Short-term Memory Impairment Research Articles

Neuropharmacological Assessment of Sulfonamide Derivatives of Para-Aminobenzoic Acid through In Vivo and In Silico Approaches

Background/Objectives: Alzheimer’s disease (AD), a complex neurogenerative disorder, manifests as dementia and concomitant neuropsychiatric symptoms, including apathy, depression, and circadian disruption. The pathology involves a profound degeneration of the hippocampus and cerebral cortex, leading to the impairment of both short-term and long-term memory. The cholinergic hypothesis is among the various theories proposed, that assume the loss of the cholinergic tract contributes to the onset of AD and proves clinically effective in managing mild to moderate stages of the disease. This study explores the potential therapeutic efficacy of sulfonamide-based butyrylcholinesterase inhibitors in mitigating scopolamine-induced amnesia in rats. Methods: Behavioral assessments utilizing Y-maze, Barnes maze, and neurochemical assays were conducted to evaluate the effectiveness of the test compounds. Results: Results demonstrated a significant reduction in the impact of scopolamine administration on behavioral tasks at a dose of 20 mg/kg for both compounds. Correspondingly, neurochemical assays corroborated these findings. In silico docking analysis on rat butyrylcholinesterase (BChE) was performed to elucidate the binding mode of the compounds. Subsequent molecular dynamics studies unveiled the formation of stable complexes between the test compounds and rat BChE. Conclusions: These findings contribute valuable insights into the potential therapeutic role of sulfonamide-based butyrylcholinesterase inhibitors in addressing memory deficits associated with AD, emphasizing their in silico molecular interactions and stability.

Radiosensitivity-related Variation in MicroRNA-34a-5p Levels and Subsequent Neuronal Loss in the Hilus of the Dentate Gyrus after Irradiation at Postnatal Days 10 and 21 in Mice.

The radiosensitivity of mice differs between postnatal days 10 (P10) and 21(P21); these days mark different stages of brain development. In the present study, Ki67 and doublecotin (DCX) immunostaining and hematoxylin staining was performed, which showed that acute radiation exposure at postnatal day 10 induced higher cell apoptosis and loss in the hilus of the dentate gyrus at day 1 postirradiation than postnatal day 21. MicroRNA (miRNA) sequencing and real-time quantitative reverse transcription PCR (qRT-PCR) analysis indicated the upregulation of miRNA-34a-5p at days 1 and 7 after irradiation at postnatal day 10, but not at postnatal day 21. Down-regulation of T-cell intracytoplasmic antigen-1 pathway (Tia1) was indicated by qRT-PCR at day 1 day but not day 7 after irradiation at postnatal day 10. Neurobehavioral testing in mature mice irradiated at postnatal day 10 demonstrated the impairment of short-term memory in novel object recognition and spatial memory, compared to those irradiated at postnatal day 21. Combined with our previous luciferase assay showing the direct interaction of miRNA34a-5p and Tia1, these findings suggest that radiation-induced abnormal miR-34a-5p/Tial interaction at day 1 after irradiation at postnatal day 10 may be involved in apoptosis of the dentate gyrus hilar, impairment of neurogenesis and subsequent short-term memory loss as observed in the novel object recognition and Barnes maze tests.

Discovery and structure − activity relationships of 2,4,5-trimethoxyphenyl pyrimidine derivatives as selective D5 receptor partial agonists

Dopamine receptors are therapeutic targets for the treatment of various neurological and psychiatric disorders, including Parkinson’s and Alzheimer’s. Previously, PF-06649751 (tavapadon), PF-2562 and PW0464 have been discovered as potent and selective G protein-biased D1/D5 receptor agonists with optimal pharmacokinetic properties. However, no selective D5R agonist has been reported yet. In this context, we designed and synthesized forty non-catecholamines-based pyrimidine derivatives and identified four pyrimidine derivatives as selective D5R partial agonists. Using cAMP-based GloSensor assay in transiently transfected HEK293T cells with human D1 or D5 receptors, we discovered that compound 5c (4-(4-bromophenyl)-6-(2,4,5-trimethoxyphenyl)pyrimidin-2-amine) exhibited modest D5R agonist activity. This leads us to explore various modifications of this scaffold to improve the D5 agonist potency and efficacy. Using molecular docking, and rational design followed by their evaluation at D1 and D5 receptors for agonist activity, we identified three new derivatives, 5j, 5h, and 5e. The most potent compound of this series 5j (4-(4-iodophenyl)-6-(2,4,5-trimethoxyphenyl)pyrimidin-2-amine), exhibited EC50 of 269.7 ± 6.6 nM. Mice microsomal stability studies revealed that 5j is quite stable (>70 % at 1 hr). Furthermore, pharmacokinetic analysis of 5j (20 mg/kg, p.o) in C57BL/6j mice showed that 5j is readily absorbed via oral route of dosing and also enters into the brain (plasma Tmax: 1 h, Cmax: 51.10 ± 13.51 ng/ml; Brain Tmax: 0.5 h, Cmax: 22.54 ± 4.08 ng/ml). We further determined the in-vivo effect of 5j on cognition in scopolamine-induced amnesia in C57BL/6j mice. We observed that 5j (10 mg/kg, p.o) alleviated scopolamine-induced impairment in short-term memory and social recognition, which were blocked by D1/D5 antagonist SCH23390 (0.1 mg/kg, i.p.). Furthermore, 5j did not exhibit any cytotoxicity (up to 10 µM) or in vivo acute toxicity up to 200 mg/kg (p.o). These results strongly suggest that 5j could be further developed for treating neurological disorders wherein the D5 receptors play pivotal roles.

The presence of cognitive impairments in the acute phase of traumatic upper limb injuries: A cross-sectional observational study

ObjectivesThe purpose of this study was to investigate the association between cognitive impairments and traumatic upper limb injuries of the acute phase. Material and methodsA cross-sectional observational study was conducted with three groups: a nerve-injury group, a without nerve injury group, and a control group (uninjured participants). Demographic characteristics (e.g. age, sex, body mass index, and education) and traumatic characteristics (duration since injury, injury side, pain, light touch sensation, hand motor function) were recorded. Short-term memory and executive functions were assessed using Rey Auditory and Verbal Learning Test (RAVLT) and Stroop Color and Word Test (SCWT, including SIECT and SIECN), respectively. ResultsThe study comprised 43 participants in the nerve-injury group, 30 participants in the group without nerve injury, and 104 participants in the control group. Generalized linear model was applied to explore the difference of cognitive functions among three groups with impactors. Significantly poorer performance on the RAVLT was observed in the nerve-injury group compared to the other two groups, and lower score of SIECT in nerve-injury group was lower compared to the control group. However, there was no significant difference of SIECN among three groups. In addition, traumatic characteristics did not significantly impact RAVLT and SIECT (p > 0.05) in all injured participants. ConclusionTraumatic nerve injury to the upper limb appears to be associated with both short-term memory and executive function impairment, whereas musculoskeletal injuries without nerve damage showed no cognitive impairment. Therefore, it is important to monitor cognitive function following upper limb nerve injuries.

Divine noni's protective impact on Swiss albino mice's short-term memory impairment caused by cyclophosphamide: A behavioral and biochemical approach

Cyclophosphamide (CYL) is a first-line cancer chemotherapeutic agent widely used for the treatment of cancer that has severe toxic effects. The primary mechanism by which CYL induces toxicity through free radical generation. Morinda citrifolia (Noni) fruit juice is an herbal remedy documented to have antioxidant properties. The aim of the current study was to investigate the protective effect of noni against CYL-induced memory impairment in Swiss albino mice. Treatment schedule: Group 1: Normal: Received vehicle; Group 2: CYL treatment: Received CYL (40.0 mg/kg b.w. i.p.) on day one; Group 3: NJ treatment: Received NJ (360 mg/b.w. p.o.) once daily for 14 days. Group 4: DNG treatment: DNG (360 mg/b.w. p.o.) once daily for 14 days, Group 5: NJ + CYL treatment: Received CYL (40.0 mg/kg b.w. i.p.) on day one and after half an hour of received NJ (360 mg/b.w. p.o.) once daily for 14 days. Group 6: DNG + CYL treatment: Received CYL (40.0 mg/kg b.w. i.p.) on day one and after half an hour received DNG (360 mg/b.w. p.o.) once daily for 14 days. Mice were subjected to the Morris water maze (MWM) challenge for two weeks as part of a behavioral study. Short-term memory impairment was observed in the behavioral activity of CYL-treated mice in the MWM test in the 1st week trial, and this effect was reversed in the 2nd week trial in the combination treatment group. The behavioral analysis proved that noni supplementation reduced the risk of memory impairment caused by CYL. Biochemical analysis revealed that CYL markedly increased the levels of AChE and MDA in brain tissue. Similarly, decreases in the levels of antioxidants, i.e., GSH, CAT, SOD and GST, were detected in the brain tissue of the mice exposed to CYL. Qualitative and quantitative examinations of histopathological examination of the mouse hippocampus supported the above findings. The results demonstrated that noni supplement therapy reversed the changes in the MDA, AChE, and antioxidant enzyme levels while improving the behavioral and histological alterations caused by CYL. Long-term hippocampal growth and memory are unaffected, suggesting that CYL is less harmful. According to our research, supplementing with noni in conjunction with CYL may be a helpful treatment strategy for treating memory impairment caused by CYL.

Patient recall of intensive care delirium: A qualitative investigation.

Many patients in the Intensive Care Unit (ICU) experience delirium. Understanding the patient perspective of delirium is important to improve care and reduce suffering. The aim of our study was to investigate the subjective patient experience of delirium, delirium-related distress, and delirium management in ICU. Our study had a qualitative multicenter design applying individual interviews and thematic analysis. Participants were critically ill adult patients that were determined delirium positive according to validated delirium screening tools during ICU admission. The interviews were conducted after ICU discharge when patients were delirium-free as assessed by the "Rapid clinical test for delirium" (4AT) and able to participate in an interview. We interviewed 30 patients choosing the main themes deductively: Delirium experience; Delirium related distress; and Delirium management. Despite variations in recollection detail, ICU survivors consistently reported delirium-related distress during and after their ICU stay, manifesting as temporal confusion, misinterpretations, and a sense of distrust towards ICU staff. Delusions were characterized by a blend of factual and fictional elements. Impaired short-term memory hindered communication and intensified feelings of isolation, neglect, and loss of control. The ICU survivors in our study recalled delirium as an unpleasant and frightening experience, often leading to delirium-related distress during and after their ICU stay, indicating the necessity for enhanced assessment and treatment.

The Effect of Trientine on AlCl3-Induced Cognitive Dysfunction and Biochemical Changes in the Hippocampus of Rats.

Cognitive impairments affect millions of people worldwide with an increasing prevalence. Research on their etiology and treatment is developing, nevertheless significant gaps remain. Trientine (TETA), as a copper chelator, has been shown to have beneficial effects in different human chronic diseases such as diabetic cardiomyopathy and neuropathy. Here, we examined the impact of TETA on AlCl3-induced neurocognitive dysfunctions and molecular changes in the hippocampus of rats.Thirty-six male Wistar rats (weighing 200-250 g) were randomly divided into four groups including control, TETA (100 mg/kg/day), AlCl3 (100 mg/kg/day), and AlCl3 (100 mg/kg/day)+TETA (100 mg/kg/day), and received chemicals by gavage for 30 days. At the end of the treatment, the open field maze, elevated plus maze, novel object recognition memory test, and shuttle box test were done. Then after, brain-derived neurotrophic factor (BDNF), glycogen synthase kinase-3 β (GSK-3β), acetylcholinesterase activity, oxidative stress markers, and inflammatory mediators were measured in the hippocampus.AlCl3 increased anxiety-like behaviors and impaired recognition and short-term memory. TETA was able to improve AlCl3-induced anxiety-like behaviors and short-term memory dysfunction. In the AlCl3-treated group, there was a significant increase in GSK-3β, oxidative stress, pro-inflammatory and pro-apoptotic markers, and decreased BDNF in the hippocampus. Co-administration of TETA was able to decrease lipid peroxidation, inflammation, GSK-3β, and acetylcholinesterase activity, and increase BDNF in the hippocampus compared with AlCl3-treated rats.It can be concluded that TETA was able to improve neurobehavioral and neurocognitive functions by alleviating oxidative stress, inflammation, and pro-apoptotic pathways leading to the normalization of BDNF and GSK-3β.

Conserving a sense of self despite significantly impaired short-term memory through songwriting and formative events

This case study reflects on the use of improvisation and songwriting to support a patient with significantly impaired short-term memory and long-term memory interference as a result of acquired brain injury. Memory has long been associated with personal identity, linking the past with the present, and enabling us to project into the future. This continuity of consciousness helps us to learn from, and make sense of our experiences, strengthening our internal representation of self. Disruption to short-term memory can significantly impact decision making, planning and initiation, all of which are key components of personal identity and self-expression. Supporting patient autonomy and self-expression through improvisation, and crafting lyrical content around personal preferences and events, sessions were designed to bolster his internalised sense of self through both revisiting old memories and facilitating new memory formation within the present. While short-term memory has been considered a conduit to long-term memory consolidation, and integral to the individual’s self-expression, this case study implies short-term memory was neither the gatekeeper to formation of long-term memories, nor critical to maintaining a sense of self, and reflects on how music helped the client create and access new learning beyond procedural memories, anchoring the self in newly internalised self-expression.

Increased Blood-Brain Barrier Permeability and Cognitive Impairment in Patients With ESKD

Background and AimsChronic kidney disease (CKD) is associated with an increased risk of cognitive impairment. This cognitive impairment is associated with an increased permeability of blood-brain barrier (BBB) in rodents with CKD, linked to activation of aryl hydrocarbon receptor (AhR) by indoxyl sulphate (IS). The objective of BREIN study is to confirm the increased BBB permeability in humans with CKD. MethodThe BREIN comparative study (NCT04328415) prospectively included patients with end-stage kidney disease (ESKD), and healthy volunteers (Ctrl) matched in age, sex, and educational level to a patient. In all participants, BBB permeability was quantified by brain 99mTc-DTPA SPECT/CT as percentage of injected activity (%IA). A battery of neuro-cognitive tests was performed, serum uremic toxins accumulation and AhR activation were assessed. ResultsFifteen ESKD patients and 14 healthy volunteers were analysed. ESKD patients had higher BBB permeability compared to controls: 0.29±0.07 vs. 0.14±0.06 %IA, p=0.002. ESKD patients displayed lower MoCA score: 22.0±5.0 vs. 27.3 ± 2.8, p=0.008, impaired short-term memory (doors test): 12.5±3.4 vs. 16.5±3.4, p=0.005, higher Beck depression score 8.1±9.1 vs. 2.7±3.4, p=0.046, and slightly more daily cognitive complaints: 42.5±29.3 vs. 29.8±14.0 p=0.060. ESKD patients displayed higher IS levels (86.1±48.4 vs. 3.2±1.7 μmol/L, p=0.001) and AhR activating potential (37.7±17.8% vs. 24.7±10.4%, p=0.027). BBB permeability was inversely correlated with MoCA score (r=-0.60, 95%CI [-0.772; -0.339], p=0.001) in the overall population. ConclusionESKD patients display an increased BBB permeability compared to matched healthy volunteers. Association with uremic toxins and cognitive impairment needs to be assessed in larger cohorts of patients.

Characterizing the association between complement-mediated TMA and cognitive dysfunction using MRI and neurocognitive assessment

AbstractComplement-mediated thrombotic microangiopathy (CM-TMA) is a rare, life-threatening thrombotic microangiopathy caused by a defect in the alternative complement pathway. It is associated with renal failure and acute encephalopathy, but long-term neurocognitive effects are uncertain. Using magnetic resonance imaging (MRI) and neurocognitive tests, we can further evaluate the long-term neurocognitive complications in CM-TMA and compare them with controls. In this study, we analyzed microstructural changes in the cerebral white matter and neurocognitive testing results of patients with CM-TMA. Seven adult patients with CM-TMA in remission and 6 healthy controls were included. All patients were treated with C5 complement blockade. They were followed-up for 12 months after study entry. All patients had consecutive MRI scans (standard-of-care and quantitative sequences) to assess for white matter changes and concurrent neurocognitive testing. Patients with CM-TMA had increased white matter signal intensity in most regions of the brain compared with controls. This was accompanied by increased depression and neurocognitive dysfunction (impaired concentration, short-term memory, and verbal memory). These findings were also present up to 12 months after the initial study visit. In summary, patients with previous CM-TMA were found to have significant, albeit nonspecific, cerebral white matter abnormalities, with impaired memory and concentration. Larger studies with longitudinal follow-up to assess neurocognitive complications in CM-TMA are required. This trial was registered at Clinical Trials Ontario (ctontario.ca; project ID: 1318).

BCI Improves Alcohol-Induced Cognitive and Emotional Impairments by Restoring pERK-BDNF.

Binge drinking causes a range of problems especially damage to the nervous system, and the specific neural mechanism of brain loss and behavioral abnormalities caused by which is still unclear. Extracellular regulated protein kinases (ERK) maintain neuronal survival, growth, and regulation of synaptic plasticity by phosphorylating specific transcription factors to regulate expression of brain-derived neurotrophic factor (BDNF). Dual-specific phosphatase 1 (DUSP1) and DUSP6 dephosphorylate tyrosine and serine/threonine residues in ERK1/2 to inactivate them. To investigate the molecular mechanism by which alcohol affects memory and emotion, a chronic intermittent alcohol exposure (CIAE) model was established. The results demonstrated that mice in the CIAE group developed short-term recognition memory impairment and anxiety-like behavior; meanwhile, the expression of DUSP1 and DUSP66 in the mPFC was increased, while the levels of p-ERK and BDNF were decreased. Micro-injection of DUSP1/6 inhibitor BCI into the medial prefrontal cortex (mPFC) restored the dendritic morphology by reversing the activity of ERK-BDNF and ultimately improved cognitive and emotional impairment caused by CIAE. These findings indicate that CIAE inhibits ERK-BDNF by increasing DUSP1/6 in the mPFC that may be associated with cognitive and emotional deficits. Consequently, DUSP1 and DUSP6 appear to be potential targets for the treatment of alcoholic brain disorders.

Distinct biological property of tau in tau-first cognitive proteinopathy: Evidence by longitudinal clinical neuroimaging profiles and compared with late-onset Alzheimer disease.

Tau-first cognitive proteinopathy (TCP) denotes a clinical phenotype of Alzheimer disease (AD) showing Florzolotau(18F) positron emission tomography (PET) positivity but a negative amyloid status. We explored the biological property of tau using longitudinal cognitive and neuroimaging data in TCP and compared with late-onset AD (LOAD). We enrolled 56 patients with LOAD, 34 patients with TCP, and 26 cognitive unimpaired controls. All of the participants had historical data of 2 to 4 three-dimensional T1 images and 2 to 6 annual cognitive evaluations over a follow-up period of 7 years. Tau topography was measured using Florzolotau(18F) PET. In the LOAD and TCP groups, we constructed tau or gray matter clusters covarying with the cognitive measurements. We used mediator analysis to explore the regional tau load as predictor, gray matter partitions as mediators, and significant cognitive test scores as outcomes. Longitudinal cognitive decline and cortical thickness degeneration pattern were analyzed using a linear mixed-effects model. The TCP group had longitudinal declines in nonexecutive domains. The deterministic factor predicting the short-term memory score in TCP was the hippocampal volume and not directly via the medial and lateral temporal tau load. These features formed the conceptual differences with LOAD. The biological properties of tau and the longitudinal cognitive-imaging trajectory support the conceptual distinction between TCP and LOAD. TCP represents one specific entity featuring salient short-term memory impairment, declines in nonexecutive domains, a slower gray matter degenerative pattern, and a restricted impact of tau.

Is ethyl chloride the new nitrous oxide? A case report

BackgroundOver the last decade, there has been an emerging trend of recreational misuse of several drugs and inhaled solvent including ethyl chloride. This case report follows CARE guidelines and highlights, with supporting video, the neurological features of ethyl chloride intoxication.Case presentationA 48-year-old man was seen for the sudden occurrence of an unsteady gait with dizziness. His only medical history was a chronic and treated HIV infection without any complications. Clinical examination revealed a cerebellar syndrome associated with impairment of short-term memory. Biological and radiological workups were normal. After several days, the patient recalled ethyl chloride inhalation. He fully recovered after being discharged from hospital.ConclusionClinicians should recognise the clinical features and neurological manifestations of ethyl chloride intoxication due to the potential fatal cardiovascular complications of this intoxication.

Gut Microbiota-Mediated Alterations of Hippocampal CB1R Regulating the Diurnal Variation of Cognitive Impairment Induced by Hepatic Ischemia-Reperfusion Injury in Mice.

Patients suffering from hepatic ischemia-reperfusion injury (HIRI) frequently exhibit postoperative cognitive deficits. Our previous observations have emphasized the diurnal variation in hepatic ischemia-reperfusion injury-induced cognitive impairment, in which gut microbiota-associated hippocampal lipid metabolism plays an important role. Herein, we further investigated the molecular mechanisms involved in the process. Hepatic ischemia-reperfusion surgery was performed under morning (ZT0, 08:00) and evening (ZT12, 20:00). Fecal microbiota transplantation was used to associate HIRI model with pseudo-germ-free mice. The novel object recognition test and Y-maze test were used to assess cognitive function. 16S rRNA gene sequencing and analysis were used for microbial analysis. Western blotting was used for hippocampal protein analysis. Compared with the ZT0-HIRI group, ZT12-HIRI mice showed learning and short term memory impairment, accompanied by down-regulated expression of hippocampal CB1R, but not CB2R. Both gut microbiota composition and microbiota metabolites were significantly different in ZT12-HIRI mice compared with ZT0-HIRI. Fecal microbiota transplantation from the ZT12-HIRI was demonstrated to induce cognitive impairment behavior and down-regulated hippocampal CB1R and β-arrestin1. Intraperitoneal administration of CB1R inhibitor AM251 (1mg/kg) down-regulated hippocampal CB1R and caused cognitive impairment in ZT0-HIRI mice. And intraperitoneal administration of CB1R agonist WIN 55,212-2 (1mg/kg) up-regulated hippocampal CB1R and improved cognitive impairment in ZT12-HIRI mice. In summary, the results suggest that gut microbiota may regulate the diurnal variation of HIRI-induced cognitive function by interfering with hippocampal CB1R.

Sleep apnea and glymphatic dysfunction as a mediator of executive dysfunction and neurodegenerative risk in cancer related cognitive impairment (CRCI).

12091 Background: Cancer survivors often experience cognitive changes, formally known as Cancer-Related Cognitive Impairment (CRCI), during or after treatment. CRCI commonly consists of executive dysfunction, which includes impairments in short-term memory, sustained attention/inhibitory control, cognitive flexibility, processing speed, and top-down processing. CRCI may be impacted by comorbidities and can increase neurodegenerative disease risk. Sleep disorders and disruptions (SDs) impair executive function in the general population. SDs may contribute to CRCI by impeding progression to deep sleep stages associated with enhanced glymphatic flow (GF) and clearance of inflammatory byproducts, leading to ventriculomegaly (VM- enlarged ventricles). VM is associated with cognitive impairment in other disorders, such as normal pressure hydrocephalus. Using data from the University of Cincinnati Cancer Cognitive Registry, we investigated relationships between the incidence and type of SD in CRCI, SDs and executive dysfunction, and evidence of altered GF in SD as measured by Evans Indices (EIs). SDs are known to be prevalent in CRCI patients. We hypothesize that evidence of impaired GF as measured by EIs will be present and associated with SDs and executive dysfunction. Identifying modifiable contributors to CRCI and their mechanisms of action are critical steps towards increasing quality of life in survivors. Methods: 174 patients referred for CRCI between 10/2021-10/2023 underwent assessments for CRCI and sleep hygiene with a cognitive battery, subjective questionnaires, and nocturnal polysomnography. Retrospective data gathered from Epic was entered into a REDCap registry. MRIs were analyzed in McKesson to calculate EIs. Results: Our data demonstrated the presence of SDs in 84% of patients and obstructive sleep apnea in 45%. Measures of apnea severity (apnea-hypopnea index-AHI) and GF (EIs) inversely correlated with executive function scores. This implicates sleep-related GF as a potential mediator of CRCI. Conclusions: CRCI and accompanying increased neurodegenerative risk may be the result of restricted cerebral spinal fluid exchange due to SDs in conjunction with systemic inflammation from cancer and its treatment. Sleep assessments should be routine in CRCI evaluations. Longitudinal assessments will help determine the relationship of SDs and their treatment to the course of CRCI and risk of neurodegenerative disease.

#1086 Blood-brain barrier permeability in patients with end-stage kidney disease: results from the BREIN study

Abstract Background and Aims Chronic kidney disease (CKD) is associated with an increased risk of cognitive impairment. In several models of CKD in rodents, we highlighted that CKD was associated with cognitive impairment and increased blood-brain barrier (BBB) permeability, quantified using 99mTc-DTPA scintigraphy imaging (SPECT/CT). BBB permeability was both correlated with cognitive impairment and with indoxyl sulfate (IS) levels. Inactivation of Aryl Hydrocarbon Receptor (AhR), receptor of the IS, protected the CKD mouse from the IS-induced BBB permeability. The objective of the BREIN study is to confirm the existence of an increased BBB permeability in humans with CKD. Method The prospective cohort study BREIN (NCT04328415) prospectively included patients with end-stage kidney disease (ESKD), and healthy volunteers (Ctrl) matched in age (±5 years), gender, and educational level to a patient. In patients and volunteers, BBB permeability was quantified by brain 99mTc-DTPA SPECT/CT performed by a senior nuclear physician and as percentage of injected activity (%IA). A battery of neuro-cognitive tests was performed, serum uremic toxins accumulation and AhR activation were assessed in all participants. Results 15 ESKD patients and 14 healthy volunteers were included. In ESKD patients had higher BBB permeability compared to controls: 0.29 0.07 vs. 0.14 0.06%IA, p < 0.0001. ESKD patients displayed lower MoCA score: 22.0 ± 5.0 vs. 27.3 ± 2.8, p = 0.008, impaired short-term memory (doors test): 12.5 ± 3.4 vs. 16.5 ± 3.4, p = 0.009, higher Beck depression score 8.1 ± 9.1 vs. 2.7 ± 3.4, p = 0.046, and slightly more daily cognitive complaints: 42.5 ± 29.3 vs. 29.8 ± 14.0 p = 0.153. ESKD patients displayed higher IS levels (2.8 ± 2.3 mmol/L vs. 0.9 ± 0.7 mmol/L, p = 0.006) and AhR activation (37.5 ± 17.8% vs. 24.7 ± 10.4%, p = 0.027). In ESKD patients, no significant correlation was found between BBB permeability and scores in cognitive tests, or serum uremic toxins levels. Conclusion This study confirms that ESKD patients display an increased BBB permeability compared to matched healthy volunteers, as well as cognitive and impairment. Association with uremic toxins and cognitive impairment needs to be assessed in larger cohorts.

#1336 Serotonin levels in hemodialysis patients with Long COVID-associated cognitive impairment

Abstract Background and Aims Long COVID comprises a broad range of persistent symptoms that emerge after COVID-19 and can last for months or years and have a direct impact on daily life. Cognitive impairment and loss of short-term memory are examples of symptoms associated with long COVID. To date, there are neither generally agreed-upon diagnostic criteria nor effective treatments available. A recent study found an association of serotonin deficiency and long COVID in the general population [1], leading to vagal dysfunction and impaired cognition. In this study, we aimed to evaluate longitudinal serotonin levels in hemodialysis (HD) patients with or without cognitive symptoms associated with long COVID. Method We analyzed routinely collected serum samples (n = 102) from 16 HD patients collected between 60 days before and 60 days after a positive SARS-CoV-2 RT-PCR. Metabolites were extracted using cold methanol and subjected to reverse phase liquid chromatography/mass spectrometry (LC/MS). Serotonin was identified by matching retention time, accurate mass, and fragmentation data against an in-house LC/MS library. Log2 of serotonin signal intensity was used for quantification. The COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) was administered shortly after positive RT-PCR test, as well as 1- and 6-months post-COVID. Patients were classified as having cognitive symptoms if they reported short-term memory loss or difficulties with concentration or communication problems as per C19-YRS. Unpaired t-test or Fisher's exact tests were performed to compare characteristics of patients with and without cognitive symptoms. We defined three study periods relative to the date of COVID-19 diagnosis: –60 to –15 days (baseline); –14 to +14 days (acute COVID); and +15 to +60 days (post-COVID). Differences in serotonin signal intensity (log2) between patients with and without cognitive symptoms were evaluated with unpaired t-tests. Linear mixed effects models with random intercepts were constructed to determine changes in serotonin levels over time with the baseline period as the comparator. This research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK130067). Results Demographic data are presented in Table 1a. Of the 16 patients, 7 (44%) were classified with cognitive symptoms associated with long COVID. There were no differences in age, sex, race, ethnicity, vintage, diabetes, and hypertension between patients with and without cognitive symptoms. Serotonin levels in patients with vs. without cognitive symptoms did not significantly differ at baseline and during acute COVID (Fig. 1). Of note, in the post-COVID phase, serotonin levels were significantly lower in the group with impaired cognition (p = 0.012) compared to symptoms-free patients (Fig. 1). Within each group, serotonin levels remained unchanged at acute-COVID or post-COVID periods compared to baseline (Table 1b). Conclusion We show that HD patients with impaired cognition have lower serotonin in the post-COVID phase compared to patients without cognitive symptoms. These results corroborate findings in the general population. Further investigation in a larger cohort is warranted to evaluate the potential of serotonin as a target for the prevention or as a marker of neurocognitive symptoms associated with long COVID.

Consolidation and Reconsolidation of Auditory-Verbal Memory in Parkinson’s Disease

The paper describes the processes of consolidation and reconsolidation of auditory-verbal memory in patients diagnosed with Parkinson’s disease (G20, ICD-10) in comparison with cerebrovascular pathologies of a chronic and acute nature. The research objective was to identify the specifics of consolidation and reconsolidation of auditory-verbal memory in patients of this nosological group. The methods involved an experiment in F. Bartlett’s schema reconstruction, as well as methods of descriptive and comparative statistics. The experiment involved 104 people (67.5 ± 4.5, 21% male), including 30 patients with Parkinson’s disease (G20) (67.8 ± 4.8, 24% male), 34 patients diagnosed with sequelae of cerebral infarction (I69.3) (67.4 ± 4.4, 20% male), and 40 patients with other specified lesions of cerebral vessels on a model of chronic cerebral ischemia (CICI) (I67.8 67.6 ± 4.4, 24% male). All codes were indicated in accordance with ICD-10. The research revealed reliably significant features of consolidation and reconsolidation of auditoryverbal memory in Parkinson’s disease. The greatest number of differences belonged to the comparative analysis with the patients with chronic cerebral ischemia. This nosology was characterized by a greater number of distortion errors but few additions and sequence violations. In Parkinson’s disease, information underwent transformations already at the storing stage, which led to impairment of short-term and long-term memory. Distortion errors were more numerous than consistency errors, which casts doubt on the kinetic factor as the key one.

Assessment of Anxiety and Depression in the Perioperative Period in Women of Reproductive Age During Regional Anesthesia

Introduction Perioperative cognitive impairment occurs in both pregnant and non-pregnant women. Prediction, early detection and effective treatment of these disorders are important for the well-being of women and their offspring.Aim of study To evaluate the effect of anesthesia and surgery on the level of anxiety, depression, short-term memory, and concentration in pregnant and nonpregnant women.Material and methods The observational prospective study included 120 patients who were divided into two equal groups — pregnant (n=60) and nonpregnant (n=60) women. A comparative analysis of testing psychosomatic reactions and cognitive functions using the MoCa test, Benton and Wechsler tests, selfassessment questionnaire, Hospital Anxiety and Depression Scale (HADS) was carried out. The relative risk and odds ratio of developing anxiety and depression were calculated.Results Anxiety indicators in pregnant women before surgery reached subclinical values of 7.5 (8.4; 6.6), and in non-pregnant women – the norm: 6.5 (7.3; 5.7) (p<0.001); Results of depression in pregnant women after surgery were 7.3 (8.5; 6.1), in non-pregnant women — the norm: 6.3 (7; 5.5) (p<0.001). The odds of developing short-term memory impairment in pregnant women before surgery was 3.1 times higher than in non-pregnant women, odds ratio 3.1 (95% CI [1.3–7.4]). In the pregnant group, short-term memory scores before surgery were 5 (5.8; 4.2), and after surgery they decreased to 3.8 (4.7; 2.9) (p<0.001). There was a decrease in concentration of attention in pregnant women: before surgery 6.2 (6.8; 5.6), and after surgery — 5 (5.8; 4.2) (p<0.001). The relative risk (RR) of developing depression in pregnant women after surgery was 6.1 times RR=6.1 (95% CI 2.4; 15.8), sensitivity Se (%)=0.9, specificity Sp (%)=0.5. The relative risk (RR) of developing short-term memory impairment after surgery was 1.1 times RR=1.1 (95% CI 1; 1.2), sensitivity Se (%)=0.5, specificity Sp (%)=0, 8. The relative risk (RR) of developing problems with concentration after surgery was 8.3 times RR=8.3 (95% CI 3.9; 18.3), sensitivity Se (%)=0.8, specificity Sp (%)=0.7.Conclusions The Results obtained allow us to conclude that before surgery, pregnant women experience a subclinical version of anxiety, against the background of which the chances of developing problems with short-term memory and concentration increase. After surgery, pregnant women experience a subclinical version of depression, along with it there is also impairment of intelligence, short-term memory and concentration. The initial impairment of memory and attention requires the selection of anesthesia in a group of pregnant women.

Attention and executive function impairments in obstructive sleep apnea are associated with decreased sleep spindles.

Sleep spindles play a key role in sleep-mediated cognitive processes. Cognitive functions are well-known to be affected in obstructive sleep apnea (OSA). Here, we analyzed attention and executive functions in patients with OSA and investigated the relationship between sleep spindles and cognitive abilities. Sixty patients with OSA (18-65years, 19 females and 41 males) and a control group (n = 41) including age-and sex-matched healthy individuals were consecutively and prospectively enrolled. All participants had a full-night polysomnography, and sleep spindles were analyzed using a semi-automated program. For the evaluation of short-term memory, attention and executive functions, Stroop test, forward and backward digit span tests were applied to all participants upon awakening following polysomnography. Scores of forward and backward digit span and Stroop tests were worse in OSA patients in compared to those in controls. Mean density of sleep spindles was decreased in OSA patients than those in controls (p = 0.044). A positive correlation was found between fast sleep spindle frequency and forward digit span (r = 2.222; p = 0.038) and backward digit span test scores (r = 2,157; p = 0.042) in OSA patients. In patients with moderate to severe OSA, sleep spindle density was positively correlated with forward (r = 2.323, p = 0.029) and backward (r = 2.500, p = 0.016) DSTs, and the duration of sleep spindles had positive correlation with backward DST (r = 2.452, p = 0.010). Our findings demonstrated that the disturbances in sleep spindle characteristics in OSA are associated with the cognitive impairments in attention, short-term memory, and executive functions, especially in patients with moderate to severe OSA.