7.48). The presence of at least two of these factors had the best accuracy in predicting SB: sensitivity = 57.6% (39.2-74.5); specificity = 75.1% (68.5-82.0); PPV = 27.9% (20.9-37.2); NPV = 91.4% (87.6-94.1). In older patients (sample 2), 23 subjects (9%) reported previous suicide attempts, which were characterized by earlier onset (25 years: OR 0.95: 0.92-0.98), impaired verbal performance (verbal fluency: OR 0.95: 0.89-0.99), higher HDL cholesterol levels (OR 1.04: 1.00-1.07) and more dyskinesias (OR 2.86: 1.22-6.70). CONCLUSION: Our findings suggest that SB is common in major depressive disorder, even when SI is not reported. In these individuals it is feasible and recommended to investigate both psychiatric and organic risk factors. The predictive power of models excluding SI is comparable to that of models including SI.

Borolatonin limits cognitive deficit and neuron loss while increasing proBDNF in ovariectomised rats.

BACKGROUND: Borolatonin is a potential therapeutic agent for some neuronal diseases such as Alzheimer's disease (AD). Its administration exerts ameliorative effects such as those induced by the equimolar administration of melatonin in behavioral tests on male rats and in neuronal immunohistochemistry assays. OBJECTIVE: In this study, motivated by sex differences in neurobiology and the incidence of AD, the ability of borolatonin to induce changes in female rats was assessed. METHODS: Effects of borolatonin were measured by the evaluation of both behavioral and immunohistopathologic approaches; additionally, its ability to limit amyloid toxicity was determined in vitro. RESULTS: Surprisingly, behavioral changes were similar to those reported in male rats, but not those evaluated by immunoassays regarding neuronal survival; while pro-brain-derived neurotrophic factor (BDNF) immunoreactivity and the limitation of toxicity by amyloid in vitro were observed for the first time. CONCLUSION: Borolatonin administration induced changes in female rats. Differences induced by the administration of borolatonin or melatonin could be related to the differences in the production of steroid hormones in sex dependence. Further studies are required to clarify the possible mechanism and origin of differences in disturbed memory caused by the gonadectomy procedure between male and female rats.

Astragalus polysaccharides ameliorate epileptogenesis, cognitive impairment, and neuroinflammation in a pentylenetetrazole-induced kindling mouse model.

Background: Epilepsy is a prevalent neurological disease where neuroinflammation plays a significant role in epileptogenesis. Recent studies have suggested that Astragalus polysaccharides (APS) have anti-inflammatory properties, which make them a potential candidate for neuroprotection against central nervous system disease. Nevertheless, the extent of their effectiveness in treating epilepsy remains enigmatic. Therefore, our study aims to investigate the potential of APS to mitigate epileptogenesis and its comorbidities by exploring its underlying mechanism. Methods: Initially, we employed pentylenetetrazol-induced seizure mice to validate APS' effectiveness. Subsequently, we employed network pharmacology analysis to probe the possible targets and signaling pathways of APS in treating epilepsy. Ultimately, we verified the key targets and signaling pathways experimentally, predicting their mechanisms of action. Results: APS have been observed to disturb the acquisition process of kindling, leading to reduced seizure scores and a lower incidence of complete kindling. Moreover, APS has been found to improve cognitive impairments and prevent hippocampal neuronal damage during the pentylenetetrazole (PTZ)-kindling process. Subsequent network pharmacology analysis revealed that APS potentially exerted their anti-epileptic effects by targeting cytokine and toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) signaling pathways. Finally, experimental findings showed that APS efficiently inhibited the activation of astrocytes and reduced the release of pro-inflammatory mediators, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In addition, APS impeded the activation of the TLR4/NF-κB signaling cascade in a PTZ-induced kindling mouse model. Conclusion: The outcomes of our study suggest that APS exerts an impact on epileptogenesis and mitigates cognitive impairment by impeding neuroinflammatory processes. The mechanism underlying these observations may be attributed to the modulation of the TLR4/NF-κB signaling pathway, resulting in a reduction of the release of inflammatory mediators. These findings partially agree with the predictions derived from network pharmacology analyses. As such, APS represents a potentially innovative and encouraging adjunct therapeutic option for epileptogenesis and cognitive deficit.

The Effects of Intensive Rehabilitation Combined with Thiamine Treatment on Cognitive Recovery in a Case of Non-Alcoholic Wernicke-Korsakoff Syndrome.

Wernicke-Korsakoff Syndrome (WKS) is a severe neurological disorder resulting from thiamine deficiency, commonly associated with alcohol consumption but also stemming from dietary imbalances or other clinical conditions. Cognitive deficits, affecting memory and executive functions, pose a serious concern, with partial recovery often not complete. A 28-year-old woman underwent surgery for acute necrotizing hemorrhagic pancreatitis, leading to admission for post-acute intensive treatment due to prolonged bed rest syndrome. Clinical examinations revealed sensory-motor neuropathy, denervation in the active phase, mammillary body hyperintensity, and cognitive impairment. The patient exhibited poor orientation, lacked awareness of her clinical condition, and experienced impaired nonverbal memory, practical constructive issues, and planning difficulties-consistent with WKS. The patient received high-dose thiamine (300 mg TDS), coupled with daily physiokinesitherapy and occupational therapy. A final neuropsychological evaluation three months later showed substantial remission of executive and memory difficulties, improved spatial-temporal orientation, and enhanced awareness. The complex case required timely multidisciplinary intervention for accurate diagnosis and effective rehabilitation. The patient experienced rapid clinical improvement and cognitive recovery with high-dose thiamine and physiotherapy.

Deterioro funcional y neurocognitivo en pacientes con esquizofrenia deficitaria en Perú y confiabilidad de la estructura bidimensional de la sintomatología negativa / Functional and neurocognitive impairment in deficit schizophrenia patients in Peru and reliability of the bidimensional structure of negative symptomatology

Resumen La mayoría de los estudios sugieren que los pacientes con esquizofrenia deficitaria presentan un deterioro funcional y neurocognitivo más grave en comparación con los pacientes con esquizofrenia no deficitaria. Sin embargo, existen pocos estudios al respecto en América Latina. Examinar las diferencias entre el funcionamiento y el deterioro neurocognitivo en pacientes con y sin esquizofrenia deficitaria; y analizar la validez de la estructura bifactorial de los síntomas negativos en una muestra de pacientes peruanos. Se reclutó a un total de 53 pacientes peruanos con esquizofrenia. Se utilizó la versión en español del Schedule for the Deficit Syndrome (SDS) para diagnosticar el síndrome deficitario, el Functioning Assessment Short Test (FAST) para evaluar el funcionamiento global, y el Screen for Cognitive Impairment in Psychiatry (SCIP) para evaluar el funcionamiento neurocognitivo. La prevalencia de esquizofrenia deficitaria fue del 62,3 %. Los pacientes con esquizofrenia deficitaria presentan un mayor deterioro en la memoria de trabajo (p = 0,003), fluidez verbal (p = 0,002), aprendizaje verbal retardado (p = 0,039) y velocidad de procesamiento (p = 0,004). En cuanto al funcionamiento global, los pacientes con esquizofrenia deficitaria muestran un rendimiento inferior en las dimensiones de autonomía (p = 0,002), laboral (p = 0,001), cognitiva (p = 0,010), finanzas (p = 0,015), relaciones interpersonales (p < 0,001) y tiempo de ocio (p < 0,001). Los pacientes con esquizofrenia deficitaria muestran un mayor deterioro en el funcionamiento global y cognitivo. La replicación de la estructura bidimensional de los síntomas negativos en una muestra peruana contribuye a la hipótesis de la universalidad del modelo de «déficit expresivo¼ y «apatía-abulia¼.

ABSTRACT Many studies suggest that patients with deficit schizophrenia exhibit a more severe functional and neurocognitive impairment than those with non-deficit schizophrenia. However, there are few studies on this topic in Latin America. To examine the differences in functioning and neurocognitive impairment between patients with and without deficit schizophrenia, and to analyze the validity of the bifactorial structure of negative symptoms in a sample of Peruvian patients. A total of 53 Peruvian patients with schizophrenia were recruited. The Spanish version of the Schedule for the Deficit Syndrome (SDS) was used to diagnose the syndrome under study. The Functioning Assessment Short Test (FAST) was employed to assess global functioning, and the Screen for Cognitive Impairment in Psychiatry (SCIP), to evaluate neurocognitive functioning. The prevalence of deficit schizophrenia was 62.3%. Patients with deficit schizophrenia exhibited greater impairment in working memory (p = 0.003), verbal fluency (p = 0.002), delayed verbal learning (p = 0.039), and processing speed (p = 0.004). Regarding global functioning, patients with deficit schizophrenia demonstrated poorer performance in the domains of autonomy (p = 0.002), occupational functioning (p = 0.001), cognitive functioning (p = 0.010), financial functioning (p = 0.015), interpersonal relationships (p < 0.001), and leisure time (p < 0.001). Patients with deficit schizophrenia display greater impairment in global and cognitive functioning. The replication of the bidimensional structure of negative symptoms in a Peruvian sample contributes to the hypothesis of the universality of the "expressive deficit" and "apathy-abulia" model.

Transforming growth factor-ß1 protects against white matter injury and reactive astrogliosis via the p38 MAPK pathway in rodent demyelinating model.

In central nervous system (CNS), demyelination is a pathological process featured with a loss of myelin sheaths around axons, which is responsible for the diseases of multiple sclerosis, neuromyelitis optica, and so on. Transforming growth factor-beta1 (TGF-ß1) is a multifunctional cytokine participating in abundant physiological and pathological processes in CNS. However, the effects of TGF-ß1 on CNS demyelinating disease and its underlying mechanisms are controversial and not well understood. Herein, we evaluated the protective potential of TGF-ß1 in a rodent demyelinating model established by lysophosphatidylcholine (LPC) injection. It was identified that supplement of TGF-ß1 evidently rescued the cognitive deficit and motor dysfunction in LPC modeling mice assessed by novel object recognition and balance beam behavioral tests. Besides, quantified by luxol fast blue staining, immunofluorescence, and western blot, administration of TGF-ß1 was found to significantly ameliorate the demyelinating lesion and reactive astrogliosis by suppressing p38 MAPK pathway. Mechanistically, the results of in vitro experiments indicated that treatment of TGF-ß1 could directly promote the differentiation and migration of cultured oligodendrocytes. Our study revealed that modulating TGF-ß1 activity might serve as a promising and innovative therapeutic strategy in CNS demyelinating diseases.