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Introduction: High blood pressure (HBP) is the leading cause of death from cardiovascular disease. Despite the advances, the percentage of undiagnosed and untreated hypertensive patients is 58.4%. The evaluation of cognitive damage in HBP focuses on preventing stroke, while functional damage is ignored. This inadequate management may be multifactorial. The objective was to analyze the opinions that doctors have about the relationship between high blood pressure and cognitive damage. Methodology: Observational, descriptive, cross-sectional study developed in the period between August 2020 and August 2023. Analysis of data obtained from a self-administered, anonymous and voluntary questionnaire. Revealing information on the professional profile, knowledge of HBP, its link with cognitive impairment (CD), diagnosis and treatment. Results: 222 professionals were included, 215 (96.8%) agree with the existence of a link between HBP and other cardiovascular risk factors in CD, and 218 (98.1%) acknowledge assisting patients at risk of suffering from CD. The CD evaluation is carried out in selected cases by 132 (59.4%) participants and 59 (26.7%) always do it. Of those who perform evaluation, 103 (54%) use the Mini Mental State Examination (MMSE), 10 (5.2%) use the Montreal Cognitive Assessment (MoCA) and 9 (4.7%) use the Clock Drawing Test. Regarding the decrease in blood pressure in elderly patients and the link with risk of CD: 54 (24.3%) do not recognize risk and 65 (29.2%) recognize a moderate-high risk. In reference to the implication of the treatment of cardiovascular disease and CD: 217 (97.7%) recognized a beneficial effect. Discussion: Given the recognition of the link between HBP and CD, it would be expected that CD would be investigated in the vast majority, however only 26.7% always evaluate it. There is no consensus on the method, the MMSE being the most used, with a low application of the MoCA test and/or Clock Drawing Test, the latter being the ones that evaluate executive function, mostly altered in CD linked to HBP. Although the treatment of cardiovascular disease is recognized as beneficial with respect to CD, the control of HBP in older adults is considered risky. A diagnosis is made of a situation where a disparity is evident between what one recognizes as knowing and what one claims to do. Conclusions: The role of vascular disease in functional brain damage is recognized, considering it necessary to know the cognitive status of patients, however there is a low application of screening tests that evaluate executive function. In this context, a gap between medical knowledge and practice is shown.
Introdução: A hipertensão arterial (HA) é a principal causa de morte por doenças cardiovasculares. Apesar dos avanços, o percentual de hipertensos não diagnosticados e não tratados é de 58,4%. A avaliação do dano cognitivo na hipertensão concentra-se na prevenção do acidente vascular cerebral, enquanto o dano funcional é ignorado. Esse manejo inadequado pode ser multifatorial. É objetivo fue analisar a opinião dos médicos sobre a relação entre hipertensão arterial e danos cognitivos. Metodologia: Estudo observacional, descritivo, transversal desenvolvido no período entre agosto de 2020 e agosto de 2023. Análise de dados obtidos a partir de questionário autoaplicável, anônimo e voluntário. Revelar informações sobre o perfil profissional, conhecimento sobre a HA, sua ligação com o comprometimento cognitivo (DC), diagnóstico e tratamento. Resultados: Foram incluídos 222 profissionais, 215 (96,8%) concordam com a existência de ligação entre hipertensão e outros fatores de risco cardiovascular na DC e 218 (98,1%) reconhecem ajudar pacientes com risco de sofrer de D.C. A avaliação da DC é realizada em casos selecionados por 132 (59,4%) participantes e 59 (26,7%) a fazem sempre. Dos que realizam avaliação, 103 (54%) utilizam o Mini Exame do Estado Mental (MEEM), 10 (5,2%) utilizam a Avaliação Cognitiva de Montreal (MoCA) e 9 (4,7%) utilizam o Clock Drawing Test. Em relação à diminuição da pressão arterial em pacientes idosos e a ligação com o risco de DC: 54 (24,3%) não reconhecem risco e 65 (29,2%) reconhecem risco moderado-alto. Em referência à implicação do tratamento de doenças cardiovasculares e DC: 217 (97,7%) reconheceram o efeito benéfico. Discussão: Dado o reconhecimento da ligação entre hipertensão e DC, seria de esperar que a DC fosse investigada na grande maioria, no entanto apenas 26,7% sempre a avaliam. Não há consenso sobre o método, sendo o MEEM o mais utilizado, com baixa aplicação do teste MoCA e/ou Clock Drawing Test, sendo estes últimos os que avaliam a função executiva, majoritariamente alterada nos DC vinculados à HA. Embora o tratamento das doenças cardiovasculares seja reconhecido como benéfico em relação à DC, o controle da HA em idosos é considerado arriscado. É feito um diagnóstico de uma situação em que é evidente uma disparidade entre o que se reconhece como saber e o que se afirma fazer. Conclusões: O papel da doença vascular no dano cerebral funcional é reconhecido, considerando-se necessário conhecer o estado cognitivo dos pacientes, porém há baixa aplicação de testes de triagem que avaliam a função executiva. Nesse contexto, evidencia-se uma lacuna entre o conhecimento e a prática médica.
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RESUMEN Los inhibidores de la bomba de protones (IBP) son los medicamentos más potentes para inhibir la secreción gástrica ácida, y se utilizan en el tratamiento de la mayor parte de las afecciones inflamatorias de la mucosa gástrica. Forman parte de los fármacos más recetados y sobreprescritos en todo el mundo; por ejemplo, en los Estados Unidos, según la Encuesta nacional de salud y nutrición, casi duplicaron su uso en los adultos de 40 años de un 4,9 % hasta un 8,3 %, entre los años 1999 a 2012. Aunque, en general, se consideran bien tolerados, algunos estudios epidemiológicos ―que extraen información a partir de grandes bases de datos― han reportado una serie de efectos adversos asociados con su uso prolongado, entre los cuales están el deterioro cognitivo, la enfermedad renal crónica, el infarto de miocardio, el accidente cerebrovascular, las fracturas óseas e incluso la muerte, entre otros. El objetivo fue realizar una revisión narrativa de la literatura acerca de los efectos del uso crónico de los IBP sobre el deterioro cognitivo en los adultos mayores. Se revisaron artículos a partir de una búsqueda en las bases de datos Pudmed, Scopus y Scielo con las palabras clave y términos Mesh/DeCS relacionados tanto en inglés como en español. Los efectos secundarios a nivel neurológico inducidos por el uso crónico de los IBP pueden estar relacionados indirectamente con la presencia de alteraciones sistémicas secundarias (deficiencia de magnesio y vitamina B12) o con efectos directos sobre el funcionamiento neuronal después de pasar a través de la barrera hematoencefálica. Si bien se han descrito varios mecanismos neurobiológicos por medio de los cuales los IBP podrían favorecer el desarrollo de la demencia ―que comprenden el funcionamiento de la proteína tau, la acumulación de beta amiloide (βA) y la deficiencia de cobalamina, entre otros―, la mayor parte de la evidencia clínica disponible no ha encontrado una asociación significativa entre el uso de los IBP y el riesgo de demencia o el deterioro cognitivo. Para establecer de una manera más clara los efectos clínicos adversos del uso crónico de los IBP, en especial, en el funcionamiento cerebral, se necesitan estudios de cohorte bien diseñados, con tamaños de muestra grandes y periodos de seguimiento prolongados, con un método confiable para ajustar los factores de confusión estandarizados y, además, realizar análisis por subgrupos.
ABSTRACT Proton pump inhibitors (PPIs) are the most potent drugs to inhibit gastric acid secretion, being used in the treatment of most inflammatory conditions of the gastric mucosa. They are among the most prescribed and overprescribed medications worldwide; for example, in the United States, according to the National Health and Nutrition Examination Survey, they almost doubled their use in adults aged 40 years and older from 4.9 % to 8.3 % between 1999 and 2012. Although they are generally considered well tolerated, some epidemiological studies extracting information from large databases have reported a number of adverse effects associated with their prolonged use, including cognitive impairment, chronic kidney disease, myocardial infarction, stroke, bone fractures and even death, among others. The objective was to conduct a narrative review of the literature on the effects of chronic use of PPIs on cognitive impairment in older adults. Articles were reviewed based on a search in the PubMed, Scopus and SciELO databases using both English and Spanish keywords and related MeSH/DeCS terms. Neurological side effects induced by chronic PPI use may be indirectly related to secondary systemic disorders (magnesium and vitamin B12 deficiency) or to direct effects on neuronal functioning after passing through the blood-brain barrier. Although several neurobiological mechanisms by which PPIs could favor the development of dementia-which involve Tau protein function, beta-amyloid [βA] accumulation and cobalamin deficiency, among others-have been described, most of the available clinical evidence has not shown a significant association between PPI use and the risk of dementia or cognitive impairment. To establish the adverse clinical effects of chronic PPI use more clearly, especially on brain functioning, well-designed cohort studies with large sample sizes and long follow-up periods, with a reliable method to adjust for standardized confounders, as well as subgroup analyses are needed.
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ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.
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Objective To explore the relationship between the levels of serum dopamine,5-hydroxytryptamine,homovanillic acid and cognitive dysfunction in patients with Parkinson's disease.Methods A total of 118 Parkinson's disease patients admitted to Bazhong Central Hospital from February 2020 to February 2022 were selected as the disease group,and 106 healthy patients who underwent physical examination in the hospital during the same period were selected as the control group.The levels of serum do-pamine,5-hydroxytryptamine and homovanillic acid were measured in all subjects,and the cognitive function was evaluated with Montreal Cognitive Assessment Scale(MoCA).Parkinson's disease patients were divided into cognitive impairment group and non cognitive impairment group according to MoCA score.The serum do-pamine,5-hydroxytryptamine,homovanillic acid levels of the cognitive impairment group and the non cogni-tive impairment group were compared.Pearson correlation analysis was used to analyze the correlation be-tween serum dopamine,5-hydroxytryptamine and homovanillic acid levels and cognitive function of Parkinson's disease patients,and the receiver operating characteristic curve was drawn to analyze the evaluation value of serum dopamine,5-hydroxytryptamine and homovanillic acid levels on cognitive dysfunction of Parkinson's disease patients.Results The levels of serum dopamine,5-hydroxytryptamine,homovanillic acid and MoCA score in the disease group were lower than those in the control group,with statistical significance(P＜0.05).The levels of serum dopamine,5-hydroxytryptamine,homovanillic acid and MoCA score in advanced patients were lower than those in early patients,and the difference was statistically significant(P＜0.05).The levels of serum dopamine,serotonin and homovanillic acid in the cognitive dysfunction group were lower than those in the non-cognitive dysfunction group,and the difference was statistically significant(P＜0.05).The results of Pearson analysis showed that the levels of serum dopamine,5-hydroxytryptamine and homovanillic acid in Parkinson's disease patients were positively correlated with MoCA score(P＜0.05).The sensitivity of the combined assessment of serum dopamine,serotonin and homovanillic acid in Parkinson's disease patients was higher than that in Parkinson's disease patients alone(x2=7.413,P=0.006;x2=9.714,P=0.002;x2=8.541,P=0.003),the area under the curve(AUC)was higher than the AUC for assessing cognitive impair-ment in Parkinson's disease alone(Z=2.479,P=0.013;Z=2.271,P=0.023;Z=2.451,P=0.014).Conclusion There are differences in serum levels of dopamine,5-hydroxytryptamine,homovanillic acid and cognitive function among different stages of Parkinson's disease patients.Serum levels of dopamine,5-hydroxytryptamine,and homovanillic acid are closely related to cognitive function in Parkinson's disease pa-tients,all of which have evaluation value for the occurrence of cognitive dysfunction in Parkinson's disease pa-tients.However,the combination of the three serum indicators is more helpful for clinical evaluation and diag-nosis.
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Objective:To explore the effects of Tongdu Tiaoshen acupuncture on vascular endothelial function and inflammatory factors in patients with mild cognitive impairment (MCI) after ischemic stroke (IS).Methods:A retrospective analysis was performed on the clinical data of 71 patients with MCI after IS in the hospital between January 2020 and September 2022. According to different treatment methods, they were divided into Tongdu Tiaoshen acupuncture group ( n=31, Tongdu Tiaoshen acupuncture + oral nimodipine tables) and routine body-acupuncture group ( n=40, routine body-acupuncture group + oral nimodipine tables). Both groups were treated for 2 courses (14 d/course). Before and after treatment, levels of serum NO and endothelin-1 (ET-1) were detected by radioimmunoassay, and levels of serum basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), plasma homocysteine (Hcy) and IL-6 were detected by ELISA. The cognitive function of patients was evaluated and intelligence level by Montreal Cognitive Assessment Scale (MoCA), Mini-Mental State Examination(MMSE) and the clinical curative effect was also evaluated. Results:The total response rates in Tongdu Tiaoshen acupuncture group and routine body-acupuncture group were 90.32% (28/31) and 70.00% (28/40), and the difference between the two groups was statistically significant ( χ2=4.33, P=0.037). After treatment, levels of plasma Hcy and IL-6 in Tongdu Tiaoshen acupuncture group were lower than those in the routine body-acupuncture group ( t=2.57, 9.36, P<0.05 or P<0.01). After treatment, levels of serum bFGF, VEGF and NO in Tongdu Tiaoshen acupuncture group were significantly higher than those in the routine body-acupuncture group ( t=10.03, 9.29, 8.17, P<0.01), while ET-1 level was significantly lower than that of the routine body-acupuncture group ( t=2.41, P=0.019). After treatment, MoCA score [(28.24±4.45) vs. (25.32±4.34), t=2.78], MMSE score [(28.73±1.44) vs. (28.02±1.22), t=2.25] in Tongdu Tiaoshen acupuncture group were higher than those in the routine body-acupuncture group ( P<0.01). Conclusion:Tongdu Tiaoshen acupuncture is beneficial to improve vascular endothelial function, reduce levels of inflammatory factors, promote the recovery of cognitive function and improve curative effect in patients with MCI after IS.
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Objective To investigate the relationship between factors related to the transforming growth factor β(TGF-β)/Aerine-threonine kinase receptors(Smads)signaling pathway and cognitive dysfunction in peripheral blood of patients with aneurysmal subarachnoid hemorrhage(aSAH).Methods The clinical data of 100 patients with aSAH admitted to Chongzuo City People's Hospital from October 2018 to March 2022 were retrospectively selected and grouped according to the patients'Montreal Cognitive Assessment Scale(MoCA)scores,including 54 cases with cognitive dysfunction and 46 cases without cognitive dysfunction.The clinical data,peripheral blood TGF-β,Smad1,Smad3,and Smad7 mRNA expression levels of the two groups were compared.The relationship between pathway-related factors and cognitive dysfunction in patients with aSAH was analyzed in a multifactorial manner.The predictive value of pathway-related factors for cognitive dysfunction in aSAH patients was assessed using the receiver operating characteristic(ROC)curve.Results Peripheral blood TGF-β,Smad1,Smad3,and Smad7 mRNA expression levels were higher in the cognitively impaired group than in the group without cognitive impairment(P<0.05).Multifactorial showed that pathway-related factors were significantly associated with cognitive impairment in patients with aSAH(P<0.05).The ROC showed that the area under the curve(AUC)of pathway-related factors jointly predicted cognitive dysfunction in patients with aSAH was superior to that predicted alone(P<0.05).Conclusion The high expression of factors related to the TGF-β/Smads signaling pathway in the peripheral blood of aSAH patients suggests that this pathway may be associated with cognitive dysfunction in patients.
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Objective To explore the effects of permissive hypercapnia on postoperative cognitive function in elderly patients with diabetes mellitus.Methods Sixty elderly patients with diabetes mellitus scheduled for laparoscopic upper abdominal surgery under general anesthesia,were randomly divided into two groups:the permissive hypercapnia ventilation diabetes mellitus group(group DH)and the routine ven-tilation diabetes mellitus group(group DR),30 patients in each group.Another sixty elderly patients with non-diabetes mellitus scheduled for laparoscopic upper abdominal surgery under general anesthesia,were randomly divided into two groups:the permissive hypercapnia ventilation non-diabetes mellitus group(group NH)and the routine ventilation group(group NR),30 patients in each group.All patients in four groups were performed with tracheal intubation and mechanical ventilation after anesthesia induction.The respiratory parameters were adjusted to maintain PaCO2 in a range of 45-65 mmHg in groups DH and NH,and PaCO2 in a range of 35-45 mmHg in groups DR and NR.PETCO2 was recorded 5 minutes before pneu-moperitoneum,5,15,and 30 minutes after pneumoperitoneum.Blood samples were taken from the radial artery and jugular bulb for blood gas analysis 5 minutes before pneumoperitoneum,5,15,and 30 minutes after pneumoperitoneum.pH value and PaCO2 were recorded and arterial internal jugular vein bulbar oxygen difference(Da-jvO2)and cerebral oxygen extraction rate(CERO2)were calculated at the same time.The serum S100β protein concentration were detected before anesthesia induction and 3 days after operation.Montreal cognitive assessment(MoCA)scores and occurrence of postoperative cognitive dysfunction were recorded 1 day before operation,and 1 day,3 days and 7 days after operation.Results Compared with the baseline value 5 minutes before pneumoperitoneum,PETCO2 and PaCO2 were significantly increased,pH value,Da-jvO2 and CERO2 were significantly decreased 5,15,and 30 minutes after pneumoperitoneum in the four groups(P＜0.05).Compared with before anesthesia induction,the serum S100β protein concen-tration were significantly increased 3 days after operation in the four groups(P＜0.05).Compared with the last day before operation,MoCA scores were significantly decreased 1 day and 3 days after operation in the four groups(P＜0.05).Compared with group DR,PETCO2 was significantly increased,pH value,Da-jvO2,and CERO2 were significantly decreased 5 minutes before pneumoperitoneum,5,15,and 30 mi-nutes after pneumoperitoneum,the serum S100β protein concentration was significantly decreased 3 days af-ter operation,MoCA scores were significantly increased 1 day and 3 days after operation,the incidence rate of POCD was significantly decreased in group DH(P＜0.05).Compared with group NR,PETCO2 was sig-nificantly increased,pH value,Da-jvO2,and CERO2 were significantly decreased 5 minutes before pneu-moperitoneum,5,15,and 30 minutes after pneumoperitoneum,the serum S100β protein concentration was significantly decreased 3 days after operation,MoCA scores were significantly increased 1 day and 3 days af-ter operation,the incidence rate of POCD was significantly decreased in group NH(P＜0.05).Compared with group NH,Da-jvO2 and CERO2 were significantly increased 5 minutes before pneumoperitoneum,5,15,and 30 minutes after pneumoperitoneum,the serum S100β protein concentration was significantly in-creased 3 days after operation,MoCA scores were significantly decreased 1 day and 3 days after operation in group DH(P＜0.05).Conclusion Permissive hypercapnia can improve the cerebral oxygen metabolism during operation,reduce postoperative serum S100β protein concentration and reduce the incidence rate of POCD in the elderly patients with diabetes mellitus.
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Epilepsy is a kind of brain dysfunction syndrome characterized by paroxysmal,transient,repetitive and rigid characteristics caused by abnormal discharge of highly synchronized neurons in the brain.Epilepsy is often accompanied by cognitive dysfunction.At present,anti-seizure medications are the most important methods of clinical treatment.Most of the traditional anti-seizure medications can cause cognitive dysfunction,and the influence of new anti-seizure medications on cognitive function is not completely clear.This paper reviews the influence of new anti-seizure medications on cognitive function and the possible related mechanisms of action based on relevant literature at home and abroad.It is expected that clinicians should pay attention to cognitive function in the process of diagnosis and treatment of epilepsy,and help clinicians realize the influence of anti-seizure medications on cognitive function,and rationally choose anti-seizure medications for patients.
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Objective To explore the role of protective function of Sestrin2(Sesn2)to mitochondria in alleviating cognitive dysfunction in mice with sepsis-associated encephalopathy(SAE).Methods 6-week-old male C57BL/6J mice were randomly divided into three groups:sham group,CLP group and CLP plus eupatilin group,40 mice in each group.A sepsis model was induced by cecal ligation and perforation(CLP).The CLP plus eupatilin group was treated with eupatilin.Neurobehavioral test and Morris water maze(MWM)were used to deter-mine neurobehavior and spatial learning and memory function in mice.The number of neurons in hippocampal CA1 area was counted by Nissl staining.HT22 cells were randomly divided into a control group(Con),lipopolysaccha-ride group(LPS),LPS plus eupatilin treatment group(LPS plus eupatilin)and LPS plus eupatilin and Nrf2 siRNA treatment group(LPS plus eupatilin and si-Nrf2).Apoptosis was analyzed by terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)staining,Mitochondrial membrane potential(MMP)was used to analyze mitochondrial damage.Results Seven days after CLP,as compared with sham mice,Sesn2 in hippocampus and cortex decreased significantly in CLP mice(P<0.01).As compared with CLP group,the survival rate in CLP plus eupatilin group increased significantly(P<0.05).As compared with sham group,the mice in CLP group showed a relatively high nerve injury score(P<0.05),and had fewer platform crossings and shorter target stay time,while the mice in CLP plus eupatilin group exhibited a lower injury score(P<0.05),and stayed in the target area for a longer time(P<0.05).As compared with sham group,the co-localization rate of neurons,Sesn2 and Nrf2 in CLP group decreased significantly(P<0.05),and the number of CD68/Iba-1 positive microglia increased significantly(P<0.05),while CLP plus eupatilin group reversed these changes.As compared with Con group,apoptosis and MMP level in LPS group increased significantly(P<0.01),while apoptosis and MMP level in LPS plus eupatilin group were lower than those in LPS group(P<0.05).However,Nrf2 knockdown(LPS plus eupatilin and si-Nrf2 group)reversed the anti-apoptosis and mitochondrial protection of eupatilin.Conclusions Eupatilin can alleviate cognitive dysfunction and neurological deficit in SAE mice by activating Sesn2-Nrf2 pathway,and improve inflammatory microenvironment by alleviating mitochondrial dysfunction.
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Objective To investigate whether salvianolic acid B(Sal B)can improve the cognitive function in rats with post-traumatic stress disorder(PTSD)by regulating GSK-3β/β-Catenin signal pathway.Methods Sixty rats were randomly grouped into the normal group,the PTSD group,the Sal B low-dose group(10 mg/kg),the Sal B high-dose group(20 mg/kg)and the GSK-3β inhibitor group(30 mg/kg CHIR-99021),with 12 rats in each group.In addition to the normal group,rats in other groups were constructed PTSD rat models by using single prolonged stress(SPS)method.Open field test and Morris water maze test were applied to evaluate the cognitive function of rats.Nissl staining was applied to observe the pathological changes of hippocampal neurons.TUNEL staining was applied to detect the apoptosis of hippocampal neurons.Western blot assay was applied to detect the expression of cleared caspase-3,B-cell lymphoma gene-2-associated X protein(Bax),proto-oncogene(c-Myc),Cyclin D1,total GSK-3β(t-GSK-3β),phosphorylated GSK-3β(p-GSK-3β),total β-Catenin(t-β-Catenin)and phosphorylated β-catenin(p-β-Catenin)proteins in hippocampus.Results Compared with the PTSD group,the number of crawling spaces,standing times,total movement distance and times of crossing the original platform of rats were higher in the Sal B low-dose group,the Sal B high-dose group and the GSK-3β inhibitor group.The escape latency and the time to cross the original platform for the first time were shorter,the apoptosis rate of hippocampal neurons and the expression levels of Bax,cleaved caspase-3,t-GSK-3β and p-β-Catenin proteins in hippocampus were lower,and the expression levels of Cyclin D1,c-Myc,p-GSK-3β,t-β-Catenin proteins were higher(P＜0.05).Conclusion Sal B can reduce the apoptosis and damage of hippocampal neurons in rats with PTSD and improve cognitive dysfunction in rats,and inhibit the GSK-3β/β-Catenin signal pathway.
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Objective To analyze the influence of intraoperative blood glucose fluctuation and postoperative insulin resistance(IR)on postoperative cognitive dyfunction(POCD)in elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia.Methods A total of 352 elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia were collected and divided into the POCD group(n=84)and the non-POCD group(n=268).The covariates between the two groups were balanced by propensity score matching method(PSM).Eighty-four cases in each group were successfully matched.The data between the two groups before and after PSM were compared.After PSM,receiver operating characteristic(ROC)curve of blood glucose fluctuation amplitude for predicting POCD was drawn,and patients were divided into the low-level blood glucose fluctuation group(n=97)and the high-level blood glucose fluctuation group(n=71)according to the cut-off value.According to the existence of postoperative IR,patients were divided into the IR group(n=53)and the non-IR group(n=115).Then,incidences of POCD between groups were compared.Logistic regression was used to analyze the influencing factors of POCD.Results Before PSM,the POCD group had older age,higher blood glucose fluctuation amplitude,IR ratio,operation time,anesthesia time,propofol dosage,remifentanil dosage and sufentanil dosage in anesthesia maintenance period than those in the non-POCD group(P＜0.05).The POCD group had higher blood glucose fluctuation amplitude and IR ratio than those in the non-POCD group after PSM(P＜0.05).After PSM,the incidences of POCD in the high-level blood glucose fluctuation group and the IR group were higher than those in the low-level blood glucose fluctuation group and the non-IR group(P＜0.05).Logistic regression analysis showed that higher intraoperative blood glucose fluctuation(OR=9.140,95%CI:4.338-19.257)and postoperative IR(OR=4.034,95%CI:1.163-13.991)were risk factors of POCD.Conclusion The risk of POCD in elderly patients undergoing thoracoscopic radical lung cancer surgery under general anesthesia is increased in patients with higher intraoperative blood glucose fluctuation and postoperative IR.
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The long-latency auditory evoked potential can not only reflect the passive sensory processing of sound signals in the brain,but also reflect the active cognitive processing of the brain in different task modes,so it is applied to the assessment of cognitive function.This article reviews the research status of exogenous components(P1,N1,P2)and endogenous components(MMN/N2a,N2b,P3a,P3b)in the long-latency auditory evoked po-tential in mild cognitive impairment and Alzheimer's disease,and provides some reference for those who carry out relevant research in China.
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BACKGROUND:Gait is one of the optimal indicators of functional status in older adults.Gait parameters are associated with adverse health outcomes in older adults. OBJECTIVE:To summarize and compare the practical value of gait parameters,and to review the progress of research on spatio-temporal parameters and the risk of adverse health outcomes in older adults. METHODS:PubMed,Web of Science,and CNKI were searched for relevant literature published from January 2010 to June 2023 using the search terms of"gait speed,walking speed,step length,cadence,step frequency,step time,walking base,aged and elderly"in English and Chinese,respectively.A total of 52 papers were finally included for the systematic review. RESULTS AND CONCLUSION:Currently,researchers have focused on three basic temporal-spatial parameters,namely,step speed,step length and step frequency,to explore their association with adverse health outcomes in older adults.Reduced gait speed in older adults may increase the risk of falls,all-cause mortality,and may be an independent predictor of all-cause mortality.Older adults with slow gait speed are at higher risk of cognitive decline,and may be the preferred gait parameter in assessing cognitive impairment in older adults.Older adults with slow gait speed are more likely to have debilitating or common chronic illnesses,and are at higher risk of hospitalization and public care.Step length is positively correlated with individual height and lower limb length,but age-induced shortening of step length is not related to height or lower limb length,and shortening of step length reflects reduced physical function in older adults,and shortening of step length is a risk factor for falls and cognitive decline in older adults.Stride frequency is often used as a measure of exercise intensity,and a stride frequency of≥100 steps/minute is predictive of all-cause mortality,and slowing of step frequency may lead to a higher risk of falls,hospitalization and all-cause mortality in older adults.Changes in gait parameters are closely related to the level of physical fitness in older adults,and there may be a bidirectional relationship between the two.The results of the study will provide a theoretical basis for further improving risk screening in clinical populations,refining health risk assessment in the elderly,improving health protection and promoting active health in the elderly.
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Contactin-1(CNTN1)is a neural cell adhesion molecule belonging to the subgroup of immunoglobulin superfamily.It is anchored on the cell surface through glycosyl phosphatidyl inositol-anchored neural membrane proteins and participates in axon guidance,synapse formation,growth and development of nervous systems,and occurrence of related disea-ses.In addition,CNTN1 can promote inflammatory response and signal communication between microglia and astrocytes through various mechanisms,playing a role in the pathological processes of various neurological and psychiatric disorders.This article discusses the role of CNTN1 in depression and cognitive dysfunction.
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Objective To investigate the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)parameters for cognitive dysfunction in first-episode stroke,thereby providing reference for the early clinical assessment of the risk of cognitive dysfunction in stroke and formulation of intervention programs.Methods A total of 122 patients with first-episode stroke were enrolled and divided into occurrence group(n=53)and non-occurrence group(n=69)according to whether they had cognitive dysfunction.Additionally,53 patients with non-cerebrovascular cognitive dysfunction were selected as control group.All patients underwent DCE-MRI examination after admission.The 3 groups and patients with different degrees of cognitive dysfunction were compared for DCE-MRI parameters,including interstitium-to-plasma rate constant(Kep),volume transfer constant(Ktrans),volume fraction of extravascular extracellular space(Ve),and volume fraction of plasma(Vp).The correlations of DCE-MRI parameters with the degree of cognitive dysfunction were analyzed,along with their diagnostic value for cognitive dysfunction and evaluation value for the risk of cognitive dysfunction after first-episode stroke.Results Both occurrence group and non-occurrence group had higher levels of Ktrans,Ve and Vp than control group,and these parameters were higher in occurrence group than non-occurrence group(P<0.05).Ktrans,Ve and Vp of patients with different degrees of cognitive dysfunction differed significantly(P<0.05),and they were increased significantly with the aggravation of cognitive dysfunction.Ktrans,Ve and Vp were all positively correlated with the degree of cognitive dysfunction (P<0.05). The AUC for the combined diagnosis using Ktrans, Ve and Vp was 0.921, significantly higher than single index (P<0.05). The risks of cognitive dysfunction in first-episode stroke patients with higher levels of Ktrans, Ve and Vp were 3.077, 1.944 and 2.313 times of the low-level, respectively. Conclusion DCE-MRI can be used to diagnose cognitive dysfunction in first-episode stroke, providing reference for early clinical prediction of cognitive dysfunction after stroke.
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BackgroundPostoperative cognitive dysfunction （POCD） is a common complication in elderly patients after surgery， and has a great impact on postoperative rehabilitation of patients. ObjectiveTo explore the effect of mindfulness-based therapy on cognitive function and sleep quality in elderly patients after surgery under local anesthesia， so as to provide references for reducing their incidence risk of POCD and improving sleep quality. MethodsThe simple random sampling method was utilized to select 78 elderly patients who underwent surgery under local anesthesia in The Third Hospital of Mianyang from March 2022 to March 2023. Participants were assigned into study group and control group， each with 39 cases. All patients were subjected to conventional treatment and nursing interventions， and study group added mindfulness-based therapy on this basis. Mini-Mental State Examination （MMSE） was administered to patients on 1 day before surgery， and on the 1st， 3rd and 5th day after surgery. Pittsburgh Sleep Quality Index （PSQI） was employed on 1 day before surgery and on the 3rd day after surgery. ResultsMMSE scores revealed a significant time effect， group effect and time×group interaction effect （F=78.251， 197.071， 371.915， P<0.05）. Analysis of simple effect denoted that study group scored higher on MMSE on the 1st， 3rd and 5th day after surgery compared with control group， with statistical significance （t=-3.579， -1.764， -0.253， P<0.05）. Study group reported lower incidence rates of POCD on the 1st， 3rd and 5th day after surgery compared with control group， with statistical significance （χ2=2.631， 3.471， 5.135， P<0.05）. On the 3rd day after surgery，study group scored lower on PSQI than control group（P<0.05）， and PSQI total score， sleep latency， subjective sleep quality， daytime dysfunction and hypnotic drug use factor scores of study group were lower than baseline， with statistical significance（F=43.175， 12.594， 11.092， 4.579， 3.514， P<0.01）. ConclusionMindfulness-based therapy may have certain value in reducing incidence of POCD and improving sleep quality in elderly patients who underwent surgery under local anesthesia.
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Exposure to occupational noise and heavy metals are common occupational hazards in workplaces. Occupational noise exposure not only leads to noise-induced hearing loss but also cognitive dysfunction. Exposure to common heavy metals such as lead, manganese, and cadmium during work is closely related to cognitive dysfunction in workers. Combined exposure to noise and heavy metals is common in workplaces. However, current research on the combined effects of exposure to occupational noise with lead or manganese on workers' cognitive function is not comprehensive or systematic. The method for cognitive dysfunction identification varies, leading to a lack of comparability. And the causality between occupational exposure and cognitive dysfunction in workers has not been clarified. Therefore, studying the cognitive dysfunction due to combined exposure to noise and common heavy metals is of great significance for workers' occupational health. In the future, it is necessary to unify the method for cognitive dysfunction identification and conduct systematic and comprehensive research on the effects, mechanisms, and combined effects of exposure to occupational noise with lead, manganese, cadmium, and other heavy metals on workers' cognitive dysfunction, to ensure the occupational health rights and interests of workers.
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The neuroimmune system is crucial for the development， aging， and damage of the central nervous system， and has gradually become a research hotspot. Triggeringreceptor expressed on myeloid cells-2 （TREM2） is a transmembrane receptor of the immunoglobulin superfamily and is mainly expressed in the microglia in the central nervous system. An increasing number of studies indicate that TREM2 has great potential to improve cognitive dysfunction related to Alzheimer's disease， vascular dementia， Parkinson's disease， postoperative cognitive impairment， obesity， etc. However， there is a lack of a systematic summary of the specific role of TREM2 in cognitive dysfunction. This paper reviews the progress in the latest research on the related mechanisms of TREM2 in cognitive dysfunction， in order to provide new strategies for the treatment of cognitive dysfunction.
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Objective:To investigate the correlation between serum ischemia modified albumin (IMA) and calmodulin (CaM) expression levels and neurological impairment in patients with cerebral small vessel disease.Methods:The clinical data of 140 patients with cerebral small vessel disease (CSVD) who received treatment at The Third People Hospital in Liaocheng between April 2020 and December 2021 were retrospectively analyzed. On admission, serum levels of CaM and IMA were measured using an enzyme-linked immunosorbent assay and an albumin-cobalt binding test. Patients' neurological function was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Patients' transient cerebral ischemia, urinary incontinence, and gait disturbance were evaluated using the National Institute of Neurological Disorders and Stroke Scale. Patients' cognitive function was evaluated using the Montreal Cognitive Assessment scale. The influential factors of serum IMA and CaM expression levels in patients with CSVD were analyzed. The factors that affect the severity of neuological imairment in patients with CSVD and their correlation with serum IMA and CaM expression levels were analyzed.Results:The gender, age, presence or absence of gait disorders, and presence or absence of urinary incontinence of patients were not correlated with serum IMA and CaM levels (all P > 0.05). The serum levels of IMA [(38.5 ± 5.3) × 103U/L, (38.5 ± 4.7) × 103U/L, (39.0 ± 4.4) × 103U/L] and CaM [(190.4 ± 34.5) μg/L, (191.2 ± 26.7) μg/L, (199.7 ± 24.8) μg/L] in patients with cognitive impairment, dizziness and vertigo, and transient cerebral ischemia were significantly higher than those in patients with normal cognitive function, patients without dizziness and vertigo, or patients without transient cerebral ischemia [(27.3 ± 4.4) × 103U/L, (21.0 ± 3.8) × 103U/L, (20.5 ± 5.1) × 103U/L, (180.6 ± 29.6) μg/L, (179.5 ± 28.6) μg/L, (168.6 ± 32.4) μg/L, t = 14.10, 24.36, 22.50, all P < 0.05]. There were significant differences in cognitive impairment (38/16/9), dizziness and vertigo (39/16/8), transient cerebral hemorrhage (35/16/9), NIHSS score [(3.6 ± 0.8) points, (7.5 ± 0.9) points, (16.2 ± 3.2) points], CaM levels [(125.3 ± 20.5) μg/L, (185.5 ± 23.6) μg/L, (237.9 ± 54.3) μg/L], and IMA levels [(21.2 ± 3.5)] × 103 U/L, [(38.5 ± 4.3) × 103 U/L, (74.9 ± 5.4) × 103 U/L] among patients with mild, moderate, and severe neurological impairment ( t = 32.87, 11.28, 12.42, 34.59, 151.73, 147.84, all P < 0.05). The results of multivariate analysis indicated that cognitive impairment ( OR = 1.578, 95% CI: 1.043-2.386), transient cerebral ischemia ( OR = 2.396, 95% CI: 1.156-4.969), dizziness and vertigo ( OR = 1.906, 95% CI: 1.086-3.345), NIHSS score ( OR = 2.171, 95% CI: 1.162-4.056), CaM level ( OR = 2.022, 95% CI: 1.268-3.224), and increased IMA levels ( OR = 2.090, 95% CI: 1.313-3.325) were independent influential factors for worsened neurological impairment (all P < 0.05). The serum levels of IMA and CaM in patients with CSVD were significantly positively correlated with the severity of neurological impairment ( r = 5.45, 8.33, both P < 0.05). Conclusion:The elevated serum levels of IMA and CaM in patients with CSVD serve as independent risk factors for neurological impairment, and these levels are positively correlated with the severity of neurological impairment.
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Objective:To analyze the effect of donepezil hydrochloride combined with memantine on cognitive function in patients with Alzheimer's disease (AD).Methods:A randomized controlled trial was conducted among 90 patients with AD who were treated at the Zaozhuang Mental Health Center from January 2021 to March 2023. The patients were divided into a donepezil group and a combination group using a random number table grouping method, with 45 patients in each group. The donepezil hydrochloride group received only oral administration of donepezil hydrochloride tablets, while the combination group received oral administration of both donepezil hydrochloride tablets and memantine tablets. The two groups were continuously treated for 12 weeks. Before and after treatment, the Activities of Daily Living scale (ADL) score, the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) score, the Mini-Mental State Scale (MMSE) score, and biochemical indicators (homocysteine, neuron-specific enolase, and S100 β) were compared between the two groups. Adverse drug reactions were observed in each group.Results:After treatment, the ADL, BEHAVE-AD, and MMSE scores in the combination group were (78.9 ± 6.1) points, (5.2 ± 0.5) points, and (22.8 ± 2.2) points, respectively, and they were (65.2 ± 5.9) points, (9.6 ± 0.9) points, and (19.4 ± 2.4) points, respectively, in the donepezil hydrochloride group. The ADL and MMSE scores in the combination group were significantly higher than those in the donepezil hydrochloride group ( t = 10.83, 7.01, both P < 0.001). The BEHAVE-AD score in the combination group was significantly lower than that in the donepezil hydrochloride group ( t = -28.67, P < 0.001). After treatment, serum levels of homocysteine, neuron-specific enolase, and S100 β in the combination group were (17.8 ± 3.6) μmol/L, (16.8 ± 2.7) μg/L, and (17.4 ± 7.5) μg/L, respectively, which were significantly lower than (21.5 ± 3.3) μmol/L, (20.4 ± 3.7) μg/L, and (23.5 ± 5.1) μg/L in the donepezil hydrochloride group ( t = -5.08, -5.27, -4.51, all P < 0.001). The incidence of adverse drug reactions in the combination group was 13.3% (6/45), which was slightly, but not significantly, higher than 8.9% (4/45) in the donepezil group ( χ2 = 0.45, P = 0.502). Conclusion:The combination of donepezil hydrochloride and memantine can effectively improve the mental and behavioral symptoms and cognitive function of patients with AD, improve daily living ability, and do not increase adverse reactions. The combined therapy has high clinical application value.