Vascular Cognitive Impairment with Kidney Yang Deficiency Syndrome and DNA Methylation Essence / 中国实验方剂学杂志

ObjectiveTo investigate the distribution of vascular cognitive impairment （VCI） with kidney Yang deficiency syndrome and explore the biological nature of VCI with kidney Yang deficiency syndrome from the perspective of DNA methylation under the combination of disease and syndrome， so as to provide an epigenetic target for traditional Chinese medicine （TCM） treatment of this disease with this syndrome in the future. MethodCommunity residents in Beijing were screened out for cognitive impairment from September 2020 to November 2022 through the scale， and VCI patients were analyzed for the syndrome. VCI patients with kidney Yang deficiency syndrome and healthy people were enrolled in this study. Peripheral venous blood was collected and subjected to genome-wide DNA methylation detection by Illumina Human Methylation 850K BeadChip. Then， differentially methylated genes （DMGs） were screened out for bioinformatics analysis. ResultA total of 1 902 people were investigated in this study， and 201 of them had VCI， accounting for 10.57%， including 72.14% with kidney Yang deficiency syndrome. The methylation results showed that compared with the normal group， the VCI group had 386 differential methylation sites， and 136 DMGs were annotated. The Kyoto Encyclopedia of Gene and Genomes（KEGG） signaling pathway enrichment analysis showed that the DMGs between the two groups were mainly involved in mammalian target of rapamycin（mTOR） signaling pathway， Estrogen signaling pathway， cyclic adenosine monophosphate（cAMP） signaling pathway， etc. Protein-protein interaction （PPI） analysis showed that DMGs， such as epidermal growth factor receptor（EGFR）， epidermal growth factor （EGF）， and signal transducer and activator of transcription 3（STAT3）， played important roles in the network. ConclusionKidney Yang deficiency is the main syndrome in VCI patients. DMGs including EGFR， EGF， and STAT3 and the related pathways such as mTOR signaling pathway， Estrogen signaling pathway， and cAMP signaling pathway may play a vital role in the occurrence and development of VCI with kidney Yang deficiency syndrome.

Effects of electroacupuncture on rats with cognitive impairment: An iTRAQ-based proteomics analysis / 中西医结合学报

OBJECTIVE@#The study explores the effects of electroacupuncture (EA) at the governing vessel (GV) on proteomic changes in the hippocampus of rats with cognitive impairment.@*METHODS@#Healthy male rats were randomly divided into 3 groups: sham, model and EA. Cognitive impairment was induced by left middle cerebral artery occlusion in the model and EA groups. Rats in the EA group were treated with EA at Shenting (GV24) and Baihui (GV20) for 7 d. Neurological deficit was scored using the Longa scale, the learning and memory ability was detected using the Morris water maze (MWM) test, and the proteomic profiling in the hippocampus was analyzed using protein-labeling technology based on the isobaric tag for relative and absolute quantitation (iTRAQ). The Western blot (WB) analysis was used to detect the proteins and validate the results of iTRAQ.@*RESULTS@#Compared with the model group, the neurological deficit score was significantly reduced, and the escape latency in the MWM test was significantly shortened, while the number of platform crossings increased in the EA group. A total of 2872 proteins were identified by iTRAQ. Differentially expressed proteins (DEPs) were identified between different groups: 92 proteins were upregulated and 103 were downregulated in the model group compared with the sham group, while 142 proteins were upregulated and 126 were downregulated in the EA group compared with the model group. Most of the DEPs were involved in oxidative phosphorylation, glycolipid metabolism and synaptic transmission. Furthermore, we also verified 4 DEPs using WB technology. Although the WB results were not exactly the same as the iTRAQ results, the expression trends of the DEPs were consistent. The upregulation of heat-shock protein β1 (Hspb1) was the highest in the EA group compared to the model group.@*CONCLUSION@#EA can effect proteomic changes in the hippocampus of rats with cognitive impairment. Hspb1 may be involved in the molecular mechanism by which acupuncture improves cognitive impairment.

Effect of electroacupuncture on regional homogeneity of brain function in rats with vascular cognitive impairment / 中国康复理论与实践

@#Objective To observe the effect of electroacupuncture at Baihui (DU20) and Shenting (DU24) on brain functional activity and working memory of rats with vascular cognitive impairment (VCI). Methods Eighteen Sprague-Dawley rats were included, in which twelve rats were ligated bilateral common carotid arteries and six rats were not ligated (sham group). The modeled rats were randomly divided into model group (n = 6) and electroacupuncture group (n = 6). The electroacupuncture group received electroacupuncture at Baihui and Shenting for four weeks. They were assessed with Y maze and Morris water maze before and after intervention, and scaned with resting-state functional magnetic resonance imaging after intervention to calculate regional homogeneity (ReHo). Results Compared with the sham group, alternation rate of Y maze decreased (P < 0.001), and escape latency of Morris water maze increased (P < 0.05) in the model group and the electroacupuncture group before intervention. Compared with the model group, alternation rate of Y maze increased (P < 0.05), and escape latency of Morris water maze decreased (P < 0.05) after intervention in the electroacupuncture group. Compared with the sham group, ReHo of bilateral hippocampus, olfactory cortex, sensory cortex and auditory cortex, and left striatum decreased in the model group; compared with the model group, ReHo of bilateral prefrontal lobe, hippocampus and olfactory cortex, and left amygdala increased in the electroacupuncture group. Conclusion Electroacupuncture at Baihui and Shenting can improve the memory function of VCI rats, which may be related to the functional activities of prefrontal lobes, hippocampus and amygdala.

Outcomes in randomized controlled trials of acupuncture for vascular cognitive impairment during recent five years / 中国针灸

The existing problems in the outcomes of randomized controlled trials (RCTs) of acupuncture for vascular cognitive impairment (VCI) during recent five years are analyzed and suggestions are proposed. The RCTs of acupuncture for VCI were selected in PubMed, EMbase, Cochrane Library, Clinical Trials, CNKI database, Wanfang database, VIP database, SinoMed database and Chinese Clinical Trial Registry (ChiCTR) from January 1, 2015 to September 14, 2020. The outcomes were extracted and analyzed. As a result, 21 RCTs were included and the outcomes used were divided into 9 categories: clinical symptom/sign indexes, quality of life indexes, neuroimaging indexes, neuroelectrophysiology indexes, blood biochemical indexes, hemorheology indexes, TCM syndrome score indexes, clinical efficacy indexes, and safety indexes. Among them, the top three of the most used outcomes were clinical symptoms/signs indexes (21, 100.0%), clinical efficacy indexes (14, 66.7%) and quality of life indexes (12, 57.1%). In the RCTs of acupuncture for VCI, attention should be paid to distinguish the primary outcomes and secondary outcomes, adopt objective and standardized efficacy evaluation, and give consideration to report the outcomes of safety, health economic and TCM characteristic indexes.

Hyperbaric oxygen therapy can augment the effectiveness of cognition training for persons with vascular cognitive impairment / 中华物理医学与康复杂志

Objective:To explore the effect of combining hyperbaric oxygen (HBO) therapy with cognition training for persons with vascular cognitive impairment (VCI).Methods:Forty-two persons with VCI were randomly divided into a control group of 19 and a research group of 23. In addition to basic treatment, the control group was given hyperbaric oxygen therapy once a day, 5 days per week for 4 weeks, while the research group received cognition training along with the hyperbaric oxygen therapy. Each person′s cognition was assessed using the Simple Mental Status Scale (MMSE) before and after the four-week treatment. Meanwhile, 3ml of venous blood was collected before eating in the morning to test the plasma levels of Klotho protein and homocysteine using enzyme-linked immunosorbent assays.Results:After the treatment the average MMSE score had improved significantly in both group, with the improvement in the research group′s average significantly greater than that in the control group. The average plasma levels of Klotho protein and homocysteine had also improved significantly more in the research group. In the control group, the only significant improvement was in the average homocysteine level.Conclusions:Hyperbaric oxygen therapy can be an effective supplement to cognition training for persons with vascular cognitive impairment.

Overview of systematic reviews of acupuncture for vascular cognitive impairment / 中国针灸

OBJECTIVE@#To overview the methodological quality, report quality and evidence quality of the systematic review (SR) of acupuncture for vascular cognitive impairment ( VCI ).@*METHODS@#The SRs regarding acupuncture for VCI were searched in PubMed, Cochrane Library, EMbase, CNKI, SinoMed, Wanfang and VIP databases. The retrieval period was from the establishment of the database to September 24, 2020. The report quality, methodological quality and evidence quality of the included SRs were evaluated by PRISMA statement, the AMSTAR 2 tool and the GRADE system.@*RESULTS@#A total of 22 SRs were included, including 102 outcome indexes. The methodological quality was generally low, with low scores on items 2, 5, 7, 10, 14, 15 and 16. The report quality was good, with scores ranging from 19 points to 24.5 points. The problems of report quality were mainly reflected in the aspects of structural abstract, program and registration, other analysis and funding sources. The level of outcome indexes of SRs was mostly low or very low, and the main leading factor was limitation, followed by inconsistency and inaccuracy.@*CONCLUSION@#Acupuncture for VCI is supported by low quality evidence of evidence-based medicine, but the methodological quality and evidence body quality of relevant SRs are poor, and the standardization is needed to be improved.

Regulation of Naoxin'an Capsule on Glial Cell Activation and Inflammatory Response in Rats with Chronic Cerebral Hypoperfusion-induced Vascular Cognitive Impairment / 中国实验方剂学杂志

Objective:To investigate the protective effect of Naoxin'an capsule （NC） against glial cell activation and inflammatory damage in brain of rats with chronic cerebral hypoperfusion-induced vascular cognitive impairment （VCI）. Method:One hundred and fifty rats were randomly divided into a sham operation group （<italic>n</italic>=20） and a modeling group （<italic>n</italic>=130）. Following the modeling with the two vessels occlusion （2-VO） technique， 87 successfully modeled rats were randomly divided into the model group， positive drug group （aricept， 0.5 mg·kg^-1）， and low-， medium-， and high-dose （0.18， 0.36， 0.72 g·kg^-1） NC groups， with 17-18 rats in each group. After intragastric administration of NC for eight weeks， the Morris water maze test and passive avoidance test were conducted to detect the effects of NC on learning and memory ability of VCI rats. Changes in neuronal structure of rat hippocampal CA1 area were observed by hematoxylin-eosin （HE） staining， and the neuronal apoptosis in hippocampus by terminal deoxynucleotidyl transferase （TdT）-mediated dUTP nick end labeling （TUNEL） staining. Western blot assay was used to detect the expression levels of glial fibrillary acidic protein （GFAP）， ionized calcium-binding adapter molecule 1 （Iba-1）， phosphorylated p38 mitogen-activated protein kinase （p38 MAPK）， and phosphorylated nuclear factor <italic>κ</italic>B （NF-<italic>κ</italic>B）， followed by the measurement of interleukin-1<italic>β</italic> （IL-1<italic>β</italic>） and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） in the brain by enzyme-linked immunosorbent assay （ELISA）. Result:Compared with the sham operation group， the model group displayed obviously decreased spatial learning and memory ability and memory retention ability （<italic>P</italic><0.05， <italic>P</italic><0.01）， neuronal damage in hippocampal CA1 area， enhanced neuronal apoptosis （<italic>P</italic><0.01）， up-regulated GFAP and Iba-1 （<italic>P</italic><0.01）， elevated phosphorylation of p38 MAPK and NF-<italic>κ</italic>B （<italic>P</italic><0.01）， and increased IL-1<italic>β</italic> and TNF-<italic>α</italic> （<italic>P</italic><0.01）. Compared with the model group， NC at each dose significantly improved the spatial learning and memory ability and memory retention ability of VCI rats （<italic>P</italic><0.05， <italic>P</italic><0.01）， ameliorated the neuronal damage in hippocampus CA1 area， reduced the apoptosis rate of nerve cells （<italic>P</italic><0.05， <italic>P</italic><0.01）， down-regulated the expression of GFAP and Iba-1 （<italic>P</italic><0.01）， decreased the phosphorylation levels of p38 MAPK and NF-<italic>κ</italic>B （<italic>P</italic><0.05， <italic>P</italic><0.01）， and lowered TNF-<italic>α</italic> and IL-1<italic>β</italic> levels （<italic>P</italic><0.01）. Conclusion:NC alleviates the inflammatory damage of the central nervous system caused by activated p38 MAPK and NF-<italic>κ</italic>B and improves chronic cerebral hypoperfusion-induced VCI in rats by inhibiting the activation of microglia and astrocytes.

Machine Learning Models for Early Prediction of Vascular Cognitive Impairment / 中国康复理论与实践

Objective:To explore the predictive performance of machine learning model based on vascular risk factors in early prediction of vascular cognitive impairment. Methods:From April to September, 2020, 70 subjects were enrolled and collected information of the demographics and vascular risk factors. They were assessed with Montreal Cognitive Assessment (MoCA), and then divided into normal group, vascular mild cognitive impairment (VaMCI) group and dementia group. The differences of vascular risk factors among the three groups were detected with one-way ANOVA, and the significant factors were selected to establish predictive models with support vector machine (SVM) and extreme learning machine (ELM). The predictive performance of two models was compared with Receiver Operating Characteristic Curve. Results:There were 32 cases in the normal group, 23 in VaMCI group and 15 in dementia group. Systolic blood pressure, fasting blood glucose, total cholesterol, low density lipoprotein and blood uric acid were significantly different among the three groups (F > 3.318, P < 0.05). The area under curve was the most (0.911) in SVM model predicting for VaMCI (P < 0.01), and the predictive efficacy was better for SVM model. Conclusion:SVM predictive model based on vascular risk factors may be more effective for predicting VaMCI.

Knockdown of lncRNA TUG1 inhibits hippocampal neuronal apoptosis and participates in aerobic exercise-alleviated vascular cognitive impairment

OBJECTIVES: Our previous study indicated that aerobic exercise relieves cognitive impairment in patients with vascular cognitive impairment (VCI) via regulating brain-derived neurotrophic factor (BDNF), but the mechanism is not yet clear. This study aimed to explore whether lncRNA taurine upregulated gene 1 (TUG1) participates in the process of VCI by regulating BDNF. METHODS: The expressions of TUG1 and BDNF in the serum of VCI patients were detected. The potential molecular mechanisms of TUG1 in regulating hippocampal neuronal apoptosis were explored in oxygen and glucose deprivation-induced (OGD-induced) hippocampal cell line HT22. The VCI mouse model was established, and TUG1 and BDNF were overexpressed via lentivirus injection. The cognitive impairment of mice was detected by the Morris water maze experiment after the aerobic exercise. RESULTS: The level of TUG1 was elevated in the serum of VCI patients compared with the control group. The knockdown of TUG1 in OGD-induced HT22 cells increased BDNF level and decreased cell apoptosis, and the downregulation of BDNF restored the decreased cell apoptosis. RNA immunoprecipitation and RNA pull-down assays showed that TUG1 could bind to BDNF protein. The aerobic exercise alleviated cognitive impairment and inhibited hippocampal apoptosis in VCI mice. Meanwhile, the overexpression of TUG1 reversed the therapeutic effects of aerobic exercise on cognitive impairment. CONCLUSIONS: The knockdown of TUG1 reduced hippocampal neuronal apoptosis and participates in the aerobic exercise-alleviated VCI, which was partly through regulating BDNF.

Oral simvastatin for 3 continuous months improves learning and memory ability of chronic cerebral hypoperfusion rats / 中国组织工程研究

BACKGROUND: Chronic cerebral hypoperfusion is significantly associated with cognitive decline. Our previous studies have found that mitochondrial aging, increased silent synapses and α-synuclein are important pathological changes of chronic cerebral hypoperfusion. Simvastatin is a traditional lipid regulation agent that can traverse the blood brain barrier, and exerts anti-atherosclerosis, anti-thrombosis and anti-inflammatory effects to improve cognitive function. OBJECTIVE: To observe the effect of continuous oral simvastatin for 3 months on cognitive function of chronic cerebral hypoperfusion male Sprague-Dawley rats, and explore the clinical significance of simvastatin in preventing and treating vascular cognitive impairment and dementia. METHODS: Sprague-Dawley rats were randomly divided into model group, sham group, solvent group and simvastatin group. In the model group, rats were subjected to bilateral common carotid artery occlusion. In the sham group, the bilateral common carotid arteries were not ligated. In the solvent group, the model rats were intragastrically treated with 0.5% carboxymethyl cellulose sodium. In the simvastatin group, the model rats were intragastrically treated with simvastatin suspension. Interventions in each group lasted for 3 months. Behavioral tests were then used to evaluate the learning and memory ability of rats in each group. The expressions of synaptophysin and post-synaptic density 95, key proteins of presynaptic and postsynaptic membrane, were detected by western blot. Ethical approval was obtained from the Animal Experimental Ethics Committee of the General Hospital of Western Theater Command with approval No. 2019ky79. RESULTS AND CONCLUSION: Compared with the sham group, the learning and memory functions of the rats in the model group were significantly impaired. In the open-field test, the moving distance within 5 minutes was significantly reduced in the model group compared with the sham group (P < 0.05), suggesting that autonomous exploration behavior was impaired. In the place navigation test, escape latency was significantly shortened in the model group, implicating the reference memory was damaged. In the spatial probe test, the frequency of passing through the platform and the time for passing through target quadrant were reduced, indicating that the space exploration ability was reduced. In the simvastatin group, however, these indexes were all improved. Western blot results showed that the protein expression of synaptophysin and post-synaptic density 95 decreased significantly in the model group (P < 0.05), but increased in the simvastatin group as compared with the solvent group. Therefore, chronic cerebral hypoperfusion can significantly impair learning and memory function and reduce cognitive level in rats. Continuous oral simvastatin for 3 months can improve cognitive function in chronic cerebral hypoperfusion rats, which indicates that simvastatin may be used as an adjunctive drug to improve the prognosis of patients with vascular cognitive impairment and dementia.

Intervention of Shenma Yizhi Prescription on Learning and Memory in Rats with Vascular Cognitive Impairment Induced by Chronic Cerebral Ischemia / 中国实验方剂学杂志

Objective:To observe the effects of Shenma Yizhi prescription（SMYZ）on learning and memory， inflammatory factors and oxidative stress related indexes of rats with chronic cerebral ischemia inducing vascular dementia caused by bilateral common carotid artery ligation. Method:The chronic cerebral ischemia model of SPF grade SD rats was prepared by bilateral common carotid artery ligation. After successful surgery， the rats with cognitive impairment were randomly divided into 5 groups，model， donepezil（0.45 mg·kg-1）， SMYZ-low， medium and high dose（2.97，5.94，11.88 g·kg-1）， with 10 rats in each group， and 10 rats in sham operation group were established. Intragastric administration were given for 8 weeks respectively then followed Morris water maze test. The pathomorphological changes of hippocampus CA1 were observed. The serum levels of acetylcholine(Ach)and acetylcholinesterase (AChE)were detected， and the levels of inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the serum of rats were detected. The contents of glutathione (GSH)， malondialdehyde (MDA)， superoxide dismutase (SOD) and glutathione peroxidase reductase (GSH-Px) were observed. Result:Compared with sham operation group， the escape latency increased significantly in the model group， and the frequency of platform search， the frequency of crossing the original platform and the percentage of swimming time in the original platform quadrant decreased significantly （P<0.05，P<0.01）. The contents of Ach and the contents of GSH and GSH-Px were significantly decreased （P<0.05，P<0.01）. The contents of AChE， IL-1β and TNF-α and the contents of MDA were significantly increased （P<0.05，P<0.01）. Compared with model group， the escape latency of rats in the in the low， medium and high dose groups of SMYZ prescription was significantly reduced （P<0.05，P<0.01）.The frequency of looking for a platform， the frequency of crossing the original platform and the percentage of swimming time in the original platform quadrant of the rats in the low， medium and high dose groups of SMYZ prescription increased significantly （P<0.05，P<0.01）. The content of AChE in high dose group were significantly reduced（P<0.01）， and the content of Ach in high dose group were significantly increased（P<0.05）， the rat serum IL-1β， TNF-α levels and MDA content were significantly reduced（P<0.05，P<0.01）. The GSH， SOD and GSH-Px levels were significantly increased （P<0.05，P<0.01）. Conclusion:SMYZ can improve the learning and memory ability of rats with vascular cognitive disorder caused by chronic cerebral ischemia caused by ligation of bilateral common carotid artery， bilateral common carotid artery ligation， improve the pathological morphology of hippocampal tissue， inhibit inflammatory response， improve cholinergic level and oxidative stress state.

Analysis of outcomes of randomized controlled trial on compound Chinese herbal medicine formulas in treatment of vascular cognitive impairment caused by cerebral small vessel / 中国中药杂志

The purpose of the study is to analyze the outcomes of randomized controlled trial(RCT) of Chinese herbal medicine formula(CHMF) in the treatment of vascular cognitive impairment caused by cerebral small vessel disease(CSVD-VCI), and provide suggestions for future studies in this field. Three English databases, four Chinese databases, and two online registration websites of clinical trials were searched with use of the search strategy established in advance. Relevant RCTs published in recent ten years were screened, and necessary information was extracted to assess the risk of bias and analyze the outcomes of these RCTs. As a result, a total of 10 461 articles were retrieved, of which 8 681 were kept after de-duplication, and 41 RCTs were included after screening, with a generally higher risk of bias. The outcomes of included RCTs were classified into 9 categories, namely, clinical symptom outcomes, neuroimaging outcomes, neuroelectrophysiological outcomes, blood biochemical outcomes, hemorheology outcomes, physical signs, syndrome scores of traditional Chinese medicine(TCM), clinical effective rate, and safety outcomes. Among them, the most frequently reported outcomes of included RCTs were blood biochemical outcomes, and clinical symptom outcomes showed the highest reporting rate. Besides, 9 RCTs reported syndrome scores of TCM as the outcomes and illustrated corresponding evaluation criteria. The analysis showed that the application of RCT outcomes in this field had clinical rationality and limitations, and there were also some deficiencies in the trial design level, namely, no distinction between primary and secondary outcomes, insufficient blind methods, not detailed description of outcomes, disunity of evaluation tools, and despised endpoint outcomes. These limitations and deficiencies were negatively affecting the quality of RCTs of CHMF in the treatment of CSVD-VCI. Therefore, we suggest that future researchers should be well prepared in the top-level design stage, and actively construct the core outcome set of this field, so as to improve the quality of clinical trials.

Psychometric properties of cognitive screening for patients with cerebrovascular diseases: a systematic review / Propriedades psicométricas de triagens cognitivas nas doenças cerebrovasculares: uma revisão sistemática

ABSTRACT. Screening instruments are ideal for acute clinical settings because they are easy to apply, fast, inexpensive and sensitive for specific samples. However, there is a need to verify the psychometric properties of screening in stroke patients. Objective: This study investigated the psychometric properties (methodological procedures) of cognitive screening for patients with cerebrovascular diseases. Methods: A systematic review of papers published on PsycINFO, Web of Knowledge, PubMed and Science Direct (2005 to 2016) was performed. Results: A total of 55 articles remained after applying exclusion criteria. The samples ranged from 20 to 657 patients. Most articles evaluated elderly individuals with four to 13 years of education who had experienced ischemic or hemorrhagic stroke. There was a tendency to find evidence of validity for criteria and to analyze the sensitivity/specificity of the instruments. Although the studies frequently used the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) to seek evidence of validity and reliability, the use of these instruments among stroke patients has been criticized due to their psychometric properties and the neuropsychological functions evaluated. Conclusion: Although there is no gold standard screen for assessing adults post-stroke, instruments devised specifically for this population have shown promise. This review helps both researchers and clinicians to select the most appropriate screen for identifying cognitive impairment in adults post-stroke.

RESUMO. Instrumentos de triagem são ideias no contexto clínico hospitalar, uma vez que são fáceis de administrar, rápidos, tem baixo custo e são sensíveis para amostras específicas. Portanto, há a necessidade de se verificar as propriedades psicométricas de instrumentos de triagem para pacientes pós acidente vascular cerebral. Objetivo: Este estudo investigou as propriedades psicométricas (procedimentos metodológicos) de triagens cognitivas para pacientes com doenças cerebrovasculares. Métodos: Foi realizada uma revisão sistemática de artigos publicados em PsycINFO, Web of Knowledge, PubMed e Science Direct (2005 a 2016). Apenas 55 artigos permaneceram após a aplicação dos critérios de exclusão. Resultados: As amostras variaram de 20 a 657 pacientes; a maioria dos artigos avaliou indivíduos idosos, com quatro a 13 anos de educação, que sofreram AVC isquêmico e hemorrágico. Houve uma tendência para encontrar evidências de validade relacionadas ao critério e analisar a sensibilidade/especificidade dos instrumentos. Embora os estudos frequentemente apliquem o Mini Exame do Estado Mental (MMSE) e o Montreal Cognitive Assessment (MoCA) para buscar evidências de validade e de fidedignidade, o uso desses instrumentos em pacientes com AVC é criticado por razões relacionadas às suas propriedades psicométricas e funções neuropsicológicas avaliadas. Conclusão: Embora não exista uma triagem padrão-ouro para avaliação de adultos pós-AVC, os instrumentos construídos especificamente para esta população mostraram-se promissores. Este estudo de revisão contribui tanto aos pesquisadores quanto aos clínicos que desejam selecionar o rastreio mais apropriado para identificar comprometimento cognitivo em adultos pós-AVC.

Serum p75 neurotrophin receptor-extracellular domain level and its relationship with inflammatory factors in patients with chronic cerebral hypoperfusion-vascular cognitive impairment / 第二军医大学学报

Objective To investigate serum p75 neurotrophin receptor-extracellular domain (p75NTR-ECD) level in patients with chronic cerebral hypoperfusion-vascular cognitive impairment (CCH-VCI) and its relationship with tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6. Methods The clinical data of patients with CCH-VCI (n＝34) were collected from Changhai Hospital, Naval Medical University (Second Military Medical University) from Aug. to Dec. 2018. Enzyme linked immunosorbent assay was applied for detection of serum levels of p75NTR-ECD, TNF-α, IL-1β and IL-6; and the results were then compared with those of ischemic stroke participants (n＝34) and healthy controls (n＝36), who were all in the same age range. Spearman correlation analysis was used to analyze the relationship between serum p75NTR-ECD level and the above-mentioned inflammatory factors in CCH-VCI patients. Results The serum p75NTR-ECD level in the CCH-VCI group was significantly higher than those in the healthy control group and the ischemic stroke group (544.36 [440.88, 628.50] pg/mL vs 276.49 [262.59, 313.87] pg/mL and 366.87 [337.09, 450.43] pg/mL, U＝87.500 and 335.500, both P0.05). The serum levels of TNF-α, IL-1β and IL-6 were 196.02 (141.20, 280.35) pg/mL, 68.23 (60.79, 91.94) pg/mL and 51.04 (40.24, 65.26) pg/mL in the CCH-VCI group, respectively, and 218.67 (143.76, 281.28) pg/mL, 76.87 (59.10, 99.91) pg/mL and 64.45 (43.13, 86.76) pg/mL in the ischemic stroke group, respectively, which were all significantly higher than those in the healthy control group (73.71 [56.94, 79.81] pg/mL, 42.98 [34.52, 51.34] pg/mL and 14.97 [11.76, 21.19] pg/mL, respectively; U＝ 31.000 and 4.000, 106.000 and 132.000, and 48.000 and 13.000; all P0.05). Serum p75NTR-ECD level in the CCH-VCI patients was correlated with TNF-α level (r＝0.391, P＝0.022), but not with IL-1β or IL-6 levels (r＝0.032 and 0.164, P＝ 0.855 and 0.355). Conclusion Serum p75NTR level may be related to inflammatory factors (TNF-α) after chronic cerebral hypoperfusion, and they may jointly participate in the pathogenesis of CCH-VCI.

Mechanism of essential oil of Ligusticum chuanxiong to prevent and treat vascular cognitive impairment induced by lipopolysaccharide in mice / 中草药

Objective: To explore the effect of volatile oil of Ligusticum chuanxiong on vascular cognitive impairment (VCI) induced by lipopolysaccharide (LPS) and its related mechanism. Methods Male C57BL/C mice were randomly divided into sham-operated group, model group, memantine (10 mg/kg) group, and volatile oil of L. chuanxiong (30, 15, and 7.5 mg/kg) groups, drugs were given by ig administration once a day for 14 d. On day 8, LPS was injected into the lateral ventricle in mice. On day 11 and day 12, the cognitive ability were checked by the Y maze and step down test. On day 15 the mice were decapitated and the brain tissue was taken to determine the levels of monoamine oxidase (MAO), acetylcholinesterase (AchE), and acetylcholine (Ach); At the same time, the effect of the drug on superoxide dismutase (SOD) in mitochondria of brain in SD rats and the activity of Ec AchE, and BV-2 cells of microgliomas injured by LPS were also investigated in vitro. Results:LPS significantly increased the levels of MAO and AchE in the brain in mice, while decreased the levels of dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE). The volatile oil of L. chuanxiong 30 or 15 mg/kg decreased the level of MAO and AchE in the brain of LPS mice. The volatile oil of L. Chuanxiong could significantly increase the times of spontaneous alternation reaction in Y maze in VCI mice, and the middle dose could significantly decrease the latency of VCI mice in step down test. In vitro, the volatile oil of L. chuanxiong 1 mg/mL had a weak inhibitory effect on AchE of electric eel. The volatile oil of L. chuanxiong 0.5 μg/mL could significantly increase the activity of SOD in brain mitochondria of rats, and decrease the levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) increased significantly in BV-2 cells induced by LPS. Conclusion: The volatile oil of L. chuanxiong can significantly improve the cognitive ability of VCI induced by LPS in mice, and its mechanism may be related to inhibit the inflammatory response in the brain and alleviate the injury of neurons.

Expressions of CDK5 and p35/p25 in the blood of patients with vascular cognitive impairment / 西安交通大学学报(医学版)

Objective: To investigate the expressions and possible roles of cyclin dependent kinase 5 (CDK5), p35 and P25 in the blood of patients with vascular cognitive impairment (VCI). Methods: Totally 91 cases of VCI were recruited as the study group, including 49 cases of non-dementia vascular cognitive impairment (VCIND) and 42 cases of vascular dementia (VAD), and 30 cases of cerebral apoplexy cognitive function (NC) and healthy control (N) group, respectively. RT-qPCR was used to detect the relative expression of CDK5 mRNA in the blood. Western blot method was used to detect the protein expressions of CDK5, p35 and p25 in each group. Results: The relative expression of CDK5 mRNA and the expression levels of CDK5, p35 and p25 protein in the four groups: VAD>VCIND>NC>N respectively, with significant differences among the groups (P<0.05). Conclusion: CDK5, p35 and p25 may be involved in the occurrence of VCI, and their expression levels are positively correlated with VCI.

Effect of Modified Guipitang Combined with Xingnao Kaiqiao Acupuncture in Treatment of Heart and Spleen Insufficiency Syndrome of Non-dementia Vascular Cognitive Impairment / 中国实验方剂学杂志

Objective: To explore the curative effect and partial mechanism of modified Guipitang combined with Xingnao Kaiqiao acupuncture in the treatment of non-dementia vascular cognitive impairment (VCIND). Method: Totally 122 patients with VCIND admitted to the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine (TCM) from May 2017 to October 2018 were randomly divided into modified decoction group (39 cases), acupuncture group (42 cases) and combination group (41 cases). All of the three groups were orally given routine anticoagulants and lipid-lowering drugs. The decoction group was orally given modified Guipitang 150 mL/times, 2 times/day, in addition to the routine treatment, the acupuncture group was treated with Xingnao Kaiqiao acupuncture method in addition to the routine treatment, involving Shuigou, Neiguan (bilateral), Sanyinjiao (bilateral), Sishencong, Xuanzhong (bilateral) and Taixi (bilateral) acupoints, 2 times/day, for six days a week, the combined group was treated with Xingnao Kaiqiao acupuncture in addition to modified Guipitang. All of the three groups were treated for 8 weeks. The Montreal cognitive assessment scale (MoCA scale, Beijing version) and activity of daily life (ADL) scale, TCM symptoms and clinical efficacy were scored before treatment, 4 weeks after treatment and 8 weeks after treatment in three groups. Serum levels of calcitonin gene-related peptide (CGRP) and cone-like protein-1 (VILIP-1) were measured by enzyme-linked immunosorbent assay at different time points. Result: Compared with decoction group and acupuncture group, MoCA score, ADL score and TCM syndrome score of the combined group were decreased, the total effective rate was increased significantly after 4 and 8 weeks of treatment, the serum CGRP content was increased, and the VILIP-1 content was decreased. Conclusion: Modified Guipitang combined with Xingnao Kaiqiao acupuncture has a definite curative effect on VCIND with heart and spleen insufficiency syndrome. Its mechanism may be related to the expansion of blood vessels, the alleviation of blood supply of brain and the reduction of neuron injury.

Clinical Efficacy of Tongqiao Huoxuetang in Treating Blood Stasis Type Vascular Cognitive Impairment / 中国实验方剂学杂志

Objective:This study aims to observe the clinical efficacy of Tongqiao Huoxuetang in treating blood stasis resistance type vascular cognitive impairment, and explore its mechanism of action. Method:A total of 60 patients who met the inclusion standards and were diagnosed as blood stasis resistance type vascular cognitive impairment were randomly divided into treatment group and control group, 30 patients in each group. Donepezil hydrochloride was administered orally in control group based on internal medicine treatment at an initial dose of 5 mg/day, changed to 10 mg/day 4 weeks later. Patients in treatment group additionally received Tongqiao Huoxuetang based on donepezil hydrochloride. Both groups were treated for 3 months. Changes of symptoms were assessed by syndrome scores; cognitive function was assessed by the mini-mental scale (MMSE); daily living ability was assessed by the activity of daily living scale (ADL), and changes of local blood perfusion (CBF value) was assessed by brain magnetic resonance perfusion imaging arterial spin labeling (MRI-ASL). Changes of homocysteine levels in plasma were measured by using an automated biochemical analyzer. Result:① The values of traditional Chinese medicine(TCM) syndrome scores (SDSVD) were significantly improved in both groups after treatment, and the improvement was more obvious than that of control group (PPPPP P Conclusion:The combination of Tongqiao Huoxuetang combined with donepezil hydrochloride can effectively improve the cognitive ability and daily living ability of the patients with vascular dementia, improve the cerebral blood flow perfusion and decrease the level of homocysteine, so it is worth popularizing in clinical practice.

Association of lipoprotein a, fibrinogen and D-dimer with vascular cognitive impairment in patients with ischemic cerebral small vessel diseases / 中华行为医学与脑科学杂志

Objective To explore the correlation between lipoprotein a (Lpa),fibrinogen (FIB) and D-dimer (D-D) and vascular cognitive impairment in patients with ischemic cerebral small vessel diseases (CSVD).Methods Totally 300 patients with ischemic CSVD who were admitted to the Department of Neurology,Affiliated Hospital of North China University of Science and Technology were selected as the research objects,and 70 healthy outpatients in the same period were selected as the control group.Cognitive function was assessed with Mini Mental State Examination (MMSE).According to the results of MMSE,patients with ischemic CSVD were divided into cognitive normal group (106 cases) and cognitive impairment group (194 cases).The cognitive impairment group was further divided into mild cognitive impairment group (100 cases),moderate cognitive impairment group (60 cases) and severe cognitive impairment group (34 cases).Lpa level was detected by latex immunoturbidimetry,FIB level by coagulation and D-D level by ELISA.The results were compared and analyzed.Results (1) Compared with the control group (Lpa:(101.67±37.37) rmg/L,FIB:(3.02±0.67) g/L,D-D:(231.49±95.00) mg/L),the levels of Lpa,FIB and D-D in normal group (Lpa:(150.58± 89.55) mg/L,FIB:(3.48 ± 0.80) g/L,D-D:(287.79± 125.25)mg/L) and cognitive impairment group (Lpa:(257.98 ± 189.23) mg/L,FIB:(3.86± 0.97) g/L,D-D:(347.23± 120.69) rmg/L)increased significantly (all P＜0.01).Compared with the cognitive normal group,the levels of Lpa,FIB and D-D in cognitive impairment group increased significantly (all P＜0.01).(2)Compared with mild cognitive impairment group (Lpa:169.08±51.63 mg/L,FIB:(3.10±0.69)g/L,D-D:(288.91±92.58) mg/L),the levels of Lpa,FIB and D-D of in moderate cognitive impairment group (Lpa:(236.78± 107.15) mg/L,FIB:(3.52±0.67) g/L,D-D:(345.03± 132.68) mg/L),severe cognitive impairment group (Lpa:(292.65±108.19) mg/L,FIB:(4.04±1.08) g/L,D-D:(401.58±84.87) mg/L)increased significantly (all P＜0.01).Compared with the moderate cognitive impairment group,the levels of Lpa,FIB and D-D in the severe cognitive impairment group increased significantly (all P＜0.01).(3) The ROC curve was fitted with cognitive impairment as state variable.The area under the ROC curve of Lpa was 0.706,P＜0.01,95％ CI was (0.646-0.766),the area under the ROC curve of FIB was 0.613,P=0.001,95％ CI was (0.548-0.679),and the area under the ROC curve of D-D was 0.670,P＜0.01,95％ CI was (0.604-0.736).(4) Lpa,FIB and D-D were positively correlated with the degree of cognitive impairment in patients with ischemic cerebral small vessel diseases (rLpa =0.522,P＜0.01;rFIB =0.410,P＜0.01;rD-D =0.488,P＜0.01).Conclusion Serum Lpa,FIB and D-D are closely related to the degree of vascular cognitive impairment and cognitive impairment in patients with ischemic CSVD,which may be involved in the occurrence and development of cognitive impairment.Detection of serum levels of Lpa,FIB and D-D is of great clinical value in the early diagnosis,assessment and treatment of cognitive impairment in ischemic CSVD.

Treatment of Vascular Cognitive Impairment by "Huayu Tongluo" Moxibustion / 针刺研究

OBJECTIVE: To observe the therapeutic effect of "Huayu Tongluo"(blood stasis-removing and meridian-collateral-dredging) moxibustion for vascular cognitive impairment(VCI) patients and changes of insulin like growth factor -1(IGF-1) levels in serum after the treatment. METHODS: Sixty patients with VCI were randomly divided into medication (control) and moxibustion groups (n＝30 in each group). Cotton cloth-separated moxibustion was applied to Baihui (GV 20) and Shenting (GV 24), and conventional moxibustion applied to Dazhui (GV 14) and Yongquan (KI 1) for 30 min, once daily, 6 times a week and for 30 days. Patients of the control group were treated by oral administration of Donepezil hydrochloride at the dose of 5 mg/night for 30 days. The core symptoms of traditional Chinese medicine (TCM), mini-mental state examination(MMSE), activity of daily living(ADL) and Montreal cognitive assessment(MoCA) scales were used to assess the therapeutic effect after the treatment. The content of serum IGF-1 was determined by ELISA. RESULTS: Of the two 30 cases in the control and moxibustion groups, 9 and 17 experienced marked improvement, 13 and were effective, 8 and 3 ineffective, with the effective rates being 73.33% and 90.00%, respectively. The effective rate in the moxibustion group was obviously higher than that in the control group (P0.05)．. CONCLUSION: "Huayu Tongluo" moxibustion has a positive effect for patients with VCI, which may be associated with its effect in up-regulating serum IGF-1 level.