Significant Cognitive Deficits Research Articles

The effect of the NLRP1 inflammasome on methamphetamine-induced cognitive impairment in rats

Methamphetamine (METH) use disorder has been shown to be in high comorbidity with cognitive deficits. METH-induced cognitive deficits are accompanied by neurotoxicity which could result from neuroinflammation. The potential role of NLRP1 inflammasome (NLRP1) and the downstream signalling pathway in METH-induced cognitive impairment was explored in the current study. Cognitive functions and the changes of NLRP1/Caspase-1/GSDMD signalling pathway were firstly determined in rats receiving daily injections of METH. Subsequently, the effects of aspirin-triggered-lipoxin A4 (ATL), a potent anti-inflammatory mediator, and NLRP1 siRNA was investigated were investigated in both METH-treated rats and HT22 cells. METH induces significant cognitive deficits in rats, using the NOR test. METH-induced cognitive impairment was in line with increased activities of NLRP1, cleaved-Caspase-11, IL-1β and TNF-α and the presence of GSDMD-mediated pyroptosis in the hippocampus of rats. NLRP1 inhibition by ATL significantly attenuated METH-induced cognitive impairment, in conjunction with the decreased activities of NLRP1 and cleaved-Caspase-1, IL-1β and TNF-α. ATL and NLRP1 siRNA also prevented the presence of apoptosis in the hippocampus of METH-treated rats and the cell death in METH-treated HT22 cells. These results reveal a novel role of NLRP1 and the downstream signaling pathways in the complex actions of METH-induced cognitive deficits.

NFB-15. "Cognitive Impairments in Children and Adolescents with Neurofibromatosis"

INTRODUCTION-BACKGROUND: Cognitive, learning and/or behavioral disorders are common (up to 70%) complications of neurofibromatosis (NF). The first multidisciplinary-clinic for neurocutaneous-disorders was established at the Aghia Sophia Children’s Hospital in Athens, Greece, in 2016. Since then, more than 200 children and adolescents with NF have been examined. SCOPE: Acknowledging and indicating awareness on the devastating life-long consequences (poor academic performance, behavioral problems, and limited career prospectives) that can result from cognitive impairment, a research collaboration with educational specialists was recently implemented to examine the neurocognitive functions of children and adolescents with NF. MATERIALS: Children and adolescents aged 7-14 years who suffer from NF type I or type II, were eligible for study entry. The third edition of the Wechsler Intelligence Scale (WISC-III) was used to measure participants’ cognitive function. RESULTS: Preliminary results of this ongoing study are presented. Patients’ recruitment was limited by the coronavirus disease 2019 (COVID-19) restrictions. At this stage, the research involved 10 participants suffering from NF, with mean (± SD) age of 11.55 (± 1.80) years and a male-to-female ratio of 1. The mean (± SD) full-scale intelligence quotient (IQ) was 85.50 (± 18.80), corresponding to the 0.3rd to 73th percentile range. The mean (± SD) scores of performance IQ and verbal IQ were 84.90 (± 17.43) and 89.40 (± 17.23) respectively, corresponding to the 1st to 73rd percentile range for both subscales. CONCLUSION: Significant cognitive deficits, according to the percentile scores of WISC-III, were demonstrated in the small number of children and adolescents suffering from NF (type I or type II). Cognitive assessment, as part of the multidisciplinary approach of these patients is warranted, to aid timely educational interventions and improve patient learning outcomes.

Deep cerebellar stimulation enhances cognitive recovery after prefrontal traumatic brain injury in rodent

Functional outcome following traumatic brain injury (TBI) varies greatly, with approximately half of those who survive suffering long-term motor and cognitive deficits despite contemporary rehabilitation efforts. We have previously shown that deep brain stimulation (DBS) of the lateral cerebellar nucleus (LCN) enhances rehabilitation of motor deficits that result from brain injury. The objective of the present study was to evaluate the efficacy of LCN DBS on recovery from rodent TBI that uniquely models the injury location, chronicity and resultant cognitive symptoms observed in most human TBI patients. We used controlled cortical impact (CCI) to produce an injury that targeted the medial prefrontal cortex (mPFC-CCI) bilaterally, resulting in cognitive deficits. Unilateral LCN DBS electrode implantation was performed 6 weeks post-injury. Electrical stimulation started at week eight post-injury and continued for an additional 4 weeks. Cognition was evaluated using baited Y-maze, novel object recognition task and Barnes maze. Post-mortem analyses, including Western Blot and immunohistochemistry, were conducted to elucidate the cellular and molecular mechanisms of recovery. We found that mPFC-CCI produced significant cognitive deficits compared to pre-injury and naïve animals. Moreover, LCN DBS treatment significantly enhanced the long-term memory process and executive functions of applying strategy. Analyses of post-mortem tissues showed significantly greater expression of CaMKIIα, BDNF and p75NTR across perilesional cortex and higher expression of postsynaptic formations in LCN DBS-treated animals compared to untreated. Overall, these data suggest that LCN DBS is an effective treatment of cognitive deficits that result from TBI, possibly by activation of ascending, glutamatergic projections to thalamus and subsequent upregulation of thalamocortical activity that engages neuroplastic mechanisms for facilitation of functional re-organization. These results support a role for cerebellar output neuromodulation as a novel therapeutic approach to enhance rehabilitation for patients with chronic, post-TBI cognitive deficits that are unresponsive to traditional rehabilitative efforts.

IMG-14. Cognitive deficits and altered functional network organization in pediatric brain tumor patients

INTRODUCTION: Survivors of pediatric brain tumors experience significant cognitive deficits from their diagnosis and treatment. Mechanisms of cognitive injury are poorly understood, and predictors of long-term outcome are lacking. Large-scale, distributed brain systems provide a window into brain organization and function that may yield insight into these mechanisms and outcomes. Recent evidence suggests that systems-level changes are related to cognitive performance across the lifespan. Here, we evaluated brain network architecture, cognitive performance, and brain-behavior relationships in pediatric brain tumor patients. METHODS: Forty-nine patients (ages 7-18y.o.) with any brain tumor diagnosis underwent resting state functional Magnetic Resonance Imaging (rsfMRI) during regularly scheduled clinical visits. All patients were tested with the NIH Toolbox Cognition Battery. One-hundred thirty-nine age- and sex-matched typically developing children were used as controls. All data were processed to minimize artifactual sources of variance. Functional brain networks were created for each patient via rsfMRI data from 300 regions of interest that sample the whole brain. Multilinear models were implemented to examine brain-behavior relationships, while accounting for demographic and clinical factors. RESULTS: Functional network organization was significantly altered in patients compared to controls (p<0.001). Network organization was more affected in patients who received whole-brain radiation therapy than those who did not (t=2.52, p<0.015). Patients demonstrated significant impairments in multiple domains of cognitive performance, e.g. attention (p<0.0001). Weak relationships were found between cognitive performance and network organization, none of which survived multiple comparison correction. CONCLUSIONS: Brain network architecture is significantly altered in pediatric brain tumor patients. Whole-brain radiation was related to the largest changes. Most network and cognitive changes were significant with large effect sizes, yet brain-behavior relationships were weak. Our results suggest that systems-level changes in brain organization may provide insight into long-term changes in brain function in pediatric brain tumor patients.

Prevalence of Late Onset Stress Symptomatology (LOSS) in geriatric combat veterans and its relation with dementia: A Pilot Study

IntroductionLate onset stress symptomatology (LOSS) is a relatively new concept in combat veterans, which includes repeated but not intrusive thoughts about combat-related experiences, irritability, or nightmares that do not cause impairment of daily functioning.ObjectivesThe objectives of this study were to identify the LOSS phenomenon in geriatric combat veterans and to establish a correlation between LOSS and cognitive deficit ± major stressors.MethodsThe electronic database was searched for the last 2 years from starting the study with the hypothesis that the LOSS phenomenon has been diagnosed with sleep, anxiety, trauma-related, or impulse control related disorders. Records were examined for trauma-related symptoms, excluding major symptoms of trauma-related stressors. The veterans were assessed objectively using LOSS, PCL-5 (PTSD checklist for DSM-5), social readjustment rating scales, and MOCA (Montreal Cognitive Assessment scale) for cognitive screening.ResultsWe reviewed 1329 patient records and identified 35 potential LOSS subjects. Four veterans were diagnosed with PTSD not otherwise specified, 2 with anxiety disorder unspecified, and 1 veteran with nightmare disorder. The majority (85%) of the veterans scored &gt;40 in PCL-5, and only one veteran fulfilled the criteria for LOSS, who scored 67 on the LOSS scale. All the veterans scored ≤25 on MOCA with a significant deficit in recent recall.ConclusionsOur study shows new onset stress-related symptoms are strongly associated with significant cognitive deficits and higher individual stress levels. The onset of PTSD symptoms in older combat veterans might have been correlated with the onset of cognitive deficits, as suggested by several other studies.DisclosureNo significant relationships.

Assessment of Cognitive Impairment in Early Intervention Settings

Background. Cognitive impairment in schizophrneia is highly prevalent, the level of impairment range from moderate to severe. It has previously beed stated that cognitive impairment was stable through the course of illness, but newer finding from long-term studies indicate that some patient have improved cognitive function. Cognitive function is marginally reactive to antipsychotic medication, and it is highly predictive of poor social and vocational outcome. Also, it constitute a ‘glass ceiling’ for psychosocial and vocational rehabilitation. Several large batteries have been developed, and internationally, there is an attempt to agree on common measurements of core areas. There is a strong rationale for cognitive remediation, namly that it might improve the ability of patients to function in everyday life and that it has no side effects. Individuals at ultra-high risk (UHR) for psychosis have significant cognitive deficits that can impede functional recovery. Methods. In this randomised, clinical trial 146 individuals at UHR for psychosis were randomly assigned to treatment as usual (TAU) or TAU plus cognitive remediation. The CR targeted neurocognitive and social cognitive remediation. Results. A total of 73 UHR individuals were assigned to TAU and 73 assigned to TAU + cognitive remediation. Cognitive remediation did not result in significant improvement on the primary outcome; the Brief Assessment of Cognition in Schizophrenia composite score at 6-month follow-up (b=-0.125, 95%CI: -0.23 to 0.172, p=0.41). Conclusion. The 20-session treatment protocol was not well received in the UHR group. Possibly situations close to everyday life could be better received and be more motivatingDisclosureNo significant relationships.

Neuropsychiatric Symptoms in Clinically Defined Parkinson's Disease: An Updated Review of Literature.

Background Neuropsychiatric symptoms (NPS) are a common and potentially serious manifestation of Parkinson's disease (PD) but are frequently overlooked in favor of a focus on motor symptomatology. Here, we conducted a literature review of the prevalence and type of NPS experienced by PD patients with a clinically defined course of their illness. Methods We identified reports of NPS in patients with PD and mean disease duration over 3 years. Three databases—PubMed, Scopus, and Dialnet—were searched for relevant literature published between 2010 and 2020. Predefined exclusion criteria were applied prior to a descriptive analysis of the literature base. Results In all, 87 unique reports were identified and 30 met inclusion and exclusion criteria. These included 7142 patients with PD (male: 67.3%; mean age: 66.2 years; mean disease duration: 6.7 years). The most frequent NPS were mood disorders (apathy, depression, and anxiety), psychosis, and impulse control disorders (ICD). Treatment with dopamine agonists was identified as an important risk factor for ICD. Co-occurrence of NPS and cognitive dysfunction was also evidenced in a number of studies. Patients with more significant cognitive deficits and higher levels of NPS appeared to be of older age with a longer disease duration and to have more severe motor symptoms. Conclusions NPS, most commonly mood disorders (apathy, depression, and anxiety), psychosis, and ICDs are frequent manifestations of PD. The results of this review reflect the need to develop unified validated assessment protocols for NPS in PD, as well as to improve their management in clinical practice.

Early posthospitalization recovery after extracorporeal membrane oxygenation in survivors of COVID-19

ObjectiveWe sought to determine the influence of venovenous extracorporeal membrane oxygenation (ECMO) on outcomes of mechanically ventilated patients with COVID-19 during the first 120 days after hospital discharge. MethodsFive academic centers conducted a retrospective analysis of mechanically ventilated patients with COVID-19 admitted during March through May 2020. Survivors had access to a multidisciplinary postintensive care recovery clinic. Physical, psychological, and cognitive deficits were measured using validated instruments and compared based on ECMO status. ResultsTwo hundred sixty two mechanically ventilated patients were compared with 46 patients cannulated for venovenous ECMO. Patients receiving ECMO were younger and traveled farther but there was no significant difference in gender, race, or body mass index. ECMO patients were mechanically ventilated for longer durations (median, 26 days [interquartile range, 19.5-41 days] vs 13 days [interquartile range, 7-20 days]) and were more likely to receive inhaled pulmonary vasodilators, neuromuscular blockade, investigational COVID-19 therapies, blood transfusions, and inotropes. Patients receiving ECMO experienced greater bleeding and clotting events (P < .01). However, survival at discharge was similar (69.6% vs 70.6%). Of the 217 survivors, 65.0% had documented follow-up within 120 days. Overall, 95.5% were residing at home, 25.7% had returned to work or usual activity, and 23.1% were still using supplemental oxygen; these rates did not differ significantly based on ECMO status. Rates of physical, psychological, and cognitive deficits were similar. ConclusionsOur data suggest that COVID-19 survivors experience significant physical, psychological, and cognitive deficits following intensive care unit admission. Despite a more complex critical illness course, longer average duration of mechanical ventilation, and longer average length of stay, patients treated with venovenous ECMO had similar survival at discharge and outcomes within 120 days of discharge.

Subarachnoid Hemorrhage Induces Sub-acute and Early Chronic Impairment in Learning and Memory in Mice.

Subarachnoid hemorrhage (SAH) leads to significant long-term cognitive deficits, so-called the post-SAH syndrome. Existing neurological scales used to assess outcomes of SAH are focused on sensory-motor functions. To better evaluate short-term and chronic consequences of SAH, we explored and validated a battery of neurobehavioral tests to gauge the functional outcomes in mice after the circle of Willis perforation-induced SAH. The 18-point Garcia scale, applied up to 4days, detected impairment only at 24-h time point and showed no significant difference between the Sham and SAH group. A decrease in locomotion was detected at 4-days post-surgery in the open field test but recovered at 30days in Sham and SAH groups. However, an anxiety-like behavior undetected at 4days developed at 30days in SAH mice. At 4-days post-surgery, Y-maze revealed an impairment in working spatial memory in SAH mice, and dyadic social interactions showed a decrease in the sociability in SAH mice, which spent less time interacting with the stimulus mouse. At 30days after ictus, SAH mice displayed mild spatial learning and memory deficits in the Barnes maze as they committed significantly more errors and used more time to find the escape box but still were able to learn the task. We also observed cognitive dysfunction in the SAH mice in the novel object recognition test. Taken together, these data suggest dysfunction of the limbic system and hippocampus in particular. We suggest a battery of 5 basic behavioral tests allowing to detect neurocognitive deficits in a sub-acute and chronic phase following the SAH.

Co-exposure of polystyrene microplastics and iron aggravates cognitive decline in aging mice via ferroptosis induction

The objective of this study was to investigate the effects of co-exposure of iron and microplastics (MPs) on the cognitive function of aged humans and animals. It was already known that individual iron or MPs exposure can initiate potential neurotoxicity. However, the combined effect of MPs and iron remained to be elucidated. In this study, the toxicity of iron, MPs, co-treatment of MPs & iron, and the underlying mechanisms were evaluated in vivo. Our findings suggest that 5 µm MPs could enter the aging mice brain and accumulate in cortex and hippocampus. In addition, MPs and iron have a good binding ability, therefore, co-exposure of MPs & iron cause significant iron overload and cognitive deficits as compared to control and individual treatments of iron and MPs. Moreover, the lipid peroxidation and inflammation, which are involved in ferroptosis, get significantly elevated by co-exposure of iron and MPs. Taken together, our results provide compelling evidence that co-exposure of iron and MPs could aggravate the cognitive impairment via disturbing brain iron homeostasis and inducing ferroptosis in cognitive-related brain areas, what’s more, the results warn that MPs may act as vectors of pollutants (mostly heavy metals) increasing the health burden on body.

Cognitive and Socioemotional Development at 5 and 9 Years of Age of Children Born with Very Low Birth Weight and Extremely Low Birth Weight in the Czech Republic.

BackgroundThere is a high prevalence of cognitive and socioemotional dysfunction in very low birth weight (VLBW <1500 g) and extremely low birth weight (ELBW <1000 g) children. This study from the Czech Republic aimed to compare the cognitive and socioemotional development at 5 and 9 years of age of children born with VLBW/ELBW with children born with normal birth weight (NBW ≥2500 g).Material/MethodsThe clinical group consisted of 118 VLBW/ELBW children and the control group consisted of 101 children with NBW at ages 5 to 9 years. The research battery included selected subscales from the Intelligence and Development Scales (IDS), A Developmental Neuropsychological Assessment – second edition (NEPSY-II), and the Behavior Rating Inventory of Executive Function (BRIEF). Data were analyzed using STATA IC v. 15 software and G*Power (descriptive statistic, analysis of variance (ANOVA), correlations, multivariate analysis of variance – MANOVA, post hoc power analysis).ResultsWe found a statistically significant difference in cognitive and socioemotional development between children with VLBW/ELBW and those with NBW. The average intelligence quotient (IQ) of VLBW/ELBW children was 96.38, while that of NBW children was 12.98 points higher (P<0.001). NBW children achieved better results on all subtests of the IDS (P<0.001) as well as in affect recognition (P<0.001). All results for both groups were within normal range. Parents of VLBW/ELBW children did not recognize impaired executive functioning (P=0.494).ConclusionsThis study has shown significant cognitive and socioemotional deficit in children born with VLBW and ELBW when evaluated at 5 and 9 years of age.

The Cognitive-Enhancing Effects of Dendrobium nobile Lindl Extract in Sleep Deprivation-Induced Amnesic Mice.

Chronic sleep deprivation (SD) causes neurological and neurodegenerative dysfunction including learning and memory deficit. The orchid Dendrobium nobile Lindl (DNL), is widely used as a Yin tonic and medicinal food throughout Asia, and has many reported pharmacological effects. This study focused on the cognitive-enhancing effects of DNL in sleep deprivation-induced amnesia in mice and its biochemical mechanisms. Our results showed that the mice displayed significant cognitive deficits after 2-week SD while treatment with the extract of DNL prevented these impairments. In the novel object recognition and object location recognition tasks, a significant increase in the discrimination index was observed in DNL-treated (200 and 400 mg/kg) mice. In the MWM test, DNL (200 and 400 mg/kg) treatment shorten the prolongation of latency and increased the crossing numbers compared with SD mice. The biochemical analysis of brain tissue showed a decrease in NE, dismutase (T-SOD) and catalase (CAT) activity and an increase in 5-HT and malondialdehyde (MDA) concentration after the treatment with DNL in mice. Our findings indicated that DNL exerted a positive effect in preventing and improving cognitive impairment induced by SD, which may be mediated via the regulation of neurotransmitters and alleviation of oxidative stress.

Fucoidan isolated from Sargassum wightii Greville ameliorates intracerebro-ventricular streptozotocin induced cognitive deficits, oxidative stress and amyloidosis in Wistar rats

Marine algae have always been an important part of diet as well as traditional medicine. They are known to consist of number of bioactive polysaccharides, fucoidan being the principal polysaccharide. The present study aimed to evaluate the protective effect of fucoidan isolated from Sargassum wightii Greville against streptozotocin induced cognitive deficits, oxidative stress and amyloidosis. Streptozotocin 3 mg/kg intracerebroventricular injection was administered by stereotaxic surgery induce sporadic Alzheimer's disease. Animals were subjected to behavioural analysis including Morris water maze, open field and single trial passive avoidance test. At the end of the study, animals were sacrificed and biochemical and histochemical studies were carried out. Streptozotocin treated animals exhibited poor performance in behavioural analysis indicating significant cognitive deficits. Marked elevation in hippocampal MDA, nitrite, AGE, AChE activity and reduction in GSH, SOD was observed in disease group. Upsurge in Aβ protein and Tau protein indicated streptozotocin induced neuronal damage in hippocampus. Treatment with fucoidan 100 and 200 mg/kg significantly ameliorated the behavioural deficits, oxidative stress, hyperphosphorylated tau protein and amyloidosis induced by intracerebroventricular streptozotocin. Histochemical studies further invigorated the neuroprotective role of fucoidan in the brain cortex and hippocampus of experiment animals. It may be suggested that fucoidan ameliorated streptozotocin induced Alzheimer's disease like pathological changes including cognitive deficits, oxidative stress and amyloidosis.

Neuropsychological follow-up of a case of encephalitis by anti-nmda receptor

ABSTRACT Anti-NMDA receptor encephalitis is an autoimmune disease with psychiatric and cognitive symptoms. Our aim is to describe the cognitive follow-up of a patient diagnosed with the disease for 4 years. The results revealed severe cognitive impairment at the initial evaluation. At 3 months, memory and executive function deficits prevailed. At 9 months, only a deficit in verbal memory was found. At 4 years, she presented a mild memory deficit. These results revealed a significant short-term cognitive deficit. Subsequently, executive functions, memory and verbal fluency recovered, while a mild deficit in verbal memory persisted.

Does essential tremor increase risk of cognitive impairment and dementia? Yes.

Essential Tremor (ET), by definition, is a disorder of movement. Yet over the years, epidemiologic, clinical, pathologic, and neuroimaging studies have converged to reveal a cognitive side of ET. The cognitive symptoms in ET are heterogeneous and are likely to reflect heterogeneous underlying mechanisms. In this chapter, we review and synthesize a diverse set of studies from both population-based settings to cohorts with more detailed investigations into cognition to consider the various mechanisms by which cognitive symptoms may emerge in a subset of individuals with ET. As part of our analysis, we consider questions surrounding ET diagnosis and the possibility of comorbid disease as potential factors that, upon closer examination, appear to strengthen the argument in favor of ET as a risk factor for dementia. Importantly, we also consider the clinical relevance of cognitive impairment in ET. While ET is not universally characterized by significant cognitive deficits, the data from epidemiological, cognitive, neuroimaging, and postmortem neuropathologic studies converge to reveal an increased risk for cognitive impairment and dementia among individuals with ET. We conclude by offering directions for future research, and a neurocognitive framework with which to consider existing findings and to use in the design of novel studies dedicated to clarifying the basis, nature, and course of cognitive impairments in ET.

Col Kirpal Singh Award

Introduction.Cognitive deficits in multiple domains are known to occur in patients with alcohol dependence and pose hindrance in management. Research in these deficits from India has been rare and course of these deficits is largely unknown.Aim:Our study aimed to find out the nature and extent of cognitive deficits using a Neuropsychological tool validated in the Indian population, and follow them up for 24 wks to ascertain change in the deficits.Materials and methods.The study was carried out at a psychiatry unit of a tertiary care centre in New Delhi, India. Eighty freshly diagnosed cases of alcohol dependence syndrome and 80 healthy controls were recruited for the study. PGI-BBD (Post graduate Institute – Battery of Brain Dysfunction) was administered on all patients and controls. The same was followed up at 2 wks, 6wks and 24 wks.Results.Compared to controls, the patients had significant dysfunction in all domains of PGI memory scale and verbal intelligence measures. However the dysfunction in the performance measures was not significant. These deficits improved significantly at 6 wks and 24 wks.Conclusion.There are significant cognitive deficits in patients with alcohol dependence syndrome and these deficits improve with abstinence. Keywords

Deficits of social cognition in bipolar disorder: Systematic review and meta-analysis.

The association between impaired social cognition and bipolar disorder (BD) is well established. However, to our knowledge, there has not been a recent systematic review that characterizes disparate dimensions of social cognition in BD. Herein, this systematic review and meta-analysis aimed to synthesize the literature on core aspects of social cognition (i.e., Theory of Mind, emotion recognition, and social judgment) to identify potential areas of impairment. Online databases (i.e., PubMed, Cochrane Libraries, PsycINFO) and Google Scholar were searched from inception to May 2021. Studies with populations ages ≥16 with DSM-IV or DSM-5 defined BD (I or II) either in a euthymic or symptomatic state were included. The risk of bias was measured using the ROBINS-1 tool, and the quality of the sources was evaluated using GRADE criteria. The results of the studies were quantitatively measured by synthesizing Hedge's g effect sizes through a random effects meta-analytic approach. A total of 29 studies were included in the final review (i.e., 12 studies on the Theory of Mind, 11 on emotion recognition, and 6 on social judgment). Overall, results demonstrated social cognition to be moderately impaired in individuals with BD (d=0.59). The individual domains ranged in effect size (0.38<d<0.70), providing evidence for variation in impairment within social cognition. Individuals with BD exhibit clinically significant deficits in social cognition during euthymic and symptomatic states. Social cognition impairments in individuals with BD are an important therapeutic target for treatment discovery and development.

Electroacupuncture treatment ameliorated the long-term cognitive impairment via activating eNOS/NO pathway and related Aβ downregulation in sepsis-survivor mice

ObjectiveSepsis is a major challenge in intensive care unit worldwide and the septic survivors are left with long-term cognitive deficits. This work aims to explore the effects of electroacupuncture (EA) on long-term cognitive function and its underlying mechanism in sepsis-survivor mice. MethodsSepsis was induced by cecal ligation and puncture in C57BL/6 male mice. Seven days post-surgery, sepsis-survivor mice were treated with EA or nonacupoint EA for 17 days twice daily. Then, cognitive function was evaluated by Morris water maze task. The hippocampus tissue were collected from the mice at 30 days post-surgery. The level of nitric oxide and the expression of endothelial nitric oxide (eNOS), phospho-eNOS (p-eNOS), and amyloid β–peptide (Aβ) were measured. ResultsCompared with the sham-operated control, sepsis-survivors had significant cognitive deficits evidenced by the increased time of escape latency and reduced crossing number in Morris water maze task, as well as lower NO and p-eNOS level and higher Aβ level. EA treatment at GV20 and ST36 acupoints but not at a nonacupoint improved the cognitive function, increased the NO and p-eNOS level, and decreased Aβ generation; while eNOS inhibitor (l-NAME) undermined the efficacy of EA treatment. ConclusionIn conclusion, repeated EA treatment could ameliorate the long-term cognitive impairment via manipulating the expression of p-eNOS and related Aβ in sepsis-survivor mice.

Social Dysfunction in Psychosis Is More Than a Matter of Misperception: Advances From the Study of Metacognition.

Many with psychosis experience substantial difficulties forming and maintaining social bonds leading to persistent social alienation and a lack of a sense of membership in a larger community. While it is clear that social impairments in psychosis cannot be fully explained by symptoms or other traditional features of psychosis, the antecedents of disturbances in social function remain poorly understood. One recent model has proposed that deficits in social cognition may be a root cause of social dysfunction. In this model social relationships become untenable among persons diagnosed with psychosis when deficits in social cognition result in inaccurate ideas of what others feel, think or desire. While there is evidence to support the influence of social cognition upon social function, there are substantial limitations to this point of view. Many with psychosis have social impairments but not significant deficits in social cognition. First person and clinical accounts of the phenomenology of psychosis also do not suggest that persons with psychosis commonly experience making mistakes when trying to understand others. They report instead that intersubjectivity, or the formation of an intimate shared understanding of thoughts and emotions with others, has become extraordinarily difficult. In this paper we explore how research in metacognition in psychosis can transcend these limitations and address some of the ways in which intersubjectivity and more broadly social function is compromised in psychosis. Specifically, research will be reviewed on the relationship between social cognitive abilities and social function in psychosis, including measurement strategies and limits to its explanatory power, in particular with regard to challenges to intersubjectivity. Next, we present research on the integrated model of metacognition in psychosis and its relation to social function. We then discuss how this model might go beyond social cognitive models of social dysfunction in psychosis by describing how compromises in intersubjectivity occur as metacognitive deficits leave persons without an integrated sense of others' purposes, relative positions in the world, possibilities and personal complexities. We suggest that while social cognitive deficits may leave persons with inaccurate ideas about others, metacognitive deficits leave persons ill equipped to make broader sense of the situations in which people interact and this is what leaves them without a holistic sense of the other and what makes it difficult to know others, share experiences, and sustain relationships. The potential of developing clinical interventions focused on metacognition for promoting social recovery will finally be explored.

Cognitive and social cognition deficits in Huntington's disease differ between the prodromal and the manifest stages of the condition: A scoping review of recent evidence.

Huntington's disease (HD) is a dramatic neurodegenerative disorder encompassing severe motor symptoms coupled to significant cognitive and social cognition deficits. However, it is not clear whether and how patients' neuropsychological profile changes between the prodromal and the manifest stages of the condition. The aim of the present in-depth review is to consider cognitive and social cognition impairment in HD patients by differentiating deficits arising before diagnosis from those evident from the manifest phase onwards. Electronic databases were searched between January 1st , 2010 and December 31st , 2020 by using multiple combinations of keywords related to the investigation of neuropsychological profile in HD for preliminary search, and by defining strict selection criteria for studies to be included. Forty-two studies were included. Evidence suggests that the neuropsychological profile in HD reflects a complex pathological spectrum of deficits. It includes impairment in the realms of executive functions, memory, attention, information processing, and social cognition. Interestingly, patients' profiles differ significantly between the manifest and the prodromal stages of their condition, not only in quantitative terms but also from a qualitative point of view. Researchers and clinicians should thus include in clinical routine timely and specific neuropsychological assessments in order to monitor patients' cognitive status as time goes by, with the ultimate goal to implement effective clinical management strategies. The neuropsychological profile in HD encompasses a complex pathological spectrum of deficits. Patients' profiles differ significantly between the manifest and the prodromal stages of their condition. Clinicians should include in everyday practice a timely and specific neuropsychological assessment. Detecting patients' cognitive status during the early stages of the condition already can contribute significantly to implement effective clinical management strategies.