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.

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.

Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.

Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

Cognitive interference decision method for air defense missile fuze based on reinforcement learning

To solve the problem of the low interference success rate of air defense missile radio fuzes due to the unified interference form of the traditional fuze interference system,an interference decision method based Q-learning algorithm is proposed.First,dividing the distance between the missile and the target into multiple states to increase the quantity of state spaces.Second,a multidimensional motion space is utilized,and the search range of which changes with the distance of the projectile,to select parameters and minimize the amount of ineffective interference parameters.The interference effect is determined by detecting whether the fuze signal disappears.Finally,a weighted reward function is used to determine the reward value based on the range state,output power,and parameter quantity information of the interference form.The effectiveness of the proposed method in selecting the range of motion space parameters and designing the discrimination degree of the reward function has been verified through offline experiments involving full-range missile rendezvous.The optimal interference form for each distance state has been obtained.Compared with the single-interference decision method,the proposed decision method can effectively improve the success rate of interference.

Latest assessment methods for mitochondrial homeostasis in cognitive diseases

Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).

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.

A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease

The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.

Effect of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction

BACKGROUND The aging of the population has become increasingly obvious in recent years,and the incidence of cerebral infarction has shown an increasing trend annually,with high death and disability rates.AIM To analyze the effects of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction.METHODS Between January 2020 and December 2023,we treated 98 cases of elderly acute insula,patients with cerebral infarction in the cerebral infarction acute phase(3-4 weeks)and for the course of 6 months in Montreal Cognitive Assessment Scale(MoCA)for screening of cognition.Notably,58 and 40 patients were placed in the cognitive impairment group and without-cognitive impairment group,respec-tively.In patients with cerebral infarction,magnetic resonance imaging was used to screen and clearly analyze the MoCA scores of two groups of patients with different infarctions,the relationship between the parts of the infarction volume,and analysis of acute insula cognitive disorder in elderly patients with cerebral RESULTS The number of patients with cognitive impairment in the basal ganglia and thalamus was significantly higher than that without cognitive impairment(P<0.05).The total infarct volume in the cognitive impairment group was higher than that in the non-cognitive impairment group,and the difference was statistically significant(P<0.05).The infarct volumes at different sites in the cognitive impairment group was higher than in the non-cognitive impairment group(P<0.05).In the cognitive impairment group,the infarct volumes in the basal ganglia,thalamus,and mixed lesions were negatively correlated with the total MoCA score,with correlation coefficients of-0.67,-0.73,and-0.77,respectively.CONCLUSION In elderly patients with acute insular infarction,infarction in the basal ganglia,thalamus,and mixed lesions were more likely to lead to cognitive dysfunction than in other areas,and patients with large infarct volumes were more likely to develop cognitive dysfunction.The infarct volume in the basal ganglia,thalamus,and mixed lesions was significantly negatively correlated with the MoCA score.

Cognitive impairment in cerebral small vessel disease induced by hypertension

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

Web-based cognitive interventions on subjective cognitive impairment in cancer survivors:A systemic review

Objective:Cancer survivors have experienced subjective cognitive impairment(SCI)when they received cancer diagnoses or treatments.Their psychosocial and emotional statuses were also impacted.With the advancement of web technologies,web-based cognitive interventions have been implemented in the management and the alleviation of the SCI,the psychosocial distress,and the emotional distress in cancer survivors.This review aimed to summarize the intervention contents of web-based cognitive interventions for SCI,and to explore the effects of the interventions on SCI,psychosocial status,and emotional health.Methods:Six databases(CINAHL Plus,Cochrane Library,Embase,APA PsycInfo,PubMed and CNKI)were searched from the establishment of databases up to December 2023.Literature references were also manually searched for related articles.Results:This review contained 21 studies that covered the contents of web-based cognitive interventions,such as computer-assisted cognitive training,online cognitive rehabilitation,cognitive behavior therapy with the Internet,telehealth physical exercise,and web-based mindfulness interventions.The effects of web-based cognitive interventions positively impacted SCI for cancer survivors.Also,these interventions showed varying degrees of effectiveness in alleviating psychosocial and emotional distresses.Conclusion:By summarizingfive types of cognitive intervention contents delivered via web technology,this review demonstrated that web-based cognitive interventions optimized SCI and overall psychosocial and emotional statuses for the cancer survivors.It is recommended that future research focus on the development of customized web-based cognitive interventions for individuals with SCI,along with their psychosocial and emotional statuses.

Women health and microbiota:Different aspects of well-being

In this editorial,we comment on the article by Marano et al recently published in the World Journal of Gastroenterology 2023;29(45):5945-5952.We focus on the role of gut microbiota(GM)in women’s health,highlighting the need to thoroughly comprehend the sex differences in microbiota.Together,the host and GM support the host’s health.The microbiota components consist of viruses,bacteria,fungi,and archaea.This complex is an essential part of the host and is involved in neu-rological development,metabolic control,immune system dynamics,and host dynamic homeostasis.It has been shown that differences in the GM of males and females can contribute to chronic diseases,such as gastrointestinal,metabolic,neurological,cardiovascular,and respiratory illnesses.These differences can also result in some sex-specific changes in immunity.Every day,research on GM reveals new and more expansive frontiers,offering a wealth of innovative oppor-tunities for preventive and precision medicine.

Cognitive Jammers Assisted Covert Communication in Cognitive Radio Networks

In this work,we investigate the covert communication in cognitive radio(CR)networks with the existence of multiple cognitive jammers(CJs).Specifically,the secondary transmitter(ST)helps the primary transmitter(PT)to relay information to primary receiver(PR),as a reward,the ST can use PT's spectrum to transmit private information against the eavesdropper(Eve)under the help of one selected cognitive jammer(CJ).Meanwhile,we propose three jammer-selection schemes,namely,link-oriented jammer selection(LJS),min-max jammer selection(MMJS)and random jammer selection(RJS).For each scheme,we analyze the average covert throughput(ACT)and covert outage probability(COP).Our simulation results show that CJ is helpful to ST's covert communication,the expected minimum detection error probability and ACT can be significantly improved with the increase of false alarm of CJ.Moreover,the LJS scheme achieves best performance in ACT and COP,followed by RJS scheme,and MMJS scheme shows the worst performance.

Brain Functional Network Changes in Patients with Poststroke Cognitive Impairment Following Acupuncture Therapy

Background: The mechanisms by which acupuncture affects poststroke cognitive impairment (PSCI) remain unclear. Objective: To investigate brain functional network (BFN) changes in patients with PSCI after acupuncture therapy. Methods: Twenty-two PSCI patients who underwent acupuncture therapy in our hospital were enrolled as research subjects. Another 14 people matched for age, sex, and education level were included in the normal control (HC) group. All the subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans;the PSCI patients underwent one scan before acupuncture therapy and another after. The network metric difference between PSCI patients and HCs was analyzed via the independent-sample t test, whereas the paired-sample t test was employed to analyze the network metric changes in PSCI patients before vs. after treatment. Results: Small-world network attributes were observed in both groups for sparsities between 0.1 and 0.28. Compared with the HC group, the PSCI group presented significantly lower values for the global topological properties (γ, Cp, and Eloc) of the brain;significantly greater values for the nodal attributes of betweenness centrality in the CUN. L and the HES. R, degree centrality in the SFGdor. L, PCG. L, IPL. L, and HES. R, and nodal local efficiency in the ORBsup. R, ORBsupmed. R, DCG. L, SMG. R, and TPOsup. L;and decreased degree centrality in the MFG. R, IFGoperc. R, and SOG. R. After treatment, PSCI patients presented increased degree centrality in the LING.L, LING.R, and IOG. L and nodal local efficiency in PHG. L, IOG. R, FFG. L, and the HES. L, and decreased betweenness centrality in the PCG. L and CUN. L, degree centrality in the ORBsupmed. R, and nodal local efficiency in ANG. R. Conclusion: Cognitive decline in PSCI patients may be related to BFN disorders;acupuncture therapy may modulate the topological properties of the BFNs of PSCI patients.

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.

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.

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.

Trends in the Application of Dyadic Coping in Older Adults with Mild Cognitive Impairment and Their Spouses

Dyadic coping plays an important role in older adults with mild cognitive impairment and their spouses. Significant correlations were found between dyadic coping and self-efficacy, anxiety and depression, marital quality, and quality of life in elderly patients with mild cognitive impairment and their spouses, and there were gender differences, with a 36.1% [P = 0.028, OR = 0.639, 95% CI (0.429, 0.952)] and 54% [P = 0.004, OR = 0.460, 95% CI (0.269, 0.785)] reduction in the risk of MCI and dementia for older men aged 65 - 69 years with a spouse and for those aged 80 years and older with a spouse, respectively. In contrast, there was no significant difference in the association between having or not having a spouse and developing MCI and dementia in older women (all P > 0.05). Psychosocial interventions, skills interventions, and exercise from the perspective of dyadic relationships were effective in improving the physical and mental health of older adults with mild cognitive impairment and their spouses. However, there is a lack of specific intervention programs for dyadic relationships in the local cultural context as an entry point. Therefore, it is necessary to draw on internal and external relevant literature to treat both partners as a whole for intervention, provide personalized social, cognitive and motor therapy for patients and promote the integration and participation of caregivers, help patients and spouses to improve the sense of well-being and intimacy, reduce the burden of caregivers, and build a dyadic coping intervention program suitable for elderly patients with mild cognitive impairment in China. The current article aims to provide a conceptual review focusing on dyadic coping care to inform the development of a dyadic intervention program suitable for older adults with mild cognitive impairment in China. This review outlines the theoretical concepts, assessment tools, current state of research, and intervention methods for mild cognitive impairment and dyadic coping.

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.

Maresin 1 alleviates neuroinflammation and cognitive decline in a mouse model of cecal ligation and puncture

Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment.Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγantagonist GW9662 to confirm the involvement of this pathway in MaR1’s effects.Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P<0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P<0.05).No significant difference in efficacy was observed between the 2 doses(all P>0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1’s protective effects.Real-time RTPCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P<0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P>0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P<0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P<0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P<0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P<0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγcompared to the MaR1-LD group(all P<0.05).Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.