STAT3 ameliorates truncated tau-induced cognitive deficits

Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.

Toward Trustworthy Decision-Making for Autonomous Vehicles:A Robust Reinforcement Learning Approach with Safety Guarantees

While autonomous vehicles are vital components of intelligent transportation systems,ensuring the trustworthiness of decision-making remains a substantial challenge in realizing autonomous driving.Therefore,we present a novel robust reinforcement learning approach with safety guarantees to attain trustworthy decision-making for autonomous vehicles.The proposed technique ensures decision trustworthiness in terms of policy robustness and collision safety.Specifically,an adversary model is learned online to simulate the worst-case uncertainty by approximating the optimal adversarial perturbations on the observed states and environmental dynamics.In addition,an adversarial robust actor-critic algorithm is developed to enable the agent to learn robust policies against perturbations in observations and dynamics.Moreover,we devise a safety mask to guarantee the collision safety of the autonomous driving agent during both the training and testing processes using an interpretable knowledge model known as the Responsibility-Sensitive Safety Model.Finally,the proposed approach is evaluated through both simulations and experiments.These results indicate that the autonomous driving agent can make trustworthy decisions and drastically reduce the number of collisions through robust safety policies.

Orientation and Decision-Making for Soccer Based on Sports Analytics and AI:A Systematic Review

Due to ever-growing soccer data collection approaches and progressing artificial intelligence(AI) methods, soccer analysis, evaluation, and decision-making have received increasing interest from not only the professional sports analytics realm but also the academic AI research community. AI brings gamechanging approaches for soccer analytics where soccer has been a typical benchmark for AI research. The combination has been an emerging topic. In this paper, soccer match analytics are taken as a complete observation-orientation-decision-action(OODA) loop.In addition, as in AI frameworks such as that for reinforcement learning, interacting with a virtual environment enables an evolving model. Therefore, both soccer analytics in the real world and virtual domains are discussed. With the intersection of the OODA loop and the real-virtual domains, available soccer data, including event and tracking data, and diverse orientation and decisionmaking models for both real-world and virtual soccer matches are comprehensively reviewed. Finally, some promising directions in this interdisciplinary area are pointed out. It is claimed that paradigms for both professional sports analytics and AI research could be combined. Moreover, it is quite promising to bridge the gap between the real and virtual domains for soccer match analysis and decision-making.

Evolutionary Decision-Making and Planning for Autonomous Driving Based on Safe and Rational Exploration and Exploitation

Decision-making and motion planning are extremely important in autonomous driving to ensure safe driving in a real-world environment.This study proposes an online evolutionary decision-making and motion planning framework for autonomous driving based on a hybrid data-and model-driven method.First,a data-driven decision-making module based on deep reinforcement learning(DRL)is developed to pursue a rational driving performance as much as possible.Then,model predictive control(MPC)is employed to execute both longitudinal and lateral motion planning tasks.Multiple constraints are defined according to the vehicle’s physical limit to meet the driving task requirements.Finally,two principles of safety and rationality for the self-evolution of autonomous driving are proposed.A motion envelope is established and embedded into a rational exploration and exploitation scheme,which filters out unreasonable experiences by masking unsafe actions so as to collect high-quality training data for the DRL agent.Experiments with a high-fidelity vehicle model and MATLAB/Simulink co-simulation environment are conducted,and the results show that the proposed online-evolution framework is able to generate safer,more rational,and more efficient driving action in a real-world environment.

Ethical Decision-Making Framework Based on Incremental ILP Considering Conflicts

Humans are experiencing the inclusion of artificial agents in their lives,such as unmanned vehicles,service robots,voice assistants,and intelligent medical care.If the artificial agents cannot align with social values or make ethical decisions,they may not meet the expectations of humans.Traditionally,an ethical decision-making framework is constructed by rule-based or statistical approaches.In this paper,we propose an ethical decision-making framework based on incremental ILP(Inductive Logic Programming),which can overcome the brittleness of rule-based approaches and little interpretability of statistical approaches.As the current incremental ILP makes it difficult to solve conflicts,we propose a novel ethical decision-making framework considering conflicts in this paper,which adopts our proposed incremental ILP system.The framework consists of two processes:the learning process and the deduction process.The first process records bottom clauses with their score functions and learns rules guided by the entailment and the score function.The second process obtains an ethical decision based on the rules.In an ethical scenario about chatbots for teenagers’mental health,we verify that our framework can learn ethical rules and make ethical decisions.Besides,we extract incremental ILP from the framework and compare it with the state-of-the-art ILP systems based on ASP(Answer Set Programming)focusing on conflict resolution.The results of comparisons show that our proposed system can generate better-quality rules than most other systems.

Influence of BPPV and Meniere's Disease on Cognitive Abilities: A Questionnaire-Based Study

The vestibular system connects the inner ear to the midbrain and subcortical structures and can affect cognition. Patients with vertigo often experience cognitive symptoms such as attention deficits, memory problems, and spatial perception difficulties. This study aimed to explore the cognitive impairments associated with Benign paroxysmal positional vertigo(BPPV) and Meniere's Disease(MD). A non-experimental group comparison design was used with 107 participants divided into three groups: Group I(clinically normal), Group II(BPPV), and Group III(MD). Participants completed a questionnaire with 10 cognition-related questions, and their responses were scored. The data were found to be non-normally distributed. The analysis revealed a significant difference in scores between Group I and both Group II and Group III. Chi-square tests showed that the responses to cognition-related questions varied among the groups, with Group II exhibiting more cognitive problems. Associated conditions like hypertension, diabetes, and hearing loss did not significantly influence the responses within each group. This study suggests a significant relationship between cognitive problems and patients with BPPV and MD. However, there was no association found between the cognitive problems experienced in BPPV and MD patients. These findings align with previous research indicating that vestibular disorders can lead to deficits in spatial memory, attention, and other cognitive functions. By understanding the link between cognition and vestibular disorders, we can improve diagnosis and rehabilitation services to enhance the quality of life for these patients.

J-shaped association between dietary thiamine intake and the risk of cognitive decline in cognitively healthy,older Chinese individuals

Background The prospective association of dietary thiamine intake with the risk of cognitive decline among the general older adults remains uncertain.Aims To investigate the association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals.Methods The study included a total of 3106 participants capable of completing repeated cognitive function tests.Dietary nutrient intake information was collected through 3-day dietary recalls and using a 3-day food-weighed method to assess cooking oil and condiment consumption.Cognitive decline was defined as the 5-year decline rate in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status-modified.Results The median follow-up duration was 5.9 years.There was a J-shaped relationship between dietary thiamine intake and the 5-year decline rate in global and composite cognitive scores,with an inflection point of 0.68 mg/day(95%confidence interval(Cl):0.56 to 0.80)and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.Before the inflection point,thiamine intake was not significantly associated with cognitive decline.Beyond the inflection point,each unit increase in thiamine intake(mg/day)was associated with a significant decrease of 4.24(95%Cl:2.22 to 6.27)points in the global score and 0.49(95%Cl:0.23 to 0.76)standard units in the composite score within 5 years.A stronger positive association between thiamine intake and cognitive decline was observed in those with hypertension,obesity and those who were non-smokers(all p<0.05).Conclusions This study revealed a J-shaped association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals,with an inflection point at 0.68 mg/day and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.

Cardiovascular risk factors among older persons with cognitive frailty in middle income country

BACKGROUND Cognitive frailty,characterized by the coexistence of cognitive impairment and physical frailty,represents a multifaceted challenge in the aging population.The role of cardiovascular risk factors in this complex interplay is not yet fully understood.AIM To investigate the relationships between cardiovascular risk factors and older persons with cognitive frailty by pooling data from two cohorts of studies in Malaysia.METHODS A comprehensive approach was employed,with a total of 512 communitydwelling older persons aged 60 years and above,involving two cohorts of older persons from previous studies.Datasets related to cardiovascular risks,namely sociodemographic factors,and cardiovascular risk factors,including hypertension,diabetes,hypercholesterolemia,anthropometric characteristics and biochemical profiles,were pooled for analysis.Cognitive frailty was defined based on the Clinical Dementia Rating scale and Fried frailty score.Cardiovascular risk was determined using Framingham risk score.Statistical analyses were conducted using SPSS version 21.RESULTS Of the study participants,46.3%exhibited cognitive frailty.Cardiovascular risk factors including hypertension(OR:1.60;95%CI:1.12-2.30),low fat-free mass(OR:0.96;95%CI:0.94-0.98),high percentage body fat(OR:1.04;95%CI:1.02-1.06),high waist circumference(OR:1.02;95%CI:1.01-1.04),high fasting blood glucose(OR:1.64;95%CI:1.11-2.43),high Framingham risk score(OR:1.65;95%CI:1.17-2.31),together with sociodemographic factors,i.e.,being single(OR 3.38;95%CI:2.26-5.05)and low household income(OR 2.18;95%CI:1.44-3.30)were found to be associated with cognitive frailty.CONCLUSION Cardiovascular-risk specific risk factors and sociodemographic factors were associated with risk of cognitive frailty,a prodromal stage of dementia.Early identification and management of cardiovascular risk factors,particularly among specific group of the population might mitigate the risk of cognitive frailty,hence preventing dementia.

Contribution of Metabolic Imaging in the Exploration of Cognitive Disorders Related to COVID-19

On March 11, 2019, the WHO declared COVID-19 a pandemic disease. It is a respiratory tropism SARS COV 2 infection. In the emergency of the pandemic, in medical imaging, only computed tomography (CT) of the lungs was favored to assess lung lesions. In addition, many cases of post-COVID-19 cognitive disorders have been reported. As the curve dips and services restart correctly, other imaging techniques have been used to better explore the disease. The objective of this presentation is to illustrate the contribution of metabolic imaging in the exploration of post COVID-19 cognitive disorders and to discuss the pathophysiological mechanisms. Hypometabolism brain lesions are objective signs of functional impairment whose pathophysiological mechanism is not yet fully understood. Metabolic imaging with PET-SCAN is a suitable tool for exploring these disorders, both for the severity and extent of the lesions and for the topography of the brain damage.

Alexa,let's train now!——A systematic review and classification approach to digital and home-based physical training interventions aiming to support healthy cognitive aging

Background:There is mounting evidence that regular physical activity is an important prerequisite for healthy cognitive aging.Consequently,the finding that almost one-third of the adult population does not reach the recommended level of regular physical activity calls for further public health actions.In this context,digital and home-based physical training interventions might be a promising alternative to center-based intervention programs.Thus,this systematic review aimed to summarize the current state of the literature on the effects of digital and home-based physical training interventions on adult cognitive performance.Methods:In this pre-registered systematic review(PROSPERO;ID:CRD42022320031),5 electronic databases(PubMed,Web of Science,Psyclnfo,SPORTDiscus,and Cochrane Library)were searched by 2 independent researchers(FH and PT)to identify eligible studies investigating the effects of digital and home-based physical training interventions on cognitive performance in adults.The systematic literature search yielded 8258 records(extra17 records from other sources),of which 27 controlled trials were considered relevant.Two reviewers(FH and PT)independently extracted data and assessed the risk of bias using a modified version of the Tool for the assEssment of Study qualiTy and reporting in EXercise(TESTEX scale).Results:Of the 27 reviewed studies,15 reported positive effects on cognitive and motor-cognitive outcomes(i.e.,performance improvements in measures of executive functions,working memory,and choice stepping reaction test),and a considerable heterogeneity concerning study-related,population-related,and intervention-related characteristics was noticed.A more detailed analysis suggests that,in particular,interventions using online classes and technology-based exercise devices(i.e.,step-based exergames)can improve cognitive performance in healthy older adults.Approximately one-half of the reviewed studies were rated as having a high risk of bias with respect to completion adherence(≤85%)and monitoring of the level of regular physical activity in the control group.Conclusion:The current state of evidence concerning the effectiveness of digital and home-based physical training interventions is mixed overall,though there is limited evidence that specific types of digital and home-based physical training interventions(e.g.,online classes and step-based exergames)can be an effective strategy for improving cognitive performance in older adults.However,due to the limited number of available studies,future high-quality studies are needed to buttress this assumption empirically and to allow for more solid and nuanced conclusions.

Stroke Risk Assessment Decision-Making Using a Machine Learning Model:Logistic-AdaBoost

Stroke is a chronic cerebrovascular disease that carries a high risk.Stroke risk assessment is of great significance in preventing,reversing and reducing the spread and the health hazards caused by stroke.Aiming to objectively predict and identify strokes,this paper proposes a new stroke risk assessment decision-making model named Logistic-AdaBoost(Logistic-AB)based on machine learning.First,the categorical boosting(CatBoost)method is used to perform feature selection for all features of stroke,and 8 main features are selected to form a new index evaluation system to predict the risk of stroke.Second,the borderline synthetic minority oversampling technique(SMOTE)algorithm is applied to transform the unbalanced stroke dataset into a balanced dataset.Finally,the stroke risk assessment decision-makingmodel Logistic-AB is constructed,and the overall prediction performance of this new model is evaluated by comparing it with ten other similar models.The comparison results show that the new model proposed in this paper performs better than the two single algorithms(logistic regression and AdaBoost)on the four indicators of recall,precision,F1 score,and accuracy,and the overall performance of the proposed model is better than that of common machine learning algorithms.The Logistic-AB model presented in this paper can more accurately predict patients’stroke risk.

Computerized cognitive remediation therapy on cognitive impairment and social function in patients with chronic schizophrenia

BACKGROUND Patients with schizophrenia may have various disease manifestations,most of which gradually tend toward incurable chronic decline,leading to mental disability.The basic symptoms of the disease can impair social function,whereas long-term hospitalization produces hospitalization syndrome,causing serious damage to social function.AIM To investigate the effects of Computerized Cognitive Remediation Therapy(CCRT)on cognitive and social functioning in patients with chronic schizophrenia.METHODS A retrospective analysis of 120 patients with chronic schizophrenia in Shanghai Pudong New Area Mental Health Center was performed.They were divided into an intervention group(60 cases treated with CCRT combined with conventional medication)and a control group(60 cases treated with conventional medication).After treatment,effects on cognitive function and social roles were observed in both groups.The Positive and Negative Syndrome Scale(PANSS)was used to assess the patients'psychiatric symptoms.The Wisconsin Card Sorting Test(WCST)was used to assess the patients'cognitive functioning,and the Social Functioning Scale for Psychiatric Inpatients(SSPI)was used to assess the social functioning of the inpatient psychiatric patients.RESULTS No significant differences were observed in the PANSS,WCST,and SSPI intergroup scores before treatment(P>0.05).After 2,4,and 6 wk of therapy,general psychopathological factors,positive symptoms,negative symptoms,and total PANSS scores of PANSS in the intervention group were lower than in the control group(P<0.05).After 2,4,and 6 wk of treatment,the number of false responses,number of persistent bugs,and total responses in the WCST were significantly lower in the intervention group than in the control group(P<0.05),and the amount of completed classification was significantly higher than in the control group(P<0.05).After 2,4,and 6 wk of therapy,the SSPI scores were significantly greater than those of the controls(P<0.05).After 6 wk of treatment,the efficacy rates of the control and intervention groups were 81.67%and 91.67%,respectively.The curative effect in the intervention group was significantly higher than that in the control group(P<0.05).CONCLUSION CCRT can significantly improve cognitive function and social abilities in patients with chronic schizophrenia.

Risk factors for cognitive impairment in patients with chronic kidney disease

BACKGROUND Chronic kidney disease(CKD)patients have been found to be at risk of concurrent cognitive dysfunction in previous studies,which has now become an important public health issue of widespread concern.AIM To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD.METHODS This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023.A questionnaire was formulated by literature review and expert consultation and included questions about age,sex,education level,per capita monthly household income,marital status,living condition,payment method,and hypertension.RESULTS Logistic regression analysis showed that patients aged 60-79 years[odds ratio(OR)=1.561,P=0.015]and≥80 years(OR=1.760,P=0.013),participants with middle to high school education(OR=0.820,P=0.027),divorced or widowed individuals(OR=1.37,P=0.032),self-funded patients(OR=2.368,P=0.008),and patients with hypertension(OR=2.011,P=0.041)had a higher risk of cognitive impairment.The risk of cognitive impairment was lower for those with a college degree(OR=0.435,P=0.034)and married individuals.CONCLUSION The risk factors affecting cognitive dysfunction are age,60-79 years and≥80 years;education,primary school education or less;marital status,divorced or widowed;payment method,selffunded;hypertension;and CKD.

Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

The Impact of Opioid Drugs on Memory and Other Cognitive Functions: A Review

Background and Purpose: Opioids, used for centuries to alleviate pain, have become a double-edged sword. While effective, they come with a host of adverse effects, including memory and cognition impairment. This review delves into the impact of opioid drugs on cognitive functions, explores underlying mechanisms, and investigates their prevalence in both medical care and illicit drug use. The ultimate goal is to find ways to mitigate their potential harm and address the ongoing opioid crisis. Methods: We sourced data from PubMed and Google Scholar, employing search combinations like “opioids,” “memory,” “cognition,” “amnesia,” “cognitive function,” “executive function,” and “inhibition.” Our focus was on English-language articles spanning from the inception of these databases up to the present. Results: The literature consistently reveals that opioid use, particularly at high doses, adversely affects memory and other cognitive functions. Longer deliberation times, impaired decision-making, impulsivity, and behavioral disorders are common consequences. Chronic high-dose opioid use is associated with conditions such as amnesiac syndrome (OAS), post-operative cognitive dysfunction (POCD), neonatal abstinence syndrome (NAS), depression, anxiety, sedation, and addiction. Alarming trends show increased opioid use over recent decades, amplifying the risk of these outcomes. Conclusion: Opioids cast a shadow over memory and cognitive function. These effects range from amnesiac effects, lessened cognitive function, depression, and more. Contributing factors include over-prescription, misuse, misinformation, and prohibition policies. Focusing on correct informational campaigns, removing punitive policies, and focusing on harm reduction strategies have been shown to lessen the abuse and use of opioids and thus helping to mitigate the adverse effects of these drugs. Further research into the impacts of opioids on cognitive abilities is also needed as they are well demonstrated in the literature, but the mechanism is not often completely understood.

The Experience and Impact of a Fitbit-Based Physical Activity and Sleep Hygiene Intervention for Older Adults Experiencing Cognitive Decline

Objectives: This study aimed to understand the experience and impact of a physical activity and sleep wrist-worn tracker (Fitbit)-based healthy lifestyle intervention for older patients attending a memory assessment service, who are experiencing cognitive impairment but do not receive a dementia diagnosis. Methods: A qualitative design was employed. Semi-structured interviews were conducted with a purposeful sample of thirteen participants recruited from a memory assessment service. Thematic analysis, that was data driven and inductive, was undertaken to analyse the data. Results: Two global themes were developed. “Understanding exercise and sleep as part of my lifestyle” was made up of themes representing how participants viewed exercise and sleep as part of their lifestyles in terms of acknowledging the positive impacts and the barriers to exercise and sleep. The second global theme “Understanding my experience of the healthy lifestyle intervention” was made up of themes that identified the positive impact of the intervention regarding improving health and wellbeing, enabling validation of proactive behaviours and motivation to engage in healthy lifestyle behaviours, so promoting positive behaviour change. Conclusion: Patients experiencing age-related cognitive impairment, applied and benefited from a healthy lifestyle Fitbit-based intervention to facilitate and promote physical activity, better sleep hygiene and healthy lifestyles.

Anesthesia,Anesthetics,and Postoperative Cognitive Dysfunction in Elderly Patients

Postoperative cognitive dysfunction(POCD)remains a major issue that worsens the prognosis of elderly surgery patients.This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients,aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols,ultimately reducing the incidence of POCD in elderly surgery patients.

Glyphosate as a direct or indirect activator of pro-inflammatory signaling and cognitive impairment

Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.

Relationship of Retinal Nerve Fiber Layer Thickness and Retinal Vessel Calibers with Cognitive Impairment in the Asymptomatic Polyvascular Abnormalities Population

Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship between different retinal metrics and CI in a particular population,emphasizing polyvascular status.Methods We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers,retinal nerve fiber layer(RNFL)thickness,and cognitive function of 3,785participants,aged 40 years or older.Logistic regression was used to analyze the relationship between retinal metrics and cognitive function.Subgroups stratified by different vascular statuses were also analyzed.Results RNFL thickness was significantly thinner in the CI group(odds ratio:0.973,95%confidence interval:0.953–0.994).In the subgroup analysis,the difference still existed in the non-intracranial arterial stenosis,non-extracranial carotid arterial stenosis,and peripheral arterial disease subgroups(P<0.05).Conclusion A thin RNFL is associated with CI,especially in people with non-large vessel stenosis.The underlying small vessel change in RNFL and CI should be investigated in the future.

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.