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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Involvement of the Expression of G Protein-Coupled Receptors in Schizophrenia.

The expression of GPCRs has been associated with schizophrenia, and their expression may induce morphological changes in brain regions responsible for schizophrenia and disease-specific behavioral changes. The articles included in this review were selected using keywords and databases of scientific research websites. The expressions of GPRs have different involvements in schizophrenia, some increase the risk while others provide protection, and they may also be potential targets for new treatments. Proper evaluation of these factors is essential to have a better therapeutic response with a lower rate of chronicity and thus improve the long-term prognosis.

Aromatic L-Amino Acid Decarboxylase Deficiency: A Genetic Screening in Sicilian Patients with Neurological Disorders.

Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare autosomal recessive neurometabolic disorder caused by AADC deficiency, an enzyme encoded by the DDC gene. Since the enzyme is involved in the biosynthesis of serotonin and dopamine, its deficiency determines the lack of these neurotransmitters, but also of norepinephrine and epinephrine. Onset is early and the key signs are hypotonia, movement disorders (oculogyric crises, dystonia and hypokinesia), developmental delay and autonomic dysfunction. Taiwan is the site of a potential founder variant (IVS6+4A>T) with a predicted incidence of 1/32,000 births, while only 261 patients with this deficit have been described worldwide. Actually, the number of affected persons could be greater, given that the spectrum of clinical manifestations is broad and still little known. In our study we selected 350 unrelated patients presenting with different neurological disorders including heterogeneous neuromuscular disorders, cognitive deficit, behavioral disorders and autism spectrum disorder, for which the underlying etiology had not yet been identified. Molecular investigation of the DDC gene was carried out with the aim of identifying affected patients and/or carriers. Our study shows a high frequency of carriers (2.57%) in Sicilian subjects with neurological deficits, with a higher concentration in northern and eastern Sicily. Assuming these data as representative of the general Sicilian population, the risk may be comparable to some rare diseases included in the newborn screening programs such as spinal muscular atrophy, cystic fibrosis and phenylketonuria.

D-ribose-L-cysteine exhibits restorative neurobehavioral functions through modulation of neurochemical activities and inhibition oxido-inflammatory perturbations in rats exposed to polychlorinated biphenyl.

Polychlorinated biphenyl (PCB) is potentially harmful environmental toxicant causing cognitive decline with depressive features. PCB-induced behavioral deficits are associated with neurochemical dysfunctions, immune changes, and oxidative stress. This study investigated the neuroprotective effects of D-ribose-L-cysteine (DRLC), a neuroprotective precursor element of glutathione on PCB-induced neurobehavioral impairments. Following the initial 15 days of PCB (2 mg/kg) exposure to rats, DRLC (50 mg/kg) was given orally for an additional 15 days, from days 16 to 30. Animals were assessed for behavioral effect such as changes in locomotion, cognition, and depression. Oxidative/nitrergic stress markers; antioxidant regulatory proteins paraoxonase-1 (PON-1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nfr2), NADPH oxidase-1 (NOX-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and neuroinflammation (NF-kß, and TNF-α); and neurochemical metabolizing enzymes (acetylcholinesterase (AChE), monoamine oxidase-A and -B (MAO-A, MAO-B)) were carried out. The PCB-induced decline in locomotion, cognitive performance, and depressive-like features were reversed by DRLC. More specifically, PCB-induced oxidative and nitrergic stress, typified by reduced levels GSH, CAT, and SOD, accompanied by elevated MDA and nitrite were attenuated by DRLC. Additionally, DRLC restored the neuroinflammatory milieu indicated by decreased NF-kß and TNF-α levels toward normal. Hyperactivities of AChE, MAO-A, MAO-B, PON-1, and NOX-1 levels as well as Nfr2, NQO1, and PON-1 due to PCB exposure were mitigated by DLRC. Our results suggest DRLC as a prospective neurotherapeutic agent against PCB-induced neurobehavioral impairments such as cognitive deficit and depressive-like feature through antioxidative and anti-nitrergic stress, anti-neuroinflammation, inhibition of brain metabolizing enzymes, and normalization of neurochemical homeostasis.

Factors predicting hospital admission and death in older adults with cognitive impairment: a longitudinal study / Factores predictivos de hospitalización y muerte en ancianos con deterioro cognitivo: un estudio longitudinal / Fatores preditores de hospitalização e óbito em idosos com comprometimento cognitivo: um estudo longitudinal

ABSTRACT Objective: to identify sociodemographic factors, clinical conditions and sarcopenia parameters that predict hospital admission and death in older adults with cognitive impairment. Method: this is a longitudinal observational study carried out with 170 older adults with cognitive impairment assessed between 2019 and 2021. Predictor variables were sociodemographic characteristics, clinical conditions and sarcopenia parameters. Sarcopenia was operationalized through handgrip muscle strength (dynamometry), muscle mass (calf circumference) and the Timed Up and Go test. Occurrence of hospital admission and death within one year after assessment of older adults were the predicted variables. Analyzes were carried out using descriptive statistics, independent Student' t-test, Mann-Whitney U test, chi-square test and univariate logistic regression. Results: most participants were female (±77.57 years old), with low education, sedentary, 15.9% with sarcopenia and 13% with a history of hospital admission. It was identified that education level had an effect on occurrence of hospital admission (U=1,423.5, p=0.027) and death (U=647.0, p=0.025) within one-year follow-up. Furthermore, there is an association between history of hospital admission in the last 6 months and occurrence of hospital admission [χ2(1)=4.729; p=0.030] and death [χ2(1)=3.919; p=0.048] within one year follow-up. It was identified that history of hospital admission in the last 6 months was associated with occurrence of hospital admission within one-year follow-up (OR=2.963; 95%CI 1.076-8.165, p=0.036). Conclusion: history of hospital admission in the last six months is associated with occurrence of hospital admission over a year in older adults with cognitive impairment.

RESUMEN Objetivo: identificar factores sociodemográficos, condiciones clínicas y parámetros de sarcopenia que predicen la hospitalización y la muerte en personas mayores con deterioro cognitivo. Método: estudio observacional longitudinal realizado con 170 personas mayores con deterioro cognitivo evaluados entre 2019 y 2021. Las variables predictoras fueron las características sociodemográficas, las condiciones clínicas y los parámetros de sarcopenia. La sarcopenia se puso en práctica mediante la fuerza de los músculos de prensión manual (dinamometría), la masa muscular (circunferencia de la pantorrilla) y la prueba Timed Up and Go. La ocurrencia de hospitalización y muerte dentro del año posterior a la evaluación del anciano configuró las variables predichas. Los análisis se realizaron mediante estadística descriptiva las pruebas t de Student independiente, U de Mann-Whitney, chi-cuadrado y regresión logística univariada. Resultados: la mayoría de los participantes fueron del sexo femenino (±77,57 años), con bajo nivel educativo, sedentarios, el 15,9% con sarcopenia y el 13% con antecedentes de hospitalización. Se identificó que el nivel de escolaridad tuvo efecto en la ocurrencia de hospitalización (U=1.423,5, p=0,027) y muerte (U=647,0, p=0,025) al año de seguimiento. Además, existe asociación entre el antecedente de hospitalización en los últimos 6 meses y la ocurrencia de hospitalización [χ2(1)=4,729; p=0,030] y muerte [χ2(1)=3,919; p=0,048] al año de seguimiento. Se identificó que el antecedente de hospitalización en los últimos 6 meses se asoció con la ocurrencia de hospitalización en un año de seguimiento (OR=2,963; IC95% 1,076-8,165, p=0,036). Conclusión: un antecedente de hospitalización en los últimos seis meses se asocia con la ocurrencia de hospitalización mayor a un año en personas mayores con deterioro cognitivo.

RESUMO Objetivo: identificar fatores sociodemográficos, condições clínicas e parâmetros de sarcopenia preditores de hospitalização e óbito em idosos com comprometimento cognitivo. Método: estudo observacional longitudinal realizado com 170 idosos com comprometimento cognitivo avaliados entre 2019 e 2021. As variáveis preditoras foram características sociodemográficas, condições clínicas e parâmetros de sarcopenia. A sarcopenia foi operacionalizada por meio da força muscular de preensão palmar (dinamometria), da massa muscular (circunferência da panturrilha) e do teste Timed Up and Go. A ocorrência de hospitalização e óbito até um ano após a avaliação do idoso configuraram as variáveis preditas. Procedeu-se análises por estatística descritiva, testes t-student independente, U Mann Whitney, Qui-Quadrado e de regressão logística univariada. Resultados: a maioria dos participantes era do sexo feminino (±77,57 anos), de baixa escolaridade, sedentários, 15,9% com sarcopenia e 13% com histórico de internação. Foi identificado que o nível de escolaridade teve efeito sobre a ocorrência de hospitalização (U=1423,5, p=0,027) e de óbito (U=647,0, p=0,025) no seguimento de um ano. Além disso, há associação do histórico de internação nos últimos 6 meses com a ocorrência de hospitalização [χ2(1)=4,729; p=0,030] e de óbito [χ2(1)=3,919; p=0,048] no seguimento de um ano. Identificou-se que o histórico de internação nos últimos 6 meses associou-se com a ocorrência de hospitalização em um ano de seguimento (OR=2,963; IC95% 1,076-8,165, p=0,036). Conclusão: o histórico de internação nos últimos seis meses está associado à ocorrência de hospitalização ao longo de um ano em idosos com comprometimento cognitivo.

Anesthesia/surgery-induced learning and memory dysfunction by inhibiting mitophagy-mediated NLRP3 inflammasome inactivation in aged mice.

Postoperative cognitive dysfunction (POCD) is a common postoperative complication, not only affects the quality of life of the elderly and increases the mortality rate, but also brings a greater burden to the family and society. Previous studies demonstrated that Nod-like receptor protein 3 (NLRP3) inflammasome participates in various inflammatory and neurodegenerative diseases. However, possible mitophagy mechanism in anesthesia/surgery-elicited NLRP3 inflammasome activation remains to be elucidated. Hence, this study clarified whether mitophagy dysfunction is related to anesthesia/surgery-elicited NLRP3 inflammasome activation. POCD model was established in aged C57BL/6 J mice by tibial fracture fixation under isoflurane anesthesia. Morris Water Maze (MWM) was used to evaluate learning and memory abilities. We found that in vitro experiments, lipopolysaccharide (LPS) significantly facilitated NLRP3 inflammasome activation and mitophagy inhibition in BV2 cells. Rapamycin restored mitophagy and improved mitochondrial function, and inhibited NLRP3 inflammasome activation induced by LPS. In vivo experiments, anesthesia and surgery caused upregulation of hippocampal NLRP3, caspase recruitment domain (ASC) and interleukin-1ß (IL-1 ß), and downregulation of microtubule-associated protein light chain 3II (LC3II) and Beclin1 in aged mice. Olaparib inhibited anesthesia/surgery-induced NLRP3, ASC, and IL-1ß over-expression in the hippocampus, while upregulated the expression of LC3II and Beclin1. Furthermore, Olaparib improved cognitive impairment in older mice. These results revealed that mitophagy was involved in NLRP3 inflammasome-mediated anesthesia/surgery-induced cognitive deficits in aged mice. Overall, our results suggested that mitophagy was related in NLRP3 inflammasome-induced cognitive deficits after anesthesia and surgery in aged mice. Activating mitophagy may have clinical benefits in the prevention of cognitive impairment induced by anesthesia and surgery in elderly patients.

Aerobic exercise combined with chlorogenic acid exerts neuroprotective effects and reverses cognitive decline in Alzheimer's disease model mice (APP/PS1) via the SIRT1/ /PGC-1α/PPARγ signaling pathway.

Alzheimer's disease (AD) is a prevalent neurodegenerative disease account for 60-80% of the total number of people with dementia, but its treatment and prevention strategies are still in a long process of exploration. It has been reported that a healthy lifestyle may be an effective non-pharmacological intervention for the prevention and treatment of AD, including increased physical activity and the consumption of polyphenol-rich foods. This study, therefore, investigated the effects of 8 weeks of moderate-intensity aerobic exercise (EX), administration of chlorogenic acid administration (GCA), and a combination of both (EX+GCA) on ß-amyloid (Aß) deposition, inflammatory factors, oxidative stress markers, neuronal damage, and cognitive performance in the brains of AD model mice (APP/PS1) and which signaling pathways may be responsible for these effects. The study used Western blot to detect the expression of signaling pathway-related proteins, enzyme-linked immunosorbent assay to detect the expression of inflammatory factors, hematoxylin-eosin staining to detect hippocampal neuronal morphology, immunohistochemistry to detect changes in Aß deposition in the hippocampus, an oxidative stress marker kit to detect oxidative stress status and the Morris water maze to detect changes in cognitive performance. This study showed that an 8-week intervention (EX/GCA/EX+GCA) activating the SIRT1/PGC-1α signaling pathway improved oxidative stress, neuroinflammation, Aß deposition, and cognitive performance in mice. However, there was no obvious difference between the EX and GCA groups. In contrast, the combined EX+GCA intervention was significantly better than phase EX or GCA. Our study suggests that although relief of Aß deposition, neuroinflammation, oxidative stress, neuronal damage, and cognitive decline could also be achieved with EX or GCA, the combined EX+GCA intervention showed better results. These relief effects on AD-related conditions may be obtained by mediating the activation of the SIRT1/PGC-1α signaling pathway. This study is the first to explore the improvement of AD-related conditions with a combined lifestyle of EX+GCA. This healthy lifestyle could be a candidate option for the treatment of AD.