Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer's Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice / 神经科学通报·英文版

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.

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.

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)

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.

DJ1 Ameliorates AD-like Pathology in the Hippocampus of APP/PS1 Mice / 生物医学与环境科学（英文）

OBJECTIVE@#To explore whether the protein Deglycase protein 1 (DJ1) can ameliorate Alzheimer's disease (AD)-like pathology in Amyloid Precursor Protein/Presenilin 1 (APP/PS1) double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD.@*METHODS@#Adeno-associated viral vectors (AAV) of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown. Mice were divided into the AD model control group (MC), AAV vector control group (NC), DJ1-overexpression group (DJ1 +), and DJ1-knockdown group (DJ1 -). After 21 days, the Morris water maze test, immunohistochemistry, immunofluorescence, and western blotting were used to evaluate the effects of DJ1 on mice.@*RESULTS@#DJ1 + overexpression decreased the latency and increased the number of platform traversals in the water maze test. DJ1 - cells were cured and atrophied, and the intercellular structure was relaxed; the number of age spots and the expression of AD-related proteins were significantly increased. DJ1 + increased the protein expression of Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), light chain 3 (LC3), phosphorylated AMPK (p-AMPK), and B cell lymphoma-2 (BCL-2), as well as the antioxidant levels of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and Glutathione peroxidase (GSH-PX), while decreasing the levels of Kelch-like hydrates-associated protein 1 (Keap1), mammalian target of rapamycin (mTOR), p62/sequestosome1 (p62/SQSTM1), Caspase3, and malondialdehyde (MDA).@*CONCLUSION@#DJ1-overexpression can ameliorate learning, memory, and AD-like pathology in APP/PS1 mice, which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.

Effect of acupuncture at the acupoints for Yizhi Tiaoshen on the functional connectivity between the hippocampus and the brain in the patients with Alzheimer's disease / 中国针灸

OBJECTIVES@#To analyze the effect of acupuncture at the acupoints for Yizhi Tiaoshen (benefiting the intelligence and regulating the spirit) on the functional connectivity between the hippocampus and the whole brain in the patients with Alzheimer's disease (AD), and reveal the brain function mechanism of acupuncture in treatment of AD using resting state functional magnetic resonance imaging (rs-fMRI).@*METHODS@#Sixty patients with mild to moderate AD were randomly divided into an acupuncture + medication group (30 cases, 3 cases dropped out) and a western medication group (30 cases, 2 cases dropped out). In the western medication group, the donepezil hydrochloride tablets were administered orally, 2.5 mg to 5 mg each time, once daily; and adjusted to be 10 mg each time after 4 weeks of medication. Besides the therapy as the western medication group, in the acupuncture + medication group, acupuncture was supplemented at the acupoints for Yizhi Tiaoshen, i.e. Baihui (GV 20), Sishencong (EX-HN 1), and bilateral Shenmen (HT 7), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6) and Xuanzhong (GB 39). The needles were retained for 30 min in one treatment, once daily; and 6 treatments were required weekly. The duration of treatment was 6 weeks in each group. The general cognitive function was assessed by the mini-mental state examination (MMSE) and Alzheimer's disease assessment scale-cognitive part (ADAS-Cog) before and after treatment in the two groups. Using the rs-fMRI, the changes in the functional connectivity (FC) of the left hippocampus and the whole brain before and after treatment were analyzed in the patients of the two groups (11 cases in the acupuncture + medication group and 12 cases in the western medication group).@*RESULTS@#After treatment, compared with those before treatment, MMSE scores increased and ADAS-Cog scores decreased in the two groups (P<0.05); MMSE score was higher, while the ADAS-Cog score was lower in the acupuncture + medication group when compared with those in the western medication group (P≤0.05). After treatment, in the western medication group, FC of the left hippocampus was enhanced with the left fusiform gyrus, the inferior frontal gyrus of the left triangular region, the bilateral superior temporal gyrus and the right superior parietal gyrus (P<0.05), while FC was weakened with the left inferior temporal gyrus, the left middle frontal gyrus and the right dorsolateral superior frontal gyrus when compared with that before treatment (P<0.05). After treatment, in the acupuncture + medication group, FC of the left hippocampus was increased with the right gyrus rectus, the left inferior occipital gyrus, the right superior temporal gyrus and the left middle occipital gyrus (P<0.05), and it was declined with the left thalamus (P<0.05) when compared with those before treatment. After treatment, in the acupuncture + medication group, FC of the left hippocampus was strengthened with the bilateral inferior temporal gyrus, the bilateral middle temporal gyrus, the right gyrus rectus, the bilateral superior occipital gyrus, the left lenticular nucleus putamen, the left calcarine fissure and surrounding cortex, the inferior frontal gyrus of the left insulae operculum, the left medial superior frontal gyrus and the right posterior central gyrus (P<0.05) compared with that of the western medication group.@*CONCLUSIONS@#Acupuncture at the acupoints for Yizhi Tiaoshen improves the cognitive function of AD patients, and its main brain functional mechanism is related to intensifying the functional connectivity of the left hippocampus with the default network (inferior temporal gyrus, middle temporal gyrus and superior frontal gyrus, gyrus rectus), as well as with the sensory (posterior central gyrus) and visual (calcarine fissure and surrounding cortex and superior occipital gyrus) brain regions.

Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways / 中国结合医学杂志

OBJECTIVE@#To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD) in vivo.@*METHODS@#Senescence-accelerated mouse prone 8 (SAMP8) mice were used as AD models and received EA at Yingxiang (LI 20, bilateral) and Yintang (GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin (2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier (BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid- β (Aβ), and ionized calcium-binding adapter molecule 1 (IBa-1) in mouse hippocampus (CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining. Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.@*RESULTS@#Fibrin was time-dependently deposited in the hippocampus of SAMP8 mice and this was inhibited by EA treatment (P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice (P<0.01), which was reversed by fibrin injection (P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability (P<0.05 or P<0.01). Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8 mice, which was reversed by fibrin injection (P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1 (HMGB1)/toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) signaling pathways (P<0.01).@*CONCLUSION@#EA may potentially improve cognitive impairment in AD via inhibition of fibrin/A β deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.

Effect of electroacupuncture on proliferation of hippocampal neural stem cells in young mice with Alzheimer's disease / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on the proliferation of endogenous neural stem cells in the hippocampus of young mice with Alzheimer's disease (AD), so as to explore its mechanisms underlying improvement of AD.@*METHODS@#Forty 1.5-month-old APP/PS1 transgenic male mice were randomly divided into an EA group and a model group, 20 mice in each group, and other 20 C57BL/6J male mice of the same age were used as the normal control group. EA (intermittment wave 10 Hz, 2 mA) was applied to "Baihui" (GV 20), "Fengfu" (GV 16) and "Shenshu" (BL 23) for 20 min, once a day, 6 days a week for 16 weeks. H.E. staining was used to assess histopathological changes of neurons of the hippocampal dentate gyrus. Immunohistochemical stain was used to detect the expression of 5-bromodeoxyuridine (BrdU)-positive in the hippocampus, and immunofluorescence double-labeled technique was used to detect the number of proliferated positive neurons of hippocampal neural stem cells. The expression levels of brain derived neurotrophic factor (BDNF) and Nestin mRNA and protein were detected by using real-time PCR and Western blot, separately.@*RESULTS@#The immunoactivity of BrdU, and the expression levels of BDNF and Nestin mRNA and protein in the hippocampus in the model group were significantly lower than in the normal control group (P<0.01, P<0.05), and considerably higher in the EA group than in the model group (P<0.01, P<0.05). The number of BrdU/NeuN dual labeled neurons was slightly increased in the model group than in the normal control group (P>0.05), and evidently increased in the EA group relevant to the model group (P<0.05), suggesting a proliferation of hippocampal neural stem cells. After modeling, the neurons of hippocampal dentate gyrus were arranged loosely and irregularly and their structure was fuzzy, with an appearance of different degrees of nuclear pyknosis, whereas in the EA group, the neuronal contour was clear and the nuclear structure was relatively distinct.@*CONCLUSION@#EA can activate the proliferation of neural stem cells in the hippocampus in AD mice, which may contribute to its function in improving the neuronal structure by upregulating the expression of BDNF.

Physical exercise is effective for neuropsychiatric symptoms in Alzheimer's disease: a systematic review / Exercício físico é efetivo para sintomas neuropsiquiátricos na doença de Alzheimer: uma revisão sistemática

ABSTRACT Background: Neuropsychiatric symptoms are disorders frequently seen in Alzheimer's disease. These symptoms contribute to reduction of brain reserve capacity and, in addition, they present unfavorable implications, such as: poor prognosis for the disease, increased functional decline, increased burden on the caregiver and institutionalization. This scenario makes neuropsychiatric symptoms one of the biggest problems in Alzheimer's disease, and gives rise to a need for treatments focused on improving these symptoms. Sow progress in drug trials has led to interest in exploring non-pharmacological measures for improving the neuropsychiatric symptoms of Alzheimer's disease, such as physical exercise. Objective: To ascertain the effect of exercise on the neuropsychiatric symptoms of Alzheimer's disease and its implications. Methods: This was a systematic review of effective longitudinal research, conducted by searching for articles in the PubMed, Web of Science, CINAHL and Scopus electronic databases, from 2009 to 2019. Studies in which the sample consisted of elderly people aged 65 years old or over with a diagnosis of Alzheimer's disease were included. Initially 334 articles were identified. After exclusions, 21 articles remained to be read in full. From these, five articles fitted the eligibility criteria, and a further two articles were added through manual searches in the references of the articles found. Results: Out of the seven articles analyzed in this review, five studies revealed that physical exercise had a positive effect on the neuropsychiatric symptoms of Alzheimer's disease. Conclusion: This systematic review indicated that physical exercise is a favorable non-pharmacological means for attenuating the neuropsychiatric symptoms of elderly people with Alzheimer's disease, with special attention to aerobic exercises.

RESUMO Introdução: Sintomas neuropsiquiátricos são desordens frequentemente observadas na Doença de Alzheimer, os quais contribuem para a diminuição da capacidade de reserva cerebral e ocasiona implicações ruins, como mau prognóstico da doença, aumento do declínio funcional, aumento da sobrecarga do cuidador e institucionalização. Esse cenário faz com que os sintomas neuropsiquiátricos se tornem um dos maiores problemas da Doença de Alzheimer, incitando, assim, o interesse em explorar medidas não-farmacológicas nos sintomas neuropsiquiátricos na Doença de Alzheimer, como o exercício físico. Objetivo: Verificar o efeito do exercício físico em sintomas neuropsiquiátricos da Doença de Alzheimer e suas implicações. Métodos: Trata-se de uma revisão sistemática com pesquisas longitudinais efetivadas por meio da busca de artigos nas bases de dados eletrônicas: PubMed, Web of Science, CINAHL e Scopus, de 2009 a 2019. Foram incluídos estudos cuja amostra foi constituída por idosos com diagnóstico de Doença de Alzheimer com idade igual ou acima de 65 anos. Inicialmente, foram identificados 334 artigos; após as exclusões, restaram 21 artigos para leitura na íntegra. Destes, cinco artigos se enquadraram nos critérios de elegibilidade, assim como dois artigos adicionados por meio de busca manual nas referências dos artigos encontrados. Resultados: Dos sete artigos analisados na presente revisão, cinco estudos revelaram um efeito positivo do exercício físico em sintomas neuropsiquiátricos na Doença de Alzheimer. Conclusão: Esta revisão sistemática indica que o exercício físico é um meio não-farmacológico favorável à atenuação dos sintomas neuropsiquiátricos de idosos com Doença de Alzheimer, com especial atenção na modalidade aeróbia.

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases / 神经科学通报·英文版

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.

Protective function of electroacupuncture on young mouse model of Alzheimer's disease and proteomic study / 中国针灸

OBJECTIVE@#To screen protein target in prevention and treatment with electroacupuncture (EA) for Alzheimer's disease (AD) and explore the potential mechanism of EA in prevention of AD.@*METHODS@#A total of 40 APP/PS1 transgenic young male mice, 1.5-month old, were randomized into an EA group and a model group, 20 mice in each one, and 20 C57BL/6J mice were chosen as the normal control group. After adaptive housing for 1 week, the mice in the EA group were stimulated with EA at "Baihui" (GV 20), "Fengfu" (GV 16) and "Shenshu" (BL 23), with intermittent wave, 10 Hz in frequency and 2 mA in electric intensity. EA was given once daily, 20 min each time. There was 1 day at interval after EA for 6 days each week. Totally, the intervention lasted for 16 weeks. On day 3 after the end of EA intervention, Morris water maze test was adopted to detect learning and memory abilities of mice in each group. After water maze test, the label-free method was used to measure the difference expressions in cerebral cortex and hippocampus. Using Western blot method, the expressions of guanylate binding protein beta 5 (GNB 5) and histone-H 3 in cerebral cortex and hippocampus were verified. Using immunohistochemical method, the expressions of amyloid beta protein (Aβ) in cerebral cortex and hippocampus were detected.@*RESULTS@#Compared with the normal control group, the escape latency (on day 2, 3 and 4) was prolonged, the frequency of crossing platform and the duration of platform stay were decreased in the mice of the model group (@*CONCLUSION@#The intervention with EA effectively prevents from the decline of learning and memory ability and the formation of Aβ senile plaques in cerebral cortex and hippocampus in young mouse models of AD after growing up. Besides, EA plays a regulatory function for protein expression differences induced by AD model.

Factors affecting the efficacy of repetitive transcranial magnetic stimulation for patients with Alzheimer's disease / 浙江大学学报·医学版

Repetitive transcranial magnetic stimulation (rTMS) is a safe and non-invasive technique. In recent years, many studies have demonstrated that rTMS can improve cognitive function in Alzheimer's disease (AD) patients and has potential as a therapeutic method for AD. However, the efficacy varies greatly with different rTMS treatment regimens, which is related to the frequency, type, location, duration, intensity and focusing power of stimulation. Recent studies have shown that high-frequency stimulation is superior to low-frequency stimulation; efficacy of intermittent theta burst stimulation (iTBS) is similar to that of conventional rTMS, but iTBS treatment session is shorter and might be more acceptable for AD patients; rTMS stimulation sites targeting AD-damaged brain regions or associated networks would be more effective; short-term intensive treatment combined with long-term maintenance treatment can gain long-term efficacy; dynamic adjustment of stimulus intensity combined with the degree of cognitive impairment can enhance the efficacy; functional connection based on functional magnetic resonance imaging may improve the focusing power of rTMS. In this article, we review the factors related to the efficacy of rTMS, to provide reference for feasible rTMS therapeutic regimens of AD.

Effect of pretreatment of acupuncture on learning-memory ability and related protein of NLRP3 inflammasome in hippocampus in Alzheimer's disease like rats / 中国针灸

OBJECTIVE@#To observe the effect of pretreatment of acupuncture on the expression of nucleotide-binding oligomerization domain-like receptor 3(NLRP3), Caspase-1, interleukin1β(IL-1β) and the number of activated microglia (MG) in the hippocampus in Alzheimer's disease (AD) like rats, so as to explore the mechanism of pretreatment of acupuncture in preventing and treating AD.@*METHODS@#A total of 36 SD rats were randomly divided into a blank group, a model group and an electroacupuncture (EA) group, 12 rats in each group. The AD like rat model was established by 8-week continuous intraperitoneal injection of D-galactose (120 mg·kg@*RESULTS@#Compared with the blank group, the average escape latency was prolonged (@*CONCLUSION@#Pretreatment of acupuncture could prevent and treat the learning-memory dysfunction in AD like rats, and its mechanism may be related to the inhibition of NLRP3 inflammatsome related protein and MG activation.

Prevalencia de factores de riesgo cardiovascular en Enfermedad de Alzheimer en Hospital Clínico Herminda Martin de Chillán, Chile / Prevalence of cardiovascular risk factors in Alzheimer's disease in Herminda Martin Clinical Hospital of Chillán, Chile

La Enfermedad de Alzheimer (EA) es un trastorno neurodegenerativo de causa incierta que afecta progresivamente las capacidades intelectuales, memoria, juicio y la conciencia. Factores de riesgo cardiovascular (FRCV) tales como Hipertensión arterial o diabetes mellitus se asocian consistentemente con mayor riesgo de desarrollar demencia vascular, mixta y EA. Objetivo: Determinar la prevalencia de FRCV en pacientes adultos mayores con EA, pertenecientes al policlínico del Hospital Clínico Herminda Martín (HCHM) entre los años 2012 al 2016. Materiales y métodos: Se recopilaron fichas clínicas de 42 pacientes con EA, 39 cumplían con los criterios de inclusión. Se calculó la prevalencia de siete FRCV considerados en el estudio. Resultados: Del total de pacientes, 56.4% fueron mujeres y 43,6% hombres. La prevalencia de presión arterial alta en la población fue 77%, hiperglicemia fue de un 38%, pacientes con índice de masa corporal (IMC) ≥ 30 Kg/m2 fueron un 15%, dislipidemia fue de un 26%. La prevalencia de Evento Cardiovascular Mayor fue de un 33,3%. Tabaquismo y consumo de alcohol, sus prevalencias fueron de 10,2% y 15,3% respectivamente. Conclusión: De los FRCV medidos, el más prevalente en EA es la presión arterial alta, por lo tanto, la implicancia que puede tener una intervención temprana sobre la esta y los otros FRCV estudiados, en la incidencia y la prevalencia de la EA sería de gran importancia para la prevención primaria de la enfermedad y/o determinar mejores tratamientos.

Alzheimer's disease (AD) is a neurodegenerative disorder of uncertain cause that progressively affects intellectual abilities, memory, impoverishment of judgment and self-awareness, one's own situation and ability. Vascular risk factors such as hypertension or diabetes mellitus are consistently associated with an increased risk of developing not only vascular dementia or mixed dementia, but also AD. Objective: To determine the prevalence of cardiovascular risk factors in elderly patients with AD, belonging to the polyclinic of the Clinical Hospital Herminda Martín (HCHM) between 2012 and 2016. Materials and methods: Clinical records of 42 patients with disease were collected of Alzheimer's, 39 met the inclusion and exclusion criteria. The prevalence of seven cardiovascular risk factor considered in the study were calculated. Results: Of the total patients, 56.4% were women and 43.6% men. The prevalence of high blood pressure in the population was 77%, of hyperglycemia was 38%, patients with BMI> 30 Kg / m2 were 15%, dyslipidemia was 26%, the prevalence of major cardiovascular event was 33%. Smoking and alcohol consumption, their prevalences were 10.2% and 15.3% respectively. Conclusion: Of the cardiovascular risk factors measured, the most prevalent in AD is high blood pressure, therefore, the implication that an early intervention on high blood pressure and the other measured CV risk factors may have on the incidence and the prevalence of Alzheimer's disease would be of great importance for primary prevention or determine better treatments.

Progress in lentiviral vector-mediated gene therapy for Alzheimer's disease and Parkinson's disease / 生物工程学报

Alzheimer's disease (AD) and Parkinson's disease (PD) are common neurodegenerative diseases in human. The pathogenesis of AD and PD is complex, and the current drugs and surgical treatments have not successfully alleviated or terminated the progression of the diseases. The lentiviral vector (LV) is a retroviral vector. In recent years, LV mediated gene therapy has been a hotspot to study the mechanisms of human disease and clinical drug discovery. This review summarizes the recent progresses in the treatment of AD and PD by the application of LV, and offers a prospect for its application.

Cápsulas de arte: memoria frente al Alzheimer / Art capsule: memory to fight Alzheimer's / Cápsula de arte: memória contra a doença de Alzheimer

El presente trabajo analiza, a través de una técnica de panel, denominada "de cohorte", las reflexiones de las investigadoras españolas en el campo del Arte y del Alzheimer, con el fin de estudiar su trayectoria profesional y de relacionar las conclusiones de sus trabajos, con los resultados del Informe Mundial de la Organización Mundial de la Salud (OMS), el cual establece, por vez primera, una correlación positiva entre las variables arte y salud, situando el compromiso ético del arte, en la vanguardia de la investigación. Las conclusiones derivadas del estudio muestran, cómo al hablar de sí mismas, las investigadoras se definen no sólo como educadoras artísticas, sino también como cuidadoras, reconociendo el papel del contexto, esto es de su propia bibliografía, como determinante en las investigaciones que han realizado en el campo de la Educación Artística aplicada al Alzheimer.(AU)

The objective of this study is to analyze—through a panel technique called "cohort"—the authors' reflections on the fields of Arts and Alzheimer's in order to study their professional path and correlate the conclusions of their work with the results presented on the Health Evidence Network synthesis report 67 of the World Health Organization (WHO). For the first time, the report establishes a positive correlation between the arts and health, highlighting the importance of the ethical commitment of the arts to the research. The conclusions of this study show how the researchers refer to themselves as both "arts educators" and "caregivers," acknowledging the decisive role of context, i.e. their won biographies, to the research conducted in the field of Arts Education applied to Alzheimer's.(AU)

O presente trabalho analisa, por meio de uma técnica de painel denominada "coorte", as reflexões das investigadoras espanholas no campo da Arte e do Alzheimer, com o fim de estudar o seu percurso profissional e de relacionar as conclusões dos seus trabalhos com os resultados do Relatório Mundial da Organização Mundial da Saúde (OMS), que estabelece, pela primeira vez, uma correlação positiva entre as variáveis arte e saúde, situando o compromisso ético da arte na vanguarda da investigação. As conclusões resultantes do estudo mostram como, ao falar de si mesmas, as pesquisadoras definem-se não só como educadoras artísticas, mas também como cuidadoras, reconhecendo o papel do contexto, isto é, de suas próprias biografias como determinantes nas investigações que realizaram no domínio da Educação Artística aplicada ao Alzheimer.(AU)

Physical therapy in patients with Alzheimer's disease: a systematic review of randomized controlled clinical trials / Fisioterapia em pacientes com doença de Alzheimer: uma revisão sistemática de ensaios clínicos randomizados controlados / Fisioterapia en pacientes con enfermedad de Alzheimer: una revisión sistemática de ensayos clínicos aleatorizados controlados

ABSTRACT The objective of this study is to evaluate the effects of physical therapy on the cognitive and functional capacity of patients with Alzheimer's Disease (AD). This is a systematic review of randomized or quasi-randomized clinical trials, using the descriptors: AD, dementia and physical therapy. Two studies were included with a total of 207 participants. In study 1, no statistically significant difference was found on the mini-mental state examination (MMSE) (MD 0.0, 95%CI −5.76 to 5.76), neuropsychiatric inventory (MD −4.50, 95%CI −21.24 to 12.24) and Pfeffer instrumental activities questionnaire (MD 0.0 95%CI −6.48 to 6.48). In study 2, there was no statistically significant difference on the MMSE (MD −1.60, 95% CI −3.57 to 0.37), clock-drawing test (MD −0.20, 95%CI −0.61 to 0.21) and Alzheimer's Disease Assessment Scale - cognitive subscale (MD 1.0, 95%CI −2.21 to 4.21) after 12 months. There was no consistent evidence on the effectiveness of physiotherapeutic intervention in improving cognitive function and functional capacity of patients with AD. More studies should be conducted for better evidence.

RESUMO O objetivo do estudo é avaliar os efeitos da fisioterapia na capacidade cognitiva e funcional de pacientes com doença de Alzheimer (DA). Trata-se de revisão sistemática de ensaios clínicos randomizados ou quasi-randomizados utilizando os descritores: DA, demência e fisioterapia. Dois estudos foram incluídos, com um total de 207 participantes. No Estudo 1, não houve diferença estatisticamente significativa no miniexame do estado mental (MEEM) (MD 0,0, IC 95% 5,76−5,76), inventário neuropsiquiátrico (MD −4,50, IC 95% 12,24−21,24) e questionário de atividades instrumentais Pfeffer (MD 0,0 IC 95% −6,48 a 6,48). No Estudo 2, não houve diferença estatisticamente significativa no MEEM (MD −1,60, IC 95% −3,57 a 0,37), teste do desenho do relógio (MD −0,20, IC95% −0,61 a 0,21) e escala de avaliação da doença de Alzheimer - subitem cognição (MD 1,0, IC95% −2,21 a 4,21) após 12 meses. Não houve evidência consistente da eficácia da intervenção fisioterapêutica na melhora da função cognitiva e capacidade funcional na DA. Recomenda-se a produção de mais estudos para encontrar possíveis evidências.

RESUMEN El presente estudio tiene como objetivo evaluar los efectos de la fisioterapia en la capacidad cognitiva y funcional de pacientes con enfermedad de Alzheimer (EA). Se trata de una revisión sistemática de ensayos clínicos aleatorizados o casi-aleatorizados, en que se utilizó los descriptores: EA, demencia y fisioterapia. Se incluyeron dos estudios, con un total de 207 participantes. En el Estudio 1, no hubo diferencias estadísticamente significativas en el Miniexamen del estado mental (MEEM) (MD 0,0, IC 95%: 5,6 -5,76), en el inventario neuropsiquiátrico (MD -4,50, IC 95%: 12,24 -21,24) y en el cuestionario de actividades instrumentales de Pfeffer (MD: 0,0 IC 95% IC: -6,48 a 6,48). En el Estudio 2, no hubo diferencias estadísticamente significativas en el MEEM (MD −1,60, IC 95% −3,57 a 0,37), el test de diseño del reloj (MD −0,20, IC 95% −0,61 a 0,21) y la escala de evaluación de la enfermedad de Alzheimer: subítem de cognición (MD 1,0, IC 95% −2,21 a 4,21) tras 12 meses. No hubo evidencia consistente de la eficacia de la intervención fisioterapéutica en la mejora de la función cognitiva y de la capacidad funcional en la EA. Se recomienda realizar estudios adicionales para encontrar posibles evidencias.

O papel da espiritualidade no enfrentamento da doença de Alzheimer / The role of spirituality in dealing with Alzheimer's disease

Objetivo: Analisar a literatura científica mais recente acerca do benefício da espiritualidade dentro do contexto do enfrentamento da doença de Alzheimer. Métodos: Revisão bibliográfica realizada por meio da busca nos bancos de dados PubMed/MEDLINE® e Scientific Electronic Library Online (SciELO), nas línguas portuguesa e inglesa. Foram utilizados, para a pesquisa, os seguintes descritores: "espiritualidade", "Alzheimer" e "envelhecimento". A busca abrangeu publicações do período entre 2007 e 2017. Resultados: Foram encontrados 1.430 artigos, tendo sido selecionados 89 deles pela leitura exploratória dos títulos. Destes, por meio da leitura dos resumos, foram selecionados 20, que se enquadravam nos critérios de inclusão. Conclusão: A espiritualidade corroborou de forma eficaz o enfrentamento da doença de Alzheimer, mas há necessidade de se explorar melhor essa relação, visto que o arsenal de informações literárias se encontra aquém do esperado. Deve haver uma melhor aplicabilidade das questões espirituais na prática médica, não só na doença de Alzheimer, mas como também nas comorbidades em geral. (AU)

Objective: To analyze the latest scientific literature based on the benefit of spirituality within the context of Alzheimer disease. Methods: This is a bibliographic review carried out through Pubmed/Medline®, and Scientific Electronic Library Online (SciELO) databases, in Portuguese and English. The following descriptors were used: "Spirituality", "Alzheimer" and "Aging". A total of 1430 articles were found through the period of 2007 and 2017, with 89 articles being selected for exploratory reading of the titles. By reading the abstracts, 20 articles met the inclusion criterias. Conclusion: Spirituality impacts effectively in coping Alzheimer disease. However, further studies should be carried out to clarify the relation between spitiruality and Alzheimer disease due to the lack of literature. It is necessary to better apply spiritual issues in medical practice, not only in Alzheimer disease but also in others comorbidities. (AU)

Políticas públicas para os idosos portadores do mal de Alzheimer / Public policies for the older carriers of Alzheimer's evil / Políticas públicas para los ancianos portadores del mal de Alzheimer

Objetivo: Conocer y analizar la producción científica en el período de 2011 a 2016 sobre las políticas públicas para los ancianos portadores del mal de Alzheimer. Método: El estudio se caracteriza como una investigación exploratoria, descriptiva con enfoque cuantitativo, realizado a través del método de la revisión integrativa. Resultados: Aunque la DA es una enfermedad progresiva e incurable, mucho se ha avanzado en beneficio del anciano portador, como la creación de instrumentos de evaluación y de criterios diagnósticos más claros, medicamentos que mejoran la cognición y disminuyen la incidencia de cambios conductuales y la la creación de leyes y decretos gubernamentales que disponen específicamente de los derechos de la persona de edad avanzada con la enfermedad de Alzheimer. Conclusión: El conocimiento acerca de los derechos de los pacientes portadores de la enfermedad de Alzheimer es de suma importancia para la promoción de la salud y el mantenimiento de la vida de esas personas

Objective: To know and analyze the scientific production in the period from 2011 to 2016 on public policies for elderly people with Alzheimer's disease. Method: The study is characterized as exploratory, descriptive research with a quantitative approach, performed through the integrative review method. Results: Although AD is a progressive and incurable disease, much has already been advanced for the benefit of the elderly patient, such as the creation of clearer diagnostic tools and criteria, medications that improve cognition and reduce the incidence of behavioral changes, and creating laws and government ordinances that specifically govern the rights of the elderly with Alzheimer's Disease. Conclusion: Knowledge about the rights of patients with Alzheimer's disease is of paramount importance for the promotion of health and maintenance of their lives

Objetivo: Conhecer e analisar a produção científica no período de 2011 a2016 sobre as políticas públicas para os idosos portadores do mal de Alzheimer. Método: O estudo caracteriza-se como pesquisa exploratória, descritiva com abordagem quantitativa, realizado por meio do método da revisão integrativa. Resultados: Embora a DA seja uma doença progressiva e incurável, muito já se avançou em benefício do idoso portador, como a criação de instrumentos de avaliação e de critérios diagnósticos mais claros, medicações que melhoram a cognição e diminuem a incidência de mudanças comportamentais e a criação de leis e portarias governamentais que dispõem especificamente dos direitos da pessoa idosa com a Doença de Alzheimer. Conclusão: O conhecimento acerca dos direitos dos pacientes portadores da Doença de Alzheimer é de suma importância para promoção da saúde e manutenção da vida dessas pessoas