Memory Deficiency Research Articles

Harmful Effects on the Hippocampal Morpho-Histology and on Learning and Memory in the Offspring of Rats with Streptozotocin-Induced Diabetes

Learning alterations in the child population may be linked to gestational diabetes as a causal factor, though this remains an open and highly controversial question. In that sense, it has been reported that maternal hyperglycemia generates a threatening condition that affects hippocampal development in offspring. The pyramidal cells of the CA3 subfield, a key structure in learning and memory processes, are particularly important in cognitive deficiencies. We evaluate the effect of the hyperglycemic intrauterine environment on hippocampal histomorphometry in offspring, correlating it with spatial learning and memory, as well as the morphology of dendrites and spines in 30-day-old pups (P30). The maternal hyperglycemia affected the body weight, height, and brain size of fetuses at 21 days of gestation (F21), newborn pups (P0) and P30 pups from diabetic rats, which were smaller compared to the control group. Consequently, this resulted in a decrease in hippocampal size, lower neuronal density and cytoarchitectural disorganization in the CA3 region of the hippocampus in the offspring at the three ages studied. The behavioral tests performed showed a direct relationship between morpho-histological alterations and deficiencies in learning and memory, as well as alterations in the morphology of the dendrites and spines. Therefore, knowing the harmful effects caused by gestational diabetes can be of great help to establish therapeutic and educational strategies that can help to improve learning and memory in children.

HIV-TAT dysregulates microglial lipid metabolism through SREBP2/miR-124 axis: Implication of lipid droplet accumulation microglia in NeuroHIV

Chronic HIV infection can dysregulate lipid/cholesterol metabolism in the peripheral system, contributing to the higher incidences of diabetes and atherosclerosis in HIV (+) individuals. Recently, accumulating evidence indicate that HIV proteins can also dysregulate lipid/cholesterol metabolism in the brain and such dysregulation could be linked with the pathogenesis of HIV-associated neurological disorders (HAND)/NeuroHIV. To further characterize the association between lipid/cholesterol metabolism and HAND, we employed HIV-inducible transactivator of transcription (iTAT) and control mice to compare their brain lipid profiles. Our results reveal that HIV-iTAT mice possess dysregulated lipid profiles and have increased numbers of lipid droplets (LDs) accumulation microglia (LDAM) in the brains. HIV protein TAT can upregulate LDs formation through enhancing the lipid/cholesterol synthesis in vitro. Mechanistically, HIV-TAT increases the expression of sterol regulatory element-binding protein 2 (SREBP2) through microRNA-124 downregulation. Cholesterol synthesis inhibition can block HIV-TAT-mediated NLRP3 inflammasome activation and microglial activation in vitro as well as mitigate aging-related behavioral impairment and memory deficiency in HIV-iTAT mice. Taken together, our results indicate an inherent role of lipid metabolism and LDAM in the pathogenesis of NeuroHIV (immunometabolism). These findings suggest that LDAM reversal through modulating lipid/cholesterol metabolism could be a novel therapeutic target for ameliorating NeuroHIV symptoms in chronic HIV (+) individuals.

Experimental studies linking Alzheimer's Disease and changes in immune cell function

Alzheimer's disease (hereafter referred to as AD), which is a neurodegenerative malady, featured basically by memory deficiency and cognitive decrease, has been increasingly linked to immune system dynamics in recent studies. This paper aims to review experimental studies that elucidate the relationship between AD and alterations in immune cell functionality. Recent research has shown progress in this area through experiments, highlighting quantitative and functional shifts in T cells, macrophages, neutrophils, and B cells on the growth of AD. The assay insinuates pro-inflammatory cells rising and a decrease in inflammation-suppressing cells. These findings offer valuable insights for future mechanistic investigations and drug development. However, there remain numerous unexplored aspects in this field, such as specific factors exacerbating AD, drug treatments, and the identification of signaling pathways. Future research may benefit from focusing on uncovering signaling pathways as a key avenue for further exploration and understanding.

Cognitive assessment in multiple sclerosis patients: electrophysiological and subjective studies

BackgroundMultiple sclerosis (MS) is a persistent inflammatory condition affecting the central nervous system, often associated with cognitive impairment. This impairment frequently presents itself as deficiencies in short-term memory, attention, and information processing speed. This research was designed to investigate P300 in patients with MS and its correlation with their cognitive function and their state of fatigue and depression. This work included two groups: the control group (20 subjects) and the study group (30 MS patients). Evaluation encompassed clinical history, audiological assessment, the Expanded Disability Status Scale (EDSS), the fatigue severity scale, the Beck Depression Inventory, Addenbrooke’s cognitive examination, and P300 component of event-related potentials (ERPs).ResultsThe study group exhibited varying degrees of fatigue and depression. The scores of Addenbrooke’s cognitive evaluation were reduced in the MS group. The MS group exhibited a considerably prolonged P300 latency compared to the control group.ConclusionThis study demonstrates the effectiveness of P300 in assessing cognitive function in persons diagnosed with MS.

Hypomyelinated vps16 Mutant Zebrafish Exhibit Systemic and Neurodevelopmental Pathologies.

Homotypic Fusion and Protein Sorting (HOPS) and Class C-core Vacuole/Endosome Tethering (CORVET) complexes regulate the correct fusion of endolysosomal bodies. Mutations in core proteins (VPS11, VPS16, VPS18, and VPS33) have been linked with multiple neurological disorders, including mucopolysaccharidosis (MPS), genetic leukoencephalopathy (gLE), and dystonia. Mutations in human Vacuolar Protein Sorting 16 (VPS16) have been associated with MPS and dystonia. In this study, we generated and characterized a zebrafish vps16(-/-) mutant line using immunohistochemical and behavioral approaches. The loss of Vps16 function caused multiple systemic defects, hypomyelination, and increased neuronal cell death. Behavioral analysis showed a progressive loss of visuomotor response and reduced motor response and habituation to acoustic/tap stimuli in mutants. Finally, using a novel multiple-round acoustic/tap stimuli test, mutants showed intermediate memory deficits. Together, these data demonstrate that zebrafish vps16(-/-) mutants show systemic defects, neurological and motor system pathologies, and cognitive impairment. This is the first study to report behavior abnormalities and memory deficiencies in a zebrafish vps16(-/-) mutant line. Finally, we conclude that the deficits observed in vps16(-/-) zebrafish mutants do not mimic pathologies associated with dystonia, but more align to abnormalities associated with MPS and gLE.

Executive Functions’ Alterations In Obsessive-Compulsive Disorder: A Systematic Literature Review

Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder characterized by persistent obsessive and compulsive symptoms. Dysfunctions in two inhibitory systems related to cognitive and behavioral processes are believed to be associated with the pathophysiology of OCD. These dysfunctions can affect not only the cognitive and behavioral symptoms, but also the neuropsychological deficits observed in this disorder, such as attention, memory, planning, and decision-making. This study presents a systematic literature review aiming to investigate alterations in executive functions in individuals with OCD. The search was conducted in the Scopus and Scielo databases, resulting in a final sample of 13 articles that met the inclusion criteria. The results indicated deficiencies in executive functions and non-verbal memory in patients with OCD when compared to healthy control groups. However, there were inconsistencies in the results across studies, possibly due to the variety of tests used and the complexity of the disorder. Therefore, it is important to consider factors such as cultural differences, medication use, and socioeconomic factors when interpreting the results, as these aspects can influence the study outcomes. Additionally, there are still gaps in understanding the alterations in executive functions in patients with OCD, requiring further research for a better comprehension of this relationship.

Alzheimer Disease

Alzheimer's disease (AD) is typified by memory deficiencies that worsen with time, along with cognitive and behavioral abnormalities that eventually result in dementia. AD is one of the most difficult diseases to treat because of its prevalence, high cost of care, effects on patients and caregivers, and lack of mechanism-based therapies. The malfunction and loss of neurons in particular circuits and locations, especially in the populations of nerve cells supporting memory and cognition, causes the AD condition.The neuropathology of AD is characterized by intracellular and extracellular protein aggregation accumulations. In the neuronal perikarya and dystrophic neurites, abnormally phosphorylated tau forms paired helical filaments (PHFs) that combine to form neurofibrillary tangles (NFTs). The extracellular deposition of β-pleated assemblies of Aβ peptide, which result in widespread and neuritic senile plaques, is the second pathogenic hallmark.

Development of a 12-Word Version of a Verbal Learning Test for Persian-Speaking Older Adults: Reliability, Construct Validity, and Normative Standards.

As people enter old age, they develop diseases, challenges, and cognitive and behavioral deficits that are associated with decreased abilities. Memory abilities and deficiencies and impaired models can be assessed using neuropsychological instruments, and a rehabilitation program can be developed based on the individuals' memory deficits. The present cross-sectional research aims to develop a new test (henceforth known as the Persian Verbal Learning Test, or PVLT) that is appropriate for Persian-speaking older adults. For normative data, we administered PVLT to a group of 374 Persian-speaking healthy older adults consisting of both genders (190 women and 184 men) who were aged 60-89years old. To determine reliability and validity, we evaluated neurologically healthy older adults and analyzed the results using intraclass correlation coefficient (ICC) and Pearson's correlation coefficient. The present findings showed that age, education, and gender significantly affect subtests of the PVLT. In the evaluation of reliability, significant positive correlations were observed between the variables of the PVLT in the standard/standard form. Furthermore, moderate correlations were observed between PVLT variables (immediate recall, short-delay recall, long-delay recall, and recognition), and the Immediate and Delayed Logical Memory subtests of Wechsler Memory Scale-Revised (WMS-R). However, subtests of the PVLT also showed significantly positive correlations with MoCA and non-verbal variables of WMS-R. According to the results of this study and given the good psychometric properties obtained, PVLT can potentially be used as a more appropriate tool than the SVLT for Persian-speaking older adults.

Pomegranate polyphenol punicalin ameliorates lipopolysaccharide-induced memory impairment, behavioral disorders, oxidative stress, and neuroinflammation via inhibition of TLR4-NF-кB pathway.

Neuroinflammation may play an important role in the development of Alzheimer's disease (AD). Previous studies have reported that lipopolysaccharide (LPS)-induced neuroinflammation causes memory impairments and behavioral disorders. We investigated the potential preventive effects of punicalin (PUN), a polyphenolic component of pomegranate, on LPS-induced memory deficiency and anxiety- and depression-like behaviors, along with the underlying mechanisms. LPS-treated cultured microglial BV2 cells and BV2 cell/Neuro-2a (N2a) cell coculture system were investigated for anti-neuroinflammatory effects of PUN in vitro. The in vivo experiments involved mice administered a 4-week course of oral gavage with 1500 mg/kg/d PUN before intraperitoneal LPS (250 mg/kg daily 7 times) injections. The in vitro results demonstrated that PUN inhibited the LPS-induced inflammatory cytokine (IL-18, IL-1β, TNF-ɑ, and IL-6) production in BV2 cells and protected N2a cells from synaptic damage mediated by BV2 microglia-induced neuroinflammation. In in vivo studies, it was observed that PUN improved memory impairment and anxiety- and depression-like behaviors caused by LPS and reduced the expression of inflammatory proteins such as iNOS, COX-2, IL-1β, IL-2, IL-6, and TNF-α. Furthermore, PUN inhibited the LPS-induced production of MDA; increased the activities of CAT, SOD, and GSH-Px, and inhibited LPS-induced Aβ1-42 generation through down-regulation of APP and BACE1 expression. Moreover, PUN also suppressed the expression of TLR4, IRAK4, TRAF6, IKK-β, NF-κB, p65, and HMGB1 in LPS-treated mouse brain and cultured microglial BV-2 cells. These results suggest that PUN inhibits LPS-induced memory impairment via anti-inflammatory and anti-amylogenic mechanisms through inhibition of TLR4-NF-kB activation.

Crocin ameliorates neuroinflammation and cognitive impairment in mice with Alzheimer's disease by activating PI3K/AKT pathway.

Crocin has a good prospect in the treatment of Alzheimer's disease (AD), but the mechanisms underlying its neuroprotective effects remain elusive. This study aimed to investigate the neuroprotective effects of Crocin and its underlying mechanisms in AD. AD mice were set up by injecting Aβ25-35 solution into the hippocampus. Then, the AD mice were injected intraperitoneally with 40mg/kg/day of Crocin for 14 days. Following the completion of Crocin treatment, an open-field test, Y-maze test and Morris water maze test were conducted to evaluate the impact of Crocin on spatial learning and memory deficiency in mice. The effects of Crocin on hippocampal neuron injury, proinflammatory cytokine expressions (IL-1β, IL-6, and TNF-α), and PI3K/AKT signaling-related protein expressions were measured using hematoxylin and eosin staining, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) experiments, respectively. Crocin attenuated Aβ25-35-induced spatial learning and memory deficiency and hippocampal neuron injury. Furthermore, the Western blot and qRT-PCR results showed that Crocin effectively suppressed inflammation and activated the PI3K/AKT pathway in Aβ25-35-induced mice. Crocin restrained neuroinflammation via the activation of the PI3K/AKT pathway, thereby ameliorating the cognitive dysfunction of AD mice.

Prolonged stress response induced by chronic stress and corticosterone exposure causes adult neurogenesis inhibition and astrocyte loss in mouse hippocampus

Chronic stress is a pervasive and complex issue that contributes significantly to various mental and physical health disorders. Using the previously established chronic unpredictable stress (CUS) model, which simulates human stress situations, it has been shown that chronic stress induces major depressive disorder (MDD) and memory deficiency. However, this established model is associated with several drawbacks, such as limited research reproducibility and the inability to sustain stress response. To resolve these issues, we developed a new CUS model (CUS+C) that included exogenous corticosterone exposure to induce continuous stress response. Thereafter, we evaluated the effect of this new model on brain health. Thus, we observed that the use of the CUS+C model decreased body and brain weight gain and induced an uncontrolled coat state as well as depressive-like behavior in adult mice. It also impaired learning memory function and cognitive abilities, reduced adult hippocampal neurogenesis as well as the number of hippocampal astrocytes, and downregulated glial fibrillary acidic protein expression in the brains of adult mice. These findings can promote the utilization and validity of the animal stress model and provide new information for the treatment of chronic stress-induced depressive and memory disorders.

Perineuronal net deglycosylation associates with tauopathy-induced gliosis and neurodegeneration.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by clinical symptoms of memory and cognitive deficiencies. Postmortem evaluation of AD brain tissue shows proteinopathy that closely associate with the progression of this dementing disorder, including the accumulation of extracellular beta amyloid (Aβ) and intracellular hyperphosphorylated tau (pTau) with neurofibrillary tangles (NFTs). Current therapies targeting Aβ have limited clinical efficacy and life-threatening side effects and highlight the need for alternative treatments targeting pTau and other pathophysiologic mechanisms driving AD pathogenesis. The brain's extracellular matrices (ECM), particularly perineuronal nets (PNNs), play a crucial role in brain functioning and neurocircuit stability, and reorganization of these unique PNN matrices has been associated with the progression of AD and accumulation of pTau in humans. We hypothesize that AD-associated changes in PNNs may in part be driven by the accumulation of pTau within the brain. In this work, we investigated whether the presence of pTau influenced PNN structural integrity and PNN chondroitin sulfate-glycosaminoglycan (CS-GAG) compositional changes in two transgenic mouse models expressing tauopathy-related AD pathology, PS19 (P301S) and Tau4RTg2652 mice. We show that PS19 mice exhibit an age-dependent loss of hippocampal PNN CS-GAGs, but not the underlying aggrecan core protein structures, in association with pTau accumulation, gliosis, and neurodegeneration. The loss of PNN CS-GAGs were linked to shifts in CS-GAG sulfation patterns to favor the neuroregenerative isomer, 2S6S-CS. Conversely, Tau4RTg2652 mice exhibit stable PNN structures and normal CS-GAG isomer composition despite robust pTau accumulation, suggesting a critical interaction between neuronal PNN glycan integrity and neighboring glial cell activation. Overall, our findings provide insights into the complex relationship between PNN CS-GAGs, pTau pathology, gliosis, and neurodegeneration in mouse models of tauopathy, and offer new therapeutic insights and targets for AD treatment.

Chronic but not acute nicotine treatment ameliorates acute inflammation-induced working memory impairment by increasing CRTC1 and HCN2 in adult male mice.

Systemic inflammation in which lipopolysaccharide (LPS) is released into circulation can cause cognitive dysfunction and we have previously shown that LPS impaired working memory (WM) which refers to the ability to guide incoming behavior by retrieving recently acquired information. However, the mechanism is not very clear, and currently, there is no approved strategy to improve inflammation-induced WM deficit. Notably, epidemiological studies have demonstrated a lower occurrence rate of inflammatory-related diseases in smoking patients, suggesting that inflammation-induced WM impairment may be improved by nicotine treatment. Here, our object is to investigate the effect and potential mechanisms of acute and chronic nicotine treatment on LPS-produced WM deficiency. Delayed alternation T-maze task (DAT) was applied for evaluating WM which includes both the short-term information storage and the ability to correct errors in adult male mice. Immunofluorescence staining and immunoblotting were used for assessing the levels and distribution of CREB-regulated transcription coactivator 1 (CRTC1) and hyperpolarization-activated cation channels 2 (HCN2) in the medial prefrontal cortex (mPFC) and hippocampus. Quantitative PCR and ELISA were employed for analyzing the mRNA and protein levels of TNF-α and IL-1β. Our results revealed that administration of LPS (i.p.) at a dose of 0.5 mg/kg significantly produced WM impairment in the DAT task accompanied by an increase in IL-1β and TNF-α expression in the mPFC. Moreover, intra-mPFC infusion of IL-1Ra, an IL-1 antagonist, markedly alleviated LPS-induced WM deficiency. More important, chronic (2 weeks) but not acute nicotine (0.2 mg/kg, subcutaneous) treatment significantly alleviated LPS-induced WM deficiency by upregulating CRTC1 and HCN2. Of note, intra-mPFC infusion of HCN blocker ZD7288 produced significant WM deficiency. In summary, in this study, we show that chronic nicotine treatment ameliorates acute inflammation-induced working memory deficiency by increasing CRTC1 and HCN2 in adult male mice.

Neuropsychological profile of Mexican paediatric patients with pharmacoresistant focal epilepsy

At least 20% of paediatric patients with epilepsy present resistance to multiple anti-crisis drugs in trials, which has a negative impact on their neuropsychological state, quality of life and prognosis; it is therefore necessary to document their neuropsychological profile in order to improve the clinical approach to them. To describe the neuropsychological profile (cognitive, academic, behavioural, emotional, adaptive, sleep disturbances and quality of life) of paediatric patients with drug-resistant focal epilepsy in the frontal, temporal and occipital lobes, and to compare performance between patients with frontal and temporal foci, and to assess the link between the duration of the condition, the frequency of seizures and the amount of anti-crisis drugs and the neuropsychological profile. The neuropsychological profile of 19 paediatric patients with a diagnosis of pharmacoresistant epilepsy with a mean age of 10.89 years was evaluated. 57.9% of the 19 patients were men. 63.2% presented frontal focus; 26.3% presented temporal focus; and 10.5% presented occipital focus. Deficiencies in attention, comprehension, verbal memory, working memory and processing speed, in addition to adaptive difficulties were observed. When the patients with frontal and temporal focus were compared, the former were found to present greater deficits in planning, while the patients with temporal focus presented more severe symptoms of anxiety. Patients with a longer disease duration were found to present greater impairment to their intelligence quotient and adaptive behavioural skills. Pharmacoresistant epilepsy in paediatric patients affects intelligence quotient and adaptive skills, as well as attention, memory and executive functions, and neuropsychological intervention programmes must therefore be implemented to improve these patients' quality of life.

Study on effects of 40 Hz light flicker stimulation on spatial working memory in rats and its neural mechanism

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment, with the predominant clinical diagnosis of spatial working memory (SWM) deficiency, which seriously affects the physical and mental health of patients. However, the current pharmacological therapies have unsatisfactory cure rates and other problems, so non-pharmacological physical therapies have gradually received widespread attention. Recently, a novel treatment using 40 Hz light flicker stimulation (40 Hz-LFS) to rescue the cognitive function of model animals with AD has made initial progress, but the neurophysiological mechanism remains unclear. Therefore, this paper will explore the potential neural mechanisms underlying the modulation of SWM by 40 Hz-LFS based on cross-frequency coupling (CFC). Ten adult Wistar rats were first subjected to acute LFS at frequencies of 20, 40, and 60 Hz. The entrainment effect of LFS with different frequency on neural oscillations in the hippocampus (HPC) and medial prefrontal cortex (mPFC) was analyzed. The results showed that acute 40 Hz-LFS was able to develop strong entrainment and significantly modulate the oscillation power of the low-frequency gamma (lγ) rhythms. The rats were then randomly divided into experimental and control groups of 5 rats each for a long-term 40 Hz-LFS (7 d). Their SWM function was assessed by a T-maze task, and the CFC changes in the HPC-mPFC circuit were analyzed by phase-amplitude coupling (PAC). The results showed that the behavioral performance of the experimental group was improved and the PAC of θ-lγ rhythm was enhanced, and the difference was statistically significant. The results of this paper suggested that the long-term 40 Hz-LFS effectively improved SWM function in rats, which may be attributed to its enhanced communication of different rhythmic oscillations in the relevant neural circuits. It is expected that the study in this paper will build a foundation for further research on the mechanism of 40 Hz-LFS to improve cognitive function and promote its clinical application in the future.

Cognitive decline and affective alterations in SCA2-58Q mice

The cerebellum is traditionally recognized as a brain region dedicated to motor control and movement coordination. Yet, the growing body of research has recently highlighted the cerebellar role in cognitive processes, learning, and emotional states. Patients with damage to this particular region of the brain exhibit deficiencies in verbal communication, impaired speech, executive functions, and memory, along with various affective disorders [1]. In the field of neurodegeneration research, the cerebellum is primarily recognized for its role in the onset of spinocerebellar ataxias (SCAs). SCA2 is an autosomal dominant polyglutamine-related neurological disorder resulting from a notable escalation in the number of CAG triplet repeats that encode the amino acid glutamine in the ATXN2 gene. The mutated protein ataxin-2 fails to perform its molecular functions, disrupting calcium homeostasis and cellular activity, ultimately resulting in widespread Purkinje neuron death in the cerebellar cortex [2]. In our research, we used SCA2-58Q transgenic mice that express the mutant human ataxin-2 gene under the action of the Purkinje-specific promoter (PCP2/L7). Each of these tests were aimed at evaluating specific aspects of the mice’s behavior. This model enabled to investigate the direct involvement of Purkinje cells in the cognitive and affective symptoms associated with SCA2. Our team conducted three behavioral tests to determine the anxiolytic behavior: the open field test, the novelty suppressed feeding test, and the light-dark place preference test. The novel object recognition and fear conditioning tests were used to assess recognition and contextual memory, respectively. The Morris water maze test was conducted to evaluate spatial learning and memory. The researchers assessed depression and anhedonia levels using the forced swimming, tail suspension, and sucrose preference tests. The study revealed anxiety, spatial memory impairment, and affective decline in 7–8-month-old SCA2 mice. Previous results of the beam walk test [3, 4] indicated a delay in motor skill development in SCA2-58Q mice, which began at 8–10 months of age. This indicates that cognitive decline and affective changes occur before the primary motor impairment in spinocerebellar ataxia type 2. Currently, there is no disease-modifying treatment for SCA2, and patients are typically given supportive therapy and treatment for individual symptoms. In conclusion, our research provides a more comprehensive clinical picture and takes a step towards optimizing the diagnosis and selecting more effective therapy options for SCA2.

Impaired Cognitive Function in Immune-TTP Is Better Predicted By Serum Thrombomodulin Than ADAMTS13 Activity: Results of a Longitudinal Multicenter Pilot Study

Background: High rates of mood disorders and cognitive dysfunction in immune-mediated thrombotic thrombocytopenic purpura (iTTP) survivors have been observed. However, there are no long-term prospective studies to precisely define the proportion of affected patients, rate of progression, and underlying mechanisms. We hypothesized that a large-scale multicenter study is essential to determine the natural history of these complications. Thus, we conducted a multicenter pilot study of iTTP patients in remission to assess feasibility, study design, and explore novel biomarkers. Given ADAMTS13 deficiency during remission is a risk factor for stroke, we also hypothesized that low ADAMTS13 activity predisposes patients to cognitive impairment. Methods: We aimed to enroll 50 participants from 3 USTMA Consortium sites, prospectively including adult iTTP patients (age ≥ 18 years) in clinical remission (ADAMTS13 remission was not required) for at least 90 days. Diagnosis of iTTP relied on ADAMTS13 activity <10% during an acute TMA episode. Over 2 years, participants underwent comprehensive assessments of mental and physical health, cognition, ADAMTS13 activity, and biomarker sample collection every 3 months. Study assessments included: Beck Anxiety Index (BAI), Beck Depression Index-II (BDI), Headache Impact Test (HIT-6), SF-36v2 (health-related quality of life), and CPT-3 (computer-based assessment of reaction-time, attention, and processing speed). Cognition was assessed annually (entry, year 1 and close) using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), with the Montreal Cognitive Assessment (MoCA) substituted the other visits. Results: Between September 2019 and July 2022, we enrolled 38 of 50 planned participants. Of the 38 enrolled, 16 completed the study (42.1%) 11 were lost to follow up because they did not complete the close-out visit (29%), and 11 have not yet completed the study (29%). After excluding lost subjects, we found that 131 of 221 visits were completed (59%). Demographics and burden of mental and physical health impairments are shown (Figure A). At enrollment, 45% (15/33) had at least moderate anxiety on BAI, and 45 % (15/33) had at least moderate depression on BDI. HIT-6 revealed69.7 % (23/33) had clinically significant headaches warranting referral to a specialist (median score 57, IQR 47-63). SF-36 found increased fatigue (median fatigue score of 30, population mean 52.15) and pain (median 57.5, population mean 78.77), as well as impairments in social functioning (median 50, population mean 78.77) and general health (median 35, population mean 56.99). The The CPT-3 test (see table) was highly unacceptable to some participants at all sites. RBANS scores at enrollment detected overall cognitive impairment (median score 18 th %ile) with marked deficiencies in immediate memory (median score 11 th %ile), visuospatial construction (median score 10 th %ile), and milder impairments in language and delayed memory with no evidence of attention deficits. We collected several novel biomarkers and observed a correlation between serum CD141 (thrombomodulin) and overall RBANS scores (Figure B) when compared between participants above and below the median baseline CD141. This association was not seen with ADAMTS13, or the other biomarkers collected (Syndecan-1, Vascular adhesion protein-1, E-selectin). Conclusions: In this pilot study, we found a high attrition rate, likely due to the frequency of study visits and the COVID-19 pandemic. We conclude a larger study is feasible but should account for high attrition, employ less frequent study visits, and avoid unacceptable study assessments to reduce lost subjects. Enrollment findings confirmed previous single-center reports of high prevalence of mental health disorders, reduced physical health, and subtle but measurable cognitive deficits. The CPT-3 test should be excluded from future studies due to poor acceptance. Surprisingly, we found no association between lower ADAMTS13 activity and cognitive impairment but observed a significant link between serum CD141 and cognitive impairment. These findings suggest CD141 is potentially a sensitive biomarker for risk of cognitive impairment during remission and may suggest a novel mechanism. A longer-term study with more subjects will be essential to fully explore the clinical and therapeutic implications of these findings.

State-level working memory and dysregulated eating in children and adolescents: An exploratory ecological momentary assessment study.

Children with loss of control (LOC) eating and overweight/obesity have relative deficiencies in trait-level working memory (WM), which may limit adaptive responding to intra- and extra-personal cues related to eating. Understanding of how WM performance relates to eating behavior in real-time is currently limited. We studied 32 youth (ages 10-17 years) with LOC eating and overweight/obesity (LOC-OW; n = 9), overweight/obesity only (OW; n = 16), and non-overweight status (NW; n = 7). Youth completed spatial and numerical WM tasks requiring varying degrees of cognitive effort and reported on their eating behavior daily for 14 days via smartphone-based ecological momentary assessment. Linear mixed effects models estimated group-level differences in WM performance, as well as associations between contemporaneously completed measures of WM and dysregulated eating. LOC-OW were less accurate on numerical WM tasks compared to OW and NW (ps < .01); groups did not differ on spatial task accuracy (p = .41). Adjusting for between-subject effects (reflecting differences between individuals in their mean WM performance and its association with eating behavior), within-subject effects (reflecting variations in moment-to-moment associations) revealed that more accurate responding on the less demanding numerical WM task, compared to one's own average, was associated with greater overeating severity across the full sample (p = .013). There were no associations between WM performance and LOC eating severity (ps > .05). Youth with LOC eating and overweight/obesity demonstrated difficulties mentally retaining and manipulating numerical information in daily life, replicating prior laboratory-based research. Overeating may be related to improved WM, regardless of LOC status, but temporality and causality should be further explored. Our findings suggest that youth with loss of control eating and overweight/obesity may experience difficulties mentally retaining and manipulating numerical information in daily life relative to their peers with overweight/obesity and normal-weight status, which may contribute to the maintenance of dysregulated eating and/or elevated body weight. However, it is unclear whether these individual differences are related to eating behavior on a moment-to-moment basis.

KESULITAN MEMBACA DAN MENULIS PADA SISWA BERKESULITAN BELAJAR DI KELAS TINGGI SD NEGERI BOJONG BARU

This study aims to describe reading and writing difficulties, factors that cause reading and writing difficulties, as well as teachers' efforts to help students who experience reading and writing difficulties in high grades in grade IV students at SDN Bojong Baru. The research was carried out using a qualitative approach with the subjects being fourth grade students at SDN Bojong Baru. Data was collected through observation, documentation and interviews. Data analysis is carried out through data reduction, display and verification. Based on the research results, it can be concluded that the forms of reading and writing difficulties in students with learning difficulties in high grades are disfluency in reading, errors in reading, deficiencies in visual memory, difficulty understanding sound symbols, illegible writing, late writing, missing or inverted letters and error in holding a pencil. The factors for difficulty in reading and writing are internal factors including hereditary factors, interest in reading and writing factors and motivation factors, while external factors include existing facilities at school and the family environment or where students live. Efforts made by teachers when dealing with students who have difficulty reading and writing, namely by providing remediation, using various learning media and reading and writing learning programs for students who are not yet fluent in reading and writing, especially in high classes, must be held in every school.

B - 81 Neuropsychological Case Study: Transient Amnesia or "Sentinel Seizure?" Potential Prodromal Symptoms of an ACoA Aneurysm Rupture.

We present the neuropsychological profile of a 33-year-old female with a history of transient amnestic events preceding frontal intraparenchymal/intraventricular hemorrhage, bilateral frontal cerebral edema and subarachnoid hemorrhage following a rupture of an anterior communicating artery aneurysm (ACoA). Comprehensive neuropsychological evaluation referral by neurology to assist with treatment planning given cognitive and behavioral changes since rupture of ACoA aneurysm. Prior to hospitalization, transient episodes of feeling as if she had been "drugged at a party," followed by behavior changes (e.g., irritability/agitation, "not herself") were notable, while the patient was amnestic to the events; spanning days at a time. Intellectual functioning was well-preserved. Neuropsychological testing revealed weaknesses in visuospatial organization, word retrieval, and aspects of executive functioning. Most salient were deficiencies in memory; patient was amnestic to tests shortly after administration. Striking emotional lability/frequent bouts of laughing disproportionate to the conversation and social comportment inappropriate to the setting were present. To our knowledge, amnestic events preceding ACoA aneurysm rupture have not been reported, and perhaps the symptoms this patient experienced prior to the event were indeed prodromal in nature. Therefore, the potentially rare phenomena in the form of transient amnesia should be further investigated. While these symptoms of memory lapses may be nonspecific and unique to the patient, we also cannot rule out possible "sentinel seizure" as a potential warning sign.