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.

Effects of ulinastatin combined with dexmedetomidine on cognitive dysfunction and emergence agitation in elderly patients who underwent total hip arthroplasty

BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture increases.Hip fracture is a common type of fracture in older people.Total hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint function.AIM To investigate the effect of ulinastatin combined with dexmedetomidine(Dex)on the incidences of postoperative cognitive dysfunction(POCD)and emergence agitation in elderly patients who underwent THA.METHODS A total of 397 patients who underwent THA from February 2019 to August 2022.We conducted a three-year retrospective cohort study in Shaanxi Provincial People’s Hospital.Comprehensive demographic data were obtained from the electronic medical record system.We collected preoperative,intraoperative,and postoperative data.One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group.One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group.One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin group.The patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were evaluated.RESULTS There was a significant difference in the 24 h visual analogue scale score among the three groups,and the score in the Dex+ulinastatin group was the lowest(P<0.05).Compared with the Dex and ulinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all P<0.05).Compared with those in the Dex and ulinastatin groups,incidence of POCD,levels of serum inflammatory cytokines in the Dex+ulinastatin group were significantly decreased at 1 and 7 d after the operation(all P<0.05).The observer’s assessment of the alertness/sedation score and Ramsay score of the Dex+ulinastatin group were significantly different from those of the Dex and ulinastatin groups on the first day after the operation(all P<0.05).CONCLUSION Ulinastatin combined with Dex can prevent the occurrence of POCD and emergence agitation in elderly patients undergoing THA.

Impact of thoracic paravertebral block and sufentanil on outcomes and postoperative cognitive dysfunction in thoracoscopic lung cancer surgery

BACKGROUND Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer(LC).This is achieved using either a thoracic paravertebral block(TPVB)or sufentanil(SUF)-based multimodal analgesia.However,the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction(POCD)remain unclear.AIM To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes.METHODS This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023.Patients receiving SUF-based multimodal analgesia(n=50)and patients receiving TPVB+SUF-based multimodal analgesia(n=57)were assigned to the control group and TPVB group,respectively.We compared the Ramsay Sedation Scale and visual analog scale(VAS)scores at rest and with cough between the two groups at 2,12,and 24 h after surgery.Serum levels of epinephrine(E),angio-tensin Ⅱ(Ang Ⅱ),norepinephrine(NE),superoxide dismutase(SOD),vascular endothelial growth factor(VEGF),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),and S-100 calcium-binding proteinβ(S-100β)were measured before and 24 h after surgery.The Mini-Mental State Examination(MMSE)was administered 1 day before surgery and at 3 and 5 days after surgery,and the occurrence of POCD was monitored for 5 days after surgery.Adverse reactions were also recorded.RESULTS There were no significant time point,between-group,and interaction effects in Ramsay sedation scores between the two groups(P>0.05).Significantly,there were notable time point effects,between-group differences,and interaction effects observed in VAS scores both at rest and with cough(P<0.05).The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased(P<0.05).The TPVB group had lower VAS scores than the control group at 2,12,and 24 h after surgery(P<0.05).The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group(P<0.05).The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery(P<0.05).Both groups had elevated serum E,Ang Ⅱ,and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels,with better indices in the TPVB group(P<0.05).Marked elevations in serum levels of VEGF,TGF-β1,TNF-α,and S-100β were observed in both groups at 24 h after surgery,with lower levels in the TPVB group than in the control group(P<0.05).CONCLUSION TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC,enhances analgesic effects,reduces postoperative stress response,and inhibits postoperative increases in serum VEGF,TGF-β1,TNF-α,and S-100β levels.This scheme also reduced POCD and had a high safety profile.

Small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells improve postoperative cognitive dysfunction in mice with diabetes

Postoperative cognitive dysfunction(POCD)is a common surgical complication.Diabetes mellitus(DM)increases risk of developing POCD after surgery.DM patients with POCD seriously threaten the quality of patients’life,however,the intrinsic mechanism is unclear,and the effective treatment is deficiency.Previous studies have demonstrated neuronal loss and reduced neurogenesis in the hippocampus in mouse models of POCD.In this study,we constructed a mouse model of DM by intraperitoneal injection of streptozotocin,and then induced postoperative cognitive dysfunction by transient bilateral common carotid artery occlusion.We found that mouse models of DM-POCD exhibited the most serious cognitive impairment,as well as the most hippocampal neural stem cells(H-NSCs)loss and neurogenesis decline.Subsequently,we hypothesized that small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells(iMSC-sEVs)might promote neurogenesis and restore cognitive function in patients with DM-POCD.iMSC-sEVs were administered via the tail vein beginning on day 2 after surgery,and then once every 3 days for 1 month thereafter.Our results showed that iMSC-sEVs treatment significantly recovered compromised proliferation and neuronal-differentiation capacity in H-NSCs,and reversed cognitive impairment in mouse models of DM-POCD.Furthermore,miRNA sequencing and qPCR showed miR-21-5p and miR-486-5p were the highest expression in iMSC-sEVs.We found iMSC-sEVs mainly transferred miR-21-5p and miR-486-5p to promote H-NSCs proliferation and neurogenesis.As miR-21-5p was demonstrated to directly targete Epha4 and CDKN2C,while miR-486-5p can inhibit FoxO1 in NSCs.We then demonstrated iMSC-sEVs can transfer miR-21-5p and miR-486-5p to inhibit EphA4,CDKN2C,and FoxO1 expression in H-NSCs.Collectively,these results indicate significant H-NSC loss and neurogenesis reduction lead to DM-POCD,the application of iMSC-sEVs may represent a novel cell-free therapeutic tool for diabetic patients with postoperative cognitive dysfunction.

Death-associated protein kinase 1 is associated with cognitive dysfunction in major depressive disorder

We previously showed that death-associated protein kinase 1(DAPK1)expression is increased in hippocampal tissue in a mouse model of major depressive disorde and is related to cognitive dysfunction in Alzheimer's disease.In addition,depression is a risk factor for developing Alzheimer's disease,as well as an early clinical manifestation of Alzheimer's disease.Meanwhile,cognitive dysfunction is a distinctive feature of major depressive disorder.Therefore,DAPK1 may be related to cognitive dysfunction in major depressive disorder.In this study,we established a mouse model of major depressive disorder by housing mice individually and exposing them to chronic,mild,unpredictable stressors.We found that DAPK1 and tau protein levels were increased in the hippocampal CA3 area,and tau was hyperphosphorylated at Thr231,Ser262,and Ser396 in these mice.Furthermore,DAPK1 shifted from axonal expression to overexpression on the cell membrane.Exercise and treatment with the antidepressant drug citalopram decreased DAPK1 expression and tau protein phosphorylation in hippocampal tissue and improved both depressive symptoms and cognitive dysfunction.These results indicate that DAPK1 may be a potential reason and therapeutic target of cognitive dysfunction in major depressive disorder.

Expression of miR-9-5p and RHOA in aluminum-induced rat cognitive dysfunction

Objective:To investigate the possible mechanism of microRNA-9-5p(miR-9-5p)and Ras homologous gene family A(RHOA)in aluminum-induced cognitive dysfunction in rats.Methods:According to the principle of randomization,48 Wistar rats were randomly divided into four groups(n=12)of blank control,low dose,medium dose and high dose.The blank control group was gavaged daily saline,and the other three dose groups were given daily gavage AlCl3 aqueous solution at three doses of 25 mg/kg,50 mg/kg,and 100 mg/kg to create a rat model of cognitive impairment for three months.The water maze(MWM)positioning navigation experiment was used to record the time t(s),namely,the incubation period,on the platform of rats,and the incubation period of each group was used to determine whether the rats in the infected group had learning and memory impairment.Hematoxylin-eosin(HE)and Nissl stains observed the pathological changes of nerve cells in the hippocampus of the four groups.Western blot detected the protein expression levels of RHOA and cranial neurotrophic factor(BDNF)in fresh rat hippocampal tissues.RT-qPCR detected the mRNA expression of miR-9-5p,RHOA,and BDNF in rat hippocampal tissues.Results:The results of Morris water maze positioning navigation test showed that the incubation period of each group was calculated on the 1st,3rd and 5th days of the experiment,and the motor incubation period of the infected group was higher than that of the control group.The results of HE staining showed that the rat nerve cells in the control group were morphologically intact,the staining was clear,the nucleus was clearly visible,and the edge of the cell membrane was sharp.The rat neurons in the infected group were damaged to varying degrees,the nucleus gradually dissolved,the cytoplasmic staining became deeper,the edges of the cell membrane were blurred and disordered,and the cells were deformed and arranged disordered.The results of Nissl staining showed that the well-stained Nissl body particles were visible in the nerve cells of rats in the control group,and the dissipation of Nissl bodies in the nerve cells of the infected group was reduced,and the staining was shallow.The results of RT-qPCR showed that compared with the control group,the mRNA expression of miR-9-5p and BDNF was decreased in the infected group,and the mRNA expression of RHOA was increased(P<0.05 or P<0.001).The Western blot results showed that compared with the control group,the relative expression of BDNF in the three infected groups was decreased,and the relative expression of RHOA increased(P<0.05).Conclusion:In aluminum-induced cognitive impairment,miR-9-5p is downregulated and RHOA is upregulatd.

Effects of Tuina on Obesity-Induced Insulin Resistance and Cognitive Dysfunction

This paper discusses the mechanism of insulin resistance in obesity from the research progress of Chinese and Western medicine and its oxidative stress,inflammatory reaction and abnormal lipid metabolism in cognitive dysfunction.It also reviews the research progress of massage,one of the external treatment methods of traditional Chinese medicine,in the treatment of insulin resistance and cognitive dysfunction in obesity,in order to provide more new ideas and new ways for clinical diagnosis and treatment of insulin resistance and related cognitive dysfunction caused by obesity.

Serum neuronal pentraxin 2 is related to cognitive dysfunction and electroencephalogram slow wave/fast wave frequency ratio in epilepsy

BACKGROUND Cognitive dysfunction in epileptic patients is a high-incidence complication.Its mechanism is related to nervous system damage during seizures,but there is no effective diagnostic biomarker.Neuronal pentraxin 2(NPTX2)is thought to play a vital role in neurotransmission and the maintenance of synaptic plasticity.This study explored how serum NPTX2 and electroencephalogram(EEG)slow wave/fast wave frequency ratio relate to cognitive dysfunction in patients with epilepsy.AIM To determine if serum NPTX2 could serve as a potential biomarker for diagnosing cognitive impairment in epilepsy patients.METHODS The participants of this study,conducted from January 2020 to December 2021,comprised 74 epilepsy patients with normal cognitive function(normal group),37 epilepsy patients with cognitive dysfunction[epilepsy patients with cognitive dysfunction(ECD)group]and 30 healthy people(control group).The minimental state examination(MMSE)scale was used to evaluate cognitive function.We determined serum NPTX2 levels using an enzyme-linked immunosorbent kit and calculated the signal value of EEG regions according to the EEG recording.Pearson correlation coefficient was used to analyze the correlation between serum NPTX2 and the MMSE score.RESULTS The serum NPTX2 level in the control group,normal group and ECD group were 240.00±35.06 pg/mL,235.80±38.01 pg/mL and 193.80±42.72 pg/mL,respectively.The MMSE score was lowest in the ECD group among the three,while no significant difference was observed between the control and normal groups.In epilepsy patients with cognitive dysfunction,NPTX2 level had a positive correlation with the MMSE score(r=0.367,P=0.0253)and a negative correlation with epilepsy duration(r=−0.443,P=0.0061)and the EEG slow wave/fast wave frequency ratio value in the temporal region(r=−0.339,P=0.039).CONCLUSION Serum NPTX2 was found to be related to cognitive dysfunction and the EEG slow wave/fast wave frequency ratio in patients with epilepsy.It is thus a potential biomarker for the diagnosis of cognitive impairment in patients with epilepsy.

Adaptive and regulatory mechanisms in aged rats with postoperative cognitive dysfunction

Inflammation may play a role in postoperative cognitive dysfunction. 5＇ Adenosine monophos- phate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-a are involved in inflammation. Therefore, these inflammatory mediators may be involved in postoperative cognitive dysfunction. Western immunoblot analysis revealed 5＇ adenosine mo- nophosphate-activated protein kinase and nuclear factor-kappa B in the hippocampus of aged rats were increased 1-7 days after splenectomy. Moreover, interleukin-1β and tumor necrosis fac- tor-α were upregulated and gradually decreased. Therefore, these inflammatory mediators may participate in the splenectomy model of postoperative cognitive dysfunction in aged rats.

Aspartic acid in the hippocampus:a biomarker for postoperative cognitive dysfunction

This study established an aged rat model of cognitive dysfunction using anesthesia with 2% iso- flurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethy- lacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid （100 μmol/L）. Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.

Penehyclidine Hydrochloride Premedication Is Not Associated with Increased Incidence of Post-Operative Cognitive Dysfunction or Delirium:A Systemic Review and Meta-Analysis

Objective Post-operative cognitive dysfunction(POCD)and post-operative delirium(POD)are two common post-operative cerebral complications.The current meta-analysis was to systematically review the effects of penehyclidine hydrochloride(PHC)on POCD and POD in surgical patients.Methods Electronic databases were searched to identify all randomized controlled trials comparing PHC with atropine/scopolamine/placebo on POCD and POD in surgical patients.Primary outcomes of interest included the incidences of POCD and POD;the secondary outcomes of interest included peri-operative minimental state examination(MMSE)scores.Two authors independently extracted peri-operative data,including patients'baseline characteristics,surgical variables,and outcome data.For dichotomous data(POCD and POD occurrence),treatment effects were calculated as odds ratio(OR)and 95%confidential interval(Cl).Each outcome was tested for heterogeneity,and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity.For continuous variables(MMSE scores),treatment effects were calculated as weighted mean difference(WMD)and 95%CI.Statistical significance was defined as P<0.05.Results Our search yielded 33 studies including 4017 patients.Meta-analysis showed that,the incidence of POCD in PHC group was comparable to that in saline group(OR=0.97;95%Ck 0.S8-1.64;P=0.92),scopolamine group(OR=0.78;95%CI:0.48-1.27;P=0.32)and atropine group(0R=1.20;95%Ch 0.86-1.67;P=0.29).The incidence of POD in PHC group was comparable to that in saline group(OR=1.53;95%CI:0.81-2.90;P=0.19)and scopolamine group(OR=0.53;95%CI:0.06-4.56;P=0.56),but higher than that in atropine group(OR=4.49;95%CI:1.34-15.01;P=0.01).Conclusions PHC premedication was not associated with increased incidences of POCD or POD as compared to either scopolamine or placebo.

Three-dimensional-arterial spin labeling perfusion correlation with diabetes-associated cognitive dysfunction and vascular endothelial growth factor in type 2 diabetes mellitus rat

BACKGROUND Type 2 diabetes mellitus(T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia.The mechanisms of diabetes-associated cognitive dysfunction(DACD) have not been fully elucidated to date.Some studies proved lower cerebral blood flow(CBF) in the hippocampus was associated with poor executive function and memory in T2DM.Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor(VEGF) expression and CBF changes in humans and animal models.In this study,we hypothesized that DACD was correlated with CBF alteration as measured by three-dimensional(3D) arterial spin labeling(3D-ASL) and VEGF expression in the hippocampus.AIM To assess the correlation between CBF(measured by 3D-ASL and VEGF expression) and DACD in a rat model of T2DM.METHODS Forty Sprague-Dawley male rats were divided into control and T2DM groups.The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM.Cognitive function was assessed using the Morris water maze experiment.The CBF changes were measured by 3D-ASL magnetic resonance imaging.VEGF expression was determined using immunofluorescence.RESULTS The escape latency time significantly reduced 15 wk after streptozotocin injection in the T2DM group.The total distance traveled was longer in the T2DM group;also,the platform was crossed fewer times.The percentage of distance in the target zone significantly decreased.CBF decreased in the bilateral hippocampus in the T2DM group.No difference was found between the right CBF value and the left CBF value in the T2DM group.The VEGF expression level in the hippocampus was lower in the T2DM group and correlated with the CBF value.The escape latency negatively correlated with the CBF value.The number of rats crossing the platform positively correlated with the CBF value.CONCLUSION Low CBF in the hippocampus and decreased VEGF expression might be crucial in DACD.CBF measured by 3D-ASL might serve as a noninvasive imaging biomarker for cognitive impairment associated with T2DM.

Expert Consensus on Cognitive Dysfunction in Diabetes

The incidence of diabetes is gradually increasing in China,and diabetes and associated complications,such as cognitive dysfunction have gained much attention in recent time.However,the concepts,clinical treatment,and prevention of cognitive dysfunction in patients with diabetes remain unclear.The Chinese Society of Endocrinology investigated the current national and overseas situation of cognitive dysfunction associated with diabetes.Based on research both in China and other countries worldwide,the Expert Consensus on Cognitive Dysfunction in Diabetes was established to guide physicians in the comprehensive standardized management of cognitive dysfunction in diabetes and to improve clinical outcomes in Chinese patients.This consensus presents an overview,definition and classification,epidemiology and pathogenesis,risk factors,screening,diagnosis,differential diagnosis,treatment,and prevention of cognitive dysfunction in patients with diabetes.

Hyperbaric oxygen preconditioning improves postoperative cognitive dysfunction by reducing oxidant stress and inflammation

Postoperative cognitive dysfunction is a crucial public health issue that has been increasingly studied in efforts to reduce symptoms or prevent its occurrence. However, effective advances remain lacking. Hyperbaric oxygen preconditioning has proved to protect vital organs, such as the heart, liver, and brain. Recently, it has been introduced and widely studied in the prevention of postoperative cognitive dysfunction, with promising results. However, the neuroprotective mechanisms underlying this phenomenon remain controversial. This review summarizes and highlights the definition and application of hyperbaric oxygen preconditioning, the perniciousness and pathogenetic mechanism underlying postoperative cognitive dysfunction, and the effects that hyperbaric oxygen preconditioning has on postoperative cognitive dysfunction. Finally, we conclude that hyperbaric oxygen preconditioning is an effective and feasible method to prevent, alleviate, and improve postoperative cognitive dysfunction, and that its mechanism of action is very complex, involving the stimulation of endogenous antioxidant and anti-inflammation defense systems.

Role of GSK-3β in Isoflurane-induced Neuroinflammation and Cognitive Dysfunction in Aged Rats

Summary： This study investigated the role of glycogen synthase kinase-3D （GSK-3β） in isoflu- rane-induced neuroinflammation and cognitive dysfunction in aged rats. The hippocampi were dissected from aged rats which had been intraperitoneally administered lithium chloride （LiC1, 100 mg/kg） and then exposed to 1.4% isoflurane for 6 h. The expression of GSK-313 was detected by Western blotting. The mRNA and protein expression levels of tumor necrosis factor （TNF）-a, interleukin （IL）-lβ and IL-6 were measured by real-time PCR and enzyme-linked immunosorbent assay （ELISA）, respectively. Mor- ris water maze was employed to detect spatial memory ability of rats. The results revealed that the level of GSK-3β was upregulated after isofurane exposure. Real-time PCR analysis demonstrated that isoflu- rane anesthesia increased mRNA levels of TNF-a IL-Iβ and IL-6, which was consistent with the ELISA results. However, these changes were reversed by prophylactic LiC1, a non-selective inhibitor of GSK-3β. Additionally, we discovered that LiC1 alleviated isoflurane-induced cognitive impairment in aged rats. Furthermore, the role of GSK-313 in isoflurae-induced neuroinflammation and cognitive dysfunction was associated with acetylation of NF-r,B p65 （Lys310）. In conclusion, these results suggested that GSK-3β is associated with isoflurane-induced upregulation of proinflammatory cytokines and cognitive disorder in aged rats.

Ginsenoside Rb1 Attenuates Isoflurane/surgery-induced Cognitive Dysfunction via Inhibiting Neuroinflammation and Oxidative Stress

Objective Anesthetic isoflurane plus surgery has been reported to induce cognitive impairment. The underlying mechanism and targeted intervention remain largely to be determined. Ginsenoside Rb1 was reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rb1 can attenuate isoflurane/surgery-induced cognitive dysfunction via inhibiting neuroinflammation and oxidative stress. Methods Five-months-old C57BL/6J female mice were treated with 1.4% isoflurane plus abdominal surgery for two hours. Sixty mg/kg ginsenoside Rb1 were given intraperitoneally from 7 days before surgery. Cognition of the mice were assessed by Barnes Maze. Levels of postsynaptic density-95 and synaptophysin in mice hippocampus were measured by Western blot. Levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in mice hippocampus were measured by ELISA. Results Here we show for the first time that the ginsenoside Rb1 treatment attenuated the isoflurane/surgery-induced cognitive impairment. Moreover, ginsenoside Rb1 attenuated the isoflurane/surgery-induced synapse dysfunction. Finally, ginsenoside Rb1 mitigated the isoflurane/surgery-induced elevation levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in the mice hippocampus. Conclusion These results suggest that ginsenoside Rb1 may attenuate the isoflurane/surgery-induced cognitive impairment by inhibiting neuroinflammation and oxidative stress pending future studies.

Promise of metformin for preventing age-related cognitive dysfunction

The expanded lifespan of people,while a positive advance,has also amplified the prevalence of age-related disorders,which include mild cognitive impairment,dementia,and Alzheimer's disease.Therefore,competent therapies that could improve the healthspan of people have great significance.Some of the dietary and pharmacological approaches that augment the lifespan could also preserve improved cognitive function in old age.Metformin,a drug widely used for treating diabetes,is one such candidate that could alleviate age-related cognitive dysfunction.However,the possible use of metformin to alleviate age-related cognitive dysfunction has met with conflicting results in human and animal studies.While most clinical studies have suggested the promise of metformin to maintain better cognitive function and reduce the risk for developing dementia and Alzheimer's disease in aged diabetic people,its efficacy in the nondiabetic population is still unclear.Moreover,a previous animal model study implied that metformin could adversely affect cognitive function in the aged.However,a recent animal study using multiple behavioral tests has reported that metformin treatment in late middle age improved cognitive function in old age.The study also revealed that cognitionenhancing effects of metformin in aged animals were associated with the activation of the energy regulator adenosine monophosphate-activated protein kinase,diminished neuroinflammation,inhibition of the mammalian target of rapamycin signaling,and augmented autophagy in the hippocampus.The proficiency of metformin to facilitate these favorable modifications in the aged hippocampus likely underlies its positive effect on cognitive function.Nonetheless,additional studies probing the outcomes of different doses and durations of metformin treatment at specific windows in the middle and old age across sex in nondiabetic and non-obese prototypes are required to substantiate the promise of metformin to maintain better cognitive function in old age.

Disturbance of cholinergic Grb2-associated-binding protein 1 signaling participate in the pathological process of cognitive dysfunction

OBJECTIVE A causal relationshiphas been postulated between cholinergic dysfunction and the progression of cognitive decline in neurodegenerative disorders. However,the cause of the cognitive dysfunction remains unclear. METHODS Gab1^(loxP/loxP) were bred with ChAT-Cre mice to generate ChAT-Cre; Gab1^(f/f) mice. Excitability of cholinergic neurons wererecorded using whole-cel patch clump. A series of behavioral analyses were used to address the changes of cognitive function in ChAT-Cre; Gab1^(f/f) mice. Neurochemical changes on brain of conditional knockout mice were evaluated by using immunohistochemistry and Western blotting analysis. RESULTS Grb2-associated-binding protein 1(Gab1) is adocking/scaffolding molecule known to play an important role in cell growth and survival. Here,wereport that Gab1 is decreased in cholinergic neurons in a mousemodel of AD. We found that selective downregulation of Gab1 in the septum impaired learning and memory and hippocampal long-term potentiation,whereas overexpression of Gab1 in the same area rescued the cognitive deficitsseen in ChAT-Cre; Gab1^(f/f) and APP^(swe)/PS1 mice.^(18)F-FDGmicroP ET imaging data indicated that Gab1 treatment had no effect on metabolic activity of glucose in APPswe/PS1 mice. Moreover,we identify abnormal function of SKchannelscontributes to increased firing in cholinergic neuronsof ChAT-Cre; Gab1^(f/f) mice. CONCLUSION Gab1 signaling may serve as a potential treatment target for neurological disorders involving dysfunction of central cholinergic neurons.

Metabolic syndrome,ApoE genotype,and cognitive dysfunction in an elderly population:A single-center,case-control study

BACKGROUND Metabolic syndrome(MetS)is related to poor cognitive function.However,the results of previous studies were inconsistent,and whether the ApoEε4 allele modifies the association remains unclear.AIM To elucidate the relationships among MetS,ApoEε4,and cognitive dysfunction in an elderly population in China.METHODS One hundred elderly patients with MetS and 102 age-and gender-matched controls were included in the study.Baseline clinical characteristics and biochemical index for glucose and lipid metabolism were obtained.The distribution of ApoEε4 was assessed with PCR restriction fragment length polymorphism analysis.Cognitive function was evaluated by mini-mental status examination at the 1-year follow-up examination.RESULTS Compared with controls,MetS patients had worse cognitive function and decreased ability to participate in activities of daily life(P=0.001 and 0.046,respectively).Patients with cognitive dysfunction had higher prevalence of MetS(62.1%vs 36.4%,P<0.001)and were more likely to carry the ApoEε4 allele(22.3%vs 10.1%,P=0.019).Multivariate logistic regression analyses showed that diagnosis with MetS,severe insulin resistance,status as an ApoEε4 carrier,higher systolic blood pressure,and larger waist circumference were risk factors for cognitive dysfunction(P<0.05).Repeated-measures analysis of variance,performed with data collected at the 1-year follow-up,revealed continuous influences of MetS and ApoEε4 on the deterioration of cognitive function(time×team,P<0.001 for both).CONCLUSION Diagnosis of MetS and ApoEε4 carrier status were persistently associated with cognitive dysfunction among an elderly population in China.

Analysis of Risk Factors Associated with Cognitive Dysfunction in Patients with Atrial Fibrillation

Objective: To discuss the risk factors of cognitive dysfunction in patients with atrial fibrillation. Methods: The 150 cases of patients with atrial fibrillation were analyzed in the first affiliated hospital of Nanchang University who were treated in the cardiovascular department, general medicine department and gerontology department from August 2018 to June 2019. We used Mini-Mental State Examination (MMSE) score to evaluate cognitive function of patients with atrial fibrillation. According to the level of education and MMSE score, patients with atrial fibrillation were divided into three groups: normal cognitive function group, mild cognitive impairment group (MCI) and dementia group. And then the demographic data, the previous use of taking drugs, the results of ultrasonic cardiogram (UCG) and laboratory test were analyzed. Results: 1) The basic situation of research object: a total of 150 patients with atrial fibrillation were enrolled in the study, and the average age of these patients was 65.05 ± 8.74 years old, which included 78 males (52%) and 72 females (48%). The mean MMSE score was 23.42 ± 4.65. According to MMSE score, 86 cases (57.3%) of cognitive dysfunction occurred in 150 patients with atrial fibrillation, which included 41 cases (27.3%) of mild cognitive impairment and 45 cases (30%) of dementia. 2) The comparison of general clinical data: there were significant differences in age, smoking, level of education, left ventricular ejection fraction, left atrial diameter, D-dimer, fibrinogen, homocysteine, platelet and previous use of taking warfarin, dabigatran, CCB, statins among the three groups (P < 0.05). 3) The linear correlational analysis between risk factors of cognitive function and MMSE score in patients with atrial fibrillation: there was a positive correlation between left ventricular ejection fraction and MMSE score, but age, left atrial diameter, homocysteine, low density lipoprotein, platelet, BMI, NT-proBNP, D-dimer were negatively correlated with MMSE score. 4) The risk factors with statistical significance in ANOVA were analyzed by ordinal and multinomial logistic regression, which showed that age (OR = 1.174, 95% CI: 0.091 - 0.231), the level of education (illiteracy OR = 4.162, 95% CI: -0.032 - 2.955, primary school OR = 2.751, 95% CI: -0.172 - 2.197, junior high school OR = 3.539, 95% CI: -0.048 - 2.577, senior high school and special secondary school OR = 1.332, 95% CI: -1.080 - 1.655), no CCB (OR = 1.174, 95% CI: 0.091 - 0.231), no warfarin (OR = 13.749, 95% CI: 1.480 - 3.762), no dabigatran (OR = 16.395, 95% CI: 1.462 - 4.131), D-dimer (OR = 2.745, 95% CI: -0.611 - 2.631), fibrinogen (OR = 3.228, 95% CI: 0.399 - 1.946) were related to the high occurrence of cognitive dysfunction. Conclusions: 1) Patients with atrial fibrillation had a higher risk of cognitive dysfunction (the incidence of 57.4%). 2) There was a positive correlation between left ventricular ejection fraction and MMSE score, but age, left atrial diameter, homocysteine, low density lipoprotein, platelet, BMI, NT-proBNP, and D-dimer were negatively correlated with MMSE score. 3) High level of education, previous use of taking warfarin and dabigatran etexilate were protective factors for cognitive function in patients with atrial fibrillation;but age, previous use of taking CCB, D-dimer and fibrinogen were the risk factors in patients with atrial fibrillation.