Recent Advances in HIV-Associated Neurocognitive Disorders

HIV-associated neurocognitive disorders (HAND) are chronic complications of HIV infection in the central nervous system. Clinical presentations include asymptomatic neurocognitive impairment (ANI), mild neurocognitive impairment (MND), and HIV-associated dementia (HAD). In the era of combination antiretroviral therapy (cART), the prevalence of HAD has significantly decreased, but the rates of ANI and MND have increased, impairing patients’ daily functioning, medical adherence, employment, driving abilities, risk of HIV transmission, overall quality of life, and posing challenges to society, economy, families, and public health. This article reviews the latest research findings regarding the pathogenesis, clinical diagnosis and treatment, neuroimaging, and neuropsychological assessment of HAND, aiming to provide insights into the prevention and management of HAND.

HIV-associated neurocognitive disorder(HAND):a review

Objective:According to the World Health Organization,the number of infected people with human immunodeficiency virus(HIV)in 2019 was about 38 million.Using combinational antiretroviral therapy in recent years has increased life expectancy in these people and HIV has been changed from a deadly disease to a chronic one.HIV-associated neurological disorders(HAND)include asymptomatic neurological disorders,Motor neurological disorders,and HIV-associated dementia.Methods:We searched 3 databases(PubMed,Science Direct and Scopus databases)from January 2015 to March 2021 for the keywords;HIV associated with a neurocognitive disorder,HAND and combinational antiretroviral therapy to provide careful consideration of various aspects of these disorders,including;risk factors,their diagnostic methods,their epidemiology,and finally the treatment of HAND.Results:In the initial search,we came across 1351 articles.Three authors did the title-abstract screening,and 270 articles were entered into full-text screening from the previous step.Four authors did the full-text screening,and the screening outcome was 21 articles.We categorized the results of our study into sub-categories,including:risk factors,pathogenicity,clinical manifestations,diagnosis,and epidemiology of HAND.Conclusions:Although the HAND subheading has made great strides,many questions about the disease remain unanswered,and many of the diagnosing established methods are not 100%accurate and as a result of that,this epidemy can’t be fully endured yet.We hope to find and apply further advances and more definitive solutions in the coming decades.

Effect of Nalmefene on Delayed Neurocognitive Recovery in Elderly Patients Undergoing Video-assisted Thoracic Surgery with One Lung Ventilation

The intravenous use of nalmefene has been found to exert neuroprotective effect in patients with severe traumatic brain injury and acute cerebral infarction;nonetheless,it is unknown whether nalmefene alleviates delayed neurocognitive recovery.Our purpose of the current research was to clarify the impact of nalmefene on delayed neurocognitive recovery in aged patients experiencing video-assisted thoracic surgery(VATS)with intraoperative use of one lung ventilation(OLV).The present study involved 120 paticents undergoing selective VATS,randomized to accept low-dose nalmefene(N1 group,n=40),high-dose nalmefene(N2 group,1n=40)or equal volume of physiologic saline(control group,1=40).A battery of neuropsychological tests were used to estimate cognitive function I day before surgery(o)and 10 days after surgery or before discharge(t).Regional cerebral oxygen saturation(rSO2)was detected 5 min before induction(t),5 min after induction(1),15 and 60 min after onset of OLV(62 and 13),and 15 min after termination of OLV(4).The plasma values of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-a1 and adiponectin(ADP)were also detected prior to induction of anesthesia(T0),1 h,2 h and 6 h after surgery(TI,T2,T3).On 1,delayed neurocognitive recovery occurred in 5/40(12.5%)patients of NI group,in 5/40(12.5%)patients of N2 group and in 13/40(32.5%)patients of control group(P<0.05).There were no statistical differences in rSO2 among three groups at different time points.At Tl,T2 and T3,IL-1β,IL-6 and TNF-a values significantly increased and ADP value significantly decreased(P<0.05)in control group.In contrast,at TI,T2 and T3,IL-1β,IL-6 and TNF-a values decreased and ADP value decreased less in N1 and N2 groups(P<0.05).At TI,T2 and T3,IL-1β,IL-6 and TNF-a concentrations presented a trend of N2 group<N1 group<control group and ADP presented a trend of N2 group>Nl group>control group(P<0.05).The result of our present research supports the hypothesis that the perioperative intravenous treatment with nalmefene to VATS with OLV ameliorates postoperative cognitive function and decreases the incidence of delayed neurocognitive recovery,most likely by suppression of inflammatory responses.

MiR-214-3p Prevents the Development of Perioperative Neurocognitive Disorders in Elderly Rats

Objective:This study aimed to identify microRNAs(miRNAs)involved in the development of perioperative neurocognitive disorders(PND).Methods:Plasma exosomal miRNA expression was examined in patients before and after cardiopulmonary bypass(CPB)using microarray and qRT-PCR and these patients were diagnosed as PND later.Elderly rats were subjected to CPB,and the cognitive functions were examined.Bioinformatics analysis was conducted to predict the targets of miR-214-3p.Rats were administered rno-miR-214-3p agomir before or after CPB to investigate the role of miR-214-3p in PND development.Results:We identified 76 differentially expressed plasma exosomal miRNAs in PND patients after surgery(P<0.05,|log2FC|>0.58),including the upregulated hsa-miR-214-3p(P=0.002399392).Prostaglandin-endoperoxide synthase 2(PTGS2)was predicted as a miR-214-3p target.In rats,CPB reduced the platform crossing numbers and target quadrant stay time,accompanied with hippocampal neuronal necrosis.The rno-miR-214-3p level was significantly increased in plasma exosomes but decreased in rat hippocampus after surgery,exhibiting a negative correlation(P<0.001,r=-0.762).A negative correlation between miR-214-3p and PTGS2 protein expression was also observed in the hippocampus after surgery.Importantly,rno-miR-214-3p agomir treatment,before or after surgery,significantly increased the platform crossing numbers(P=0.035)and target quadrant stay time(P=0.029)compared with negative control.Hippocampal PTGS2 protein level was increased in the untreated surgery group and decreased in response to rno-miR-214-3p agomir treatment before or after surgery(both P<0.05 vs.negative control).Conclusion:These data suggest that miR-214-3p/PTGS2 signaling contributes to the development of PND,serving as a potential therapeutic target for PND.

Antiretroviral therapy improves neurocognitive impairment in people living with HIV? A meta-analysis

Objectives:Although effective antiretroviral therapy(ART)has been used for more than two decades,HIV-associated neurocognitive disorder remains prevalent.Thus,whether ART can improve neurocognitive impairment is controversial.This review aims to explore the effects of ART on cognitive impairment in people living with HIV(PLWH).Methods:A systematic literature search was conducted in eight databases(PubMed,Embase,Web of Science,Cochrane Library,CNKI,VIP,China Biology Medicine disc,and WanFang)to identify studies that compare cognitive function between study groups who are administered and not administered ART.We searched for articles published up to April 2019.Article evaluation and data extraction were independently conducted by two reviewers.Results:Sixteen articles(6,694 participants)-14 cross-sectional studies and 2 cohort studies—were included in this meta-analysis.The cross-sectional studies demonstrated that ART group did not perform better than the non-ART group(OR=1.16;95%CI,1.03-1.30).However,the cohort studies reported a significant improvement in cognitive function at three months(OR=4.01;95%CI,2.35-6.85)and six months(OR=9.24;95%CI,1.71-49.96)after ART initiation compared with the baseline data.No significant cognitive improvement was found in participants younger than 55 years old,but the two crosssectional studies showed that ART may improve cognitive function in PLWH under 65 years old with poor physical condition and immune status.Conclusions:ART could improve cognitive function in PLWH with poor physical condition and immune status,but it does not considerably improve cognition in the entire PLWH population.

Alterations in blink and masseter reflex latencies in older adults with neurocognitive disorder and/or diabetes mellitus

BACKGROUND Blink and masseter reflexes provide reliable,quantifiable data on the function of the central nervous system:Delayed latencies have been found in patients with neurocognitive disorder(ND)and type 2 diabetes mellitus(T2DM),but this has not been studied in patients with both pathologies.AIM To investigate if older adults with ND plus T2DM have prolonged latencies of blink and masseter-reflex and if they were associated with disease progression.METHODS This cross-sectional study included 227 older adults(>60 years)from Colima,Mexico.Neurocognitive disorder was identified by a neuropsychological battery test,and T2DM identified by medical history,fasting glucose,and glycosylated hemoglobin.Latencies in the early reflex(R1),ipsilateral late(R2),and contralateral late(R2c)components of the blink reflex were analyzed for all subjects,and 183 subjects were analyzed for latency of the masseter reflex.RESULTS In 20.7%of participants,ND was detected.In 37%,T2DM was detected.Latencies in R1,R2,and R2c were significantly prolonged for groups with ND plus T2DM,ND,and T2DM,compared with the control group(P<0.0001).The masseter reflex was only prolonged in older adults(regardless of T2DM status)with ND vs controls(P=0.030).In older adults with ND and without T2DM,the more the cognitive impairment progressed,the more prolonged latencies in R2 and R2c presented(P<0.01).CONCLUSION These findings suggest that blink and masseter reflexes could be used to evaluate possible changes in brainstem circuits in older adults with ND and T2DM.

The value of neurocognitive testing for acute outcomes after mild traumatic brain injury

Background: Traditionally, neurocognitive testing is performed weeks to months after head injury and is mostly performed on patients who continue to have symptoms or difficulties. In this study, we sought to determine whether these tests, when administered acutely, could assist in predicting short-term outcomes after acute traumatic brain injury(TBI).Methods: This is an IRB-approved prospective study of adult patients who came to the emergency department of our Level-1 trauma center with TBI. Patients were enrolled prospectively after providing written informed consent and underwent three separate neurocognitive tests: the Galveston Orientation Amnesia Test(GOAT), the Rivermead PostConcussion Survey Questionnaire(RPCSQ), and the Mini Mental Status Examination(MMSE).Results: A lower GOAT score was significantly associated with hospitalization(P=0.0212) and the development of post-concussion syndrome(PCS) at late follow-up(P=0.0081). A higher RPCSQ score was significantly associated with hospital admission(P=0.0098), re-admission within 30 days of discharge(P=0.0431) and evidence of PCS at early follow-up(P=0.0004). A higher MMSE score was significantly associated with not being admitted to the hospital(P=0.0002) and not returning to the emergency department(ED) within 72 hours of discharge(P=0.0078). Lower MMSE was also significantly associated with bleeding or a fracture on the brain CT(P=0.0431).Conclusions: While neurocognitive testing is not commonly performed in the ED in the setting of acute head injury, it is both feasible and appears to have value in predicting hospital admission and PCS. These data are especially important in terms of helping patients understand what to expect, thus, aiding in their recovery.

Growth and Development of the HIV Exposed Uninfected Children below 5 Years in Developing Countries: Focus on Nutritional Challenges, Mortality and Neurocognitive Function

The future of any population is children. Resource limited settings with a high prevalence of HIV infection notably also have an excessive burden of malnutrition. The advances in prevention of mother to child HIV transmission programmes have led to very effective combination antiretroviral regimens resulting in growing numbers of HIV exposed but uninfected children. The mortality of HIV exposed but uninfected children below 5 years is high in resource limited settings. It is also important to pay particular attention to their longitudinal growth and neurodevelopmental outcomes. In these settings, the contribution of feeding practices, choice of complementary foods and micronutrient deficiencies, to health outcomes of HIV exposed uninfected children are not clearly defined. This review highlights some gaps in research that need to be addressed in areas with increasing numbers of HIV exposed but uninfected children. Interventions to reduce mortality, improve growth and neurodevelopmental outcomes in HIV exposed uninfected children from resource limited areas should be prioritized.

Development and validation of a screening instrument for cognitive fluctuation in patientswith neurocognitive disorder with Lewy bodies(NCDLB):the Mayo Fluctuations Scale-Thai version

Background Prevalence of neurocognitive disorder with Lewy bodies(NCDLB) is low in Asian populations, which may partially reflect its diagnostic difficulty. The Mayo Fluctuations Scale, a short questionnaire that evaluates cognitive fluctuation, has been shown to significantly differentiate NCDLB from Alzheimer's disease.Aim This study aimed to develop the Mayo Fluctuations Scale-Thai version and assess its validity to screen NCDLB in an elderly population.Methods The Mayo Ructuations Scale was translated into Thai. The process involved back-translation, cross-cultural adaptation, field testing of the prefinal version, as well as final adjustments. From all patients attending the Psychiatric and Memory Clinic at Ramathibodi Hospital, 135 patients accompanied by their primary caregivers were included.Caregivers were interviewed by research assistants using a four-item scale, and psychiatrists determined patients*diagnosis based on the diagnostic and statistical manual of mental disorders(DSM)-5 criteria. Evaluations performed by psychiatrists and research assistants were blinded.Results Seventeen participants had been diagnosed with major NCDLB. At a cut-off score of 2 or over, the Mayo Fluctuations Scale exhibited excellent performance to differentiate major NCDLB from other major neurocognitive disorders(NCDs), with a sensitivity of 94.1%and a specificity of 71.4%, and acceptable performance to differentiate mild NCDLB from other mild NCDs, with a sensitivity of 60% and a specificity of 93.1 %.Conclusion The Mayo Fluctuations Scale-Thai version is an excellent screening tool for major NCDLB and an acceptable tool that may be used with other additional tests for mild NCDLB. The tool is practical for use in memory and psychiatric clinics. Further validation studies in participants with other specific clinical conditions are required.

Determinants of Neurocognitive Impairment in HIV in a Cohort of Patients on Antiretroviral Therapy Followed in Bangui (Central African Republic)

Infection with HIV is one of the deadliest epidemics of our time and its type is widespread in the Central African Republic. It is frequently accompanied by neurological complications. Objective: To contribute to a better understanding of neurocognitive disorders in patients living with HIV (PLHIV) in Bangui, and to identify associated factors using the International HIV Dementia Scale (IHDS) as a screening tool. We conducted a descriptive and analytical cross-sectional study from 1 December 2014 to 30 January 2015, in a cohort of patients seen on one of the supported sites in Bangui. A total of 400 patients were received in follow-up visit during the study period of which 244 met the inclusion criteria. The prevalence of neurocognitive disorders was 25%, 95% CI [19.70 - 30.92]. The mean age of subjects was 42.77 ± 9.58 with extremes ranging from 24 - 64 years. The sex ratio (F/M) was 4.5 in. The average score for different tests was 10.93 ± 1.13 with extremes of 7 and 12. The disorder was more about the gestural sequence. Determinants of neurocognitive disorders in the cohort were older age and lower educational level (p < 0.05). It is useful to conduct further studies to confirm these results by combining a battery of neuropsychological tests to recommend this test for all the support sites of PLHIV in the country.

Neurocognitive and mental health outcomes in children with tungiasis:a cross-sectional study in rural Kenya and Uganda

Background Tungiasis,a neglected tropical parasitosis,disproportionately afects children.Few empirical studies have reported neurocognitive and mental health outcomes of children with ectoparasitic skin diseases like tungiasis.Pathophysiology of tungiasis suggests it could detrimentally afect cognition and behaviour.This study pioneered the investigation of neurocognitive and mental health outcomes in children with tungiasis.Methods This was a multi-site cross-sectional study including 454 quasi-randomly sampled school-children aged 8-14 from 48 randomly selected schools in two counties in Kenya and a district in Uganda.The participants were stratifed into infected and uninfected based on the presence of tungiasis.The infected were further classifed into mild and severe infection groups based on the intensity of the infection.Adapted,validated,and standardized measures of cognition and mental health such as Raven Matrices and Child Behaviour Checklist were used to collect data.Statistical tests including a multilevel,generalized mixed-efects linear models with family link set to identity were used to compare the scores of uninfected and infected children and to identify other potential risk factors for neurocognitive and behavioural outcomes.Results When adjusted for covariates,mild infection was associated with lower scores in literacy[adjustedβ(aβ)=−8.9;95%confdence interval(CI)−17.2,−0.6],language(aβ=−1.7;95%CI−3.2,−0.3),cognitive fexibility(aβ=−6.1;95%CI−10.4,−1.7)and working memory(aβ=−0.3;95%CI−0.6,−0.1).Severe infection was associated with lower scores in literacy(aβ=−11.0;95%CI−19.3,−2.8),response inhibition,(aβ=−2.2;95%CI−4.2,−0.2),fne motor control(aβ=−0.7;95%CI−1.1,−0.4)and numeracy(aβ=−3;95%CI−5.5,−0.4).Conclusions This study provides frst evidence that tungiasis is associated with poor neurocognitive functioning in children.Since tungiasis is a chronic disease with frequent reinfections,such negative efects may potentially impair their development and life achievements.

General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells.Oligodendrocytes perform essential roles in the central nervous system,including myelin sheath formation,axonal metabolism,and neuroplasticity regulation.They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation,differentiation,and apoptosis.Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes.These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways,but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function.In this review,we summarize the effects of general anesthetic agents on oligodendrocytes.We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

Exploring the Association between Oral Microbiome and Mild Cognitive Impairment: A Narrative Review

Objective: Some studies have investigated the association between oral microbiome and mild cognitive impairment (MCI). However, there needs to be more narrative reviews synthesizing this evidence. This study aimed to bridge this gap in the current knowledge. Methods: A comprehensive search was conducted on PubMed (MEDLINE) to identify studies examining the association between the oral microbiome and MCI. Search parameters and inclusion criteria were clearly defined, encompassing terms related to the oral microbiome, MCI, and their association. Two authors independently selected relevant studies and performed data extraction. Result: Four studies were included. Two cohort studies and two case-control reported an association between the oral microbiome and MCI. Conclusion: Based on the evidence synthesized from the included studies, the review suggests an association between MCI and the oral microbiome. Specifically, all included studies identified significant differences in the abundance of specific microbial species between individuals with MCI and those with normal cognitive function, underscoring the potential role of these species in neuroinflammatory diseases.

Neurocognitive Graphs of First-Episode Schizophrenia and Major Depression Based on Cognitive Features

Neurocognitive deficits are frequently observed in patients with schizophrenia and major depressive disorder(MDD). The relations between cognitive features may be represented by neurocognitive graphs based on cognitive features, modeled as Gaussian Markov random fields. However, it is unclear whether it is possible to differentiate between phenotypic patterns associated with the differential diagnosis of schizophrenia and depression using this neurocognitive graph approach. In this study, we enrolled 215 first-episode patients with schizophrenia(FES), 125 with MDD, and 237 demographically-matched healthy controls(HCs). The cognitive performance of all participants was evaluated using a battery of neurocognitive tests. The graphical LASSO model was trained with aone-vs-one scenario to learn the conditional independent structure of neurocognitive features of each group. Participants in the holdout dataset were classified into different groups with the highest likelihood. A partial correlation matrix was transformed from the graphical model to further explore the neurocognitive graph for each group. The classification approach identified the diagnostic class for individuals with an average accuracy of 73.41% for FES vs HC, 67.07% for MDD vs HC, and 59.48% for FES vs MDD. Both of the neurocognitive graphs for FES and MDD had more connections and higher node centrality than those for HC. The neurocognitive graph for FES was less sparse and had more connections than that for MDD.Thus, neurocognitive graphs based on cognitive features are promising for describing endophenotypes that may discriminate schizophrenia from depression.

Impact of edaravone on serum CXC chemokine ligand-13 levels and perioperative neurocognitive disorders in elderly patients with hip replacement

Background:Perioperative neurocognitive disorders(PND)are a series of severe complications in the perioperative and anesthetic periods with a decline in memory,execution ability,and information processing speed as the primary clinical manifestation.This study aimed to evaluate the impact of edaravone(EDA)on PND and peripheral blood C-X-C motif chemokine ligand 13(CXCL13)levels in elderly patients with hip replacement.Methods:A total of 160 elderly patients undergoing hip arthroplasty in Affiliated Dongguan People’s Hospital of Southern Medical University(from March 2016 to March 2018)were randomly and double-blindly categorized into an EDA group and a control group(CON).Group EDA was administered intravenously EDA 30 min before surgery,and group CON was administered intravenously saline.The cognitive function of the two groups was evaluated 1-day before the operation and at 1 and 12 months after surgery,and the incidence of post-operative delirium was tested on days 1,3,and 7 after surgery using the Chinese version of the confusion assessment method.Serum CXCL13 and interleukin(IL)-6 concentrations were measured before anesthesia,during surgery(30 min after skin incision),and on days 1,3,and 7 after surgery.The continuous variables in accordance with normal distribution were tested using the Student’s t test,the continuous variables without normal distribution using the Mann-Whitney U test,and categorical variables by the x 2 test or Fisher exact test.Results:The incidence of post-operative delirium within 7 days after surgery was significantly higher in group CON than that in group EDA(31.3%vs.15.0%,t=-5.6,P<0.001).The modifiedtelephone interview for cognitive status andactivities of daily life scores were significantly higher in the group EDA than those in the group CON at 1 month(39.63±4.35 vs.33.63±5.81,t=-2.13,P<0.05and 74.3±12.6 vs.61.2±13.1,t=-1.69,P<0.05)and 12 months(40.13±5.93 vs.34.13±5.36,t=-3.37,P<0.05 and 79.6±11.7 vs.65.6±16.6,t=-2.08,P<0.05)after surgery;and the incidence of neurocognitive dysfunction was significantly lower in the group EDA than that in the group CON(P<0.05).Serum CXCL13 and IL-6 concentrations were significantly lower in the group EDA than those in the group CON during and after surgery(P<0.05).Conclusion:EDA can significantly reduce the serum concentrations of CXCL13 and IL-6 and improve the PND of patients.

Memory and behavior-related problems of patients with neurocognitive disorders and the attitudes of their caregivers

Objective:The purpose of this study was to investigate the memory and behavior-related problems of patients with neurocognitive disorders and the attitudes of their caregivers so as to provide an effective basis for nursing interventions against such problems.Methods:The subjects were selected from patients who were under treatment or short-term hospitalization between April 2011 and March 2012.One hundred fifty-three patients with neurocognitive disorders and their major caregivers were selected from 9 grade 3 Class A hospitals of Hunan Province.The Revised Memory and Behavior Problems Checklist(RMBPC)was used to measure the memory and behavior-related problems of patients with neurocognitive disorders and the influence on their caregivers.The occurrence of different memory and behavior-related prob-lems and the distress on their caregivers was compared.Results:The RMBPC investigation showed that among 153 patients and their caregivers,152(99.3%)had memory-related problems,137(89.5%)had depression,and 136 patients(88.9%)had destructive behaviors.The incidence of memory-related problems was higher than depression and destructive behaviors(P<0.01).Caregivers bore more distress when encountering destructive behaviors(1.95±1.13 points)than memory-related problems and depression(0.91±0.76 points and 0.89±0.85 points;P<0.01).Curve fitting was used to analyze the relationship between the number of memory and behavior-related problems and the distress on their caregivers.A curve correlation existed between the two factors(the recorded maximum value of the Cubic equation curve was 0.278,F=229.212,P<0.05).Conclusion:Among patients with neurocognitive disorders,memory-related problems had the highest incidence,while the caregivers bore the strongest distress when encountering destructive behaviors,thus interventions should be conducted in consideration of patient memory and behavior-related problems,and caregivers’attitude to further reduce caregiver burden.

Effects of biscuit-type feeding supplementation on the neurocognitive outcomes of HIV-affected school-age children:a randomized,double-blind,controlled intervention trial in Kenya

Objective:To determine if meat or soy protein dietary supplementation will enhance the neuro-cognitive performance of HIV-affected children at-risk of malnutrition and food insecurity.Methods:A randomized,double-blind,controlled intervention trial evaluated the effect of nu-tritional supplementation on the neurocognitive outcomes of 49 HIV-affected school-age children in western Kenya.The intervention consisted in providing the mother,target child,and siblings with one of three isocaloric biscuit-type supplements-soy,wheat,or beef-on 5 days per week for 18 months.Neurocognitive outcomes of the target children were assessed by a battery of eight measures and followed up longitudinally for up to 24 months.Results:Mixed effects modeling demonstrated significant differences in the rates of increase over time among all three groups(F test degrees of freedom of 2,P<0.05)for Raven’s progressive matrices performance,but not for verbal meaning,arithmetic,digit span backward,forward,and total,embedded figure test,and Beery visual-motor integration scores.Conclusion:HIV-affected school-age children provided with soy protein supplementation showed greater improvement in nonverbal cognitive(fluid intelligence)performance compared with peers who received isocaloric beef or wheat biscuits.Soy nutrients may have an enhancing effect on neurocognitive skills in HIV-affected school-age children.

Protective effects of curcumin against human immunodeficiency virus 1 gp120 V3 loop-induced neuronal injury in rats

Curcumin improves the learning and memory deficits in rats induced by the gp120 V3 loop. The present study cultured rat hippocampal neurons with 1 nM gp120 V3 loop and 1 μM curcumin for 24 hours. The results showed that curcumin inhibited the gp120 V3 loop-induced mitochondrial membrane potential decrease, reduced the mRNA expression of the pro-apoptotic gene caspase-3, and attenuated hippocampal neuronal injury.

Curcumin ameliorates hippocampal neuron damage induced by human immunodeficiency virus-1

Our previous studies have shown that infection with the gp120 V3 loop can cause human immunodeficiency virus-1 associated neurocognitive disorders. Curcumin has been shown to improve these effects to some degree, but the precise mechanisms remain unknown. The present study analyzed the neuroprotective effect and mechanism of curcumin in relation to hippocampal neurons. Results showed that 1 nmol/L gp120 V3 loop suppressed the growth of synapses. After administration of 1 !umol/L curcumin, synaptic growth improved. Curcumin is neuroprotective against gp120 V3 loop-induced neuronal damage by inhibiting the activation of L-type calcium currents, relieving intracellular Ca^2＋ overload, promoting Bcl-2 expression, and inhibiting Bax activation. The effect of curcumin was identical to nimodipine, suggesting that curcumin has the same neuroprotective effects against gp120 V3 loop-induced neuronal damage.

Fingolimod(FTY720) improves postoperative cognitive dysfunction in mice subjected to D-galactose-induced aging

Neurocognitive dysfunction is a common postoperative complication,especially in older adult patients.Fingolimod(FTY720)is a sphingosine-1-phosphate receptor modulator that has been found to be neuroprotective in several animal models of central nervous system disease.However,few reports have examined whether FTY720 could mitigate postoperative cognitive dysfunction.In this study,we investigated whether FTY720 could prevent postoperative neurocognitive impairment in mice subjected to D-galactose-induced aging.We induced an accelerated model of aging by administering an intraperitoneal injection of D-galactose.Subsequently,we performed a partial hepatolobectomy under sevoflurane anesthesia.FTY720(1 mg/kg)was administered intraperitoneally 3 hours before and 24 hours after anesthesia and surgery.Our results indicated that anesthesia and surgery significantly impaired spatial memory in the Y-maze test 6 hours after surgery.We also found that problem solving ability and long-term memory in the puzzle box test on postoperative days 2–4 were significantly improved by FTY720 treatment.Immunohistochemical staining and western blot assay demonstrated that FTY720 significantly inhibited microglial activation in the hippocampal CA1 region of mice 6 hours and 3 days after anesthesia,and down-regulated the expression of synaptic-related proteins postsynaptic density protein 95 and GluR2 in the hippocampus.These results indicate that FTY720 improved postoperative neurocognitive dysfunction in mice subjected to D-galactose-induced aging.This study was approved by the Experimental Animal Ethics Committee of the Third Xiangya Hospital of Central South University of China(approval No.LLSC(LA)2016-025)on September 27,2016.