Avaliação dos subtipos de transtorno neurocognitivo (demência) em ambulatório de referência do Distrito Federal, Brasil de 2010 a 2018 / Evaluation of subtypes of neurocognitive disorder (dementia) in a reference outpatient clinic in the Federal District, Brazil from 2010 to 2018

Objetivos: estabelecer diagnóstico diferencial das demências em ambulatório de geriatria no Distrito Federal, calculando-se sua prevalência por meio de exame clínico e avaliação multifuncional. Método: estudo longitudinal, retrospectivo, com amostra de pessoas com 60 anos ou mais residentes no Distrito Federal-Brasil, com déficit cognitivo caracterizado por Transtorno Neurocognitivo (TNC) Maior (demência), cadastradas durante os anos de 2010 a 2018. A coleta de dados foi realizada em prontuários para selecionar e avaliar o perfil do idoso com diagnóstico de TNC seguida de avaliação geriátrica ampla e avaliação multifuncional. A análise de dados foi realizada com o cálculo da prevalência, estatística descritiva e índice V de Cramer. Resultados: 158 indivíduos conseguiram concluir todas as avalições. 52,5% possuem de 80 a 89 anos, 62,5% são mulheres e 62,7% caucasianos, 50,6% viúvos e 47,5% analfabetos. A prevalência inicial de Doença de Alzheimer (DA) foi de 45,6%, reduzindo-se para 35,4% após um período de acompanhamento e a demência vascular (DV) foi de 34,2%, inicialmente, e 45,6% ao final. Utilizou-se o Coeficiente V de Cramer, em que se encontrou uma relação fraca de fatores de risco com os diagnósticos das demências apresentados. Conclusão: DV foi a mais prevalente na área estudada. Entende-se ser a maior frequência de DA esteja relacionada à avaliação superficial uma vez que esse tipo de demência é mundialmente mais frequente

Objetivos: estabelecer diagnóstico diferencial das demências em ambulatório de geriatria no Distrito Federal, calculando-se sua prevalência por meio de exame clínico e avaliação multifuncional. Método: estudo longitudinal, retrospectivo, com amostra de pessoas com 60 anos ou mais residentes no Distrito Federal-Brasil, com déficit cognitivo caracterizado por Transtorno Neurocognitivo (TNC) Maior (demência), cadastradas durante os anos de 2010 a 2018. A coleta de dados foi realizada em prontuários para selecionar e avaliar o perfil do idoso com diagnóstico de TNC seguida de avaliação geriátrica ampla e avaliação multifuncional. A análise de dados foi realizada com o cálculo da prevalência, estatística descritiva e índice V de Cramer. Resultados: 158 indivíduos conseguiram concluir todas as avalições. 52,5% possuem de 80 a 89 anos, 62,5% são mulheres e 62,7% caucasianos, 50,6% viúvos e 47,5% analfabetos. A prevalência inicial de Doença de Alzheimer (DA) foi de 45,6%, reduzindo-se para 35,4% após um período de acompanhamento e a demência vascular (DV) foi de 34,2%, inicialmente, e 45,6% ao final. Utilizou-se o Coeficiente V de Cramer, em que se encontrou uma relação fraca de fatores de risco com os diagnósticos das demências apresentados. Conclusão: DV foi a mais prevalente na área estudada. Entende-se ser a maior frequência de DA esteja relacionada à avaliação superficial uma vez que esse tipo de demência é mundialmente mais frequente

Deterioro cognitivo de origen vascular y demencia vascular esporádica: revisión narrativa de tema basada en la evidencia / Cognitive impairment of vascular origin and sporadic vascular dementia: an evidence-based narrative topic review

RESUMEN INTRODUCCIÓN: La enfermedad cerebrovascular y las demencias están unidas por el deterioro cognitivo y la demencia vascular. Se trata de condiciones de salud potencialmente prevenibles, capaces de generar discapacidad, especialmente en la población adulta mayor. METODOLOGÍA: El propósito de este trabajo es caracterizar el deterioro cognitivo vascular y el espectro de la demencia vascular esporádica, mediante una revisión de tema con énfasis neurocognitivo. RESULTADOS: Entre el 30 % y el 40 % de las personas con enfermedad cerebrovascular experimentan algún grado de compromiso cognitivo. Después de los tres meses de haber presentado una enfermedad cerebro-vascular, alrededor del 20 % al 30 % de los pacientes serán diagnosticados con demencia, y entre un 10 % y un 35 %, con deterioro cognitivo. El deterioro cognitivo vascular y la demencia vascular tienen una serie de factores comunes a la enfermedad cerebrovascular y a la enfermedad de Alzheimer. La demencia vascular presenta subtipos: la demencia multiinfarto, caracterizada por varios infartos cerebrales que se acumulan en el tiempo; la demencia por infarto estratégico, en la que hay infartos localizados en zonas cortico-subcorticales con gran conectividad; y la demencia por enfermedad isquémica de pequeñas arterias, producida por infartos lacunares o lesiones difusas de sustancia blanca, que afecta principalmente la velocidad de procesamiento y las funciones ejecutivas. CONCLUSIONES: El deterioro cognitivo en personas con enfermedad cerebrovascular involucra pérdidas en el rendimiento de una o varias funciones mentales superiores, situación que puede evolucionar hasta la demencia, en la que un déficit permanente en las funciones mentales afecta de manera importante el desempeño y el funcionamiento. Sin embargo, es un tema que permite hablar y promover activamente el control o la modificación de factores de riesgo cardiovascular.

ABSTRACT INTRODUCTION: Cerebrovascular disease and dementias are linked by cognitive impairment and dementia of vascular origin. Potentially preventable health conditions capable of generating disability, especially in the older adult population. METHODOLOGY: The purpose is to characterize the cognitive impairment of vascular origin and the spectrum of sporadic vascular dementia, through a review of the topic with a neurocognitive emphasis. RESULTS: Between 30 % to 40 % of people with cerebrovascular disease acquire some degree of cognitive impairment. After three months of having experienced a cerebrovascular disease, about 20 % to 30 % of patients will be diagnosed with dementia and between 10 % and 35 % with cognitive impairment. Vascular cognitive impairment and vascular dementia have several factors common to cerebrovascular disease and Alzheimer's disease. Vascular dementia has subtypes: multi-infarct dementia characterized by several cerebral infarcts that accumulate over time; dementia due to strategic infarction, where there are infarcts located in cortico-subcortical areas with great connectivity; and dementia due to ischemic disease of the small arteries, produced by lacunar infarcts or diffuse lesions of the white matter, which mainly affect processing speed and executive functions. CONCLUSIONS: Cognitive impairment in people with cerebrovascular disease involves losses in the performance of one or several higher mental functions, a situation that can evolve to dementia, where a permanent deficit in mental functions significantly affects performance and functioning. However, it is a topic that allows to speak and actively promote the control and / or modification of cardiovascular risk factors.

Effects of Longshengzhi capsule on learning and memory ability of vascular dementia model rats and study on its metabolomics / 中国药房

OBJECTIVE To study the effect of Longsheng zhi capsule on lear ning and memory ability of vascular dementia model rats and explore its mechanism based on metabonomics. METHODS Totally 90 SD rats were randomly divided into sham operation group ，model group ，Dihydroergotoxin mesylate tablet group （positive control ，0.54 mg/kg），Longshengzhi capsule high-dose，medium-dose and low-dose groups （2.16，1.08 and 0.54 g/kg），with 15 rats in each group. In addition to sham operation group （only threading without ligation ），the vascular dementia model was prepared by permanent ligation of bilateral common carotid arteries in each group ，which was administered by gavage for 28 d. Morris water maze test was used to determine the learning and memory ability of rats ；hematoxylin eosin （HE）staining was used to observe the histopathological changes of hippocampus；the serum levels of superoxide dismutase （SOD），malondialdehyde（MDA）and glutathione peroxidase （GSH-Px） were detected ；the serum metabolic map was analyzed by ultra high performance liquid chromatography quadrupole time of flight tandem mass spectrometry （UPLC-Q-TOF/MS），the specific metabolites were screened by multivariate statistical analysis ，and the metabolic pathway was enriched and analyzed. RESULTS Morris water maze test showed that compared with model group ，the escape latency of rats in each administration group was significantly shortened ，the number of crossing the platform was significantly increased ，and the residence time in the target quadrant was significantly prolonged （P＜0.01 or P＜ 0.05）. The results of serum biochemical indexes showed that compared with model group ， the s erum level of SOD increased significantly in Dihydroergotoxine mesylate tablet group and Longshengzhi capsule high-dose group ，the serum level of GSH-Px increased significantly while the MDA level decreased significantly in each administration group （P＜0.05 or P＜0.01）. HE staining showed that Longshengzhi capsule could improve the histopathological damage of hippocampus in vascular dementia model rats. A total of 14 differential metabolites were screened and identified by UPLC-Q/TOF-MS and orthogonal partial least squares discriminant analysis model （VIP＞1 and P＜0.05）. The results of metabolic pathway enrichment analysis showed that the metabolic pathways involved in vascular dementia in rats mainly included vitamin B 6 metabolism，fatty acid metabolism and steroid hormone biosynthesis. CONCLUSIONS Longshengzhi capsule can improve the learning and memory ability of rats caused by vascular dementia. Its effect may be related to improving the oxidative stress injury caused by lipid accumulation in the process of vascular dementia. The metabolic pathways involved mainly include vitamin B 6 metabolism，fatty acid metabolism and steroid hormone biosynthesis.

Effect of Zishen Huoxue Prescription on Regulation of Mitophagy and Neurogenesis in Hippocampal CA1 Region of Vascular Dementia Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Zishen Huoxue prescription on promoting neurogenesis in hippocampal CA1 region of vascular dementia （VD） rats by regulating mitophagy. MethodThe 2-VO method was used to establish the VD rat model and 60 SD rats were randomly divided into sham operation group， model group， donepezil hydrochloride group， and Zishen Huoxue prescription low-dose（8.9 g·kg-1）， medium-dose（17.8 g·kg-1） and high-dose（35.6 g·kg-1） groups. Morris water maze test was performed to detect the escape latency and the number of crossing platform in each group. The expression of phosphatase and tensin homology-induced kinase 1 （PINK1） and Parkinson protein （Parkin） mRNA in hippocampal CA1 region was detected by Real-time fluorescent quantitative polymerase chain reaction（Real-time PCR）. Western blot was used to determine the expression of mitochondrial autophagy signaling pathway-related proteins Parkin， prohibitin 2 （PHB2）， mitofusin 2 （Mfn2） and dynamin-related protein 1 （Drp1） in hippocampal CA1 region. The neurogenesis in hippocampal CA1 region was tested by Brdu method. ResultCompared with the conditions in the sham operation group， the learning and spatial memory abilities of the model group were decreased （P<0.05）， with damaged mitochondrial structure and autolysosome formation in the hippocampal CA1 region. The expressions of Parkin， Pink1 mRNA and Parkin， PHB2， and Drp1 proteins were up-regulated （P<0.05）， while the expression of Mfn2 protein and the neuronal regeneration in hippocampal CA1 region were reduced （P<0.05， P<0.05）. Compared with the conditions in the model group， Zishen Huoxue prescription enhanced the learning and spatial memory abilities of VD rats （P<0.05）， increased the number of autophagosomes in hippocampal CA1 region and improved the mitochondrial structure. The expression of Parkin， Pink1 mRNA and Parkin， PHB2， and Drp1 proteins in hippocampal CA1 region was up-regulated （P<0.05， P<0.01）while the expression of Mfn2 protein was down-regulated（P<0.05， P<0.01）. The number of new neurons in hippocampal CA1 region was also increased（P<0.05， P<0.01）. ConclusionThe promoting effect of Zishen Huoxue prescription on the neurogenesis in hippocampal CA1 region of VD rats was related to the mitophagy mediated by Pink1/Parkin signaling pathway.

Pharmacodynamic study of chiral oxiracetam on neuroprotection and anti-dementia / 药学学报

To compare the neuroprotective and anti-dementia pharmacological effects of chiral oxiracetam, glutamate and calcium ions were used to establish neuronal injury models in vitro, and the protective effects of chiral oxiracetam on primary neurons were assayed by MTT. Permanent bilateral common carotid artery occlusion (2-VO)-induced rats were randomly divided into sham group, model group, galantamine 3 mg‧kg-1 group, oxiracetam groups (30, 100 and 200 mg‧kg-1), S-oxiracetam groups (30, 100 and 200 mg‧kg-1) and R-oxiracetam 200 mg‧kg-1 group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College. Morris water maze and step-down test were applied to evaluate the cognitive dysfunction induced by cerebral hypoperfusion in rats. Oxiracetam, S-oxiracetam and R-oxiracetam exerted protective effects on primary neuronal damage caused by various stimuli, and oxiracetam and S-oxiracetam showed better neuro-protective effects. Morris water maze and step-down results showed that oxiracetam, S-oxiracetam and R-oxiracetam improved the cognition of 2-VO rats. In summary, S-oxiracetam exerted a better neuro-protective effect than oxiracetam and R-oxiracetam.

Longshengzhi Capsules Improves Cognitive Function of Vascular Dementia Model Rats / 中国实验方剂学杂志

ObjectiveTo study the effect of Longshengzhi capsules on the cognitive function of vascular dementia （VD） rats and reveal the underlying mechanism. MethodA VD rat model was established by permanent ligation of bilateral common carotid arteries. The model rats were randomly assigned into the model group （normal saline for gavage）， Hydergine （0.54 mg·kg-1） group， and high-， medium-， and low-dose （2.16， 1.08， and 0.54 g·kg-1， respectively） Longshengzhi capsules groups， with 15 rats each group. Additionally， a sham group （normal saline for gavage） was designed in this study. Morris water maze test was conducted in the last week. Hematoxylin-eosin （HE） staining was employed for observation of the pathological changes in the hippocampal area of rat brain. Serum oxidative stress indicators including superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） were examined. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of B cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， protein kinase B （Akt）， p-Akt， nuclear factor-κB （NF-κB）， intercellular cell adhesion molecule-1 （ICAM-1）， and matrix metallopeptidase-9 （MMP-9） were determined by Western blot. ResultMorris water maze results showed that compared with sham operation group， the escape latency of rats in model group was significantly prolonged， and the number of crossing platform was significantly reduced. Compared with model group， the time of escape latency in Longshengzhi capsules high- and medium-dose groups was significantly shortened， and the number of crossing platform was significantly increased. Compared with sham operation group， SOD and GSH-Px levels in model group were significantly decreased （P<0.05， P<0.01）， MDA levels were significantly increased （P<0.05）， TNF-α， IL-6 and IL-1β levels were significantly increased （P<0.01）. Compared with model group， the level of SOD in serum of Longshengzhi capsules high-dose group was significantly increased （P<0.05）， the level of GSH-Px in serum of Longshengzhi capsules high-， medium- and low-dose groups was significantly increased （P<0.05， P<0.01）， and the level of MDA was significantly decreased （P<0.05）. TNF-α， IL-6 and IL-1β levels were significantly decreased （P<0.05， P<0.01）. HE staining showed that Longshengzhi capsules could improve pathological damage in hippocampus of VD rats. Western blot results showed that compared with sham operation group， the protein expressions of Bax， NF-κB， MMP-9 and ICAM-1 in model group were significantly increased （P<0.01）， and the protein expressions of Bcl-2， Akt and p-Akt were significantly decreased （P<0.05， P<0.01）. The protein expression of Bax， NF-κB， MMP-9 and ICAM-1 in Longshengzhi capsules high-， medium- and low-dose groups was significantly decreased （P<0.05， P<0.01）， and the protein expression of Bcl-2 was significantly increased （P<0.05， P<0.01）. The protein expression of Akt in Longshengzhi capsules high- and medium-dose groups was significantly increased （P<0.05）. The expression of p-Akt protein in Longshengzhi capsules high-dose group was significantly increased （P<0.01）. ConclusionLongshengzhi capsules can improve the cognitive function of VD rats， and its mechanism may be related to the inhibition of oxidative stress， inflammatory response and apoptosis. ConclusionLongshengzhi capsules can improve the cognitive function of VD rats by inhibiting oxidative stress， inflammatory reaction， and neuronal apoptosis.

Structure-based discovery of orally efficient inhibitors via unique interactions with H-pocket of PDE8 for the treatment of vascular dementia

Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe 3a. However, compound 3a is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead 15 exhibited potent inhibitory activity against PDE8A (IC50 = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of 15 significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse model. Notably, the X-ray crystal structure of the PDE8A-15 complex showed that the potent affinity and high selectivity of 15 might come from the distinctive interactions with H-pocket including T-shaped π-π interactions with Phe785 as well as a unique H-bond network, which have never been observed in other PDE-inhibitor complex before, providing new strategies for the further rational design of novel selective inhibitors against PDE8.

Expression of serum soluble triggering receptor expressed on myeloid cells 2 in patients with vascular dementia and its relationship with β-amyloid 1-42 and lipoprotein-associated phospholipase 2 / 中华老年医学杂志

Objective:To investigate the expression levels of serum soluble triggering receptor expressed on myeloid cells 2(sTREM2)in patients with vascular dementia(VD)and its relationship with β-amyloid 1-42(Aβ1-42)and lipoprotein-associated phospholipase 2(Lp-PLA2), as well as its value in diagnosis and differential diagnosis.Methods:A total of 152 patients with ischemic stroke receiving routine treatment in our hospital from January 2018 to January 2020 were included and divided into a VD group(n=76)and a non-VD group(n=76)according to evaluation from subsequent visits at 3 months.General data, Mini-Mental State Examination Scale(MMSE), Hachinski Ischemic Scale(HIS)scores, and the levels of biochemical indicators were compared and analyzed for the two groups.Results:There were statistically significant differences in lesion size between the VD group and the non-VD group( P<0.05). The MMSE score in the VD group was significantly lower than that in the non-VD group.The HIS score, serum levels of sTREM2[(3.34±1.18)μg/L and(2.78±1.25)μg/L, t=2.121, P=0.036], Aβ1-42[(93.69±14.45)ng/L and(81.24±14.21)ng/L, t=4.003, P<0.001]and Lp-PLA2 levels[(58.67±14.15)μg/L and(43.18±13.86)μg/L, t=5.096, P<0.001]were significantly higher in patients with VD than in patients without VD( P<0.05). Serum sTREM2 was positively correlated with Aβ1-42( r=0.723, P<0.001)and Lp-PLA2( r=0.714, P<0.001), and Aβ1-42 was positively correlated with Lp-PLA2( r=0.698, P<0.001)in VD patients.The cut-off value, sensitivity, specificity, and area under the curve of serum sTREM2 for differentiating VD from non-VD were 3.96 μg/L, 81.30%, 78.40%, and 0.838, respectively. Conclusions:Serum sTREM2 is abnormally elevated in VD patients, and is significantly correlated with Aβ1-42 and LP-PLA2, thus STREM2 may be an indicator in the differential diagnosis of VD and non-VD.

Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD).@*METHODS@#The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table, including sham, four-vessel occlusion (4-VO), 4-VO+EA, 4-VO+non-EA, sham+EA, 4-VO+lipopolysaccharide (LPS), 4-VO+LPS+EA, and 4-VO+TAK-242 groups. The VaD model was established by the 4-VO method. Seven days later, rats were treated with EA at 5 acupoints of Baihui (DV 20), Danzhong (RN 17), Geshu (BL 17), Qihai (RN 6) and Sanyinjiao (SP 6), once per day for 3 consecutive weeks. Lymphocyte subsets, lymphocyte transformation rates, and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were measured to assess immune function and inflammation in VaD rats. Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus. The levels of TLR4, MyD88, IL-6, and TNF-α were detected after EA treatment. TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA.@*RESULTS@#Compared with the 4-VO group, EA notably improved immune function of rats in the 4-VO+EA group, inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats, reduced the expressions of serum IL-6 and TNF-α (all P0.05).@*CONCLUSIONS@#EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway. Thus, EA may be a promising alternative therapy for the treatment of VaD.

Acupuncture for improving neuroinflammation in vascular dementia rats by regulating Th1/Th2 cells balance in peripheral blood / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture on the balance of T helper (Th) 1/Th2 cells in peripheral blood, inflammatory reaction and intracerebral neuroinflammation in vascular dementia (VD) rats, and to explore the mechanism of acupuncture for improving cognitive function in VD.@*METHODS@#A total of 60 SPF Wistar rats were randomized into a normal group (n=12), a sham operation group (n=12) and an operation group (n=36). Bilateral common carotid artery occlusion was adopted to establish the VD model in rats of the operation group. The rats of successful modeling were randomized into a model group and an acupuncture group, 12 rats in each one. In the acupuncture group, Sanjiao acupuncture was applied at "Danzhong" (CV 17), "Zhongwan" (CV 12), "Qihai" (CV 6), "Xuehai" (SP 10) and "Zusanli" (ST 36), the needles were manipulated for 30 s at each acupoint, without retaining. The intervention was given once a day for 15 days, and there was 1-day rest on day 8. Morris water maze test was adopted to observe the ethology, flow cytometry was used to detect the ratio of Th1/Th2 in peripheral blood, and Luminex liquid chip technology was used to detect the levels of interleukin (IL)-4, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in serum and hippocampus.@*RESULTS@#There were no significant differences in various indexes between the normal group and the sham operation group (P>0.05). Compared with the sham operation group, in the model group, the escape latency of hidden platform test and reversal platform test was prolonged (P<0.01), the residence time of the original platform quadrant was shortened and the number of crossing the original platform was reduced in probe test (P<0.01, P<0.05), the proportion of Th1 cells was increased, the proportion of Th2 cells was decreased and the ratio of Th1/Th2 cells was increased in peripheral blood (P<0.01), the levels of TNF-α and IFN-γ were increased, the levels of IL-4 and IL-10 were decreased in serum and hippocampus (P<0.05, P<0.01). Compared with the model group, in the acupuncture group, the escape latency of hidden platform test and reversal platform test was shortened (P<0.01), the residence time of the original platform quadrant of the probe test was prolonged (P<0.05), the proportion of Th1 cells was decreased, the proportion of Th2 cells was increased and the ratio of Th1 / Th2 cells was decreased in peripheral blood (P<0.05), the levels of TNF-α and IFN-γ were decreased, the levels of IL-4 and IL-10 were increased in serum and hippocampus (P<0.05, P<0.01).@*CONCLUSION@#Acupuncture can improve the cognitive dysfunction and reduce the intracerebral neuroinflammation in VD rats, its mechanism may relate to the regulation of Th1/Th2 cells balance and reduce the inflammatory reaction in peripheral blood.

Vascular mild cognitive impairment and its relationship to hemoglobin A1c levels and apolipoprotein E genotypes in the Dominican Republic / Comprometimento cognitivo leve vascular e sua relação com os níveis de hemoglobina a1c e genótipos apolipoproteína e na república dominicana

ABSTRACT. Dementia and vascular mild cognitive impairment (VaMCI) currently impose a tremendous human and economic burden on patients from aging populations and their families worldwide. Understanding the interplay of cardiometabolic risk factors and apolipoprotein E (APOE) may direct us to a more personalized medicine and preventative care in MCI and dementia. Objective: To evaluate the relationship of cardiometabolic risk factors with MCI and assess the APOE genotype's role in an elderly cohort in the Dominican Republic. Methods: We studied a cohort of 180 participants 65 years of age and older using a combined assessment of cardiometabolic risk factors, neuropsychological battery tests, and APOE genotyping. We used the number of failed tests as a proxy to predict MCI. Results: We found that patients with the ε3-ε4 APOE genotype had 2.91 higher number of failed cognitive tests (p=0.027) compared to patients with the ε3-ε3 genotyped. The rate of test failures increased 10% (p=0.025) per unit increase in HbA1c percentage. Conclusions: Increased Hemoglobin A1c levels and ε3-ε4 APOE genotypes seem to have an association with the development of VaMCI.

RESUMO. A demência e o comprometimento cognitivo leve vascular (VaMCI) atualmente impõem uma enorme carga humana e econômica aos pacientes de populações envelhecidas e suas famílias em todo o mundo. Compreender a interação dos fatores de risco cardiometabólicos e apolipoproteína E (APOE) pode nos direcionar para uma medicina mais personalizada e de cuidados preventivos em MCI e demência. Objetivo: Avaliar a relação dos fatores de risco cardiometabólicos com o MCI e o papel do genótipo APOE em uma coorte de idosos na República Dominicana. Métodos: Estudamos uma coorte de 180 participantes com 65 anos de idade ou mais, utilizando uma avaliação combinada de fatores de risco cardiometabólicos, uma bateria de testes neuropsicológicos e genotipagem APOE. Adotou-se o número de testes com mau desempenho para o diagnóstico de MCI. Resultados: Verificou-se que os pacientes com o genótipo ε3-ε4 do APOE apresentaram 2,91 vezes mais testes cognitivos com mau desempenho (p=0,027) em comparação com os pacientes com o genótipo ε3-ε3. A taxa de falhas de teste aumentou 10% (p=0,025) por aumento de unidade na porcentagem de HbA1c. Conclusões: Níveis mais altos de HbA1c e os genótipos ε3-ε4 do APOE parecem estar associados ao desenvolvimento de VaMCI.

Effect of Allicin on Learning and Memory Ability of Vascular Dementia Rats and Its Mechanism / 中国实验方剂学杂志

Objective:To investigate the effect of allicin （ALL） on learning and memory ability of rats with vascular dementia （VD） and the possible mechanism. Method:The VD rats induced by modified bilateral common carotid artery occlusion （BCCAO） were randomly divided into the VD group， low- and high-dose ALL （ALL-L and ALL-H） groups， and the sham operation （S） group， with 15 rats in each group. In the ALL-L and ALL-H groups， ALL was injected into the femoral vein at 5 mg·kg^-1 and 20 mg·kg^-1， respectively， while the same volume of normal saline was injected in the S and VD groups， once a day， for two successive weeks. Morris water maze （MWM） was used to test the learning and memory ability of rats. Hematoxylin and eosin （HE） staining was conducted to observe the pathological changes in hippocampal tissue， followed by the detection of inflammatory factors tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-6 （IL-6）， and IL-1<italic>β</italic> as well as oxidative stress indexes malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px） in rat hippocampus. The apoptosis of hippocampal cells was detected by TdT-mediated dUTP Nick end Labeling（TUNEL） assay. The expression levels of apoptosis and autophagy-related proteins cysteinyl aspartate-specific protease-3 （Caspase-3）， B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， microtubule-associated protein light chain 3Ⅱ （LC3Ⅱ）， LC3Ⅰ， and the mammalian homolog of yeast ATG6 （Beclin 1） in hippocampus were determined by Western blot. Result:The comparison with the VD group revealed that the learning and memory abilities of rats in the ALL-H and ALL-L groups were significantly improved （<italic>P</italic><0.05）. The TNF-<italic>α</italic>， IL-6， IL-1<italic>β</italic>， and MDA levels in hippocampus were lowered （<italic>P</italic><0.05）， whereas the SOD and GSH-Px activities were enhanced （<italic>P</italic><0.05）. The apoptosis rates were declined （<italic>P</italic><0.05）， with an even lower rate noticed in the ALL-H group （<italic>P</italic><0.05）. The expression levels of Caspase-3， Bax， LC3Ⅱ/LC3Ⅰ ratio， and Beclin-1 in the ALL-H and ALL-L groups were significantly down-regulated in contrast to those in the VD group （<italic>P</italic><0.05）， while that of Bcl-2 was up-regulated （<italic>P</italic><0.05）. The ALL-H group exhibited better performances than the ALL-L group （<italic>P</italic><0.05）. Conclusion:ALL could improve the learning and memory ability of VD rats to some extent， which may be attributed to its inhibition against inflammatory reaction， oxidative stress， and neuronal apoptosis and autophagy.

Clinical Efficacy of Modified Dihuangyin on Vascular Dementia Due to Kidney Empty Phlegm and Blood Stasis Syndrome / 中国实验方剂学杂志

Objective:To observe the effect of modified Dihuangyin on vascular dementia due to kidney empty phlegm and blood stasis syndrome，and its effect on phosphoinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway ［PI3K，microtuble-associated protein 1 light chain 3（LC3）Ⅱ/LC3Ⅰ，Akt，phosphorylatedprotein kinase B（p-Akt）］ in peripheral blood. Method:Totally 100 cases were randomly divided into control group （50 cases） and observation group （50 cases），and were given donepezil，modified Dihuangyin combined with donepezil for 30 d，respectively. The main efficacy indicators ［mini-mental state examination （MMSE），clinical dementia rating （CDR），activity of daily living scale （ADL），traditional Chinese medcine（TCM） syndrome］ were compared in two groups. The cerebral blood flow dynamics ［middle cerebral artery （MCA），basilar artery （BA），anterior cerebral artery （ACA），posterior cerebral artery （PCA）］ speed，serum inflammatory factors ［tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>），interleukin-6 （IL-6），transforming growth factor-<italic>β</italic> （TGF-<italic>β</italic>），C-reactive protein （CRP）］，oxidative stress indicators ［malondialdehyde （MDA），superoxide dismutase （SOD），glutathione peroxidase （GSH-Px） ，homocysteine （Hcy）］，peripheral blood PI3K/Akt signaling pathway （PI3K，LC3Ⅱ/LC3Ⅰ，Akt，p-Akt） were tested. The efficacy and adverse reactions of the two groups were compared. Result:The total effective rate was 95.9% in observation group was higher than that 72.3% in control group （<italic>χ</italic>²=5.673，<italic>P</italic><0.05）. Compared with the control group after treatment，the MMSE，ADL，SOD，GSH-Px，TGF-<italic>β</italic>，PI3K，Akt and p-Akt in the observation group were increased （<italic>P</italic><0.05），CDR，MCA，BA，ACA and PCA were increased （<italic>P</italic><0.05），and the TCM syndromes，MDA，Hcy，TNF-<italic>α</italic>，IL-6，CRP，LC3Ⅱ/LC3Ⅰ were decreased （<italic>P</italic><0.05）. There was no significant difference incidence of adverse reactions between two groups. Conclusion:Modified Dihuangyin can significantly improve the clinical symptoms of patients with vascular dementia due to kidney empty phlegm and blood stasis syndrome，and the mechanism of action may be related to PI3K/Akt signaling pathway in peripheral blood.

Xiaoyaosan Promotes Myelin Regeneration and Alleviates Depressive Symptoms in Vascular Dementia Mice with Depression via Promoting Microglia Polarization / 中国实验方剂学杂志

Objective:To investigate the effect of Xiaoyaosan on depressive behavioral phenotype in mice with vascular dementia （VaD） mice and its possible mechanism. Method:Sixty three-month-old male C57/BL6 mice were divided into the normal control group， model group， positive control group， as well as low-， medium-， and high-dose Xiaoyaosan groups. Mice in all groups except for the normal control group underwent bilateral carotid artery stenosis. Two weeks later， they were subjected to chronic restraint stress， 6 h per day， for inducing VaD complicated with depression. Mice in the low-， medium-， and high-dose Xiaoyaosan groups were treatment with intragastric administration of Xiaoyaosan decoction （5， 10， 20 g·kg^-1）， the ones in the positive control group with fluoxetine （10 mg·kg^-1）， and those in the normal control group and model group with an equal volume of normal saline for four weeks， during which the restraint stress was maintained. The depressive behavioral phenotype of mice was observed in sugar water preference test and tail suspension test. The fluorescence expression of myelin basic protein （MBP） in ventral hippocampus （vHIP） was detected by fluorescence immunoassay. The ultrastructure of myelin sheath in vHIP was observed by transmission electron microscopy. The protein expression levels of MBP， myelin oligodendrocyte glycoprotein （MOG）， myelin-associated glycoprotein （MAG）， triggering receptor expressed on myeloid cells-2 （TREM2）， inducible nitric oxide synthase （iNOS）， arginase 1 （Arg1）， interleukin-I<italic>β</italic> （IL-1<italic>β</italic>）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） were assayed by Western blot. Result:As revealed by behavioral test， compared with the normal control group， the model group exhibited prolonged immobility time and decreased percentage of sugar water preference （<italic>P</italic><0.01）. Compared with the model group， Xiaoyaosan significantly shortened the immobility time of mice （<italic>P</italic><0.05） and increased the percentage of sugar water preference （<italic>P</italic><0.01）. Western blot results showed that the protein expression levels of MBP， MOG， and MAG in vHIP of the model group were remarkably decreased as compared with those of the normal control group （<italic>P</italic><0.01）. The protein expression levels of MBP， MOG， and MAG in vHIP of the low-dose Xiaoyaosan group were increased in contrast to those in the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the protein expression of iNOS was decreased （<italic>P</italic><0.01）. The protein expression levels of MBP， MOG， MAG， TREM2， Arg1， IL-4， and IL-10 in the medium- and high-dose Xiaoyaosan groups were up-regulated （<italic>P</italic><0.05， <italic>P</italic><0.01）， whereas those of iNOS， IL-1<italic>β</italic>， and TNF-<italic>α</italic> were down-regulated （<italic>P</italic><0.01）. The immunofluorescence findings demonstrated that the mean fluorescence intensity of MBP in the model group declined in comparison with that in the normal control group （<italic>P</italic><0.01）， while the mean fluorescence intensities of MBP in the low-， medium-， and high-dose Xiaoyaosan groups were enhanced to different degrees （<italic>P</italic><0.01）. It was observed under the transmission electron microscope that the myelin structure of the model group was loosened and the dense layer was separated and irregularly arranged. Xiaoyaosan improved the structural integrity of myelin sheath and the looseness of lamellar structure. Conclusion:Xiaoyaosan ameliorates the depressive behavioral phenotype of VaD mice， which may be related to the up-regulation of TREM2， the induction of M2 polarization of microglia cells， the enhancement of their anti-inflammatory and phagocytic abilities， and the promotion of damaged myelin sheath regeneration.

Effect of Bushen Tongluo Prescription on Synaptic Plasticity of Hippocampal Neurons of Vascular Dementia Model Rats Based on PI3K/Akt/mTOR Pathway / 中国实验方剂学杂志

Objective:To explore the effect of Bushen Tongluo prescription （BSTLP） on the synaptic plasticity of hippocampal neurons in vascular dementia （VD） model rats and its mechanism. Method:SD male rats of SPF grade were selected. The rat model of VD was established by permanent bilateral ligation of the common carotid artery several times. The model rats were randomly divided into a model group， an insulin-like growth factor-1 （IGF-1， 20 μg·kg^-1） group， high-dose （3 g·kg^-1）， medium-dose （1.5 g·kg^-1）， and low-dose （0.75 g·kg^-1） BSTLP groups. A sham operation group was also set. Drugs were administered to rats by gavage once a day for four weeks. The model group and the sham operation group received the same volume of normal saline. After the last administration， all the rats were detected for spatial learning and memory by the Morris water maze. The apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase （TdT） dUTP nick-end labeling （TUNEL） assay. The changes in synaptic morphological structure and the number of dendritic spines in hippocampal neurons were detected by Golgi's method. The expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， mammalian target of rapamycin （mTOR）， synaptophysin （SYP）， and amyloid precursor protein （APP） in hippocampal neurons were detected by Western blot. Result:Compared with the sham operation group， the model group showed prolonged escape latency， lengthened swimming distance， dwindled the number of times for the platform crossing after platform removal （<italic>P</italic><0.05）， increased apoptotic cells （<italic>P</italic><0.05）， declining synaptic dendritic spines （<italic>P</italic><0.05）， down-regulated expression levels of PI3K， Akt， mTOR， and SYP proteins， and up-regulated expression level of APP protein in hippocampal neurons （<italic>P</italic><0.05）. Compared with the model group， the BSTLP groups and the IGF-1 group showed shortened escape latency and swimming distance， increased number of times for the platform crossing after platform removal （<italic>P</italic><0.05），declining apoptotic cells （<italic>P</italic><0.05）， up-regulated expression levels of PI3K， Akt， mTOR， and SYP proteins， and down-regulated expression level of APP protein in hippocampal neurons （<italic>P</italic><0.05）. Compared with the IGF-1 group， the high-dose BSTLP group showed no significant difference in the escape latency， swimming distance， the number of times for the platform crossing after platform removal， apoptotic cells， synaptic dendritic spines， and expression levels of PI3K， Akt， mTOR， SYP， and APP proteins in hippocampal neurons. However， the differences were significant in the medium-dose and low-dose BSTLP groups （<italic>P</italic><0.05）. Conclusion:BSTLP can improve the learning and memory of rats with VD. The mechanism is presumedly related to the activation of thePI3K/Akt/mTOR pathway and improvement of synaptic plasticity of hippocampal neurons.

Domestic clinical application of vascular dementia scales / 中国中药杂志

To analyze the domestic clinical application of vascular dementia scales, and provide the basis for the refinement of clinical scales. VIP, SinoMed, Wanfang and CNKI databases were searched by computer to analyze the clinical application of vascular dementia scales published in Chinese Core Periodicals in Library of Peking University, CSSCI and CSCD, with time limit from database establishment to August 31, 2020. According to the inclusion or exclusion criteria, the combination of Note Express software and manual search was used to complete the literature duplicate detection and screening. According to the research needs, the relevant data were extracted and a new database was established. In this study, a total of 4 246 related literatures were initially searched, 2 048 repetitive literatures were eliminated, 1 484 literatures were manually screened out, and finally 714 literatures and 44 scales were included. The total using frequency of scales was 2 660. The results of descriptive analysis showed that there were many kinds of clinical scales for vascular dementia. In order to avoid the repeated use of scales with similar functions, it is correct to include the possible influences such as the purpose of use, way, frequency and function of the scales into reference factors of scale selection according to the disease diagnostic criteria. It is necessary to develop the scales with traditional Chinese medicine characteristic for objective clinical evaluation of traditional Chinese medicine.

Effect of moxibustion on cognitive function and proteins related with apoptosis of hippocampal neurons in rats with vascular dementia / 中国针灸

OBJECTIVE@#To observe the effect of moxibustion on proteins related with apoptosis of hippocampal neurons in rats with vascular dementia (VD), and to explore the possible mechanism of moxibustion on improving VD.@*METHODS@#Thirty SD rats were selected from 100 rats (3 rats were excluded) and randomly divided into a normal group and a sham operation group, 15 rats in each group. The remaining 67 rats were treated with ischemia-reperfusion method at bilateral common carotid artery to establish VD model. The 45 rats with successful VD model were randomly divided into a model group, a moxibustion group and a medication group, 15 rats in each group. On the 7th day after successful modeling, the rats in the moxibustion group were treated with suspended moxibustion at "Guanyuan" (CV 4), "Mingmen" (GV 4) and "Dazhui" (GV 14), 15 min per acupoint, once a day; there was 1 d of rest after 6 d of moxibustion, and the treatment was given for 4 weeks. The rats in the medication group was treated with nimodipine tablets by gavage, 2 mg/kg per day, 3 times a day for 4 weeks. Before and after intervention, the Morris water maze test was used to detect the escape latency of rats in each group; after the intervention, the TUNEL method was used to detect the apoptosis rate of neurons in hippocampal CA1 area; the immunofluorescence double labeling method was used to detect the number of co-expression positive cells of B-cell lymphoma-2 (Bcl-2)/neuronal nuclear antigen (NeuN) and Bcl-2-associated X protein (Bax)/NeuN in hippocampal CA1 area; the immunofluorescence single labeling method was used to detect cytochrome C (cytC) and outer mitochondrial membrane receptor Tom20 (Tom20) in hippocampal CA1 area; the Western blot method was used to detect the p53 upregulated modulator of apoptosis (PUMA) in hippocampus.@*RESULTS@#Before intervention, compared with the normal group and the sham operation group, the escape latency in the model group, the moxibustion group and the medication group was prolonged (@*CONCLUSION@#Moxibustion could improve the cognitive function of VD rats, which may be related to reducing the expression of Bax, cytC, Tom20 and PUMA protein in hippocampal CA1 area, promoting the release of Bcl-2 and inhibiting the apoptosis of hippocampal neurons.

Effect of early acupuncture on cognitive function in patients with vascular dementia after cerebral infarction / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of early acupuncture for vascular dementia (VD) after cerebral infarction, and explore its possible mechanism.@*METHODS@#A total of 120 patients with VD after cerebral infarction were randomized into an acupuncture combined with medication group (60 cases, 1 case dropped off) and a western medication group (60 cases, 1 case dropped off). In the western medication group, oxiracetam capsules were given orally, 2 capsules each time, 3 times a day. On the basis of the treatment as the western medication group, @*RESULTS@#The total effective rate was 89.8% (53/59) in the acupuncture combined with medication group, which was superior to 76.3% (45/59) in the western medication group (@*CONCLUSION@#Early acupuncture could improve cognitive function and activities of daily living in patients with VD after cerebral infarction, its mechanism may be related to improving the blood flow velocity of MCA, promoting blood circulation, and improving cerebral perfusion.

Systematic review of efficacy and safety of Compound Danshen Injection combined with Western medicine in treatment of vascular dementia / 中国中药杂志

To evaluate the efficacy and safety of Compound Danshen Injection combined with Western medicine in the treatment of vascular dementia. Databases of Cochrane Library, PubMed, EMbase, CNKI, SinoMed, VIP, Wanfang Data were electronically retrieved for collecting randomized controlled trial(RCT)about vascular dementia treated with Western medicine alone or combined with Compound Danshen Injection from the year of database establishment to January 2020. Two researchers independently screened out li-teratures, extracted data, and evaluated the risk of bias for inclusion in the study. Meta-analysis was conducted using RevMan 5.3 software. A total of 5 RCTs were included, involving 588 patients, with 299 in treatment group and 289 in control group. Meta-analysis results showed that compared with Western medicine alone, Compound Danshen Injection combined with Western medicine was better in the effective rate(RR=1.23,95%CI[1.14,1.33],P<0.000 01), MMSE score(MD=3.54,95%CI[3.01,4.06],P<0.000 01), ADL score(MD=11.49,95%CI[8.05,14.93],P<0.000 01), the level of CRP(MD=-0.72,95%CI[-1.25,-0.20],P=0.007) and the level of IL-6(MD=-7.64,95%CI[-9.65,-5.63],P<0.000 01). Adverse reactions mainly included rash and skin prick, which did not affect the treatment effect. Based on the findings, the combination of Compound Danshen Injection in the treatment of vascular dementia could improve the effective rates, relieve the mental state damage and improve the daily living ability, with mild adverse reactions and a low incidence. However, due to the low quality of the included literatures, high-quality and large-scale randomized controlled trials are needed for further verification.

Targeting redox-altered plasticity to reactivate synaptic function: A novel therapeutic strategy for cognitive disorder

Redox-altered plasticity refers to redox-dependent reversible changes in synaptic plasticity