Memory Performance Research Articles

Synergistic effects of plasma S100B and MRI measures of cerebrovascular disease on cognition in older adults.

There is growing interest in studying vascular contributions to cognitive impairment and dementia (VCID) and developing biomarkers to identify at-risk individuals. A combination of biofluid and neuroimaging markers may better profile early stage VCID than individual measures. Here, we tested this possibility focusing on plasma levels of S100 calcium-binding protein B (S100B), which has been linked with blood-brain-barrier (BBB) integrity, and neuroimaging measures assessing BBB function (water exchange rate across the BBB (kw)) and cerebral small vessel disease (white matter hyperintensities (WMHs)). A total of 74 older adults without dementia had plasma samples collected and underwent cognitive assessment. A subsample had neuroimaging data including diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) for assessment of BBB kw and T2-weighted fluid-attenuated inversion recovery (FLAIR) for quantification of WMHs. Results indicated that higher plasma S100B levels were associated with poorer episodic memory performance (β = - .031, SE = .008, p < .001). Moreover, significant interactions were observed between plasma S100B levels and parietal lobe BBB kw (interaction β = .095, SE = .042, p = .028) and between plasma S100B levels and deep WMH volume (interaction β = - .025, SE = .009, p = .007) for episodic memory. Individuals with the poorest memory performance showed both high plasma S100B and either low BBB kw in the parietal lobe or increased deep WMH burden. Taken together, our results provide support for the combined use of biofluid and neuroimaging markers in the study of VCID.

Regional hippocampal thinning and gyrification abnormalities and associated cognition in children with prenatal alcohol exposure

Abstract Background Prenatal alcohol exposure (PAE) impacts hippocampal structure and function, contributing to deficits in memory and decision-making in affected individuals. Here, we evaluate hippocampal anomalies in children with PAE and an unexposed comparison group using advanced MRI methods that characterize hippocampal curvature and thickness. Methods Participants, ages 8 to 16 years, included children with PAE (n = 48) and an unexposed comparison group (n = 46) who underwent a dysmorphology exam, neuropsychological assessment, and an MRI scan. Height, weight, head circumference, and dysmorphic facial features were evaluated. Of those with PAE, 4.2% had fetal alcohol syndrome (FAS), 22.9% had partial FAS, and 72.9% had alcohol-related neurodevelopmental disorder. Neuropsychological testing included measures of intelligence and memory functioning. T1-weighted anatomical data were processed with the Hippunfold pipeline, which “unfolds” the complex hippocampal structure onto a template surface and provides measures of thickness and gyrification/curvature at each vertex. Permutation Analysis of Linear Models (PALM) was used to test for group differences (PAE vs. comparison) in hippocampal thickness and gyrification at each vertex and also to assess correlations with cognitive functioning. Results There were significant regional differences in thickness and gyrification across bilateral hippocampi, with the PAE group showing substantially thinner tissue and less curvature than the comparison group, especially in CA1 and subiculum regions. For those with PAE, thinner subicular tissue (bilateral) was associated with lower IQ. Also in the PAE group, lower episodic memory performance was associated with thinness in the right hippocampus, especially in the subiculum region. There were no significant regional hippocampal patterns that were associated with cognitive functioning for individuals in the unexposed comparison group. Conclusions We used a novel MRI method to evaluate hippocampal structure in children with PAE and an unexposed comparison group. The data suggest that PAE disrupts hippocampal development, impacting both the early-stage folding of the structure and its ultimate thickness. The data also demonstrate that these developmental anomalies have functional consequences in terms of core memory functions as well as global intellectual functioning in children with PAE.

Memory function and early exit from paid employment through different pathways among ageing European workers.

Understanding memory function's role in early workforce exit is key in supporting sustainable employment among ageing workers. This study examined the impact of memory function on early exit from paid employment, analyzed changes in memory function before, during and after such transitions, and assessed memory function trajectories in relation to the presence or absence of effort-reward imbalance at work. This study included 16 339 respondents from the Survey of Health, Ageing, and Retirement in Europe (SHARE) between age 50 and the country-specific retirement age. The effects of objective and subjective memory functioning on early exit were assessed using Cox proportional hazards with Fine-Gray sub distribution models. Changes in memory function before and after a transition to non-employment were assessed using generalized linear mixed-effects models. These changes were described and compared based on exposure to job effort-reward imbalance. Workers with poor subjective memory were 2.3 times more likely to exit employment prematurely due to disability ([sub-distribution hazard ratio (SHR) 2.30, 95% confidence interval (CI) 1.77-3.00] and 1.3 times more likely to exit through unemployment (SHR 1.29, 95% CI 1.06-1.55). Workers with low objective memory were 1.6 times more likely to exit through unemployment (SHR 1.56, 95% CI 1.30-1.87). Subjective memory generally declined prior to, and during early exit from paid employment. While subjective memory generally improved post-exit, objective memory function declined after exiting. An accelerated decline in objective memory functioning was noted among early retirees who had been exposed to effort-reward imbalance at work (β -0.45, standard error 0.16). Workers with poor memory function are at higher risk of early involuntary exit from paid employment. Promoting memory function and balancing job efforts and rewards may help mitigate the risk of a premature exit.

Subjective Cognitive Concerns are Associated with Worse Performance on Mobile-App Based Cognitive Assessment: An Observational Study in Cognitively Normal Older Adults.

Subjective cognitive concerns (SCC) may be among the earliest clinical symptoms of dementia. There is growing interest in applying mobile app-based cognitive assessment to remotely screen for cognitive status in preclinical dementia, but the relationship between SCC and relevant mobile assessment metrics is uncertain. We characterized the relationship between SCC and adherence, satisfaction, and performance on mobile-app assessments in cognitively unimpaired older adults. Participants (N=122, Mage=69.85, Meducation=16.52, %female=66.7, %White=86.2) completed 8 assessment days using Mobile Monitoring of Cognitive Change (M2C2), an app-based testing platform, with brief daily sessions within morning, afternoon, and evening time windows (24 total testing sessions). M2C2 includes digital working memory, processing speed, and episodic memory tasks. Participants provided feedback about their satisfaction and motivation related to M2C2 upon study completion. SCC was assessed using the Cognitive Function Instrument (CFI). Regression analyses evaluated the association between SCC and adherence, satisfaction, and performance on M2C2, controlling for age, sex, depression, and loneliness. Linear-mixed effects models evaluated whether SCC predicted M2C2 subtest performance over the 8-day testing period, controlling for covariates. SCC was not associated with app satisfaction or protocol motivation, but it was significantly associated with lower rates of protocol adherence (ß=-0.197, p=.037, 95% CI -0.647, -0.021). Higher SCC endorsement significantly predicted worse overall episodic memory performance (ß=-0.200, p = .020, 95% CI -0.020, -0.002), but not working memory or processing speed. There was a main effect of SCC on working memory performance at day 1 (Est=-1.047, SE=0.47, p=0.031) and a significant interaction between SCC and working memory over the 8-day period (Est=0.048, SE=0.02, p=0.031), such that SCC was associated with initially worse, then progressively better working memory performance. SCCs are associated with worse overall memory performance on mobile-app assessments, patterns of cognitive inefficiency (variable working memory) and mildly diminished adherence across an 8-day assessment period. Findings suggest that mobile app assessments may be sensitive to subtle cognitive changes, with important implications for early detection and treatment for individuals at risk for dementia.

Memory deficits in children and adolescents with a psychotic disorder: a systematic review and meta-analysis.

Early-onset psychosis (EOP) is a severe disorder which takes place before 18years. It entails diverse clinical and functional implications, and it may lead to critical impairments in neurocognitive functions. Although deficits in memory are well described in adult populations and they appear to be clinically related with psychosis, impairments in memory in EOP show inconsistencies between studies. This study aimed to gain insight into the relationship between EOP and memory impairments, studying the potential contribution of moderators (storage source and memory content) on the observed memory deficits. This systematic review and meta-analysis was conducted following the PRISMA-2020 guidelines. Search was conducted in English and Spanish in five databases. Case-control studies which met all requirements were selected. Overall effect size was calculated under the random-effects model and Z-based tests were used. Heterogeneity was analysed by the I2 statistic. Mixed-effects meta-regression analysis was used to study the influence of methodological quality of studies, mean age, proportion of female participants within sample, mean diagnosis, memory storage type, memory content as moderators on individual effect size variability. As a result, 32 articles were finally selected, pooling data from 2636 participants (49.29% EOP participants). Overall effect size was Hedges' g = - 1.01, CI95 = [ - 1.35, - 0.67], p < .01, indicating lower memory performance in the EOP group in comparison to healthy controls. Diagnosis and memory storage were found as significant moderators in the memory performance variance: larger deficits were found in children with psychosis and in working memory tasks.

Bidirectional synapse based on anti-resonance modulation of a photonic microring

A synaptic device is fundamental for memory and learning functions of neural networks. In this work, we demonstrated a GST (Ge2Sb2Te5)-based microring synapse with nonvolatile reconfigurable characteristics. The device shows bidirectional weight modulation during unidirectional crystallization or amorphization of GST, simulating long-term depression (LTD) and long-term potentiation (LTP). In addition, we adopted an anti-resonance pump scheme to reduce the fluctuations in pump energy coupled into the device to less than 12%. This scheme significantly enhances the programming precision of the microring synapse, achieving 24 resolvable states over 15 cycles. This work holds promise for laying the foundation for novel, to the best of our knowledge, photonic computing architectures and provides possibilities for the implementation of vision and adaptive optical neural networks that rely on bidirectional plasticity.

Remembering what did not happen: the role of hypnosis in memory recall and false memories formation

Memory recall is subject to errors that can lead to the formation of false memories. Several factors affect memory processes, such as attention deficits or emotional distress. Additionally, cardiovascular diseases may lead to cognitive decline and memory loss, also increasing the occurrence of false events recall. Hypnosis has proved to affect the autonomic nervous system, positively impacting the cardiovascular response. Hypnosis has also been suggested as a tool to enhance memory and autobiographical events recall in both healthy and unhealthy individuals; however, this approach has led to several controversies. Particularly, the employment of hypnosis in autobiographical recall (hypnotic regression) has been accused of favoring the creation of false memories, leading to therapeutic fallacy. In this paper, we review the current literature on the mechanisms behind the creation of false memories and the role played by hypnosis in memory enhancement and false memory recall. The evidence here collected suggests that cardiovascular diseases affect brain health contributing to cognitive decline and memory impairments, also increasing the occurrence of false memories. Hypnosis induces an increase in parasympathetic activity and a decrease in sympathetic activity, suggesting a potential role in preventing some cardiovascular diseases, such as hypertension, which in turn may improve brain health. Additionally, hypnosis has been shown to have some effectiveness in enhancing memory functions, although contradictory findings reported by several studies make it difficult to draw proper conclusions. Hypnotic regression and guided imagery should be used with caution as they may unintentionally lead to false memory recall. Nevertheless, further studies are required to better understand the effects of hypnosis on the brain and the heart and how it can be used to enhance memory, especially in people with cognitive decline.

Gyral peak variations between HCP and CHCP: functional and structural implications.

Significant culture and ethnic diversity play an important role in shaping brain structure and function. Many attempts have been undertaken to connect ethnic variations with brain function, which, however, fluctuates over time and is costly, limiting its utility to identify consistent brain markers as well as its application to a broad population. In contrast, brain anatomy is less altered during a short period of time, but it is not fully understood whether it could serve as the ethnicity-sensitive landmark, or its variation is associated with functional one. In this study, We utilized gyral peaks, a set of early cortical folds, as cortical landmarks to explore the role of ethnic factors in brain anatomy and their relationship to brain function. Comparative experiments were conducted using the Human Connectome Project and the Chinese Human Connectome Project. In populations with similar ethnic backgrounds, gyral peak patterns showed greater consistency. For groups with significantly different ethnic backgrounds, we identified both shared peaks and peaks unique to each group. Compared to shared peaks, unique peaks showed significant differences in anatomical and functional network attributes and were spatially associated with working memory networks, which exhibited increased activation in their presence. Gene enrichment analysis provided additional support, suggesting that the unique peaks are associated with genes linked to working memory functions. These findings could provide new knowledge to understanding how ethnic diversity interplay with brain functions and associate with brain shapes.

Cognition and objective sleep quality in post-COVID-19 patients

In the current study, we aimed (i) to evaluate sleep quality via wrist actigraphy monitoring of nonhospitalized and hospitalized post-COVID-19 condition (PCC) participants; (ii) to correlate actigraphy measures with subjective measures of sleep quality, such as the Pittsburgh Sleep Quality Index (PSQI); and (iii) to investigate whether total sleep time or sleep efficiency could affect PCC cognitive performance. We included 49 individuals with PCC from the NAUTILUS Project (NCT05307549 and NCT05307575) who were monitored for 1 week via actigraphy and who were also assessed with a comprehensive neuropsychological battery and the PSQI. We found that there were significant differences between nonhospitalized PCCs and hospitalized PCCs in the number of awakenings. We also found a correlation between the total sleep time of both measures (actigraphy and PSQI), but we did not observe correlations between objective and subjective parameters of latency and sleep efficiency. Regarding cognition and actigraphy measures, there was a trend of statistical significance in the performance of immediate visual memory, attention span and social cognition according to sleep efficiency. In conclusion, results indicate that although the PSQI provides clinically relevant indicators of sleep, there are divergent results between self-reported and objective sleep measures (actigraphy). Furthermore, we found a tendency toward statistical significance in cognitive performance in PCC participants according to their sleep efficiency which could indicate that is more important for cognitive function of post-COVID-19 patients than total sleep time.

Effects of home-based exercise with or without cognitive training on cognition and mobility in cardiac patients: A randomized clinical trial.

This randomized controlled trial compared the effects of home-based exercise, with or without cognitive training, on cognition and physical function in individuals aged 50years and older with stable CVD during the COVID-19 pandemic. 122 patients (67.3 ± 7.9years, 71% men) with stable CVD (77% coronary heart disease) were randomly assigned (1:1) to (1) Home-based physical exercise alone, or (2) Home-based physical exercise combined with cognitive training. Cognition (executive functions (primary outcome), processing speed, episodic memory, and working memory) and physical functions were assessed remotely at baseline, 3months, and 6months. Adjusted mean changes from baseline to 3months and 6months for executive functions, episodic memory, working memory, sit-to-stand test, gait speed, and timed up-and-go test were significant in the overall sample (p < 0.05). Furthermore, executive functions, episodic memory, sit-to-stand test, and timed up-and-go performances were significantly improved at 6months in both groups when analyzed separately although no group differences were observed. Mean exercise dose differed significantly between the 2 groups: 1413 vs 953 METs.min-1week-1 respectively for the exercise and combined group (p < 0.01). Mean cognitive training duration was 25.6 ± 16.6min.week-1 for the combined intervention group. Results remained unchanged after accounting for the exercise dose. In adults affected by CVD, a remote combined intervention integrating sequential cognitive and exercise training yields comparable enhancements in executive function, episodic memory, and physical performances compared to exercise training alone. ClinicalTrials.gov: NCT04661189.

Choice Behaviors and Prefrontal-Hippocampal Coupling are Disrupted in a Rat Model of Fetal Alcohol Spectrum Disorders.

Fetal alcohol spectrum disorders (FASDs) are characterized by a range of physical, cognitive, and behavioral impairments. Determining how temporally specific alcohol exposure (AE) affects neural circuits is crucial to understanding the FASD phenotype. Third trimester AE can be modeled in rats by administering alcohol during the first two postnatal weeks, which damages the medial prefrontal cortex (mPFC) and hippocampus (HPC), structures whose functional interactions are required for working memory and executive function. Therefore, we hypothesized that AE during this period would impair working memory, disrupt choice behaviors, and alter mPFC-HPC oscillatory synchrony. To test this hypothesis, we recorded local field potentials from the mPFC and dorsal HPC as male and female AE and sham intubated (SI) rats performed a spatial working memory task in adulthood and implemented algorithms to detect vicarious trial and errors (VTEs), behaviors associated with deliberative decision-making. We found that, compared to the SI group, the AE group performed fewer VTEs and demonstrated a disturbed relationship between VTEs and choice outcomes, while spatial working memory was unimpaired. This behavioral disruption was accompanied by alterations to mPFC and HPC oscillatory activity in the theta and beta bands, respectively, and a reduced prevalence of mPFC-HPC synchronous events. When trained on multiple behavioral variables, a machine learning algorithm could accurately predict whether rats were in the AE or SI group, thus characterizing a potential phenotype following third trimester AE. Together, these findings indicate that third trimester AE disrupts mPFC-HPC oscillatory interactions and choice behaviors.Significance statement Fetal alcohol spectrum disorders (FASDs) occur at an alarmingly high rate worldwide. Prenatal alcohol exposure leads to significant perturbations in brain circuitry that are accompanied by cognitive deficits, including disrupted executive functioning and working memory. These deficits stem from structural changes within several key brain regions including the prefrontal cortex and hippocampus. To better understand the cognitive deficits observed in FASD patients, we employed a rodent model of alcohol exposure during the third trimester, a period when these regions are especially vulnerable to alcohol-induced damage. We show that alcohol exposure disrupts choice behaviors and prefrontal-hippocampal functional connectivity during a working memory task, identifying the prefrontal-hippocampal network as a potential therapeutic target in FASD treatment.

Intermediate Layer‐Assisted Trap Density Reduction in Low‐Power Optoelectronic Memristors for Multifunctional Systems

AbstractThe rapid expansion of the Internet of Things demands low‐power devices that integrate memory, sensors, and logic functions. Perovskite materials show promise for low‐power optoelectronic memristors; however, challenges such as nonuniform trap distribution and uncontrolled filament formation hinder their resistive switching performance. To overcome these issues, a TiO2 nanofilm via atomic layer deposition as a base layer for filament formation, is introduced. This layer passivates interfacial defects by forming strong chemical interactions with Pb2+ and I− ions at the perovskite interface, significantly reducing trap densities (interface trap density decreases 15‐fold to 3.0 × 1016 cm−3, and bulk trap density to 1.8 × 1014 cm−3). Improved energy band alignment enables efficient electron transport, yielding a low‐V SET (+0.24 V) and excellent low‐power (≈0.7 µW) nonvolatile memory performance. Additionally, the device reliably detects near‐infrared illumination as an optical input and enables reconfigurable image recognition using a 5 × 5 array under combined stimuli. It also facilitates the implementation of complex logic gates, such as AND, OR, and flip‐flops. This paper demonstrates the potential for integrating nonvolatile memory, sensing, and logic functionalities into a single low‐power device through the incorporation of a TiO2 nanolayer.

Bauhinia coccinea extract prevents memory loss induced by scopolamine through activation of antiapoptotic and antioxidant pathways in mice

Alzheimer’s disease (AD) is characterized by oxidative stress-mediated memory dysfunction and neuronal cell death. This study investigated the effects of an ethanol extract from Bauhinia coccinea (EEBC) on memory impairment and neuronal damage in a memory deficit mouse model. EEBC was administered to ICR mice at doses of 50, 100, or 200 mg/kg daily for 3 weeks. Cognitive impairment was induced via scopolamine (SCO) injection. Brain tissues were analyzed for acetylcholine (ACh) levels, acetylcholinesterase (AChE) activity, neuronal apoptosis, and antioxidant markers. Behavioral tests showed that SCO injection induced memory loss, whereas EEBC significantly ameliorated SCO-mediated memory impairment. EEBC regulated the cholinergic system by decreasing ACh levels and enhancing AChE activity. Nissl staining and immunohistochemistry for NeuN showed that EEBC exerted neuroprotective effects in SCO-injected mice brains. Moreover, EEBC significantly reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptotic cells increased by SCO treatment. EEBC also reversed the SCO-induced changes in apoptosis-related protein expression in brain tissues. Furthermore, EEBC significantly reduced malondialdehyde levels and activated catalase in SCO-administered brains. Quantitative RNA sequencing showed involvement of lipid metabolism in EEBC memory function regulation. Thus, EEBC is a promising candidate for attenuating AD progression as it targets the cholinergic system and neuronal apoptosis.

Differences in Memory Performance between Cannabis Use Primary Methods in Young Adult Hbcu Undergraduates

Differences in Memory Performance between Cannabis Use Primary Methods in Young Adult Hbcu Undergraduates

Abstract TMP116: Gut-derived extracellular vesicles promote neurovascular damage and cognitive impairment in diabetic mice

Background and Purpose: Gut microbiota dysfunction is associated with diabetic cognitive impairment (DCI). However, the mechanisms underlying the interaction of gut microbiota dysbiosis and DCI remain poorly understood. We tested the hypothesis that extracellular vesicles generated by diabetic gut microbiota exacerbate DCI by promoting the impairment of cerebral vascular function. Methods: Gut-EVs from the stools of male non-diabetic dm (dm-gut-EVs) and diabetic (db/db mice) with DCI (db-gut-EVs) mice at 20 weeks of age (20W) were isolated and characterized by means of ultracentrifugation and 16S rRNA sequencing, respectively. Given that db/db mice develop cognitive deficits at 20W, prediabetic db/db mice at 8 weeks of age (8W) were treated with gut-EVs at a dose of 1x10 10 particles/injection intravenously twice a week for 12 weeks. Cognitive performance was assessed using a battery of behavioral tests. Results: 16S rRNA analysis revealed significant alterations in the microbiota composition of db-gut-EVs derived from 20W db/db mice with DCI compared to dm-gut-EVs (n=5/group). Db/db mice treated with db-gut-EVs extracted at 20W, but not with dm-gut-EVs, exhibited a significant decline in learning and memory function, as assayed by the Novel object recognition, Social recognition memory, and Morris water maze assay, starting at 16W and worsening at 20W, compared to db/db mice treated with saline (n=10/group). Additionally, db/db mice treated with db-gut-EVs exhibited increased cerebral vascular thrombosis (18±2 vs 11±2 Fibrin+ vessels/mm 2 in saline, p&lt;0.05, n=5/group), whereas db/db mice treated with dm-gut-EVs showed a reduction of thrombosis (5±0.5 Fibrin+ vessels/mm 2 , p&lt;0.05). In vitro, treatment of human cerebral endothelial cells (hCECs) with db-gut-EVs significantly (p&lt;0.05) upregulated pro-coagulation and inflammatory proteins, including plasminogen activator inhibitor-1 (PAI-1), tissue factor (TF), NF-κB, and intercellular adhesion molecule 1 (ICAM-1), while reducing tight junction protein ZO-1 expression. Conclusions: Our findings indicate that db-gut-EVs promote DCI by inducing cerebral vascular damage, and underscore a major role for gut microbiota-brain communication in the development of DCI.

HEBE: A novel chimeric chronokine for ameliorating memory deficits in Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-β and Tau protein depositions, with treatments focusing on single proteins have shown limited success due to the complexity of pathways involved. This study explored the potential of chronokines -proteins that modulate aging-related processes- as an alternative therapeutic approach. Specifically, we focused on a novel pleiotropic chimeric protein named HEBE, combining s-KL, sTREM2 and TIMP2, guided by bioinformatic analyses to ensure the preservation of each protein's conformation, crucial for their functions. In vitro studies confirmed HEBE's stability and enzymatic activities, even suggesting it has different activities compared to the individual chronokines. In vivo experiments on APP/Tau mice revealed improved learning and memory functions with HEBE treatment, along with decreased levels of phosphorylated Tau and minor effects on amyloid-β levels. These findings suggest that HEBE is as a promising therapeutic candidate for ameliorating memory deficits and reducing pTau in an AD mouse model.

Inhibition of STAT3 phosphorylation attenuates perioperative neurocognitive disorders in mice with D-galactose-induced aging by regulating pro-inflammatory reactive astrocytes.

Perioperative Neurocognitive Disorders (PND) are associated withanesthesia and surgery, especially in the elderly. Astrocyte activation in old mice correlates with PND development. These cells can switch to a pro-inflammatory or an anti-inflammatory phenotype, regulated by the STAT3 pathway. It remains unclear whether STAT3 can alleviate PND symptoms in elderly mice by modulating the transitions between these astrocyte phenotypes. Senescence was induced in eight-week-old male C57BL/6J mice with D-galactose, followed by tibial fracture surgery under anesthesia to model PND. On the third postoperative day, cognitive function was assessed using fear conditioning, synaptic plasticity using Golgi/ electrophysiology, and astrocyte phenotype /STAT3/pSTAT3(phosphorylated STAT3) using Western blot/immunofluorescence. The content of neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), was also measured. Primary astrocytes were stimulated with the conditioned medium referred to as ACM to induce pro-inflammatory reactive astrocytes. Stattic, an inhibitor of STAT3 phosphorylation, was used to investigate its effects on astrocyte phenotypic transformation and hippocampus-dependent learning and memory in aging mice, both in vitro and in vivo. On the third postoperative day, pSTAT3 levels and pro-inflammatory astrocytes increased in the hippocampal CA1 region, with no change in total STAT3 or anti-inflammatory astrocytes, accompanied by a decrease in GDNF and BDNF.ACM treatment of primary astrocytes promoted pro-inflammatory phenotype conversion, which was inhibited by stattic without affecting anti-inflammatory phenotype. Intraperitoneal injection of stattic in mice reduced the accumulation of pro-inflammatory astrocytes, increased the levels of BDNF and GDNF, enhanced synaptic plasticity, and improved hippocampus-dependent learning and memory functions in anesthesia-induced senescent mice, without altering anti-inflammatory astrocytes. Inhibiting STAT3 phosphorylation may improve synaptic plasticity in the CA1 region of the hippocampus by modulating pro-inflammatory astrocytes, thereby alleviating perioperative neurocognitive dysfunction in D-galactose-induced aging mice.

IGF1 enhances memory function in obese mice and stabilizes the neural structure under insulin resistance via AKT-GSK3β-BDNF signaling.

Obesity is a prevalent metabolic disorder linked to insulin resistance, hyperglycemia, increased adiposity, chronic inflammation, and cognitive dysfunction. Recent research has focused on developing therapeutic strategies to mitigate cognitive impairment associated with obesity. Insulin growth factor-1 (IGF1) deficiency is linked to insulin resistance, glucose intolerance, and the progression of obesity-related central nervous system (CNS) disorders. In this study, we investigated the neuroprotective effects of IGF1 in two obesity models: diet-induced obesity (high-fat diet mice) and genetic obesity (ob/ob mice which is genetically deficient in leptin), and in vitro Neuro2A neuronal cells and primary cortical neurons under insulin resistance conditions. We performed RNA sequencing analysis using the cortex of high-fat diet mice injected with IGF1. Also, we detected cytokine levels in blood of high-fat diet mice injected with IGF1. In addition, we conducted the Barnes maze test as a spatial memory function test and open field test as an anxiety behavior test in ob/ob mice. We measured the levels of proteins and mRNAs related to insulin signaling, including synaptic density proteins in brain cortex of ob/ob mice. Our results showed that IGF1 injection enhanced spatial memory function and synaptic plasticity in obese mice. Furthermore, in vitro data demonstrated that IGF1 treated neurons revealed enhanced neural complexity and improved neurite outgrowth under insulin resistance condition through the AKT-GSK3β-BDNF pathway related to antidepressant, cognitive function and anti-apoptotic mechanisms. Therefore, our results provided that IGF1 have potential to alleviate cognitive impairment by promoting synaptic plasticity and neural complexity in the obese brain.

Selectively Blocking Small Conductance Ca2+-Activated K+ Channels Improves Cognition in Aged Mice

Aging is associated with decreased neuronal sensitivity and activity that creates deficits in cognitive processes, including learning, memory, motivation, general activity, and other behaviors. These effects are due in part to decreased intracellular Ca2+ homeostasis, increasing hyperpolarization of the resting potential in aged neurons and therefore decreasing their excitability. To reduce hyperpolarization in aged mice, we used apamin, a selective small conductance Ca2+-activated K+ (sKCa) channel blocker. By blocking the sKCa channels, apamin decreases the egress of the K+ out of the cell, reducing its hyperpolarization and causing it to be closer to threshold potential. As a result, neurons should be more sensitive to excitatory stimuli and more active. We evaluated the performance of aged mice in a selection of cognitive and behavioral tests prior to and after systemic applications of apamin or the vehicle saline. Apamin improved performance in short-term memory, increased attention to tasks, and decreased anhedonia. Apamin had no significant effect on long-term spatial and recognition memory, risk-taking behavior, sociability, and anxiety. Our results are compatible with the known effects of sKCa channel blockade on neuronal sensitivity and activity; however, these short-term effects were not reflected in longer-term alterations of neural plasticity responsible for long-term spatial and recognition memory or other more complex cognitive processes we evaluated.

Cognitive function at first episode in patients subsequently developing treatment-resistant schizophrenia.

Research on cognitive functions in treatment-resistant schizophrenia (TRS) has focused on chronic patients, complicating the distinction between disease-related deficits from those influenced by chronicity or antipsychotic exposure. Identifying early cognitive differences could offer insights into the nature of TRS cognitive performance and serve as potential markers of treatment resistance. Cohort study of 81 first-episode schizophrenia patients from Chile. Patients were followed-up and classified as TRS if they met TRRIP criteria or were prescribed clozapine at any point. 57 healthy controls were recruited for group comparisons. Cognitive performance was assessed using the MATRICS Consensus Cognitive Battery. 51 patients were allocated to the treatment-responsive group (TRESP) and 30 to the TRS sample. Multivariable analyses controlling for age and sex revealed a worse TRS performance in processing speed, verbal fluency, attention/vigilance and working memory (p values <0.05). After multiple comparison corrections, only speed of processing remained significant. When accounting for symptom severity, antipsychotic dose and duration of untreated psychosis (DUP), TRS subjects still showed significantly lower processing speed (BACS, p=0.036; TMT-A, p=0.027), which was not significant after correcting for multiple comparisons. TRS patients show slower processing speed compared to TRESP already during first episode, that is not entirely driven by symptom severity, antipsychotic dose and DUP. Processing speed emerges as an early deficit that could aid in the timely identification of patients on a treatment resistance trajectory and facilitate the prompt implementation of treatments such as clozapine.