Recently,the glymphatic system has been recognised as an important‘waste solutes transport channel’within the brain.1 Studies have shown that blockage of the glymphatic system leads to increased beta-amyloid deposit...Recently,the glymphatic system has been recognised as an important‘waste solutes transport channel’within the brain.1 Studies have shown that blockage of the glymphatic system leads to increased beta-amyloid deposits,accelerating the onset and progression of Alzheimer’s disease(AD).12 Given that cervical lymph nodes receive cerebrospinal fluid from the brain’s glymphatic system,34 we speculated that decompression of the lymphatic trunk and cervical lymphatic-venous anastomosis(LVA)could facilitate the flow of cerebrospinal fluid in the cranial glymphatic system,potentially accelerating the clearance of harmful beta-amyloid and tau proteins.We collaborated with surgeons who specialise in LVA supermicrosurgery for maxillofacial tumours and lymphoedema to develop a procedure to relieve the blockage of the glymphatic system.This surgery employs supermicrosurgery techniques to create LVA connecting the bilateral cervical,deep lymphatic vessels to the veins,resulting in lymphatic trunk decompression,which allows the lymph fluid in the high-pressure lymphatic vessels to flow into the low-pressure venous system.The goal of the minimally invasive surgery is to enhance the removal of proteins,such as beta-amyloid and tau,from the brain’s lymphatic systems to the maxillofacial lymphatic vessels,unclogging protein blockages within the brain.This extracranial procedure is safer than intracranial approaches.展开更多
Curculigoside(CCG)is a phenolic glycoside compound extracted from the root of a natural plant called Curculigo orchioides Gaertn.In this study,the neuroprotective effect of CCG through oxidative stress mediated mitoch...Curculigoside(CCG)is a phenolic glycoside compound extracted from the root of a natural plant called Curculigo orchioides Gaertn.In this study,the neuroprotective effect of CCG through oxidative stress mediated mitochondrial dysfunction on L-glutamate(L-Glu)-damaged hippocampal neuron cell line(HT22)and APPswe/PSEN1dE9 transgenic(APP/PS1)mice were investigated.Observably,CCG in L-Glu-damaged HT22 cells suppressed apoptosis,reduced the accumulation of reactive oxygen species,balanced the mitochondrial membrane potential and prevented the over-influx of calcium.In APP/PS1 mice,4-week CCG administration significantly improved their memory and behavioral impairments,enhanced the function of cholinergic system,reduced the deposition of Aβand neurofibrillary fiber tangles caused by tau phosphorylation,and suppressed the development and progression of oxidative stress in brains of APP/PS1 mice.Based on the screening of proteomic analysis on hippocampus,CCG were confirmed that it could regulate the expression levels of proteins related to mitochondrial dysfunction,mainly through activating on AMPK/Nrf2 signaling,in APP/PS1 mice and L-Glu-exposed HT22 cells.CCG has a prominent neuroprotective effect on regulate the AMPK/Nrf2-mediated mitochondrial dysfunction in cells APP/PS1 mice support CCG is a potentially potent drug for AD treatment and merits further investigation.展开更多
Purpose:Measuring the exact technology complementarity between different institutions is necessary to obtain complementary technology resources for R&D cooperation.Design/methodology/approach:This study constructs...Purpose:Measuring the exact technology complementarity between different institutions is necessary to obtain complementary technology resources for R&D cooperation.Design/methodology/approach:This study constructs a morphology-driven method for measuring technology complementarity,taking medical field as an example.First,we calculate semantic similarities between subjects(S and S)and action-objects(AO and AO)based on the Metathesaurus,forming clusters of S and AO based on a semantic similarity matrix.Second,we identify key technology issues and methods based on clusters of S and AO.Third,a technology morphology matrix of several dimensions is constructed using morphology analysis,and the matrix is filled with subjects-action-objects(SAO)structures according to corresponding key technology issues and methods for different institutions.Finally,the technology morphology matrix is used to measure the technology complementarity between different institutions based on SAO.Findings:The improved technology complementarity method based on SAO is more of a supplementary and refined framework for the traditional IPC method.Research limitations:In future studies we will reprocess and identify the SAO structures which were not in the technology morphology matrix,and find other methods to characterize key technical issues and methods.Furthermore,we will add the comparison between proposed method and traditional and mostly used complementarity measurement method based on industry chain and industry code.Practical implications:This study takes medical field as an example.The morphology-driven method for measuring technology complementarity can be migrated and applied for any given field.Originality/value:From the perspective of complementary technology resources,this study develops and tests a more accurate morphology-driven method for technology complementarity measurement.展开更多
Given its increasing global prevalence,Alzheimer’s disease(AD)has become a major public health challenge worldwide.The symptomatic treatments available for AD have shown no significant efficacy,and no disease-modifyi...Given its increasing global prevalence,Alzheimer’s disease(AD)has become a major public health challenge worldwide.The symptomatic treatments available for AD have shown no significant efficacy,and no disease-modifying interventions are capable of slowing the progression of the disorder.The potential of lifestyle-related factors,including diet,is increasingly recognized as an important consideration in the primary prevention of AD.Numerous mechanisms potentially underlying neuroprotective effects of bioactive components contained in tea,such as(-)-epigallocatechin-3-gallate,as well as their preventive efficacy against AD,have been elucidated in preclinical studies.However,in contrast to the abundance of mechanistic findings in animals,clinical results demonstrating efficacy in humans are scarce.While epidemiological studies have provided some evidence indicating that green tea consumption is associated with a reduced risk of age-related cognitive decline and AD,a causal relationship cannot be established on the basis of these observations.The clinical evidence regarding preventive or therapeutic effects of green tea and its bioactive components is unsatisfactory.A role of green tea in the prevention of AD cannot be recommended until well-designed,randomized,placebo-controlled clinical trials using standardized formulations confirm the purported beneficial effects of green tea.展开更多
Alzheimer’s disease(AD)is the most prevalent cause of dementia worldwide.Treatments achieving a marked improvement in symptoms or preventing or delaying the progression of the disease are not available.Various diet-r...Alzheimer’s disease(AD)is the most prevalent cause of dementia worldwide.Treatments achieving a marked improvement in symptoms or preventing or delaying the progression of the disease are not available.Various diet-related risk factors for AD have been identified.Evidence for a protective effect of the Mediterranean diet on AD risk is inconclusive.Medical foods are designed to meet specific dietary needs for certain diseases.Improvements in symptomatology and regional brain atrophy in AD have been claimed for several medical foods,for example,those providing ketone bodies as alternative energy supply to neurons,those containing precursors believed to improve synaptic function,and those addressing oxidative stress related to memory loss.Many methodological shortcomings render the interpretation of the available findings of medical food trials in AD difficult.Optimal results of medical foods in AD may be expected when administered in presymptomatic or early stages of the disease.This requires the reliable identification of minimal neuropathological changes related to AD.The outcome measures currently used may not be able to detect subtle changes in cognition and function in early AD.Large-scale clinical studies using valid,sensitive,and reliable assessment tools are needed to establish the efficacy of medical foods in AD.展开更多
Alzheimer’s disease(AD)is a progressive neurodegenerative disorder characterized by decline in cognitive functions and associated with the neuropathological hallmarks of amyloid-peptide plaques and neurofibrillary ta...Alzheimer’s disease(AD)is a progressive neurodegenerative disorder characterized by decline in cognitive functions and associated with the neuropathological hallmarks of amyloid-peptide plaques and neurofibrillary tangles.Cerebral glucose uptake and metabolism deteriorate in AD and this hypometabolism precedes the onset of clinical signs in AD.The early decline in brain glucose metabolism in AD has become a potential target for therapeutic intervention.This has led to investigations assessing the supplementation of the normal glucose supply with ketone bodies which are produced by the body during glucose deprivation and can be metabolized by the brain when glucose utilization is impaired.The present review provides a synopsis of preclinical studies and clinical trials assessing the efficacy of ketogenic diets in the treatment of AD.Both the direct administration of ketone bodies and the use of high-fat,low-carbohydrate ketogenic diets have been shown to be efficacious in animal models of AD and clinical trials with AD patients.The mechanism underlying the efficacy of ketogenic diets remains unclear,but some evidence points to the normalization of aberrant energy metabolism.At present there is only limited evidence of the usefulness of ketogenic diets in AD.However,this dietary approach seems to be promising and deserves further clinical investigations.展开更多
Background There have been no effective treatments for slowing or reversing Alzheimer’s disease(AD)until now.Growing preclinical evidence,including this study,suggests that mesenchymal stem cells-secreted exosomes(MS...Background There have been no effective treatments for slowing or reversing Alzheimer’s disease(AD)until now.Growing preclinical evidence,including this study,suggests that mesenchymal stem cells-secreted exosomes(MSCs-Exos)have the potential to cure AD.Aims The first three-arm,drug-intervention,phase I/II clinical trial was conducted to explore the safety and efficacy of allogenic human adipose MSCs-Exos(ahaMSCs-Exos)in patients with mild to moderate AD.Methods The eligible subjects were assigned to one of three dosage groups,intranasally administrated with ahaMSCs-Exos two times per week for 12 weeks,and underwent follow-up visits at weeks 16,24,36 and 48.Results No adverse events were reported.In the medium-dose arm,Alzheimer’s Disease Assessment Scale–Cognitive section(ADAS-cog)scores decreased by 2.33(1.19)and the basic version of Montreal Cognitive Assessment scores increased by 2.38(0.58)at week 12 compared with baseline levels,indicating improved cognitive function.Moreover,the ADAS-cog scores in the medium-dose arm decreased continuously by 3.98 points until week 36.There were no significant differences in altered amyloid or tau deposition among the three arms,but hippocampal volume shrank less in the medium-dose arm to some extent.Conclusions Intranasal administration of ahaMSCs-Exos was safe and well tolerated,and a dose of at least 4×10^(8)particles could be selected for further clinical trials.展开更多
Background The prevalence of Alzheimer's disease(AD)comorbid with depression is common.However,the mechanisms of AD with depression remain unclear.Aims To investigate the regional alterations of brain activity of ...Background The prevalence of Alzheimer's disease(AD)comorbid with depression is common.However,the mechanisms of AD with depression remain unclear.Aims To investigate the regional alterations of brain activity of AD with depression in resting-state functional magnetic resonance imaging(rs-fMRI).Methods 154 patients with AD who met the inclusion criteria were recruited from the Zhejiang Provincial People’s Hospital from October 2014 to October 2016.According to whether the core symptoms of depression were present,patients were divided into two groups,22 patients with AD with depression(AD-D)and 52 patients with AD without depression(AD-nD).The amplitude of low frequency fluctuations(ALFF)was compared between two groups by performing independent-samples f-test.Results Compared with the AD-D group,increased ALFF values in the bilateral superior frontal gyrus,left middle frontal gyrus and left inferior frontal gyrus were observed in the AD-nD group.The brain activity in the AD-nD group in the bilateral superior frontal gyrus,left middle frontal gyrus and the left inferior frontal gyrus was higher than the AD-D group.Conclusions Resting-state brain functional alterations may be closely bound up with the pathophysiologic features of patients with AD with depressive symptoms.展开更多
Short-term memory decline is the typical clinical manifestation of Alzheimer’s disease(AD).However,early-onset AD usually has atypical symptoms and may get misdiagnosed.In the present case study,we reported a patient...Short-term memory decline is the typical clinical manifestation of Alzheimer’s disease(AD).However,early-onset AD usually has atypical symptoms and may get misdiagnosed.In the present case study,we reported a patient who experienced symptoms of memory loss with progressive non-fluent aphasia accompanied by gradual social withdrawal.He did not meet the diagnostic criteria of AD based on the clinical manifestation and brain MRI.However,his cerebrospinal fluid examination showed a decreased level of beta-amyloid 42,and increased total tau and phosphorylated tau.Massive amyloid β-protein deposition by 11C-Pittsburgh positron emission tomography confirmed the diagnosis of frontal variant AD.This case indicated that early-onset AD may have progressive non-fluent aphasia as the core manifestation.The combination of individual and precision diagnosis would be beneficial for similar cases.展开更多
Alzheimer's disease is a neurodegenerative disease with complex etiology.Gut microbiota influences the gutbrain axis,which may affect pathways related to the pathogenesis of Alzheimer's disease.Additionally,di...Alzheimer's disease is a neurodegenerative disease with complex etiology.Gut microbiota influences the gutbrain axis,which may affect pathways related to the pathogenesis of Alzheimer's disease.Additionally,diet and physical activity are likely to affect the pathology of Alzheimer's disease as well as the gut microbiota.This demonstrates that it may be possible to prevent or halt the progression of Alzheimer's disease by regulating the gut microbiota using diet and physical activity strategies.Therefore,the present study reviews the association between these two interventions and gut microbiota in the human body.It also summarizes how these two interventions benefit Alzheimer's disease.Furthermore,the primary limitations of these two interventions are discussed and promising strategies are proposed,which may be beneficial to further study and develop the intervening measure for the progression of Alzheimer's disease.展开更多
The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based inte...The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements.Here,we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment(EE)training.In this study,we found that compared with EE or B.breve treatment alone,B.breve intervention combined with EE amplified its neuroprotective effects on AD mice,as reflected by improved cognition,inhibited neuroinflammation and enhanced synaptic function.Moreover,using microbiome and metabolome profiling,we found that the combination of B.breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes.Finally,by integrating behavioural and neurological data with metabolomic profiles,we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions.Collectively,combined B.breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome.Our findings provide a promising multidomain intervention strategy,with a combination of dietary microbiome-based and lifestyle-targeted interventions,to promote brain function and delay the progression of AD.展开更多
Alzheimer’s disease(AD),the major form of neurodegenerative diseases that can severely impede normal cognitive function,makes it one of the most common fatal diseases.There are currently over 50 million AD patients w...Alzheimer’s disease(AD),the major form of neurodegenerative diseases that can severely impede normal cognitive function,makes it one of the most common fatal diseases.There are currently over 50 million AD patients worldwide.The neuropathology of AD is perplexing and there is a scarcity of disease-modifying treatments.Currently,early diagnosis of AD has been made possible with the discovery of biological markers associated with pathology,providing strong support for the improvement of the disease status.The search for inhibitors of AD markers from dietary supplements(DSs)has become a major hot topic.Especially with the widespread use of DSs,DSs containing polyphenols,alkaloids,terpenes,polysaccharides and other bioactive components can prevent AD by reducing Aβdeposition,inhibiting tau protein hyperphosphorylation,reconstructing synaptic dysfunction,weakening cholinesterase activity,regulating mitochondrial oxidative stress,neuronal inflammation and apoptosis.This review summarizes the anti-AD effects of the main DSs and their bioactive constituents,as well as the potential molecular mechanisms covers from 2017 to 2023.Additionally,we discussed the opportunities and challenges faced by DSs in the process of AD prevention and treatment,aiming to further provide new perspectives for functional food development.展开更多
Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impai...Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impairment(MCl)and evidence of AD's pathology.At this stage,disease-modifying interventions should be used to prevent the progression to dementia.Given the inherent heterogeneity of MCl,more specific biomarkers are needed to elucidate the underlying AD's pathology.Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology,their clinical applications are limited by their high costs and invasiveness,particularly in low-income areas in China.Therefore,to improve the early detection of Alzheimer's disease(AD)pathology through cost-effective screening methods,a panel of 45neurologists,psychiatrists andgerontologistswas invited to establish a formal consensus on the screening of pAD in China.The supportive evidence and grades of recommendations are based on a systematic literature review andfocus group discussion.National meetings were held to allow participants to review,vote and provide their expert opinions to reach a consensus.A majority(two-thirds)decision was used for questions for which consensus could not be reached.Recommended screening methods are presented in this publication,including neuropsychological assessment,peripheral biomarkers and brain imaging.In addition,a general workflow for Screening pAD in China is established,which will help clinicians identify individuals at high risk and determine therapeutic targets.展开更多
Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst s...Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst stimulation(iTBS)is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for AD.However,the long-term effects of iTBS on cognitive decline and brain structure in patients with AD areunknown.Aims We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with AD.Methods In this randomised,assessor-blinded,controlled trial,iTBS was administered to the left dorsolateral prefrontal cortex(DLPFC)of 42 patients with AD for 14days every 13weeks.Measurements included the Montreal Cognitive Assessment(MoCA),a comprehensive neuropsychological battery,and the grey matter volume(GMV)of the hippocampus.Patients were evaluated at baseline and after follow-up.The longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over time.Results The iTBS group maintained MoCA scores relative to the control group(t=3.26,p=0.013)and reduced hippocampal atrophy,which was significantly correlated with global degeneration scale changes.The baseline Mini-Mental State Examination(MMSE)score,apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at follow-up.Moreover,the GMV of the left(t=0.08,p=0.996)and right(t=0.19,p=0.977)hippocampus were maintained in the active group but significantly declined in the control group(left:t=4.13,p<0.001;right:t=5.31,p<0.001).GMV change in the left(r=0.35,p=0.023)and right(r=0.36,p=0.021)hippocampus across the intervention positively correlated with MoCA changes;left hippocampal GMV change was negatively correlated with global degeneration scale(r=-0.32,p=0.041)changes.Conclusions DLPFC-iTBS maybe a feasible and easy-to-implement non-pharmacological intervention to slow down the progressive decline of overall cognition and quality of life in patients with AD,providing a new AD treatment option.Trial registration number NCT04754152.展开更多
Alzheimer’s disease(AD)is the most common neurodegenerative disease characterized by cognitive decline and memory impairment.Many lines of evidence indicate that excessiveβ-amyloid peptide(Aβ)generation and aggrega...Alzheimer’s disease(AD)is the most common neurodegenerative disease characterized by cognitive decline and memory impairment.Many lines of evidence indicate that excessiveβ-amyloid peptide(Aβ)generation and aggregation play pivotal roles in the initiation of AD,leading to various biochemical alteration including oxidative damage,mitochondrial dysfunction,neuroinflammation,signaling pathway and finally resulting in neuronal death.AD has a complex pathogenic mechanism,and a single-target approach for anti-AD strategy is thus full of challenges.To overcome these limitations,the present study focused to review on one of multiple target-compounds,(-)-epigallocatechin-3-gallate(EGCG)for the prevention and treatment of AD.EGCG is a main bioactive polyphenol in green tea and has been reported to exert potent neuroprotective properties in a wide array of both cellular and animal models in AD.This review demonstrated multiple neuroprotective efficacies of EGCG by focusing on the involvement of Aβ-evoked damage and its Aβregulation.Furthermore,to understand its mechanism of action on the brain,the permeability of the blood-brain barrier was also discussed.展开更多
基金supported by the National Key R&D Program of China(2023YFC36003200)Shanghai Mental Health Center investigator-initiated trial programme(2024-TX-001)+1 种基金Shanghai's Top Priority Research Center(2022ZZ01017)CAMS Innovation Fund for Medical Sciences(2019-12M-5-037).
文摘Recently,the glymphatic system has been recognised as an important‘waste solutes transport channel’within the brain.1 Studies have shown that blockage of the glymphatic system leads to increased beta-amyloid deposits,accelerating the onset and progression of Alzheimer’s disease(AD).12 Given that cervical lymph nodes receive cerebrospinal fluid from the brain’s glymphatic system,34 we speculated that decompression of the lymphatic trunk and cervical lymphatic-venous anastomosis(LVA)could facilitate the flow of cerebrospinal fluid in the cranial glymphatic system,potentially accelerating the clearance of harmful beta-amyloid and tau proteins.We collaborated with surgeons who specialise in LVA supermicrosurgery for maxillofacial tumours and lymphoedema to develop a procedure to relieve the blockage of the glymphatic system.This surgery employs supermicrosurgery techniques to create LVA connecting the bilateral cervical,deep lymphatic vessels to the veins,resulting in lymphatic trunk decompression,which allows the lymph fluid in the high-pressure lymphatic vessels to flow into the low-pressure venous system.The goal of the minimally invasive surgery is to enhance the removal of proteins,such as beta-amyloid and tau,from the brain’s lymphatic systems to the maxillofacial lymphatic vessels,unclogging protein blockages within the brain.This extracranial procedure is safer than intracranial approaches.
基金supported by the Science and Technology Develop Project in Jilin Province of China(20200201030JC)the Scientific Research Project of Education Department of Jilin Province in China(JJKH20211461KJ)Characteristic Innovation Project for Guangdong University of China(2019KTSCX221).
文摘Curculigoside(CCG)is a phenolic glycoside compound extracted from the root of a natural plant called Curculigo orchioides Gaertn.In this study,the neuroprotective effect of CCG through oxidative stress mediated mitochondrial dysfunction on L-glutamate(L-Glu)-damaged hippocampal neuron cell line(HT22)and APPswe/PSEN1dE9 transgenic(APP/PS1)mice were investigated.Observably,CCG in L-Glu-damaged HT22 cells suppressed apoptosis,reduced the accumulation of reactive oxygen species,balanced the mitochondrial membrane potential and prevented the over-influx of calcium.In APP/PS1 mice,4-week CCG administration significantly improved their memory and behavioral impairments,enhanced the function of cholinergic system,reduced the deposition of Aβand neurofibrillary fiber tangles caused by tau phosphorylation,and suppressed the development and progression of oxidative stress in brains of APP/PS1 mice.Based on the screening of proteomic analysis on hippocampus,CCG were confirmed that it could regulate the expression levels of proteins related to mitochondrial dysfunction,mainly through activating on AMPK/Nrf2 signaling,in APP/PS1 mice and L-Glu-exposed HT22 cells.CCG has a prominent neuroprotective effect on regulate the AMPK/Nrf2-mediated mitochondrial dysfunction in cells APP/PS1 mice support CCG is a potentially potent drug for AD treatment and merits further investigation.
基金This work was supported by the General Program of National Natural Science Foundation of China under(Grant Nos.71774012,72104246,71673024)the Fundamental Research Funds for the Central Universities(22CX04010B)the strategic research project of the Development Planning Bureau of the Chinese Academy of Sciences(Grant No.GHJ-ZLZX-2019-42).The findings and observations in this paper are those of the authors and do not necessarily reflect the views of the supporters.
文摘Purpose:Measuring the exact technology complementarity between different institutions is necessary to obtain complementary technology resources for R&D cooperation.Design/methodology/approach:This study constructs a morphology-driven method for measuring technology complementarity,taking medical field as an example.First,we calculate semantic similarities between subjects(S and S)and action-objects(AO and AO)based on the Metathesaurus,forming clusters of S and AO based on a semantic similarity matrix.Second,we identify key technology issues and methods based on clusters of S and AO.Third,a technology morphology matrix of several dimensions is constructed using morphology analysis,and the matrix is filled with subjects-action-objects(SAO)structures according to corresponding key technology issues and methods for different institutions.Finally,the technology morphology matrix is used to measure the technology complementarity between different institutions based on SAO.Findings:The improved technology complementarity method based on SAO is more of a supplementary and refined framework for the traditional IPC method.Research limitations:In future studies we will reprocess and identify the SAO structures which were not in the technology morphology matrix,and find other methods to characterize key technical issues and methods.Furthermore,we will add the comparison between proposed method and traditional and mostly used complementarity measurement method based on industry chain and industry code.Practical implications:This study takes medical field as an example.The morphology-driven method for measuring technology complementarity can be migrated and applied for any given field.Originality/value:From the perspective of complementary technology resources,this study develops and tests a more accurate morphology-driven method for technology complementarity measurement.
文摘Given its increasing global prevalence,Alzheimer’s disease(AD)has become a major public health challenge worldwide.The symptomatic treatments available for AD have shown no significant efficacy,and no disease-modifying interventions are capable of slowing the progression of the disorder.The potential of lifestyle-related factors,including diet,is increasingly recognized as an important consideration in the primary prevention of AD.Numerous mechanisms potentially underlying neuroprotective effects of bioactive components contained in tea,such as(-)-epigallocatechin-3-gallate,as well as their preventive efficacy against AD,have been elucidated in preclinical studies.However,in contrast to the abundance of mechanistic findings in animals,clinical results demonstrating efficacy in humans are scarce.While epidemiological studies have provided some evidence indicating that green tea consumption is associated with a reduced risk of age-related cognitive decline and AD,a causal relationship cannot be established on the basis of these observations.The clinical evidence regarding preventive or therapeutic effects of green tea and its bioactive components is unsatisfactory.A role of green tea in the prevention of AD cannot be recommended until well-designed,randomized,placebo-controlled clinical trials using standardized formulations confirm the purported beneficial effects of green tea.
文摘Alzheimer’s disease(AD)is the most prevalent cause of dementia worldwide.Treatments achieving a marked improvement in symptoms or preventing or delaying the progression of the disease are not available.Various diet-related risk factors for AD have been identified.Evidence for a protective effect of the Mediterranean diet on AD risk is inconclusive.Medical foods are designed to meet specific dietary needs for certain diseases.Improvements in symptomatology and regional brain atrophy in AD have been claimed for several medical foods,for example,those providing ketone bodies as alternative energy supply to neurons,those containing precursors believed to improve synaptic function,and those addressing oxidative stress related to memory loss.Many methodological shortcomings render the interpretation of the available findings of medical food trials in AD difficult.Optimal results of medical foods in AD may be expected when administered in presymptomatic or early stages of the disease.This requires the reliable identification of minimal neuropathological changes related to AD.The outcome measures currently used may not be able to detect subtle changes in cognition and function in early AD.Large-scale clinical studies using valid,sensitive,and reliable assessment tools are needed to establish the efficacy of medical foods in AD.
文摘Alzheimer’s disease(AD)is a progressive neurodegenerative disorder characterized by decline in cognitive functions and associated with the neuropathological hallmarks of amyloid-peptide plaques and neurofibrillary tangles.Cerebral glucose uptake and metabolism deteriorate in AD and this hypometabolism precedes the onset of clinical signs in AD.The early decline in brain glucose metabolism in AD has become a potential target for therapeutic intervention.This has led to investigations assessing the supplementation of the normal glucose supply with ketone bodies which are produced by the body during glucose deprivation and can be metabolized by the brain when glucose utilization is impaired.The present review provides a synopsis of preclinical studies and clinical trials assessing the efficacy of ketogenic diets in the treatment of AD.Both the direct administration of ketone bodies and the use of high-fat,low-carbohydrate ketogenic diets have been shown to be efficacious in animal models of AD and clinical trials with AD patients.The mechanism underlying the efficacy of ketogenic diets remains unclear,but some evidence points to the normalization of aberrant energy metabolism.At present there is only limited evidence of the usefulness of ketogenic diets in AD.However,this dietary approach seems to be promising and deserves further clinical investigations.
基金supported by the Ministry of Science and Technology of the People's Republic of China(2021ZD0201804,GW)National Natural Science Foundation of China(92068111,81973272,XG,81903582,QS)+1 种基金Natural Science Foundation of Shanghai(219ZR1431500,GW)Shanghai Science and Technology Committee(121XD1422200,XG)and Cellular Biomedicine Group(CBMG,Shanghai,China).
文摘Background There have been no effective treatments for slowing or reversing Alzheimer’s disease(AD)until now.Growing preclinical evidence,including this study,suggests that mesenchymal stem cells-secreted exosomes(MSCs-Exos)have the potential to cure AD.Aims The first three-arm,drug-intervention,phase I/II clinical trial was conducted to explore the safety and efficacy of allogenic human adipose MSCs-Exos(ahaMSCs-Exos)in patients with mild to moderate AD.Methods The eligible subjects were assigned to one of three dosage groups,intranasally administrated with ahaMSCs-Exos two times per week for 12 weeks,and underwent follow-up visits at weeks 16,24,36 and 48.Results No adverse events were reported.In the medium-dose arm,Alzheimer’s Disease Assessment Scale–Cognitive section(ADAS-cog)scores decreased by 2.33(1.19)and the basic version of Montreal Cognitive Assessment scores increased by 2.38(0.58)at week 12 compared with baseline levels,indicating improved cognitive function.Moreover,the ADAS-cog scores in the medium-dose arm decreased continuously by 3.98 points until week 36.There were no significant differences in altered amyloid or tau deposition among the three arms,but hippocampal volume shrank less in the medium-dose arm to some extent.Conclusions Intranasal administration of ahaMSCs-Exos was safe and well tolerated,and a dose of at least 4×10^(8)particles could be selected for further clinical trials.
基金This study was funded by Science and Technology Department of Zhejiang Province(2014C33126)Public Welfare Technology Research and Social Development Projects(2014-)+3 种基金This study is also funded by the National Natural Science Foundation of China(81201057)Shanghai Municipal Health Bureau Project(20124109)Chinese Medical Association,Psychiatry-Servier Youth Research Fund,Shanghai Mental Health Center international cooperation project(2013-)Shanghai Municipal Center for Mental Health Clinical Research Program.This study is funded by Key Research Project of Zhejiang TCM Science and Technology Plan of China(2018ZZ010).
文摘Background The prevalence of Alzheimer's disease(AD)comorbid with depression is common.However,the mechanisms of AD with depression remain unclear.Aims To investigate the regional alterations of brain activity of AD with depression in resting-state functional magnetic resonance imaging(rs-fMRI).Methods 154 patients with AD who met the inclusion criteria were recruited from the Zhejiang Provincial People’s Hospital from October 2014 to October 2016.According to whether the core symptoms of depression were present,patients were divided into two groups,22 patients with AD with depression(AD-D)and 52 patients with AD without depression(AD-nD).The amplitude of low frequency fluctuations(ALFF)was compared between two groups by performing independent-samples f-test.Results Compared with the AD-D group,increased ALFF values in the bilateral superior frontal gyrus,left middle frontal gyrus and left inferior frontal gyrus were observed in the AD-nD group.The brain activity in the AD-nD group in the bilateral superior frontal gyrus,left middle frontal gyrus and the left inferior frontal gyrus was higher than the AD-D group.Conclusions Resting-state brain functional alterations may be closely bound up with the pathophysiologic features of patients with AD with depressive symptoms.
基金This study was supported by a grant of Clinical Research Centre Project of Shanghai Mental Health Centre(CRC2017ZD02)Scientific Research Program of Shanghai Jing an District Health Committee(2020MS16).
文摘Short-term memory decline is the typical clinical manifestation of Alzheimer’s disease(AD).However,early-onset AD usually has atypical symptoms and may get misdiagnosed.In the present case study,we reported a patient who experienced symptoms of memory loss with progressive non-fluent aphasia accompanied by gradual social withdrawal.He did not meet the diagnostic criteria of AD based on the clinical manifestation and brain MRI.However,his cerebrospinal fluid examination showed a decreased level of beta-amyloid 42,and increased total tau and phosphorylated tau.Massive amyloid β-protein deposition by 11C-Pittsburgh positron emission tomography confirmed the diagnosis of frontal variant AD.This case indicated that early-onset AD may have progressive non-fluent aphasia as the core manifestation.The combination of individual and precision diagnosis would be beneficial for similar cases.
基金financially supported by National Natural Science Foundation of China(32171035)the major fund project of Ningbo Science and Technology Bureau(2019B10034)+4 种基金Opened-end Fund of Key Laboratory(KFJJ-202101,ZPKLP202202)Public Project of Ningbo(202002N3167)Project of Yinzhou(2022AS025)Ningbo Rehabilitation Hospital(2022KY02)sponsored by a K.C.Wong Magna Fund in Ningbo University。
文摘Alzheimer's disease is a neurodegenerative disease with complex etiology.Gut microbiota influences the gutbrain axis,which may affect pathways related to the pathogenesis of Alzheimer's disease.Additionally,diet and physical activity are likely to affect the pathology of Alzheimer's disease as well as the gut microbiota.This demonstrates that it may be possible to prevent or halt the progression of Alzheimer's disease by regulating the gut microbiota using diet and physical activity strategies.Therefore,the present study reviews the association between these two interventions and gut microbiota in the human body.It also summarizes how these two interventions benefit Alzheimer's disease.Furthermore,the primary limitations of these two interventions are discussed and promising strategies are proposed,which may be beneficial to further study and develop the intervening measure for the progression of Alzheimer's disease.
基金supported by the National Natural Science Foundation of China(31972052,32021005,31820103010)the Fundamental Research Funds for the Central Universities(JUSRP22006,JUSRP51501)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements.Here,we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment(EE)training.In this study,we found that compared with EE or B.breve treatment alone,B.breve intervention combined with EE amplified its neuroprotective effects on AD mice,as reflected by improved cognition,inhibited neuroinflammation and enhanced synaptic function.Moreover,using microbiome and metabolome profiling,we found that the combination of B.breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes.Finally,by integrating behavioural and neurological data with metabolomic profiles,we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions.Collectively,combined B.breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome.Our findings provide a promising multidomain intervention strategy,with a combination of dietary microbiome-based and lifestyle-targeted interventions,to promote brain function and delay the progression of AD.
基金financially supported by the National Key R&D Program of China(2022YFF1100301)Yunnan Revitalization Talents Support Plan-Young Talent Project(YNWRQNBJ-2018-357)。
文摘Alzheimer’s disease(AD),the major form of neurodegenerative diseases that can severely impede normal cognitive function,makes it one of the most common fatal diseases.There are currently over 50 million AD patients worldwide.The neuropathology of AD is perplexing and there is a scarcity of disease-modifying treatments.Currently,early diagnosis of AD has been made possible with the discovery of biological markers associated with pathology,providing strong support for the improvement of the disease status.The search for inhibitors of AD markers from dietary supplements(DSs)has become a major hot topic.Especially with the widespread use of DSs,DSs containing polyphenols,alkaloids,terpenes,polysaccharides and other bioactive components can prevent AD by reducing Aβdeposition,inhibiting tau protein hyperphosphorylation,reconstructing synaptic dysfunction,weakening cholinesterase activity,regulating mitochondrial oxidative stress,neuronal inflammation and apoptosis.This review summarizes the anti-AD effects of the main DSs and their bioactive constituents,as well as the potential molecular mechanisms covers from 2017 to 2023.Additionally,we discussed the opportunities and challenges faced by DSs in the process of AD prevention and treatment,aiming to further provide new perspectives for functional food development.
基金the National Natural Science Foundation of China(82171198,U20A20354)the Sci-Tech Innovation 2030 Agenda of China(2022ZD0211603).
文摘Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impairment(MCl)and evidence of AD's pathology.At this stage,disease-modifying interventions should be used to prevent the progression to dementia.Given the inherent heterogeneity of MCl,more specific biomarkers are needed to elucidate the underlying AD's pathology.Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology,their clinical applications are limited by their high costs and invasiveness,particularly in low-income areas in China.Therefore,to improve the early detection of Alzheimer's disease(AD)pathology through cost-effective screening methods,a panel of 45neurologists,psychiatrists andgerontologistswas invited to establish a formal consensus on the screening of pAD in China.The supportive evidence and grades of recommendations are based on a systematic literature review andfocus group discussion.National meetings were held to allow participants to review,vote and provide their expert opinions to reach a consensus.A majority(two-thirds)decision was used for questions for which consensus could not be reached.Recommended screening methods are presented in this publication,including neuropsychological assessment,peripheral biomarkers and brain imaging.In addition,a general workflow for Screening pAD in China is established,which will help clinicians identify individuals at high risk and determine therapeutic targets.
基金the National Natural Science Foundation of China(No.82101498 to XW)STI2030-Major Prjects of China(No.20212D0201801 to PH)+1 种基金National Natural Science Foundation of China(No.82171917 to PH,No.82090034 and 31970979 to KW and 32071054 to YT)the 2021 Youth Foundation Training Program of the First Affiliated Hospital of Anhui Medical University(No.2021kj19 to XW).
文摘Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst stimulation(iTBS)is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for AD.However,the long-term effects of iTBS on cognitive decline and brain structure in patients with AD areunknown.Aims We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with AD.Methods In this randomised,assessor-blinded,controlled trial,iTBS was administered to the left dorsolateral prefrontal cortex(DLPFC)of 42 patients with AD for 14days every 13weeks.Measurements included the Montreal Cognitive Assessment(MoCA),a comprehensive neuropsychological battery,and the grey matter volume(GMV)of the hippocampus.Patients were evaluated at baseline and after follow-up.The longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over time.Results The iTBS group maintained MoCA scores relative to the control group(t=3.26,p=0.013)and reduced hippocampal atrophy,which was significantly correlated with global degeneration scale changes.The baseline Mini-Mental State Examination(MMSE)score,apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at follow-up.Moreover,the GMV of the left(t=0.08,p=0.996)and right(t=0.19,p=0.977)hippocampus were maintained in the active group but significantly declined in the control group(left:t=4.13,p<0.001;right:t=5.31,p<0.001).GMV change in the left(r=0.35,p=0.023)and right(r=0.36,p=0.021)hippocampus across the intervention positively correlated with MoCA changes;left hippocampal GMV change was negatively correlated with global degeneration scale(r=-0.32,p=0.041)changes.Conclusions DLPFC-iTBS maybe a feasible and easy-to-implement non-pharmacological intervention to slow down the progressive decline of overall cognition and quality of life in patients with AD,providing a new AD treatment option.Trial registration number NCT04754152.
文摘Alzheimer’s disease(AD)is the most common neurodegenerative disease characterized by cognitive decline and memory impairment.Many lines of evidence indicate that excessiveβ-amyloid peptide(Aβ)generation and aggregation play pivotal roles in the initiation of AD,leading to various biochemical alteration including oxidative damage,mitochondrial dysfunction,neuroinflammation,signaling pathway and finally resulting in neuronal death.AD has a complex pathogenic mechanism,and a single-target approach for anti-AD strategy is thus full of challenges.To overcome these limitations,the present study focused to review on one of multiple target-compounds,(-)-epigallocatechin-3-gallate(EGCG)for the prevention and treatment of AD.EGCG is a main bioactive polyphenol in green tea and has been reported to exert potent neuroprotective properties in a wide array of both cellular and animal models in AD.This review demonstrated multiple neuroprotective efficacies of EGCG by focusing on the involvement of Aβ-evoked damage and its Aβregulation.Furthermore,to understand its mechanism of action on the brain,the permeability of the blood-brain barrier was also discussed.
