Significant Cognitive Impairment Research Articles

Alterations in the Glymphatic System and Association with Brain Structure and Cognitive Function in Moyamoya Disease.

The glymphatic system is crucial for clearing metabolic waste from the brain, maintaining neural health and cognitive function. This study explores the glymphatic system's role in Moyamoya disease (MMD), characterized by progressive cerebral artery stenosis and brain structural lesions. We assessed 33 MMD patients and 21 healthy controls using diffusion tensor imaging along the perivascular space (DTI-ALPS) and global cortical gray matter-cerebrospinal fluid (CSF) coupling indices (gBOLD-CSF), which are indirect measurements of the glymphatic system. Cerebral perfusion in patients was evaluated via computed tomography perfusion imaging. We also measured the peak width of skeletonized mean diffusivity (PSMD), white matter hyperintensity (WMH) burden, and cognitive function. MMD patients exhibited lower ALPS and gBOLD-CSF coupling indices compared to controls (P < 0.01), indicating disrupted glymphatic function. Significant cognitive impairment was also observed in MMD patients (P < 0.01). ALPS indices varied with cerebral perfusion stages, being higher in earlier ischemic stages (P < 0.05). Analysis of brain structure showed increased CSF volume, PSMD index, and higher WMH burden in MMD patients (P < 0.01). The ALPS index positively correlated with white matter volume and cognitive scores, and negatively correlated with CSF volume, PSMD, and WMH burden (P < 0.05). Mediation analysis revealed the number of periventricular WMH significantly mediated the relationship between glymphatic dysfunction and cognitive impairment. In summary, MMD patients exhibit significant glymphatic system impairments, associated with brain structural changes and cognitive deficits.

Cognitive Phenotyping of GBA1-Parkinson's Disease: A Study on Deep Brain Stimulation Outcomes

BackgroundHeterozygous variants in the glucocerebrosidase (GBA1) gene are the most common genetic risk factor for Parkinson’s Disease (PD). GBA1-PD patients exhibit earlier disease onset, severe motor impairment, and heightened cognitive decline. Deep Brain Stimulation (DBS) offers motor improvement for PD patients, but its cognitive effects, particularly in GBA1-PD, are debated. MethodsThis study involved 96 PD patients who underwent subthalamic nucleus DBS at Hospital de la Santa Creu i Sant Pau between 2004 and 2023. Clinical and neuropsychological assessments were conducted pre- and post-surgery, focusing on Mattis Dementia Rating Scale (MDRS) and Frontal Systems Behavior Scale (FrSBe). Patients were categorized into GBA1-PD and non-GBA1-PD groups, with non-GBA1-PD further divided into cognitive fast-progressors and slow-progressors. ResultsGBA1 variants were present in 13.5% of patients. GBA1-PD patients showed greater cognitive decline over time, particularly in attention, conceptualization, and memory, compared to non-GBA1-PD. Non-GBA1-PD fast-progressors exhibited significant cognitive deterioration in initiation and conceptualization within the first year post-DBS. Motor outcomes improved similarly across all groups, but slow-progressors showed a greater reduction in Levodopa Equivalent Daily Dose (LEDD). ConclusionsGBA1-PD patients experience more rapid cognitive decline, particularly in posterior-cortical and fronto-striatal functions. Additionally, a subset of non-GBA1-PD patients shows significant early cognitive decline post-DBS, especially in executive functions. Baseline MDRS scores do not predict cognitive outcomes, highlighting the need for further research to refine prognostic tools. Despite cognitive challenges, GBA1-PD patients benefit from DBS in terms of motor outcomes, underscoring the importance of individualized assessments for DBS suitability, regardless of genetic status.

Autism and psychopathology - prevalence, identification, and symptoms equivalence: study protocol.

Despite increasing evidence of high psychopathological vulnerability in people with Autism Spectrum Disorder (ASD) and/or Intellectual disability (ID), comprehensive data on prevalence and presentation of psychiatric disorders (PD) in people with significant cognitive and communication impairment are lacking. The extent to which PD can present with behavioral/observable symptoms and include Problem Behaviors (PB) has also been scarcely evaluated through population-based studies. The paper presents the protocol of a cross-sectional study aimed at filling these gaps, referred to a large multicentric Italian population-based sample of adolescents and adults. A battery of validated scales, SPAIDD, DASH-II, DiBAS-R, and STA-DI, is used to support and control for clinical diagnoses of PD. Study population is stratified according to different independent variables such as the severity of ID and ASD, gender, age group, and source of recruitment. A network analysis will be carried out to identify the most central behavioral symptoms for the various PD and their relationship with PB. Overlap between psychiatric symptoms and ASD and ID phenotypes is also addressed. This study should provide valuable insight into better diagnostic accuracy, leading to well-informed interventions to improve the quality of life of people with ASD and/or ID.

Multidimensional Sleep Profiles via Machine learning and Risk of Dementia and Cardiovascular Disease.

Sleep health comprises several dimensions such as duration and fragmentation of sleep, circadian activity, and daytime behavior. Yet, most research has focused on individual sleep characteristics. Studies are needed to identify sleep profiles incorporating multiple dimensions and to assess how different profiles may be linked to adverse health outcomes. To identify actigraphy-based 24-hour sleep/circadian profiles in older men and to investigate whether these profiles are associated with the incidence of dementia and cardiovascular disease (CVD) events over 12 years. Data came from a prospective sleep study with participants recruited between 2003-2005 and followed until 2015-2016. Multicenter population-based cohort study. Among the 3,135 men enrolled, we excluded 331 men with missing or invalid actigraphy data and 137 with significant cognitive impairment at baseline, leading to a sample of 2,667 participants. Leveraging 20 actigraphy-derived sleep and circadian activity rhythm variables, we determined sleep/circadian profiles using an unsupervised machine learning technique based on multiple coalesced generalized hyperbolic mixture modeling. Incidence of dementia and CVD events. We identified three distinct sleep/circadian profiles: active healthy sleepers (AHS; n=1,707 (64.0%); characterized by normal sleep duration, higher sleep quality, stronger circadian rhythmicity, and higher activity during wake periods), fragmented poor sleepers (FPS; n=376 (14.1%); lower sleep quality, higher sleep fragmentation, shorter sleep duration, and weaker circadian rhythmicity), and long and frequent nappers (LFN; n=584 (21.9%); longer and more frequent naps, higher sleep quality, normal sleep duration, and more fragmented circadian rhythmicity). Over the 12-year follow-up, compared to AHS, FPS had increased risks of dementia and CVD events (Hazard Ratio (HR)=1.35, 95% confidence interval (CI)=1.02-1.78 and HR=1.32, 95% CI=1.08-1.60, respectively) after multivariable adjustment, whereas LFN showed a marginal association with increased CVD events risk (HR=1.16, 95% CI=0.98-1.37) but not with dementia (HR=1.09, 95%CI=0.86-1.38). We identified three distinct multidimensional profiles of sleep health. Compared to healthy sleepers, older men with overall poor sleep and circadian activity rhythms exhibited worse incident cognitive and cardiovascular health. These results highlight potential targets for sleep interventions and the need for more comprehensive screening of poor sleepers for adverse outcomes. Question: Are there distinct sleep/circadian profiles in older men, and if so, are they associated with the incidence of dementia and cardiovascular disease (CVD) events over 12 years?Findings: Three actigraphy-based profiles were identified: active healthy sleepers [AHS], fragmented poor sleepers [FPS], and long and frequent nappers [LFN]. Compared to AHS, FPS had increased risks of dementia and CVD events whereas LFN had marginal risk of CVD events.Meaning: Older men with distinct sleep/circadian profiles are at increased risk of incident dementia and CVD events, suggesting their potential as target populations for sleep interventions and screening for adverse outcomes.

Cognitive assessment of a sample of Egyptian patients with amyotrophic lateral sclerosis

BackgroundCognitive and behavioral changes in ALS are featured as an integral part of the disease. A noticeable proportion of ALS patients present with a full-blown picture of frontotemporal dementia, which is considered the most common form of cognitive impairment in ALS.ResultsA total of 30 ALS cases and 30 sex, age and education matched healthy controls were enrolled; their sociodemographic data were statistically insignificant as regards (age, sex, education). Regarding cognitive and behavioral assessment using the ECAS-EG, both ECAS mean total score and subdomains mean scores were significantly lower in ALS patients compared to controls (p-value < 0.001), with statistically significant relation between ALS clinical staging and ECAS total scores (p-value < 0.001). Furthermore, it was found that mean scores of nearly all ECAS domains are lower in early-onset group with longer duration of illness than late onset with short duration of illness but with a non-statistically significant difference.ConclusionALS causes significant cognitive impairment, with relation between functional status and clinical staging of the disease with the severity of cognitive and behavioral dysfunctions and although early-onset cases had lower score on ECAS compared to those with late onset, but it was non-significant.

Intelligent non-invasive elderly fall monitoring by designing software defined radio frequency sensing system

The global increase in life expectancy poses challenges related to the safety and well-being of the elderly population, especially in relation to falls. While falls can lead to significant cognitive impairments, timely intervention can mitigate their adverse effects. In this context, the need for non-invasive, efficient monitoring systems becomes paramount. Although wearable sensors have gained traction for monitoring health activities, they may cause discomfort during prolonged use, especially for the elderly. To address this issue, we present an intelligent, non-invasive Software-Defined Radio Frequency (SDRF) sensing system, tailored red for monitoring elderly people's falls during routine activities. Harnessing the power of deep learning and machine learning, our system processes the Wireless Channel State Information (WCSI) generated during regular and fall activities. By employing sophisticated signal processing techniques, the system captures unique patterns that distinguish falls from normal activities. In addition, we use statistical features to streamline data processing, thereby optimizing the computational efficiency of the system. Our experiments, conducted for a typical home environment while using treadmill, demonstrate the robustness of the system. The results show high classification accuracies of 92.5%, 95.1%, and 99.8% for three Artificial Intelligence (AI) algorithms. Notably, the SDRF-based approach offers flexibility, cost-effectiveness, and adaptability through software modifications, circumventing the need for hardware overhaul. This research attempts to bridge the gap in RF-based sensing for elderly fall monitoring, providing a solution that combines the benefits of non-invasiveness with the precision of deep learning and machine learning.

Integrated Genome-Wide Analysis of DNA Methylation and Gene Expression in the Hippocampi of 5xFAD Alzheimer's Disease Mouse Model.

DNA methylation forms 5-methylcytosine and its regulation in the hippocampus is critical for learning and memory. Indeed, dysregulation of DNA methylation is associated with neurological diseases. Alzheimer's disease (AD) is the predominant of dementia and a neurodegenerative disorder. We examined the learning and memory function in 3- and 9-month-old wild-type and 5xfamiliar Alzheimer's disease (5xFAD) transgenic mice by performing the object recognition memory and Y-maze tests, and identified the hippocampal amyloid beta burden. To investigate the epigenetically regulated genes involved in the development or neuropathology of AD, we performed genome-wide DNA methylation sequencing and RNA sequencing analyses in the hippocampus of 9-month-old wild-type and 5xFAD tg mice. To validate the genes inversely regulated by epigenetics, we confirmed their methylation status and mRNA levels. At 9 months of age, 5xFAD tg mice showed significant cognitive impairment and amyloid-beta plaques in the hippocampus. DNA methylation sequencing identified a total of 13,777 differentially methylated regions, including 4484 of hyper- and 9293 of hypomethylated regions, that are associated with several gene ontology (GO) terms including 'nervous system development' and 'axon guidance'. In RNA sequencing analysis, we confirmed a total of 101 differentially expressed genes, including 52 up- and 49 downregulated genes, associated with GO functions such as 'positive regulation of synaptic transmission, glutamatergic' and 'actin filament organization'. Through further integrated analysis of DNA methylation and RNA sequencing, three epigenetically regulated genes were selected: thymus cell antigen 1, theta (Thy1), myosin VI (Myo6), and filamin A-interacting protein 1-like (Filip1l). The methylation level of Thy1 decreased and its mRNA levels increased, whereas that of Myo6 and Filip1l increased and their mRNA levels decreased. The common functions of these three genes may be associated with the neural cytoskeleton and synaptic plasticity. We suggest that the candidate genes epigenetically play a role in AD-associated neuropathology (i.e., amyloid-beta plaques) and memory deficit by influencing neural structure and synaptic plasticity. Furthermore, counteracting dysregulated epigenetic changes may delay or ameliorate AD onset or symptoms.

Association between the performance of executive function and the remission of depressive state after clinical treatment in patients with depression

BackgroundPrevious studies have reported that patients with depression have significant cognitive impairment. The aim of this study is to comprehensively evaluate the impairment of executive functions in patients with depression and whether the cognitive behavior performance of executive function is association with remission of depressive state after clinical treatment. MethodsWe used cognitive-behavioral test to evaluate the performance of executive functions of 95 inpatients with depression before hospitalization and conducted two follow-up evaluations of their depression status on the 15th day of hospitalization and approximately 9 months after discharge. ResultsThe performance of executive function except the accuracy of inhibition control in patients with depression were significantly worse than that of healthy controls. Multivariate linear regression analysis found that the reaction time of working memory not only had a significant linear relationship with the baseline depression scores of patients with depression, but also had a significant linear relationship with the reduced depression scores after two follow-up visits. LimitationsWe only used cognitive-behavioral data as indicators to evaluate the cognitive performances of participants and only measured three components of executive function. ConclusionsThe reaction time of working memory was a stable and effective predictor of symptom relief in patients with depression after clinical treatment. These results provide initial evidence for working memory to predict the clinical prognosis of inpatients with depression prospectively, which could be further leveraged to improve intervention approaches and analyze the heterogeneity of depression.

Assessing pain in older people with normal, mildly impaired or severely impaired cognition.

Pain is a relatively common experience among older people, but unrelieved pain has significant functional, cognitive and emotional consequences for this population. A comprehensive and accurate pain assessment is essential for effective pain management. Self-report tools are suitable to assess pain in older people with normal or mildly impaired cognition, while observational tools are suitable for use with those with significant cognitive impairment or communication difficulties. However, pain assessment in older people can be challenging. The use of one tool on its own is rarely sufficient and it is crucial to involve family carers in assessment of pain in older people with severe cognitive impairment. This article discusses different tools and strategies, including the benefits and limitations, for assessing pain in older people.

Endocrine-Disrupting Chemicals Exposure and Neurocognitive Function in the General Population: A Community-Based Study.

Endocrine-disrupting chemicals (EDCs) are pervasive in everyday environments. The impacts of these chemicals, along with EDC-related lifestyle and dietary habits on neurocognitive function, are not well understood. The Chang Gung Community Medicine Research Center conducted a cross-sectional study involving 887 participants. From this initial cohort, 120 individuals were selected based on their EDC exposure scores for detailed analysis. Among these, 67 participants aged 55 years or older were further chosen to undergo cognitive impairment assessments using the Ascertain Dementia-8 (AD-8) questionnaire. These 67 older participants did not significantly differ in age, albuminuria, or estimated glomerular filtration rate compared to those with lower impairment scores. This study revealed that mono-(2-ethylhexyl) phthalate (MEHP) levels (8.511 vs. 6.432 µg/g creatinine, p = 0.038) were associated with greater risk of cognitive impairment (AD-8 ≥ 2). Statistical models adjusting for age, gender, and diabetes indicated that MEHP levels positively correlated with AD-8 scores, achieving statistical significance in more comprehensive models (β ± SE: 0.160 ± 0.076, p = 0.042). Logistic regression analysis underscored a significant positive association between high MEHP levels and higher AD-8 scores (odds ratio: 1.217, p = 0.006). Receiver operating characteristic curves highlighted the association of high MEHP levels and EDC exposure scores for significant cognitive impairment, with areas under the curve of 66.3% and 66.6%, respectively. Exposure to EDCs, specifically di-(2-ethylhexyl) phthalate, the precursor to MEHP, may be associated with neurocognitive impairment in middle-aged and older adults.

Synthesis, biological evaluation, molecular docking, and MD simulation of novel 2,4-disubstituted quinazoline derivatives as selective butyrylcholinesterase inhibitors and antioxidant agents

Alzheimer’s disease is the most prevalent neurodegenerative disorder characterized by significant memory loss and cognitive impairments. Studies have shown that the expression level and activity of the butyrylcholinesterase enzyme increases significantly in the late stages of Alzheimer’s disease, so butyrylcholinesterase can be considered as a promising therapeutic target for potential Alzheimer’s treatments. In the present study, a novel series of 2,4-disubstituted quinazoline derivatives (6a–j) were synthesized and evaluated for their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinestrase (BuChE) enzymes, as well as for their antioxidant activities. The biological evaluation revealed that compounds 6f, 6h, and 6j showed potent inhibitory activities against eqBuChE, with IC50 values of 0.52, 6.74, and 3.65 µM, respectively. These potent compounds showed high selectivity for eqBuChE over eelAChE. The kinetic study demonstrated a mixed-type inhibition pattern for both enzymes, which revealed that the potent compounds might be able to bind to both the catalytic active site and peripheral anionic site of eelAChE and eqBuChE. In addition, molecular docking studies and molecular dynamic simulations indicated that potent compounds have favorable interactions with the active sites of BuChE. The antioxidant screening showed that compounds 6b, 6c, and 6j displayed superior scavenging capabilities compared to the other compounds. The obtained results suggest that compounds 6f, 6h, and 6j are promising lead compounds for the further development of new potent and selective BuChE inhibitors.

Mechanism research on microRNA-669f-5p/deoxycytidylate deaminase axis mediating sevoflurane-induced cognitive dysfunction in aged mice.

To investigate the role of the microRNA (miRNA)-669f-5p/deoxycytidylate deaminase (Dctd) axisin sevoflurane inducing cognitive dysfunction in aged mice. Sixty-six C57BL/6J mice were used in the experiment model and were randomly divided into the sevoflurane group and the control group. The mice in the sevoflurane group were anesthetised with 3.4% sevoflurane, whereas those in the control group were air-treated for the same period. The study was then performed using bioinformatics sequencing, as well as in vitro and in vivo validation. The mice in the sevoflurane group showed significant cognitive impairments in terms of a decrease in both spatial learning and memory abilities. Experimental doses of miR-669f-5p agonist exhibited no obvious effect on cognitive function following sevoflurane inhalation, but inhibiting the expression of miR-669f-5p could alleviate the impairments. Based on the results of the bioinformatics sequencing, miR-669f-5p/Dctd and the toll-like receptor (TLR) signalling pathway could be the key miRNA, gene and pathway leading to postoperative cognitive dysfunction following sevoflurane inhalation. The aged mice showed significantly increased expression of miR-669f-5p in the hippocampus following sevoflurane inhalation, and upregulating/inhibiting its expression could increase/decrease TLR expression in the hippocampus. Furthermore, miR-669f-5p could reduce the expression of the Dctd gene by binding to its 3'untranslated region. The miR-669f-5p/Dctd axis plays an important role in sevoflurane inducing cognitive dysfunction in aged mice, providing a new direction for further development of therapeutic strategies concerning the prevention and treatment of cognitive dysfunction associated with sevoflurane anaesthesia.

Gadd45A-mediated autophagy regulation and its impact on Alzheimer's disease pathogenesis: Deciphering the molecular Nexus

BackgroundThe growth arrest and DNA damage-inducible 45 (Gadd45) gene has been implicated in various central nervous system (CNS) functions, both normal and pathological, including aging, memory, and neurodegenerative diseases. In this study, we examined whether Gadd45A deletion triggers pathways associated with neurodegenerative diseases including Alzheimer's disease (AD). MethodsUtilizing transcriptome data from AD-associated hippocampus samples, we identified Gadd45A as a pivotal regulator of autophagy. Comprehensive analyses, including Gene Ontology enrichment and protein-protein interaction network assessments, highlighted Cdkn1A as a significant downstream target of Gadd45A. Experimental validation confirmed Gadd45A's role in modulating Cdkn1A expression and autophagy levels in hippocampal cells. We also examined the effects of autophagy on hippocampal functions and proinflammatory cytokine secretion. Additionally, a murine model was employed to validate the importance of Gadd45A in neuroinflammation and AD pathology. ResultsOur study identified 20 autophagy regulatory factors associated with AD, with Gadd45A emerging as a critical regulator. Experimental findings demonstrated that Gadd45A influences hippocampal cell fate by reducing Cdkn1A expression and suppressing autophagic activity. Comparisons between wild-type (WT) and Gadd45A knockout (Gadd45A−/−) mice revealed that Gadd45A−/− mice exhibited significant cognitive impairments, including deficits in working and spatial memory, increased Tau hyperphosphorylation, and elevated levels of kinases involved in Tau phosphorylation in the hippocampus. Additionally, Gadd45A−/− mice showed significant increases in pro-inflammatory cytokines and decreases autophagy markers in the brain. Neurotrophin levels and dendritic spine length were also reduced in Gadd45A−/− mice, likely contributing to the observed cognitive deficits. ConclusionsThese findings support the direct involvement of the Gadd45A gene in AD pathogenesis, and enhancing the expression of Gadd45A may represent a promising therapeutic strategy for the treatment of AD.

Effect of Young Plasma Therapy on Cognition, Oxidative Stress, miRNA-134, BDNF, CREB, and SIRT-1 Expressions and Neuronal Survey in the Hippocampus of Aged Ovariectomized Rats with Alzheimer's.

Menopause may increase the risk of Alzheimer's disease (AD) dementia. This study aimed to use young plasma therapy (YPT) to improve dementia caused by AD in aged ovariectomized rats. Female Wistar rats were used in the following groups: (a) young (CY) (180-200 g, 2-3 months, n = 10) and (b) old groups (250-350 g, 22-24 months, n = 60). The old rats were randomly assigned to six sub-groups: (1) control, (2) sham, (3) ovariectomized group (OVX), (4) OVX + Alzheimer disease (OVX + AD), (5) OVX + AD+ 17β-Estradiol (OVX + AD + E), and (6) OVX + AD + young plasma (OVX + AD + YP). Cognitive behaviors were evaluated using NOR, MWM, and PAL tests. MiR-134a, SIRT-1, CREB, and BDNF expressions were measured using real-time PCR and western blot, respectively. Oxidative stress in hippocampal tissue was assayed using ELISA kits. OVX and AD caused significant cognitive impairment (p < 0.001), up-regulated miR-134a (p < 0.001), down-regulated SIRT-1, CREB, and BDNF protein expression (p < 0.001), and decreased antioxidant marker levels (p < 0.001) compared to the sham group. YPT significantly restored miR-134a (p < 0.001), SIRT-1 (p < 0.001), CREB (p < 0.001), and BDNF (p < 0.001) protein expression in OVX + AD rats. YPT, as much as or more than estrogen therapy (ERT), significantly improved oxidative stress and down-regulated miR-134a expression and the up-regulation of SIRT-1, CREB, and BDNF proteins in OVX + AD rats (p < 0.001). YPT significantly improved histological alteration compared to the OVX + AD group (p < 0.001). As a non-pharmacological treatment, YPT can improve the expression of miR-134a and SIRT-1, CREB, and BDNF proteins as much as or more than estrogen therapy, ameliorating AD-induced dementia in aged OVX rats.

The 22q11.2 Deletion Syndrome from A Biopsychosocial Perspective: A Series of Cases with an ICF-Based Approach.

A descriptive, cross-sectional case series study with seven 22q11.2DS children. A questionnaire with an ICF checklist for 22q11.2DS was completed using a structured interview. The Wechsler Abbreviated Scale of Intelligence (WASI) was used to determine the Intelligence Quotient (IQ). Seven participants from 7 to 12 years old, presented some level of IQ impairment. It was observed that 22q11.2DS children experience significant intellectual, cognitive, and speech impairments across ICF Body Function domains. Impairments related to nose and pharynx were found in only one patient. The most relevant categories considered limitations in the Activity and Participation components pertained to producing nonverbal messages, communication, handling stress, and social interaction. Family, health professionals, and acquaintances were perceived as facilitators in the component Environmental Factors. The sample has its functioning affected by aspects that go beyond impairments in body structure and function. The organization of information from the perspective of the ICF is a different approach that helps clinical reasoning.

IGF-1’s protective effect on OSAS rats’ learning and memory

Abstract Purpose Patients with obstructive sleep apnea syndrome (OSAS) frequently experience cognitive dysfunction, which may be connected to chronic intermittent hypoxia (CIH). Insulin-like growth factor-1 (IGF-1) is thought to be closely associated with cognitive function, but its role in cognitive impairment caused by OSAS is unclear. The purpose of this study was to investigate the potential protective effect of IGF-1 on cognitive impairment in OSAS rats. Methods Healthy male SD rats (n = 40) were randomly assigned into four groups: control group, CIH group, NS + CIH group, and IGF-1 + CIH group. All experimental rats except for those in the control group were exposed to intermittent hypoxic (IH) environments for 8 h per day over 28 days. Prior to daily exposure to IH, rats in the IGF-1 + CIH group received subcutaneous injections of IGF-1. The Morris water maze test was conducted on all experimental rats. Brain tissue testing methods included Enzyme-Linked Immunosorbent Assay, Hematoxylin and eosin staining, Immunohistochemistry, and Western blotting. Results The rat model of OSAS was successfully established following exposure to CIH and exhibited significant cognitive impairment. However, daily subcutaneous injections of IGF-1 partially restored the impaired cognitive function in OSAS rats. Compared with the control group, there was a significant decrease in the expression levels of IGF-1, p-IGF-IR, and SYP in the CIH group; however, these expression levels increased significantly in the IGF-I + CIH group. Conclusion In OSAS rats, IGF-1 enhances learning memory; this effect may be linked to increased p-IGF-1R and SYP protein production in the hippocampus.

Cognitive Impairment and Mortality after Hospitalization for Community-Acquired Pneumonia

Introduction Community-acquired pneumonia (CAP) affects approximately 1.5 million patients annually in the United States, leading to significant acute and long-term clinical outcomes. CAP is increasingly recognized as a multisystemic disease with potential sequelae affecting various organ systems, including the neurologic, pulmonary, cardiovascular, musculoskeletal, metabolic, and renal systems. The primary objective of this study is to review literature on long-term cognitive impairment, dementia, and decreased survival following CAP hospitalization. Additionally, the potential role of the gut-lung-brain axis in the pathogenesis of these outcomes is explored. Methods A comprehensive review of existing literature was conducted, focusing on studies that examined cognitive impairment, dementia, and mortality in patients hospitalized for CAP. Relevant studies were identified through a systematic search of medical databases, and data were extracted on study design, population characteristics, cognitive assessments, and outcomes. The review also incorporated mechanistic insights into the gut-lung-brain axis to hypothesize its role in the long-term sequelae of CAP. Results The review identified multiple studies demonstrating an increased risk of cognitive impairment and dementia following CAP hospitalization. Patients hospitalized for CAP had a 1.5 to 2.5 times higher risk of developing cognitive deficits compared to controls. This cognitive decline was not limited to elderly patients but spanned all adult age groups. Furthermore, CAP was associated with a significant reduction in life expectancy. Patients discharged after CAP hospitalization reached 50% mortality within three years, compared to seven years for those hospitalized for other reasons. The most pronounced decrease in survival was observed in CAP patients requiring ICU admission and immunocompromised patients. Conclusion CAP is associated with significant long-term cognitive impairment and decreased survival. The proposed gut-lung-brain axis mechanism suggests that CAP-related dysbiosis leads to chronic systemic inflammation and neuroinflammation, potentially contributing to cognitive decline and increased mortality. Understanding the role of this axis may offer new therapeutic strategies for managing the long-term neurological consequences of CAP. Future research should focus on high-risk populations to develop targeted interventions aimed at mitigating these severe outcomes.

Sevoflurane-induced overexpression of extrasynaptic α5-GABAAR via the RhoA/ROCK2 pathway impairs cognitive function in aged mice.

Perioperative neurocognitive disorder (PND) is a serious neurologic complication in aged patients and might be associated with sevoflurane exposure. However, the specific pathogenesis is still unclear. The distribution of α5-GABAAR, a γ-aminobutyric acid type A receptor (GABAAR) subtype, at extrasynaptic sites is influenced by the anchor protein radixin, whose phosphorylation is regulated via the RhoA/ROCK2 signaling pathway and plays a crucial role in cognition. However, whether sevoflurane affects the ability of radixin phosphorylation to alter extrasynaptic receptor expression is unknown. Aged mice were exposed to sevoflurane to induce cognitive impairment. Both total proteins and membrane proteins were extracted for analysis. Cognitive function was evaluated using the Morris water maze and fear conditioning test. Western blotting was used to determine the expression of ROCK2 and the phosphorylation of radixin. Furthermore, the colocalization of p-radixin and α5-GABAAR was observed. To inhibit ROCK2 activity, either an adeno-associated virus (AAV) or fasudil hydrochloride was administered. Aged mice treated with sevoflurane exhibited significant cognitive impairment accompanied by increased membrane expression of α5-GABAAR. Moreover, the colocalization of α5-GABAAR and p-radixin increased after treatment with sevoflurane, and this change was accompanied by an increase in ROCK2 expression and radixin phosphorylation. Notably, inhibiting the RhoA/ROCK2 pathway significantly decreased the distribution of extrasynaptic α5-GABAAR and improved cognitive function. Sevoflurane activates the RhoA/ROCK2 pathway and increases the phosphorylation of radixin. Excess α5-GABAAR is anchored to extrasynaptic sites and impairs cognitive ability in aged mice. Fasudil hydrochloride administration improves cognitive function.

Étude prospective longitudinale sur l’évolution de la mémoire autobiographique de patients irradiés pour une tumeur bénigne de la base du crâne

PurposeCranial irradiation can lead to long-term neurological complications, in particular memory disorders. The aim of this prospective study is to evaluate the impact of irradiation of benign skull base tumours located near the hippocampi on autobiographical memory. Patients and methodsFrom 2016 to 2019, patients with cavernous sinus meningioma or pituitary adenoma treated with normofractionated irradiation were included. Patients underwent full neuropsychological assessment at baseline, 1year and 2years post-treatment. Neuropsychological tests were converted to Z-Score for comparability. ResultsTwelve of the 19 patients included had a complete neuropsychological evaluation at 2years and were analysed. On the “TEMPau” test, no significant difference in autobiographical memory was found at 2years, regardless of the period of autobiographical memory. The mean hippocampal dose had no impact on the variation in autobiographical memory. There was no significant cognitive impairment in the other domains assessed, such as attention, anterograde memory, working memory and executive functions. Autobiographical memory was independent of these other cognitive domains, which justifies its specific study. ConclusionRadiotherapy to the skull base for a benign pathology does not lead to significant cognitive impairment. Longer follow-up would be needed to confirm these results.

Patient satisfaction followed by remote monitoring

Abstract Introduction Remote monitoring (RM) of cardiac implantable electronic devices has increased significantly in the last years. The safety and efficacy of RM have been demonstrated, however, there are few data on patient satisfaction. The objective of this study was to evaluate the satisfaction of patients with an implanted pacemaker (PM) followed through remote monitoring. Methods Patients implanted with a conventional or leadless PM who had been using RM system for at least 3 months were included. Patients had to be able to understand and answer questionnaires, having no significant cognitive impairment. An specific, and previous validate, patient satisfaction RM questionnaire with 30-item, self-completed, measured on a 5-point Likert scale (0=No, nothing, 4=Yes, a lot) was administered. The questionnaire is structured in 5 dimensions: Information on cardiac condition, device convenience, transmission process, satisfaction with medical monitoring, and benefits. The results are presented as mean. The difference between mean was analyzed using the T-Student test. Results A total of 98 patients were included (77.8±8.2 years old, 67% male), 82 % had conventional PM and 18 % leadless PM. According RM connectivity 70% had daily automatic transmission, 12% automatic transmission and 18% manual transmission. On average, participants answered 83% of the items. The overall satisfaction of the patient was high (3.66). The mean score for each dimension is summarized in Table 1. The Device convenience had the highest mean (3.75), and the Transmission process had the lowest mean (3.56). There was no difference between patients with a conventional pacemaker versus leadless pacemakers (Fig 1, p=0,30). Results Patients with PM followed through RM have a high level of satisfaction when evaluated using an specific questionnaire. The level of satisfaction is independent of the type of PM or the connectivity of the system.Table 1Mean dimension score by device type