Qualidade de vida do cuidador informal de idosos com doença de alzheimer na pandemia COVID-19 / Quality of life of informal caregivers of aged people with alzheimer's disease during the COVID-19 pandemic

Objetivo: Desvelar sobre a qualidade de vida dos cuidadores informais de idosos com Doença de Alzheimer em tempos de pandemia da COVID-19. Método: Estudo descritivo, qualitativo, por meio de entrevista semiestruturada com 12 cuidadores informais de idosos, selecionados por conveniência. O processamento dos dados foi realizado pelo software IraMuTeQ e análise das classes pelo método de Strauss e Corbin, da qual emergiram 4 classes: rede social e mudança na rotina dos cuidadores informais no período da pandemia da COVID-19; fatores que interferem na QV do cuidador informal; vivenciando o diagnóstico de Alzheimer pelo cuidador informal e sentimentos despertados pela sobrecarga dos cuidadores informais de idosos com DA. Resultados: O perfil feminino se sobressaiu, com destaque para cuidadores com idade entre 40 a 49 anos, casados, ensino médio incompleto, desempenhando esta função por mais de cinco anos e em tempo integral. Os fatores que interferem na qualidade de vida são a falta de tempo, sobrecarga do cuidado, falta de lazer, baixas atividades sociais e sentimentos de tristeza, ansiedade, nervosismo, depressão e desespero. Conclusão: Constatou-se que os aspectos encontrados foram impactados ainda mais durante o período da pandemia da COVID-19, que reconfigurou a rotina do idoso com Alzheimer e do cuidador informal. Descritores: Doença de Alzheimer; Cuidadores. Idosos; Coronavírus; Qualidade de Vida.

Objective:To reveal the quality of life of informal caregivers of aged people with Alzheimer's disease in times of the COVID-19 pandemic. Method:Adescriptive and qualitative study conducted through semi-structured interviews with 12 informal caregivers of older adults, selected by convenience. Data processing was performed using the IraMuTeQ software and class analysis using the Strauss and Corbin method, from which 4 classes emerged, namely: Social network and change in the routine of informal caregivers during theCOVID-19 pandemic period; Factors that interfere with the QoL of informal caregivers; How informal caregivers experience the Alzheimer's disease diagnosis; and Feelings awakened by the burden of informal caregivers of aged people with AD. Results:The female profile stood out, with emphasis on caregivers aged from 40 to 49 years old, married, incomplete High School, and performing this role for more than five years and full-time. The factors that interfere with quality of life are lack of time, care burden, lack of leisure, few social activities and feelings of sadness, anxiety, nervousness, depression and despair. Conclusion:It was verified that the aspects found were impacted even more during the COVID-19 pandemic period, which reconfigured the routine of older adults with Alzheimer's and of informal caregivers. Descriptors: Alzheimer Disease; Caregivers; Aged; Coronavirus; Quality of Life.

O cuidado do idoso com alzheimer e a resiliência do cuidador informal / El cuidado de los mayores con alzheimer y la resiliencia del cuidador informal / The care of the elderly with Alzheimer and the resilience of the informal caregiving

Objetivo:compreender o cuidado com o idoso com a doença de Alzheimer e a resiliência do cuidador informal. Método:pesquisa qualitativa com 20 cuidadores de idosos realizada de agosto a dezembro de 2019 através de um roteiro sociodemográfico-econômico e questões norteadoras analisadas pela Análise de conteúdo e Teoria das Representações Sociais. Resultados:foi observada a complexidade, singularidade e dualidade de sentimentos no cuidado com o idoso com a doença de Alzheimer. Apesar dos cuidadores não compreenderem o significado de resiliência, existe o desenvolvimento de habilidades para o enfrentamento do cotidiano de cuidados. Conclusões:o cuidador convive com a ambivalência de sentimentos e experiências, de caráter semelhante ou oposto, que interferem inteiramente no cuidado prestado e que contribuem na construção do processode resiliência deste cuidador informal familiar.

Objective: to understand the care of the elderly with Alzheimer's disease and the resilience of the informal caregiver. Method: qualitative research with 20 caregivers of the elderly carried out from August to December 2019 through a sociodemographic-economic script and guiding questions that were analyzed by Content Analysis and Theory of Social Representations. Results: the complexity, uniqueness and duality of feelings in the care of the elderly with Alzheimer's disease were observed. Although caregivers do not understand the meaning of resilience, there is the development of skills to cope with daily care. Conclusions: the caregiver lives with the ambivalence of feelings and experiences, of a similar or opposite nature, that interfere entirely in the care provided and that contribute to the construction of the resilience process of this informal family caregiver.

Objetivo: comprender el cuidado del anciano con enfermedad de Alzheimer y la resiliencia del cuidador informal. Método: investigación cualitativa con 20 cuidadores de ancianos realizada de agosto a diciembre de 2019 a través de un guión sociodemográfico-económico y preguntas orientadoras que fueron analizadas por Análisis de Contenido y Teoría de las Representaciones Sociales. Resultados: se observó la complejidad, singularidad ydualidad de sentimientos en el cuidado de ancianos con enfermedad de Alzheimer. Aunque los cuidadores no comprendan el significado de resiliencia, existe el desarrollo de habilidades para afrontar el cuidado diario. Conclusiones: el cuidador vive con la ambivalencia de sentimientos y vivencias, de naturaleza análoga o contraria, que interfieren totalmente en el cuidado prestado y que contribuyen a la construcción del proceso de resiliencia de este cuidador familiar informal.

Assistência de enfermagem em pacientes com Demência do Corpo de Lewy / Nursing assistance in patients with Lewy's Body Dementia

Objetivo: Investigar sobre a assistência de Enfermagem a pacientes com Demência do Corpo de Lewy. Método: Revisão integrativa da literatura, pela busca nas bases de dados, entre os anos de 2009 a 2021, utilizando os descritores: Doença por corpos de Lewy, Doença de Alzheimer, Doença de Parkinson, Assistência de Enfermagem. Resultado: A Demência do Corpo de Lewy é uma doença de difícil diagnóstico, por causa das semelhanças com as Doenças de Alzheimer e Parkinson, seu tratamento é baseado nessas patologias, não seguindo protocolos específicos da doença. A enfermagem tem por função principalmente orientar a família e oferecer uma assistência integral tanto para o paciente, quanto para o cuidador. Conclusão: É necessária, a realização de mais estudos, para entender como assistir um paciente diagnosticado com esta patologia adequadamente, dando suporte para um cuidado de enfermagem mais científico e integral, estabelecendo rotinas, promoveno assim qualidade de vida ao paciente e sua família.(AU)

Objective: To investigate Nursing care for patients with Lewy Body Dementia. Method: Integrative literature review, using the Scielo database, between 2009 and 2021, using the descriptors: Lewy body disease, Alzheimer's disease, Parkinson's disease, Nursing care. Result: Lewy Body Dementia is a disease that is difficult to diagnose, because of the similarities with Alzheimer's and Parkinson's Diseases, its treatment is based on these pathologies, not following disease-specific protocols. Nursing's main function is to guide the family and offer comprehensive care for both the patient and the caregiver. Conclusion: Further studies are needed to understand how to properly care for a patient diagnosed with this pathology, supporting a more scientific and comprehensive nursing care, establishing routines, thus promoting quality of life for patients and their families.(AU)

Objetivo: Investigar el cuidado de Enfermería a pacientes con Demencia con Cuerpos de Lewy. Método: Revisión integrativa de la literatura, utilizando la base de datos Scielo, entre 2009 y 2021, utilizando los descriptores: Enfermedad de cuerpos de Lewy, Enfermedad de Alzheimer, Enfermedad de Parkinson, Cuidados de enfermería. Resultado: La Demencia con Cuerpos de Lewy es una enfermedad de difícil diagnóstico, debido a las similitudes con el Alzheimer y el Parkinson, su tratamiento se basa en estas patologías, no siguiendo protocolos específicos de la enfermedad. La función principal de enfermería es orientar a la familia y ofrecer una atención integral tanto al paciente como al cuidador. Conclusión: Se necesitan más estudios para comprender cómo cuidar adecuadamente a un paciente diagnosticado con esta patología, apoyando un cuidado de enfermería más científico e integral, estableciendo rutinas, promoviendo así la calidad de vida de los pacientes y sus familias.(AU)

Regulación del calcio por SERC-A antes de la enfermedad de Alzheimer y durante la misma / Calcium regulation by SERC-A before and during Alzheimer disease

Hay muchos factores implicados en la incidencia de la enfermedad de Alzheimer que, en combinación, terminan por impedir o dificultar las funciones neuronales normales. Actualmente, poco se conoce sobre la regulación del calcio, antes de la enfermedad y durante la misma. La inestabilidad interna de los niveles de calcio se asocia a un mayor riesgo vascular, condición prevalente en un gran número de individuos ya comprometidos por la enfermedad de Alzheimer. Esta revisión proporciona una reevaluación de los mecanismos moleculares de la ATPasa dependiente de Ca2+ del retículo sarcoendoplásmico (SERC-A) en la enfermedad y analiza los aspectos más destacados de la función de los canales de calcio dependientes de voltaje; de esta manera, se podrán abrir nuevas alternativas de tratamiento. Estos mecanismos de regulación son clínicamente relevantes, ya que se ha implicado la función irregular de SERC-A en diversas alteraciones de la función cerebral.

There are many factors involved in the incidence of Alzheimer's disease that, in combination, impede or hinder normal neuronal functions. Little is currently known about calcium regulation before and during the disease. Internal instability of calcium levels is associated with increased vascular risk, a prevalent condition in a high number of individuals already compromised by Alzheimer's disease. This review provides a reevaluation of the molecular mechanism of the sarcoendoplasmic reticulum calcium ATPase (SERC-A) in the disease and discusses salient aspects of voltage-gated calcium channel function; in these way new alternatives could be open for its treatment. These regulation mechanisms are clinically relevant since the irregular functions of SERC+A has been implicated in pathologies of brain function.

Uncária Tomentosa (Wild.) D.C. em processos inflamatórios na doença de Alzheimer / Uncária Tomentosa (Wild.) D.C. en procesos inflamatorios en la enfermedad de Alzheimer / Uncária Tomentosa (Wild.) D.C. in inflammatory processes in Alzheimer's disease

Objetivo: explorar os mecanismos envolvidos no desencadeamento e progressão da Doença de Alzheimer (DA) de forma a embasar a sugestão da planta Uncaria Tomentosa (Wild.) como mais uma possiblidade terapêutica coadjuvante para prevenção e tratamento da DA. Método: Trata-se de uma revisão narrativa da literatura realizada com busca de artigos publicados em bases indexadas e diretamente nas revistas de interesse, utilizando-se como descritores "Uncária Tomentosa", "Doença de Alzheimer", e os respectivos termos em inglês. Resultados: com os avanços para a compreensão dos mecanismos moleculares que desencadeiam os efeitos apresentados no desenvolvimento da DA, os diversos mecanismos dos fitocompostos presentes na planta sugerem sua utilização como neuroprotetor, por mecanismos anti-inflamatórios, imunomoduladores e antioxidantes, cujas evidências em literatura são apresentadas para defesa de sua utilização nesta patologia. Conclusão: foram encontradas evidências para sugerir a inclusão da Uncaria tomentosa (Wild.) como possível terapêutica complementar no tratamento da DA. Sua utilização deve ser melhor explorada para aplicação como tratamento complementar as terapêuticas convencionais para a DA

Objective: to explore the mechanisms involved in the triggering and progression of Alzheimer's disease (AD) in order to support the suggestion of the Uncaria Tomentosa (Wild.) plant as another adjuvant therapeutic possibility for the prevention and treatment of AD. Method: This is a narrative review of the literature conducted with a search for articles published on indexed bases and directly in the journals of interest, using as descriptors "Uncária Tomentosa", "Alzheimer's disease", and the respective terms in English. Results: with advances to understand the molecular mechanisms that trigger the effects presented in the development of AD, the various mechanisms of phytocompounds present in the plant suggest its use as neuroprotector, by anti-inflammatory, immunomodulatory and antioxidant mechanisms, whose evidence in the literature is presented to defend its use in this pathology. Conclusion: evidence was found to suggest the inclusion of Uncaria tomentosa (Wild.) as a possible complementary therapy in the treatment of AD. Its use should be better explored for application as a complementary treatment to conventional therapies for AD.

Objetivo: explorar los mecanismos implicados en el desencadenamiento y progresión de la enfermedad de Alzheimer (EA) con el fin de apoyar la sugerencia de la planta Uncaria Tomentosa (silvestre) como otra posibilidad terapéutica adyuvante para la prevención y tratamiento de la EA. Método: Se trata de una revisión narrativa de la literatura realizada con una búsqueda de artículos publicados en bases indexadas y directamente en las revistas de interés, utilizando como descriptores "Uncária Tomentosa", "Alzheimer's disease", y los términos respectivos en inglés. Resultados: con los avances para comprender los mecanismos moleculares que desencadenan los efectos presentados en el desarrollo de la EA, los diversos mecanismos de fitocompuestos presentes en la planta sugieren su uso como neuroprotector, por mecanismos antiinflamatorios, inmunomoduladores y antioxidantes, cuya evidencia en la literatura se presenta para defender su uso en esta patología. Conclusión: se encontró evidencia que sugiere la inclusión de Uncaria tomentosa (Silvestre) como una posible terapia complementaria en el tratamiento de la EA. Su uso debe explorarse mejor para su aplicación como tratamiento complementario a las terapias convencionales para la EA.

Mitigating the dilemma in dementia: A case series of the first amyloid brain PET scans in the Philippines

@#Diagnosis of Alzheimer dementia is done clinically using criteria set by different neurological associations. Inevitably, clinicians encounter cases that do not fulfill the set definitions and have to resort to supporting data to form a clinical judgment. Part of the ancillary work-up for dementia is the brain amyloid PET scan that has recently been available in the Philippines. It involves a radiopharmaceutical with high-affinity binding to amyloid plaques which for a time were thought to be central pathological finding for Alzheimer dementia. This study describes the first four amyloid PET scans in the Philippines and detail the protocol as well as interpretation of such studies. The procedure is not as simple and reproducible as one might think hence following the recommended protocol and interpretation guidelines are of utmost importance. We recommend standardization of the reporting of results for all centers that will cater to patients being worked up for dementia, which include reporting SUVRs for both whole cerebellum and cerebellar cortex. More studies are recommended to generate a local Florbetaben SUVR cutoff.

The triggering receptor expressed on myeloid cells 2-apolipoprotein E signaling pathway in diseases / 中华医学杂志(英文版)

Triggering receptor expressed on myeloid cells 2 (TREM2) is a membrane receptor on myeloid cells and plays an important role in the body's immune defense. Recently, TREM2 has received extensive attention from researchers, and its activity has been found in Alzheimer's disease, neuroinflammation, and traumatic brain injury. The appearance of TREM2 is usually accompanied by changes in apolipoprotein E (ApoE), and there has been a lot of research into their structure, as well as the interaction mode and signal pathways involved in them. As two molecules with broad and important roles in the human body, understanding their correlation may provide therapeutic targets for certain diseases. In this article, we reviewed several diseases in which TREM2 and ApoE are synergistically involved in the development. We further discussed the positive or negative effects of the TREM2-ApoE pathway on nervous system immunity and inflammation.

Effects of Yizhi Tiaoshen acupuncture on learning and memory function and the expression of phosphorylated tau protein in the hippocampus of Alzheimer's disease model rats / 中国针灸

OBJECTIVE@#To observe the effects of Yizhi Tiaoshen (benefiting mental health and regulating the spirit) acupuncture on learning and memory function, and the expression of phosphorylated tubulin-associated unit (tau) protein in the hippocampus of Alzheimer's disease (AD) model rats, and explore the effect mechanism of this therapy on AD.@*METHODS@#A blank group and a sham-operation group were randomly selected from 60 male SD rats, 10 rats in each one. AD models were established in the rest 40 rats by the intraperitoneal injection of D-galactose and okadaic acid in the CA1 region of the bilateral hippocampus. Thirty successfully-replicated model rats were randomly divided into a model group, a western medication group and an acupuncture group, 10 rats in each one. In the acupuncture group, acupuncture was applied to "Baihui" (GV 20), "Sishencong" (EX-HN 1), "Neiguan" (PC 6), "Shenmen" (HT 7), "Xuanzhong" (GB 39) and "Sanyinjiao" (SP 6); and the needles were retained for 10 min. Acupuncture was given once daily. One course of treatment was composed of 6 days, with the interval of 1 day; the completion of treatment included 4 courses. In the western medication group, donepezil hydrochloride solution (0.45 mg/kg) was administrated intragastrically, once daily; it took 7 days to accomplish one course of treatment and a completion of intervention was composed of 4 courses. Morris water maze (MWM) and novel object recognition test (NORT) were used to assess the learning and memory function of the rats. Using HE staining and Nissl staining, the morphological structure of the hippocampus was observed. With Western blot adopted, the protein expression of the tau, phosphorylated tau protein at Ser198 (p-tau Ser198), protein phosphatase 2A (PP2A) and glycogen synthase kinase-3β (GSK-3β) in the hippocampus was detected.@*RESULTS@#There were no statistical differences in all of the indexes between the sham-operation group and the blank group. Compared with the sham-operation group, in the model group, the MWM escape latency was prolonged (P<0.05), the crossing frequency and the quadrant stay time in original platform were shortened (P<0.05), and the NORT discrimination index (DI) was reduced (P<0.05); the hippocampal cell numbers were declined and the cells arranged irregularly, the hippocampal neuronal structure was abnormal and the numbers of Nissl bodies decreased; the protein expression of p-tau Ser198 and GSK-3βwas increased (P<0.05) and that of PP2A decreased (P<0.05). When compared with the model group, in the western medication group and the acupuncture group, the MWM escape latency was shortened (P<0.05), the crossing frequency and the quadrant stay time in original platform were increased (P<0.05), and DI got higher (P<0.05); the hippocampal cell numbers were elevated and the cells arranged regularly, the damage of hippocampal neuronal structure was attenuated and the numbers of Nissl bodies were increased; the protein expression of p-tau Ser198 and GSK-3β was reduced (P<0.05) and that of PP2A was increased (P<0.05). There were no statistically significant differences in the above indexes between the acupuncture group and the western medication group (P>0.05).@*CONCLUSION@#Acupuncture therapy of "benefiting mental health and regulating the spirit" could improve the learning and memory function and alleviate neuronal injure of AD model rats. The effect mechanism of this therapy may be related to the down-regulation of GSK-3β and the up-regulation of PP2A in the hippocampus, and then to inducing the inhibition of tau protein phosphorylation.

Eficacia de la terapia de estimulación cognitiva asistida por tecnología en pacientes con demencia / Efficacy of technology-assisted cognitive stimulation therapy in patients with dementia

De la mano del envejecimiento poblacional, la demencia o trastorno neurocognitivo mayor afecta a una cantidad cada vez mayor de personas, lo que implica un alto costo para los servicios de salud. Las guías de práctica clínica recomiendan ofrecer terapias de estimulación cognitiva a las personas afectadas y cada vez es más común el empleo de herramientas tecnológicas que permiten su aplicación a gran escala a pesar de la incertidumbre acerca de su beneficio.En este artículo revisamos la evidencia más actualizada sobre la eficacia de las herramientas computarizadas para el entrenamiento cognitivo de pacientes con demencia. Encontramos algunos estudios que sugieren que podría haber una posible mejora cognitiva en los pacientes con demencia y en la calidad de vida de sus cuidadores. Sin embargo, la mayoría de los estudios no fueron de buena calidad metodológica, fueron realizados con un número limitado de pacientes, en periodos poco prolongados, y los desenlaces fueron evaluados a través de múltiples pruebas de difícil interpretación. (AU)

With the increasing population aging, dementia or major neurocognitive disorder affects a growing number of people,incurring a substantial burden on healthcare services. Clinical practice guidelines recommend providing cognitive stimulation therapies to affected individuals, and the use of technological tools for implementing therapies on a large scale is increasingly common despite the uncertainty about their benefits.In this article, we reviewed the most up-to-date evidence on the effectiveness of computerized tools for cognitive training in patients with dementia. We found some studies that suggest that there could be a possible cognitive improvement in patients with dementia and in the quality of life of their caregivers. However, most studies were not of good methodological quality, were carried out with a limited number of patients, in short periods of time, and the outcomes were evaluated through multiple tests that were difficult to interpret. (AU)

Updated Understanding of the Glial-Vascular Unit in Central Nervous System Disorders / 神经科学通报·英文版

The concept of the glial-vascular unit (GVU) was raised recently to emphasize the close associations between brain cells and cerebral vessels, and their coordinated reactions to diverse neurological insults from a "glio-centric" view. GVU is a multicellular structure composed of glial cells, perivascular cells, and perivascular space. Each component is closely linked, collectively forming the GVU. The central roles of glial and perivascular cells and their multi-level interconnections in the GVU under normal conditions and in central nervous system (CNS) disorders have not been elucidated in detail. Here, we comprehensively review the intensive interactions between glial cells and perivascular cells in the niche of perivascular space, which take part in the modulation of cerebral blood flow and angiogenesis, formation of the blood-brain barrier, and clearance of neurotoxic wastes. Next, we discuss dysfunctions of the GVU in various neurological diseases, including ischemic stroke, spinal cord injury, Alzheimer's disease, and major depression disorder. In addition, we highlight the possible therapies targeting the GVU, which may have potential clinical applications.

Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease / 神经科学通报·英文版

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.

A study on factors associated with age of Alzheimer's disease onset / 中华流行病学杂志

Objective: To understand the distribution characteristics of age of Alzheimer's disease (AD) onset and influencing factors. Methods: Based on the follow-up data of Alzheimer's Disease Neuroimaging Initiative from 2005 to 2022, participants with normal cognition (CN) or mild cognitive impairment (MCI) at baseline survey, and those with progression to AD during follow-up period were selected as study subjects. Univariate analysis and multiple linear regression analysis were performed to explore the associations of gender, race, number of ApoE ε4 genes carried, family history, years of education and marital status with the age of AD onset. Results: A total of 405 participants, with an average age of (74.0±6.9) years at baseline survey, progressed to AD during follow up period. The age of AD onset was (76.6±7.5) years, and age of onset in men was about 1.9 years later than women. Multiple linear regression analysis showed that for each increase in ApoE ε4 gene number, the age of AD onset was about 0.344 years earlier. The age of AD onset was 4.007 years earlier for those with MCI at baseline survey compared with those with CN. Years of education were not significantly associated with the age of onset of AD (P>0.05). Conclusion: Those who carry ApoE ε4 gene, and have MCI at baseline survey might have earlier age of AD onset.

Research progress of fibroblast growth factor in nervous system diseases / 浙江大学学报·医学版

Fibroblast growth factors (FGF) are a group of structurally related polypeptides which constitute an elaborate signaling system with their receptors. Evidence accumulated in the years suggests that the FGF family plays a key role in the repair of central nervous system injury. The main protective mechanisms include activating the expression of PI3K-Akt, peroxisome proliferator-activated receptor (PPARγ) and other signals; inhibiting NF-κB-mediated inflammatory response, oxidative stress and apoptosis; regulating neuronal differentiation and neuronal excitability as well as participating in protection of neurovascular units and nerve function repair. This paper comprehensively summarizes the latest research progress in FGF signaling related to diseases of the central nervous system such as cerebral infarction, cerebral hemorrhage, traumatic brain injury, Alzheimer's disease, Parkinson's disease, epilepsy and depression, aiming to provide scientific basis and reference for the development of innovative FGF drugs for the prevention and treatment of neurological diseases.

Visual analysis of research on traditional Chinese medicine treatment of Alzheimer's disease in recent ten years / 中国中药杂志

This study employed bibliometrics tools to review the studies of traditional Chinese medicine(TCM) treatment of Alzheimer's disease(AD) in recent ten years, aiming to explore the research status, hotspots, and future trends in this field at home and abroad. The relevant literature published from January 1, 2012 to August 15, 2022 was retrieved from Web of Science and CNKI. CiteSpace 6.1R2 and VOSviewer 1.6.15 were used for the visual analysis of authors, countries, institutions, keywords, journals, etc. A total of 2 254 Chinese articles and 545 English articles were included. The annual number of articles published showed a rising trend with fluctuations. The country with the largest number of relevant articles published and the largest centrality was China. SUN Guo-jie and WANG Qi were the authors publishing the most Chinese articles and English articles, respectively. Hubei University of Chinese Medicine and Beijing University of Chinese Medicine published the most articles in Chinese and English, respectively. Journal of Ethnopharmacology and Neuroscience Letters published the articles with the highest cited frequency and the highest centrality. According to the keywords, the research on TCM treatment of AD mainly focused on the mechanism of action and treatment methods. Metabolomics, intestinal flora, oxidative stress, tau hyperphosphorylation, β-amyloid(Aβ), inflammatory cytokines, and autophagy were the focuses of the research on mechanism of action. Acupuncture, clinical effect, kidney deficiency and phlegm stasis, and dredging governor vessel to revitalize mind were the hotspots of clinical research. This research field is still in the stage of exploration and development. Exchanges and cooperation among institutions should be encouraged to carry out more high-quality basic research on TCM treatment of AD, obtain high-level evidence, and clarify the pathogenesis and prescription mechanism.

Mechanism of Sijunzi Decoction in treatment of Alzheimer's disease based on UPLC-Q-TOF-MS, network pharmacology, and experimental verification / 中国中药杂志

The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.

Review of traditional Chinese medicines in ameliorating neuropsychiatric diseases by improving the levels of monoamine neurotransmitters via gut microbiota regulation / 中国中药杂志

The degeneration of monoaminergic system and the reduction of monoamine neurotransmitters(MNTs) are associated with the occurrence of a variety of neuropsychiatric diseases, becoming the key indicators for clinical diagnosis and treatment. Recent studies suggested gut microbiota could influence the occurrence, development, and treatment of neuropsychiatric diseases by directly or indirectly regulating the synthesis and metabolism of MNTs. Rich clinical experience has been accumulated in the amelioration and treatment of neuropsychiatric diseases by traditional Chinese medicines. The traditional oral administration method demonstrates obvious advantages in regulating gut microbiota. It provides a new idea for explaining the pharmacodynamic material basis and mechanism of traditional Chinese medicines in ameliorating neuropsychiatric disease by improving the levels of MNTs via gut microbiota regulation. Focusing on three common neuropsychiatric diseases including Alzheimer's disease, Parkinson's disease, and major depression, we summarized the pathways of gut microbiota in regulating the levels of MNTs and the paradigms of traditional Chinese medicines in ameliorating neuropsychiatric diseases via the "bacteria-gut-brain axis", aiming to provide ideas for the development of drugs and treatment schemes.

Mechanism of Berberis atrocarpa anthocyanin against Alzheimer's disease based on network pharmacology and experimental verification / 中国中药杂志

This study aimed to explore the potential mechanism of Berberis atrocarpa Schneid. anthocyanin against Alzheimer's disease(AD) based on network pharmacology, molecular docking technology, and in vitro experiments. Databases were used to screen out the potential targets of the active components of B. atrocarpa and the targets related to AD. STRING database and Cytoscape 3.9.0 were adopted to construct a protein-protein interaction(PPI) network and carry out topological analysis of the common targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed on the target using the DAVID 6.8 database. Molecular docking was conducted to the active components and targets related to the nuclear factor kappa B(NF-κB)/Toll-like receptor 4(TLR4) pathway. Finally, lipopolysaccharide(LPS) was used to induce BV2 cells to establish the model of AD neuroinflammation for in vitro experimental validation. In this study, 426 potential targets of active components of B. atrocarpa and 329 drug-disease common targets were obtained, and 14 key targets were screened out by PPI network. A total of 623 items and 112 items were obtained by GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking results showed that NF-κB, NF-κB inhibitor(IκB), TLR4, and myeloid differentiation primary response 88(MyD88) had good binding abilities to the active components, and malvidin-3-O-glucoside had the strongest binding ability. Compared with the model group, the concentration of nitric oxide(NO) decreased at different doses of malvidin-3-O-glucoside without affecting the cell survival rate. Meanwhile, malvidin-3-O-glucoside down-regulated the protein expressions of NF-κB, IκB, TLR4, and MyD88. This study uses network pharmacology and experimental verification to preliminarily reveal that B. atrocarpa anthocyanin can inhibit LPS-induced neuroinflammation by regulating the NF-κB/TLR4 signaling pathway, thereby achieving the effect against AD, which provides a theoretical basis for the study of its pharmacodynamic material basis and mechanism.

Effect on Danggui Shaoyao Powder on mitophagy in rat model of Alzheimer's disease based on PINK1-Parkin pathway / 中国中药杂志

This study investigated the mechanism of Danggui Shaoyao Powder(DSP) against mitophagy in rat model of Alzheimer's disease(AD) induced by streptozotocin(STZ) based on PTEN induced putative kinase 1(PINK1)-Parkin signaling pathway. The AD rat model was established by injecting STZ into the lateral ventricle, and the rats were divided into normal group, model group, DSP low-dose group(12 g·kg~(-1)·d~(-1)), DSP medium-dose group(24 g·kg~(-1)·d~(-1)), and DSP high-dose group(36 g·kg~(-1)·d~(-1)). Morris water maze test was used to detect the learning and memory function of the rats, and transmission electron microscopy and immunofluorescence were employed to detect mitophagy. The protein expression levels of PINK1, Parkin, LC3BⅠ/LC3BⅡ, and p62 were assayed by Western blot. Compared with the normal group, the model group showed a significant decrease in the learning and memory function(P<0.01), reduced protein expression of PINK1 and Parkin(P<0.05), increased protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05), and decreased occurrence of mitophagy(P<0.01). Compared with the model group, the DSP medium-and high-dose groups notably improved the learning and memory ability of AD rats, which mainly manifested as shortened escape latency, leng-thened time in target quadrants and elevated number of crossing the platform(P<0.05 or P<0.01), remarkably activated mitophagy(P<0.05), up-regulated the protein expression of PINK1 and Parkin, and down-regulated the protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05 or P<0.01). These results demonstrated that DSP might promote mitophagy mediated by PINK1-Parkin pathway to remove damaged mitochondria and improve mitochondrial function, thereby exerting a neuroprotective effect.

Therapeutic potential of targeting SIRT1 for the treatment of Alzheimer's disease / 生理学报

Silent information regulator 1 (SIRT1) is one of the seven mammalian proteins of the sirtuin family of NAD+-dependent deacetylases. SIRT1 plays a pivotal role in neuroprotection and ongoing research has uncovered a mechanism by which SIRT1 may exert a neuroprotective effect on Alzheimer's disease (AD). Growing evidence demonstrates that SIRT1 regulates many pathological processes including amyloid-β precursor protein (APP) processing, neuroinflammation, neurodegeneration, and mitochondrial dysfunction. SIRT1 has recently received enormous attention, and pharmacological or transgenic approaches to activate the sirtuin pathway have shown promising results in the experimental models of AD. In the present review, we delineate the role of SIRT1 in AD from a disease-centered perspective and provides an up-to-date overview of the SIRT1 modulators and their potential as effective therapeutics in AD.

Effect of electroacupuncture at different frequencies on brain insulin signaling transduction pathway in Alzheimer's disease mice / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at different frequencies on learning and memory functions, as well as the relevant proteins of brain insulin signal transduction pathway in Alzheimer's disease (AD) mice and explore the effect mechanism of EA in treatment of AD.@*METHODS@#Seventy-two SPF Kunming male mice were randomized into a blank group, a sham-operation group, a model group, a 2 Hz EA group, a 15 Hz EA group and a 30 Hz EA group, 12 mice in each one. In the model group and each EA group, AD model were established by the injection with streptozotocin (ST2) solution (8 mg/kg) into the left lateral ventricles. In the sham-operation group, 0.9% sodium chloride solution of the same volume was injected into the left lateral ventricles. After successful modeling, in each EA group, EA was applied at "Baihui" (GV 20), "Dazhui" (GV 14) and "Shenshu" (BL 23) with corresponding frequencies, once daily. One course of EA intervention consisted of 7 treatments and 2 courses were given totally at interval of 1 day. After modeling and intervention, Morris water maze test was conducted for the mice of each group. Using immunohistochemistry and Western blot method, the protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K) was detected in the hippocampal of the mice after intervention.@*RESULTS@#Compared with the blank group, in the model group, the 2 Hz, 15 Hz and 30 Hz EA groups, the escape latency and the first time of crossing the platform were all extended (P<0.01), and the number of crossing the platform was reduced (P<0.01) after modeling. When compared with the blank group, the escape latency and the first time of crossing the platform were all extended (P<0.01), and the number of crossing the platform was reduced (P<0.01) in the model group after intervention. In the 2 Hz, 15 Hz and 30 Hz EA groups, the escape latency and the first time of crossing the platform were all shortened (P<0.01), and the number of crossing the platform was increased (P<0.05, P<0.01) after intervention when compared with the model group. The escape latency and the first time of crossing the platform were all shortened (P<0.01, P<0.05), and the number of crossing the platform was increased (P<0.05) in the 15 Hz and 30 Hz EA groups in comparison with the 2 Hz EA group. The protein expression levels of IR, IRS-1 and PI3K were reduced in the model group when compared with those of the blank group (P<0.01, P<0.05); and these protein expression levels were increased in the 15 Hz and 30 Hz EA groups compared with the model group (P<0.05, P<0.01). Compared with the 2 Hz EA group, the protein expression levels of IR, IRS-1 and PI3K were all elevated in the 15 Hz and 30 Hz EA groups (P<0.05).@*CONCLUSION@#The learning and memory function of AD mice may be improved through regulating brain insulin signaling transconduction pathway with electroacupuncture, and electroacupuncture at 15 Hz and 30 Hz obtains the overall better effect compared with the intervention at 2 Hz.