Cognitive Deficits Research Articles

Proposed Mechanisms of Cell Therapy for Alzheimer’s Disease

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by mitochondria dysfunction, accumulation of beta-amyloid plaques, and hyperphosphorylated tau tangles in the brain leading to memory loss and cognitive deficits. There is currently no cure for this condition, but the potential of stem cells for the therapy of neurodegenerative pathologies is actively being researched. This review discusses preclinical and clinical studies that have used mouse models and human patients to investigate the use of novel types of stem cell treatment approaches. The findings provide valuable insights into the applications of stem cell-based therapies and include the use of neural, glial, mesenchymal, embryonic, and induced pluripotent stem cells. We cover current studies on stem cell replacement therapy where cells can functionally integrate into neural networks, replace damaged neurons, and strengthen impaired synaptic circuits in the brain. We address the paracrine action of stem cells acting via secreted factors to induce neuroregeneration and modify inflammatory responses. We focus on the neuroprotective functions of exosomes as well as their neurogenic and synaptogenic effects. We look into the shuttling of mitochondria through tunneling nanotubes that enables the transfer of healthy mitochondria by restoring the normal functioning of damaged cells, improving their metabolism, and reducing the level of apoptosis.

Diacerein ameliorates thioacetamide-induced hepatic encephalopathy in rats via modulation of TLR4/AQP4/MMP-9 axis

AbstractAstrocyte swelling, blood brain barrier (BBB) dissipation and the subsequent brain edema are serious consequences of persistent hyperammonemia in hepatic encephalopathy (HE) in which if inadequately controlled it will lead to brain death. The current study highlights the potential neuroprotective effect of diacerein against thioacetamide (TAA)-induced HE in acute liver failure rat model. HE was induced in male Sprague–Dawley rats via I.P. injection of TAA (200 mg/kg) for three alternative times/week at 3rd week of the experiment. Diacerein (50 mg/kg) was gavaged for 14 days prior to induction of HE and for further 7 days together with TAA injection for an overall period of 21 days. Diacerein attenuated TAA-induced HE in acute liver failure rat model; as proofed by significant lowering of serum and brain ammonia concentrations, serum AST and ALT activities and significant attenuation of both brain and hepatic MDA contents and IL-1β with marked increases in GSH contents (P < 0.0001). The neuroprotective effect of diacerein was demonstrated by marked improvement of motor and cognitive deficits, brain histopathological changes; hallmarks of HE. As shown by immunohistochemical results, diacerein markedly downregulated brain TLR4 expression which in turn significantly increased the GFAP expression, and significantly decreased AQP4 expression; the astrocytes swelling biomarkers (P < 0.0001). Moreover, diacerein preserved BBB integrity via downregulation of MMP-9 mediated digestion of tight junction proteins such as occludin (P < 0.0001). Collectively, diacerein ameliorated cerebral edema and maintained BBB integrity via modulation of TLR4/AQP4/MMP-9 axis thus may decrease the progression of HE induced in acute liver failure.

The ways of communication for children with autism spectrum disorder

Deficits in social cognition underlie many of the profound challenges individuals with autism spectrum disorder face interacting with and understanding others. This study aimed to evaluate abilities predicting behavioral, verbal, and emotional responses during simulated social scenarios in 42 autistic children. Additionally, communication patterns were analyzed across solitary, peer, and group settings. A multifaceted assessment battery including the “prognostic stories” technique, expert observational ratings, cultural congruence metrics, and activity mapping provided insights into participants’ capacity forecasting actions, statements, and feelings in interpersonal situations. Results revealed marked variability across skill domains, with greatest impairments anticipating emotions. Communication quality and self-regulation strongly correlated with predictive accuracy. Cluster analysis indicated four distinct functional profiles (“proactive planners”, “regulatory navigators”, “quiet observers”, and “balanced responders”) highlighting heterogeneous strengths warranting support. Despite challenges inferring psychological states, personalized interventions targeting highly correlated skill deficits offer optimal social adaptation. Findings reiterate calls for balanced approaches recognizing autistic diversity while compassionately addressing barriers to inclusion. With acceptance and opportunity, individuals across the spectrum have much to contribute. Limitations include sample size and gender imbalance. Follow-up longitudinal tracking is warranted.

Activation of Hippocampal Neuronal NADPH Oxidase NOX2 Promotes Depressive-Like Behaviour and Cognition Deficits in Chronic Restraint Stress Mouse Model.

Nicotinamide adenosine dinucleotide phosphate oxidases (NOX) play important roles in mediating stress-induced depression. Three NOX isotypes are expressed mainly in the brain: NOX2, NOX3 and NOX4. In this study, the expression and cellular sources of these NOX isoforms was investigated in the context of stress-induced depression. Chronic restraint stress (CRS)-induced depressive-like behaviour and cognitive deficits were evaluated by tail suspension tests, forced swimming tests and the Morris water maze test. Hippocampal NOX expression was determined by immunofluorescence staining and western blotting. The hippocampal levels of the brain-derived neurotrophic factor (BDNF) mRNA were determined via quantitative real-time -polymerase chain reaction. Glucocorticoid levels in the hippocampus were measured using ELISA kits. In the mouse CRS model, a significant increase in NOX2 expression was observed in the hippocampus, whereas no significant changes in NOX3 and NOX4 expression were detected. Next, NOX2 expression was primarily localised to neurons (NeuN+) but not microglia (Iba-1+) or astrocytes (GFAP+). Treatment with gp91ds-tat, a specific NOX2 inhibitor, effectively mitigated the behavioural deficits induced by CRS. The decreased expression of the BDNF mRNA in the hippocampus of CRS mice was restored upon gp91ds-tat treatment. A positive correlation was identified between neuronal NOX2 expression and serum glucocorticoid levels. Our study indicated that neuronal NOX2 may be a critical mediator of depression-like behaviours and spatial cognitive deficits in mice subjected to CRS. Blockade of NOX2 signalling may be a promising therapeutic strategy for depression.

Cognitive Function in Individuals with Chronic Hypoparathyroidism - A Prospective Observational Study.

"Brain fog" is a frequently reported, distressing experience among individuals with chronic hypoparathyroidism, characterized by reduced concentration and reduced ability to perform day-to-day tasks. However, evidence linking chronic hypoparathyroidism to cognitive impairment is limited and inconsistent. This study aimed to explore cognitive function in these patients using a validated neurocognitive test battery, compare results with a matched healthy control group, and analyze the frequency of cognitive impairment based on normative data. The participants' cognitive performance was tested using a cognitive test battery, including the Trail Making Test A/B, the Color-Word Interference Test, and the California Verbal Learning Test. These tests were used to evaluate the cognitive domains of "attention and processing speed," "verbal learning and memory, " and "executive function." In total, 30 individuals with hypoparathyroidism and 30 healthy controls were included. 24 patients were women (80.0%), with a median age of 44.5±13.1 and a median disease duration of 8.7 years (±5.3). Individuals with chronic hypoparathyroidism showed poorer cognitive performance in "attention and processing speed" (F(1,57) = 8.65, p = 0.005*, η² = 0.13) compared to healthy controls. A significantly higher percentage of patients had cognitive deficits in both "attention and processing speed" (56.7% vs. 3.3%) and "executive function" (60.0% vs. 16.7%). This study provides evidence that cognitive dysfunction, particularly in "attention and processing speed" is common in chronic hypoparathyroidism. Recognizing cognitive impairment in these patients is crucial, especially when discussing workability. Neuropsychological training as an adjunct therapy strategy may be beneficial in managing these cognitive deficits.

Chronic implantable flexible serpentine probe reveals impaired spatial coding of place cells in epilepsy

Abstract Developing minimally invasive and reliable electrode probes for neural signal recording is crucial for advancing neuroscience and treating major brain disorders. Flexible neural probes offer superior long-term recording capabilities over traditional rigid probes. This study introduces a parylene-based serpentine electrode probe for stable, long-term neural monitoring. Inspired by the flexibility and morphology of snakes, the probe's serpentine design ensures stable anchorage within the brain tissue during subject movement. The probe features a hydrophilic surface and is combined with a biodegradable silk fibroin-PEG coating, significantly enhancing biocompatibility and mitigating inflammatory responses. In vivo experiments demonstrate that these probes maintain stable, high-quality neural recordings for over eight months. The probes are also used to investigate the neural bases of epilepsy-induced cognitive deficits. By analyzing place cell dynamics in mice pre- and post-epileptic events, we identified the correlation between impaired spatial encoding and the observed cognitive deficits in epileptic mice. This study highlights the potential of our flexible probes in neurological research and medical applications.

Variations in inflammatory regulators in male patients with chronic schizophrenia associated with psychopathology and cognitive deficits.

Immune dysregulation has been identified as a contributing factor in the pathophysiology of schizophrenia. This study aimed to investigate variations in specific immune regulators and their correlation with psychopathology and cognitive functions in male patients with chronic schizophrenia. Employing a cross-sectional design, this study included 72 male patients with chronic schizophrenia. The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status were utilized to assess psychopathology and cognitive functions, respectively. Serum levels of interleukin (IL)-4, IL-10, IL-12p40, IL-13, and monocyte chemoattractant protein-1 (MCP-1) were measured. There were significantly increased levels of IL-4, IL-13, and MCP-1, alongside decreased levels of IL-10 in patients compared to controls (all P < 0.05). IL-4 levels showed a significant negative association with PANSS positive symptoms (beta=-0.222, P = 0.042). After controlling for antipsychotic medication, BMI, and smoking, this correlation was no longer significant (r=-0.232, P = 0.055). Additionally, positive correlations of IL-4 (beta = 0.297, P = 0.008), IL-13 (beta = 0.371, P = 0.001), and MCP-1 (beta = 0.280, P = 0.013) with language scores were observed. Increased levels of IL-4 (P = 0.044, OR = 1.994), IL-13 (P = 0.019, OR = 2.245), as well as IL-4 and MCP-1 interactions (P = 0.043, OR = 2.000) were positively associated with the risk of chronic schizophrenia, while lower levels of IL-10 (P = 0.003, OR = 0.2.867) were also linked to an increased risk. The identified associations between specific immune markers and the clinical and cognitive features of chronic schizophrenia in males underscored the potential immune-mediated mechanisms underlying schizophrenia.

Additive effect of clove essential oil combined with hydrogen inhalation improves psychological harm caused by lipopolysaccharide in mice.

Psychological anxiety and depression, as well as memory impairment, are frequently linked to inflammation. Clove essential oil (CEO) administration and hydrogen (H2) inhalation have been proven to have anti-inflammatory and alleviating effects on related psychological disorders in the past. The current study investigated the potential to improve anxiety-like behaviors and cognitive function by a combination of CEO and H2 treatment. The mice were administered lipopolysaccharide (LPS) to induce inflammation and oxidative stress response and cause psychological disorders. Using this animal model, we conducted experiments to test whether essential oil and H2 inhalation could improve the psychological damage in behavior caused by LPS. Subsequently, elevated plus maze (EPM), forced swimming test (FST), and passive avoidance (PA) test were performed for evaluation of mice anxiety, depression, and response to electric shock, respectively. Furthermore, the biochemical analysis was used to examine the expression levels of inflammatory and oxidative stress markers. Our results showed that CEO administration and H2 inhalation alone or in combination positively improved inflammation-induced anxiety, depression, and cognitive memory deficits in the mice. In the single treatment groups, CEO demonstrated better results than H2 inhalation in the elevated plus maze, forced swimming, and passive avoidance tests, while combined treatment with both provided a further improved enhancement effect. Biochemical analysis of the cerebral cortex revealed that CEO and H2 therapy reversed the LPS-induced inflammation and oxidative stress response. Our results suggest that a combination of CEO and H2 has the potential to treat psychological disorders or neuropsychiatric disorders.

Changes in cognitive functional performance and basic activities of daily living in patients with traumatic brain injury after two methods of cognitive retraining

Introduction: Evidence supports a bottom-up approach to assist in addressing functional cognitive deficits in patients with traumatic brain injury (TBI). There is however, little evidence supporting the use of online programmes for this purpose. The aim of this research was to describe the outcomes for cognitive functional performance and basic activities of daily living (bADL) or self-care functioning after cognitive retraining using an online programme versus task-oriented intervention for patients with acute mild and moderate traumatic brain injury (TBIs). Methods: A quantitative, quasi experimental, longitudinal research design was used for determining within-group and between-groups changes for cognitive functional performance and bADL functioning in two sample groups with mild to moderate TBI. Intervention using an online programme (n=7) or task-oriented activities (n=15) was evaluated at three assessment intervals: on recruitment into the study (Assessment 1), on completion of inpatient hospital intervention (Assessment 2) and after four weeks of home programme intervention and fortnightly outpatient intervention (Assessment 3). Results: Results for both groups showed a statistically significant change for cognitive functional performance assessed on the Bay Area Functional Performance Evaluation (BaFPE) while the task-oriented cognitive training group also achieved a statistically significant change in bADL scores during the first inpatient assessment period. Only the online programme group had statistically significant improvement during the home programme in the third assessment period. Conclusion: Cognitive retraining using an online programme or task-oriented activities resulted in positive change in a therapist directed inpatient programme but a structured, graded, online programme was more effective in supporting significant improvement in cognitive functional performance when used with an outpatient home programme. Implications for practice Cognitive retraining using an online programme or task orientated activities have a positive outcome for cognitive functional performance in patients with mild or moderate TBI in a therapist directed inpatient intervention. A task orientated approach for cognitive retraining appears to have positive effect on bADL outcomes. Cognitive retraining using an online programme intervention should be considered as a home programme to improve cognitive functional performance in patients with mild or moderate TBI.

Mechanisms and research progress of motor imagery combined with action observation in cognitive rehabilitation

Introduction：Cognitive deficits refer to impairments in the brain's ability to process information, memory, attention, reasoning, decision-making, and other cognitive functions.Cognitive rehabilitation (CR) is a therapeutic approach aimed at improving cognitive function through various strategies, training, and interventions, ultimately enhancing quality of life. Motor imagery (MI) and action observation (AO) are key rehabilitation methods in the cognitive domain and have been widely used in related studies. Recently, the combination of motor imagery and action observation therapy (AO+MI) has emerged as a promising research direction, receiving increasing support in the academic community. Aim of the study: This study aims to explore the mechanisms behind the combination of action observation and motor imagery (AO+MI) and assess the effectiveness of this innovative approach in cognitive rehabilitation. Material and methods: A literature review was conducted by searching databases such as PubMed, Web of Science, and Google Scholar for English-language articles. Keywords including "motor imagery," "action observation," and "cognitive rehabilitation" were used in the search. Conclusions: Both motor imagery (MI) and action observation (AO) have demonstrated positive effects on cognitive function. However, the combination of MI and AO may produce three distinct states that require further investigation. Preliminary findings suggest that AO+MI has shown promising results in enhancing corticospinal excitability (CE), benefiting children with developmental coordination disorder (DCD), and improving outcomes in stroke patients. However, some scholars have raised concerns, emphasizing the need for further experimental validation.

Comprehensive Approach to Speech and Language Assessment in Recurrent Meningioma: A Case Study

Meningioma is a tumor that arises from the meninges - the membranes that surround the brain and spinal cord. It compresses the adjacent brain tissues, nerves and vessels, leading to changes in vision, loss of smell, headaches, hearing loss or ringing in the ears, memory loss, seizure and most importantly communication difficulty. It affects mainly the elderly above the age of 60, at a female: male ratio of 3:2. Recurrence and progression are well known and are frequent characteristics of meningiomas. The present study aimed to perform a comprehensive approach to speech and language assessment in a case with recurrent meningioma. A case reported following postsurgical recurrent meningioma in the left parietal temporal area, exhibiting symptoms of language, speech and swallowing difficulty associated with a weakness in the left upper and lower limb. The evaluation process from a speech and language perspective involved perceptual and instrumental assessment of cognition, communication and swallowing using tests and tools. The case was found to have comorbid disorders of nonfluent aphasia associated with neuro cognitive deficit, mild dysphagia, mild dementia and dysarthria of speech. Though the presence of language and speech disorders in case of recurrent meningioma is not common, the severity of the disorder may lead to severe communication deficit. Assessing and interpreting an individual's communication ability involves the integration of a variety of information collected in the evaluation process. Keywords: Recurrent meningioma, dysphagia, aphasia, dysarthria

Normal pressure hydrocephalus in adult mice causes gait impairment, cognitive deficits, and urinary frequency with incontinence.

Normal pressure hydrocephalus (NPH) is marked by enlarged cerebral ventricles with normal intracranial pressure, plus three stereotypical symptoms: gait impairment, cognitive dysfunction, and urinary frequency with urge-incontinence. The neural circuit dysfunction responsible for each of these symptoms remains unknown, and an adult mouse model would expand opportunities to explore these mechanisms in preclinical experiments. Here, we describe the first mouse model of chronic, communicating hydrocephalus with normal intracranial pressure. Hydrocephalic male and female mice had unsteady gait and reduced maximum velocity. Despite performing well on a variety of behavioral tests, they exhibited subtle learning impairments. Hydrocephalic mice also developed urinary frequency, and many became incontinent. This mouse model, with symptoms resembling human NPH, can be combined with molecular-genetic tools in any mouse strain to explore the neural circuit mechanisms of these symptoms. Preclinical work using this hydrocephalus model will lead to the development of new treatments for NPH symptoms.Significance Statement Like human patients with normal pressure hydrocephalus (NPH), mice with communicating hydrocephalus develop enlarged cerebral ventricles with normal intracranial pressure plus three stereotypical symptoms: gait impairment, cognitive dysfunction, and urinary frequency with incontinence. This mouse model, with symptoms resembling human NPH, can be combined with molecular-genetic tools in any mouse strain to explore neural circuit mechanisms of NPH symptoms.

International expert perspectives on access, engagement, and implementation of cognitive remediation for schizophrenia: A Delphi study.

Cognitive remediation (CR) for schizophrenia has been extensively studied and has proven effective in improving both cognition and functioning. Yet, implementation into mental health services is poor, with implementation and engagement barriers and facilitators not understood. The present study aimed to assess expert opinions on CR barriers and facilitators that pertain to staff, mental health services, and consumers. Thirty-seven international CR experts (clinicians/researchers) responded to Likert-scale questions on implementation and engagement facilitators, essential CR components, barriers in mental health facilities, barriers for clinicians, and barriers for consumer access and engagement across three rounds of a Delphi survey. The main barriers to CR implementation were (a) lack of staff training, (b) lack of perceived relevance/lack of knowledge about cognitive deficits in schizophrenia and CR usefulness in both clinicians and consumers, as well as (c) lack of staff employed in cognitive rehabilitation roles. The presence of defeatist beliefs and difficulty in accessing the place of delivery were both barriers to consumer engagement and access. The most important facilitators for CR were a good therapeutic alliance, CR delivered as part of integrated rehabilitation services, psychoeducation provided to families and stakeholders, and CR focusing on generalization of learning to everyday life. This study highlights the barriers to CR implementation from experts. A multitude of factors were identified that need attention. It is also apparent that CR cost-effectiveness studies are needed to facilitate organizational change and national guideline recommendations for improving mental health services policy around serious mental illness/schizophrenia health care provisions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Epileptic encephalopathy, autism and cognitive deficit caused by the SYNGAP1 gene mutation

The paper analyzes data from scientific publications and presents a clinical case study of a rare genetic epileptic encephalopathy caused by a mutation in the SYNGAP1 gene. The case study focuses on a 4-year-old girl who has been diagnosed with epileptic encephalopathy due to the mutation. The paper describes the anamnesis of the child’s illness, including family history, neurological, neuropsychological, and speech assessments, as well as the results of genetic testing, electroencephalography, and magnetic resonance imaging (MRI). The findings indicate that the main symptoms of the condition are typically epilepsy, autism spectrum disorder, difficulty with phrasal speech, and mental retardation. Common types of seizures include atypical absence seizures, myoclonic seizures, atonic seizures, and eyelid myoclonia with absences. On the electroencephalogram, there is a slowdown in occipital activity and diffuse, prolonged «peak-polypic-slow-wave» complexes. Pathognomonic neuroimaging changes in the brain are typically absent. Valproic acid, levetiracetam, and ethosuximide have been shown to be the most effective treatments for controlling epileptic seizures. Due to the rarity of this syndrome, the authors have provided a detailed clinical case report from their practice.Conclusion. SYNGAP1-related epileptic encephalopathy has a specific clinical presentation, including characteristic EEG findings and a particular pattern of seizures. The diagnostic approach for children with this condition, autism spectrum disorder, and delayed language development should include video electroencephalography with sleep deprivation, as well as genetic testing if necessary, using next-generation sequencing, to ensure early detection and appropriate treatment planning.

Inferring social signals from the eyes in male schizophrenia.

Nonverbal communication habitually leaks out in ways that expose underlying thoughts, true feelings, and integrity of a counterpart. Social cognition is deficient in a wide range of mental disorders, including schizophrenia (SZ). Inferring social signals through the eyes is pivotal for social interaction but remains poorly investigated. The present work aims to fill this gap by examining whether and, if so, how reading language of the eyes is altered in SZ. We focused on male SZ, primarily because the disorder manifests a gender-specific profile. Patients and matched typically developing (TD) individuals were administered the Reading the Mind in the Eyes Test-Modified (RMET-M) and Emotions in Masked Faces (EMF) task that provide comparable visual information. The findings indicate that in SZ, the emotion recognition profile is similar to TD, with a more accurate recognition of some emotions such as fear, neutral expressions, and happiness than the others (sadness and disgust). In SZ, however, this profile is shifted down: all emotions are recognized less accurately than in TD. On the RMET-M, patients are also less precise, albeit they perform better on items with positive valence. In SZ only, recognition accuracy on both tasks is tightly linked to each other. The outcome reveals global challenges for males with SZ in inferring social information in the eyes and calls for remediation programs to shape social cognition. This work offers novel insights into the profiles of social cognitive deficits in mental disorders that differ in their gender prevalence.

Autoimmune encephalitis with coexisting antibodies to GABABR, GAD65, SOX1 and Ma2.

Autoimmune encephalitis (AE) is a disease caused by an abnormal reaction between the body's autoimmunity and the central nervous system, in which the abnormal immune response targets antigenic components within or on the surface of neuronal cells. The main manifestations are mental and behavioural changes, cognitive impairment, impaired consciousness, seizures, movement disorders, etc. Most cell surface antibodies respond well to immunotherapy, intracellular antibodies, on the other hand, are usually associated with more tumours and are relatively difficult to treat with a poor prognosis. In recent years, autoimmune encephalitis that is positive for multiple anti-neuronal antibodies has been gradually recognized in the clinic, with complex and varied clinical manifestations, especially in combination with malignant tumours, which have worse treatment and prognosis. Current clinical studies on the coexistence of multiple anti-neuronal antibodies in patients with AE are mainly disseminated case reports. Patients with AE in which four anti-neuronal antibodies coexist are even rarer. We report a patient who initially presented with an irritating dry cough and hyponatraemia and a chest CT suspicious for malignancy, followed by progressive deterioration of persistent status epilepticus, consciousness and cognitive deficits, and psycho-behavioural abnormalities. Serum and cerebrospinal fluid antibodies against neuronal surface or intracellular antigens were detected using a cell-based assay (CBA) method. Serum and cerebrospinal fluid were found to be positive for anti-GABABR, GAD65, SOX1 and Ma2 antibodies. And a definitive diagnosis of small cell lung cancer was made by immunohistochemistry. He eventually received gammaglobulin, steroid pulsed therapy and tumour chemotherapy. The coexistence or overlap of multiple anti-neuronal surface antibodies with anti-neuronal intracellular antibodies is rare and increases the likelihood of underlying malignancy. Elucidating the impact of individualized immunotherapy and coexisting antibodies on the clinical presentation of patients has the potential to improve long-term prognosis.

Eye movement characteristics of emotional face recognizing task in patients with mild to moderate depression

ObjectiveDepression is a complex affective disorder characterized by high prevalence and severe impact, commonly presenting with cognitive impairment. The objective diagnosis of depression lacks precise standards. This study investigates eye movement characteristics during emotional face recognition task (EFRT) in depressive patients to provide empirical support for objective diagnosis.MethodsWe recruited 43 patients with depression (Depressive patients, DP) from a psychiatric hospital and 44 healthy participants (Healthy Control, HC) online. All participants completed an EFRT comprising 120 trials. Each trial presented a gray screen for 800 ms followed by a stimulus image for judgment. Emotions were categorized as positive, neutral, or negative. Eye movement trajectories were recorded throughout the task. Latency of First Fixation (LFF), Latency of First Fixation for Eye AOI, and Latency of First Fixation for Mouth AOI were used as representative indicators of early attention, Proportion of Eye AOI, and Proportion of Mouth AOI as measures of intermediate attention, Accuracy (ACC) and Reaction Time (RT) as behavioral indicators of late-stage attention. In this study, these metrics were employed to explore the differences between patients with depression and healthy individuals.ResultsCompared to healthy participants, individuals with depression exhibit longer first fixation latencies on the eyes and mouth during the early attention stage of emotional face recognition, indicating an avoidance tendency toward key facial recognition cues. In the mid-to-late attention stages, depressive individuals show an increased fixation ratio on the eyes and a decreased fixation ratio on the mouth, along with lower accuracy and longer response times. These findings suggest that, relative to healthy individuals, individuals with depression have deficits in facial recognition.ConclusionThis study identified distinct attention patterns and cognitive deficits in emotional face recognition among individuals with depression compared to healthy individuals, providing an attention-based approach for exploring potential clinical diagnostic markers for depression.

Acute introduction of monomeric or multimeric α-synuclein induces distinct impacts on synaptic vesicle trafficking at lamprey giant synapses.

Synaptic aggregation of α-synuclein often occurs in Parkinson's disease (PD), dementia with Lewy bodies (DLB) and other synucleinopathies and is associated with cognitive deficits and dementia. Thus, it is important to understand how accumulation of α-synuclein affects synapse structure and function. Native, physiological α-synuclein comprises a mixture of tetramers and related physiological oligomers (60-100kDa) in equilibrium with monomeric α-synuclein. We previously demonstrated that acutely increasing the levels of physiologicalα-synuclein impaired intracellular synaptic vesicle trafficking and produced a pleiotropic phenotype, raising questions about which aspects of the synaptic phenotype were due to multimeric versus monomeric α-synuclein. Here, we address this by taking advantage of the unique features of the lamprey giant reticulospinal (RS) synapse, a vertebrate synapse that is amenable to acute perturbations of presynaptic processes via microinjection of purified proteins. α-Synuclein monomers and multimers were purified from HEK cells and separately introduced to lamprey synapses. Ultrastructural analysis revealed that both multimeric and monomeric α-synuclein impaired intracellular vesicle trafficking, leading to a loss of synaptic vesicles and buildup of endosomes. However, while monomeric α-synuclein additionally induced atypical fusion/fission at the active zone and impaired clathrin-mediated endocytosis, multimeric α-synuclein did not. Conversely, multimeric α-synuclein led to a decrease in synaptic vesicle docking, which was not observed with monomeric α-synuclein. These data provide further evidence that different molecular species of α-synuclein produce distinct and complex impacts on synaptic vesicle trafficking and reveal important insights into the cell biological processes that are affected in PD and DLB. KEY POINTS: α-Synuclein accumulation at synapses is associated with cognitive decline and dementia in Parkinson's disease and other synucleinopathies. We previously showed that acute introduction of excess human brain-derived α-synuclein to lamprey giant synapses caused pleiotropic phenotypes on synaptic vesicle trafficking, probably due to the mixture of molecular species of α-synuclein. Here, we dissected which aspects of the synaptic phenotypes were caused by monomeric (14kDa) or multimeric (60-100kDa) α-synuclein by purifying each molecular species and introducing each one separately to synapses via axonal microinjection. While monomeric α-synuclein inhibited clathrin-mediated synaptic vesicle endocytosis, multimeric α-synuclein primarily impaired endosomal trafficking. These findings reveal that different molecular species of α-synuclein have distinct impacts on synapses, suggesting different cellular and molecular targets.

NCOG-41. COMPARATIVE ANALYSIS OF MORTALITY AND SHORT-TERM SIDE EFFECTS IN PATIENTS WITH GLIOBLASTOMA MULTIFORME TREATED WITH TEMOZOLOMIDE VERSUS TEMOZOLOMIDE PLUS BEVACIZUMAB CHEMOTHERAPY

Abstract INTRODUCTION Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor in adults with limited treatment options and poor prognosis. Temozolomide (TMZ) chemotherapy is the standard treatment for GBM, but alternative therapies have shown limited success. Bevacizumab (BEV), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is used to restrict GBM growth and spread. This study evaluates the efficacy of combining TMZ with BEV compared to TMZ alone in managing GBM. METHODS A retrospective cohort study was conducted using TriNetX database data, focusing on patients diagnosed with GBM and receiving chemotherapy. Cohorts were defined by treatment: TMZ plus BEV versus TMZ alone. Propensity-score matching balanced baseline characteristics, including demographics and health conditions. Primary outcomes included mortality rates and short-term side effects within the first year of treatment, such as cognitive communication deficits, headache, dizziness, insomnia, and nausea/vomiting. RESULTS After matching, 922 patients were included in each cohort. There were no significant demographic differences post-matching. The mortality rate was higher in the TMZ plus BEV group compared to TMZ alone (51.30% vs. 36.98%, RR: 1.387, 95% CI: 1.249-1.541). However, TMZ plus BEV was associated with a lower incidence of cognitive communication deficits (1.95% vs. 4.34%, RR: 0.45, 95% CI: 0.26-0.779) and dizziness (7.27% vs. 10.52%, RR: 0.691, 95% CI: 0.513-0.93). No significant differences were found in headache, insomnia, or nausea/vomiting rates between the groups. CONCLUSION This study indicates that combining bevacizumab with temozolomide may increase mortality in GBM patients but reduce certain side effects such as cognitive deficits and dizziness. These findings emphasize the need to carefully consider the benefits and risks of different chemotherapy regimens for GBM and highlight the necessity for further research to optimize treatment strategies and improve patient outcomes.

NCOG-44. EXPLORING THE IMPACT OF PRE-OPERATIVE MAJOR DEPRESSIVE DISORDER ON POSTOPERATIVE OUTCOMES IN PATIENTS UNDERGOING SURGICAL EXCISION OF MENINGIOMAS

Abstract INTRODUCTION Meningiomas are prevalent brain tumors that can cause significant morbidity for patients. Major depressive disorder (MDD), especially in the setting of other medical conditions, is associated with poor prognoses and increased mortality. This study aims to investigate whether pre-operative MDD is a risk factor for postoperative mortality and cognitive impairment in patients with meningiomas undergoing surgical excision. METHODS A retrospective cohort study was conducted using the TriNetX database including adults undergoing craniotomy for meningioma excision, one group comprising patients with pre-operative MDD and the other without. Propensity-score matching was performed to control for age, sex, race, ethnicity, history of cognitive impairment, neurodegenerative diseases, other psychiatric disorders, and socioeconomic barriers to care. Primary outcomes were postoperative mortality, depressive episodes, and cognitive impairment measured within 5 years postoperatively. RESULTS After matching, the study included 289 patients per cohort. Postoperative mortality rates for patients with pre-operative MDD compared to those without were similar (11.42% vs 9.69%, RR: 1.179, 95% CI: 0.732-1.898). Patients with MDD had a significantly higher prevalence of postoperative depressive episodes compared to those without MDD (64.71% vs 38.06%, RR: 1.7, 95% CI: 1.434-2.015). There were no statistically significant differences between the two groups in the prevalence of attention and concentration deficits (5.88% vs 4.15%, RR: 1.417, 95% CI: 0.689-2.913), cognitive communication deficits (8.99% vs 6.57%, RR: 1.368, 95% CI: 0.775-2.416), or executive function deficits (3.46% vs 3.46%, RR: 1, 95% CI: 0.423-2.366). CONCLUSION This study suggests no significant relationship between pre-operative MDD and post-operative mortality and cognitive deficits in patients undergoing meningioma resection. However, the risk of experiencing a depressive episode within 5 years post-operation is very high, especially in those with pre-operative MDD. Therefore, preoperative psychiatric evaluation and postoperative monitoring in patients with meningiomas and MDD are crucial. Further research is warranted to elucidate underlying mechanisms and relationships.