The rising incidence of dementia and associated neurodegenerative disorders poses a growing public health challenge.These conditions have traditionally been studied as isolated central nervous system disorders;however...The rising incidence of dementia and associated neurodegenerative disorders poses a growing public health challenge.These conditions have traditionally been studied as isolated central nervous system disorders;however,emerging evidence suggests that broader systemic factors,including chronic inflammation,immune dysregulation,metabolic dysfunction,and genetic susceptibility,may also play a role.This review ex-amines the interconnection between autoimmune diseases and metabolic syndromes in the pathogenesis and exacerbation of neurodegeneration.Conditions such as rheu-matoid arthritis,systemic lupus erythematosus,and type 1 diabetes mellitus have been associated with a heightened risk of developing dementia through chronic immune activation,blood-brain barrier disruption,and neuroinflammatory signaling.Similarly,metabolic disorders such as diabesity promote insulin resistance and oxidative stress,accelerating cognitive decline.The review also discusses glaucoma as a neurodegenera-tive condition with autoimmune features,underscoring the need for expanded classifi-cation and treatment strategies.A key focus is the utilization of the Collaborative Cross(CC)mouse model,which enables the study of gene-environment interactions across genetically diverse backgrounds.Findings from CC mice reveal strain-dependent sus-ceptibility to inflammation,cognitive impairment,and gut-brain axis dysfunction,pro-viding a translational bridge to human variability.This review highlights the importance of integrating precision-based approaches to dementia research that consider systemic influences.Advancing our understanding of these multiorgan interactions holds po-tential for designing precision-based therapeutic approaches to postpone the onset or reduce the incidence of neurodegenerative conditions.展开更多
Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an i...Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an important factor influencing the onset and progression of vascular dementia.The myelin sheath is a critical component of white matter,and damage and repair of the white matter are closely linked to myelin sheath integrity.This article reviews the role of microglia in vascular dementia,focusing on their effects on myelin sheaths and the potential therapeutic implications.The findings suggest that ischemia and hypoxia cause disruption of the blood-brain barrier and activate microglia,which may worsen blood-brain barrier damage through the release of matrix-degrading enzymes.Microglia-mediated metabolic reprogramming is recognized as an important driver of inflammation.Damage to the blood-brain barrier and subsequent inflammation can lead to myelin injury and accelerate the progression of vascular dementia.Early activation of microglia is a protective response that contributes to the maintenance of blood-brain barrier integrity through sensing,debris-clearing,and defensive mechanisms.However,prolonged activation can trigger a shift in microglia toward the pro-inflammatory M1 phenotype,resulting in myelin damage and cognitive impairment.Triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells 1 have been identified as potential biomarkers for vascular dementia,as both are closely linked to cognitive decline.Although effective clinical treatments for myelin damage in the central nervous system are currently lacking,researchers are actively working to develop targeted therapies.Several drugs,including nimodipine,dopaminergic agents,simvastatin,biotin,and quetiapine,have been evaluated for clinical use in treating microglial and myelin damage.Future research will face challenges in developing targeted therapeutic strategies for vascular dementia,requiring further investigation into the timing,duration,and specific mechanisms of microglial activation,as well as the exploration of new drug combinations and additional therapeutic targets.展开更多
Objective:To observe the efficacy of acupuncture combined with traditional Chinese herbs in the treatment of poststroke vascular dementia(VD)and the effects on serum interleukin(IL)-6 and superoxide dismutase(SOD).Met...Objective:To observe the efficacy of acupuncture combined with traditional Chinese herbs in the treatment of poststroke vascular dementia(VD)and the effects on serum interleukin(IL)-6 and superoxide dismutase(SOD).Methods:A total of 240 patients with poststroke VD were selected and randomly divided into two groups according to the random number table method,with 120 cases in each group.Both groups received Hua Tan Tong Luo(phlegmresolving and collateral-activating)formula,once daily;the observation group was additionally treated with Yi Shen Tiao Du(kidney-tonifying and Governor Vessel-regulating)acupuncture once daily for 6 consecutive days,followed by 1 d of rest.Both groups were treated for 15 d as one course,for a total of 2 courses.After treatment,the total effective rate was compared.Changes in scores of traditional Chinese medicine(TCM)symptoms,clinical dementia rating(CDR),National Institutes of Health stroke scale(NIHSS),and Chinese version of mini-mental state examination(MMSE),and serum levels of IL-6 and SOD were observed in both groups.Results:The total effective rate in the observation group was higher than that in the control group(P<0.05).After treatment,TCM symptom,CDR,and NIHSS scores,and serum IL-6 levels in both groups were lower than those before treatment(P<0.05),while MMSE scores and serum SOD levels were higher than those before treatment(P<0.05).After treatment,the observation group showed lower TCM symptom,CDR,and NIHSS scores,and serum IL-6 levels than the control group(P<0.05),and higher MMSE scores and serum SOD levels than the control group(P<0.05).Conclusion:Compared to Hua Tan Tong Luo formula alone,Yi Shen Tiao Du acupuncture combined with Hua Tan Tong Luo formula demonstrates better efficacy in reducing dementia severity,improving cognitive and neurological function,and inhibiting inflammation in patients with poststroke VD.展开更多
Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has ...Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.展开更多
Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia r...Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2500 g),normal birth weight(2500-3999 g),and macrosomia(≥4000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.展开更多
Objective:To translate and adapt the dementia knowledge assessment scale(DKAS)into Sinhala version and to evaluate its psychometric properties among nursing students.Methods:A cross-sectional validation study was cond...Objective:To translate and adapt the dementia knowledge assessment scale(DKAS)into Sinhala version and to evaluate its psychometric properties among nursing students.Methods:A cross-sectional validation study was conducted in two phases:(i)translation and adaptation and(ii)evaluating psychometric properties(N=394 nursing students).Results:The DKAS was adapted to the Sinhala(Si-DKAS)version,and the content validity index(CVI=0.9)was satisfactory.Exploratory factor analysis(EFA)and confirmatory factor analysis(CFA)resulted in an 18-item Si-DKAS with a four-factor model:“care considerations,”“causes and characteristics of dementia,”“health promotion,”and“misconceptions about dementia.”The model fit indices were suboptimal(comparative fix index[CFI]=0.809 and Turker-Lewis index[TLI]=0.773),and some indices were acceptable(standardized root-mean-squared residual[SRMR]=0.040 and root-mean-squared error of approximation[RMSEA]=0.053).Internal consistency(0.7)and test-retest correlation(0.9)were acceptable.Discriminant validity was confirmed by knowledge score differences based on academic years.Conclusions:This is a valid and reliable tool for assessing knowledge of dementia among Sinhala-speaking nursing students.展开更多
Background Depression is a common comorbidity in Parkinson's disease(PD)and Lewy body dementia(LBD).However,studies examining the rate of incident depression in the period preceding and following the diagnosis of ...Background Depression is a common comorbidity in Parkinson's disease(PD)and Lewy body dementia(LBD).However,studies examining the rate of incident depression in the period preceding and following the diagnosis of PD and LBD are lacki ng in the literature.Aims To quantify the incidence of depression in the period preceding and following the diagnosis of PD and LBD.Methods We conducted a retrospective case-control study.Specifically,we used Danish registers to identify all patients with a diagnosis of PD or LBD in the period from 2007 to 2019.These patients were matched by age,calendar year of diagnosis and sex with up to three patients diagnosed with rheumatoid arthritis(RA),chronic kidney disease(CKD)or osteoporosis,respectively.The outcome was incident depression.The incidence of depression was assessed for up to 10 years before and up to 10 years after the diagnosis of PD or LBD.Hazard rates of incident depression for patients with PD or LBD,both before and after diagnosis,were compared with those for patients with RA,CKD or osteoporosis using a Coxproportional hazards model.Results We identified 17711 patients with PD or LBD.Their median age was 74.98(68.10-80.85)years,and39.92%were females.These patients were matched to 19556,40842 and 47809 patients with RA,CKD and osteoporosis,respectively.From 7 to 8 years before diagnosis to 5 years after diagnosis,patients with PD and LBD consistently had higher hazard rates of incident depression than all comparator groups.Conclusions These findings are compatible with depression being an early manifestation of the neurodegenerative changes eventually leading to PD and LBD and imply that incident depression at a late age should raise awareness of potential PD and LBD.展开更多
Rarer dementias are associated with atypical symptoms and younger onset,which result in a higher burden of care.We provide a review of the global literature on longitudinal decline in activities of daily living(ADLs)i...Rarer dementias are associated with atypical symptoms and younger onset,which result in a higher burden of care.We provide a review of the global literature on longitudinal decline in activities of daily living(ADLs)in dementias that account for less than 10%of dementia diagnoses.Published studies were identified through searches conducted in Medical Literature Analysis and Retrieval System Online(MEDLINE),Excerpta Medica Database(Embase),Excerpta Medica Care(Emcare),PsycINFO,and Cumulative Index in Nursing and Allied Health Literature(CINAHL).The search criteria included terms related to‘rarer dementias’,‘activities of daily living’and‘longitudinal or cross-sectional studies’following a predefined protocol registered.Studies were screened,and those that met the criteria were citation searched.Quality assessments were performed,and relevant data were extracted.20 articles were selected,of which 19 focused on dementias within the frontotemporal dementia/primary progressive aphasia spectrum,while one addressed posterior cortical atrophy.Four studies were cross-sectional and 16 studies were longitudinal,with a median duration of 2.2 years.The Disability Assessment for Dementia was used to measure decline in 8 of the 20 studies.The varied sequences of ADL decline reported in the literature reflect variation in diagnostic specificity between studies and within-syndrome heterogeneity.Most studies used Alzheimer’s disease staging scales to measure decline,which cannot capture variant-specific symptoms.To enhance care provision in dementia,ADL scales could be deployed postdiagnosis to aid treatment and planning.This necessitates staging scales that are variant-specific and span the disease course from diagnosis to end of life.展开更多
With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic...With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.展开更多
Dementia is a contemporary global health issue with far reaching consequences, not only for affected individuals and their families, but for national and global socio-economic conditions. The hallmark feature of demen...Dementia is a contemporary global health issue with far reaching consequences, not only for affected individuals and their families, but for national and global socio-economic conditions. The hallmark feature of dementia is that of irreversible cognitive decline, usually affecting memory, and impaired activities of daily living. Advances in healthcare worldwide have facilitated longer life spans, increasing the risks of developing cognitive decline and dementia in late life. Dementia remains a clinical diagnosis. The role of structural and molecular neuroimaging in patients with dementia is primarily supportive role rather than diagnostic, American and European guidelines recommending imaging to exclude treatable causes of dementia, such as tumor, hydrocephalus or intracranial haemorrhage, but also to distinguish between different dementia subtypes, the commonest of which is Alzheimer’s disease. However, this depends on the availability of these imaging techniques at individual centres. Advanced magnetic resonance imaging (MRI) techniques, such as functional connectivity MRI, diffusion tensor imaging and magnetic resonance spectroscopy, and molecular imaging techniques, such as 18F fluoro-deoxy glucose positron emission tomography (PET), amyloid PET, tau PET, are currently within the realm of dementia research but are available for clinical use. Increasingly the research focus is on earlier identification of at risk preclinical individuals, for example due to family history. Intervention at the preclinical stages before irreversible brain damage occurs is currently the best hope of reducing the impact of dementia.展开更多
Objective:This study aimed to observe the effects of xiusanzhen acupuncture(olfactory three-needling therapy)on the behavior,hippocampal histopathology and microglial(MG)activation of rats with vascular dementia(VD),a...Objective:This study aimed to observe the effects of xiusanzhen acupuncture(olfactory three-needling therapy)on the behavior,hippocampal histopathology and microglial(MG)activation of rats with vascular dementia(VD),and to assess the role of the trigeminal nerve.Methods:Sprague-Dawley(SD)rats were randomly assigned to the sham-operation,model,xiusanzhen,and trigeminal neurotomy groups(n=15 per group).Bilateral common carotid artery ligation was performed to prepare the VD models.Models of trigeminal neurotomy were prepared through the excision of the frontal nerve and infraorbital nerve.Xiusanzhen acupuncture was delivered via electric stimulation.The acupoints selected were bilateral“Yingxiang(LI20)”and“Yintang(EX-HN3)”,and the stimulation parameters were as follows:disperse-dense wave,at a frequency of 2/15HZ and intensity of 1 mA.The course of treatment was once daily,with one course lasting five days,followed by an interval of two days,yielding a total of four courses.Behavioral changes were detected using the Morris water maze,changes in histomorphology in the hippocampal CA1 region were determined with hematoxylin and eosin(HE)staining,and MG activation in the hippocampal CA1 region was detected using immunofluorescence.Results:The escape latency:From days 3 to 5,the escape latency was higher in the model group compared to the sham-operation group(P<0.05),but was lower in the xiusanzhen group compared to the model and trigeminal neurotomy groups(P<0.05).The frequency for platform crossing and swimming distance:both were reduced in the model group compared to the sham-operation group(P<0.01);and were elevated in the xiusanzhen group compared to the model group and trigeminal neurotomy group(P<0.01).Hippocampal pathomorphological changes:In the sham-operation group,the morphological structure and nucleoli were well-defined;in the model group and the trigeminal neurotomy group,cell numbers were reduced and karyopyknosis increased;while in the xiusanzhen group,the cell numbers were elevated and karyopyknosis was reduced compared with the model group.MG:the positive rate was higher in the model group compared to the sham-operation group(P<0.05);lower in the xiusanzhen group compared to the model group(P<0.05);and higher in the trigeminal neurotomy group compared to the xiusanzhen group(P<0.05).Conclusion:Xiusanzhen acupuncture attenuates cognitive impairment in VD rats,inhibits MG activation,and reduces hippocampal tissue damage.Its effects depend on the structural integrity of the trigeminal nerve.展开更多
Objective:To clarify the concept of in-home respite care in dementia care and identify changes in the service content over time to help providers and users better understand this sustainable service.Method:A literatur...Objective:To clarify the concept of in-home respite care in dementia care and identify changes in the service content over time to help providers and users better understand this sustainable service.Method:A literature search was conducted through Chinese databases China National Knowledge Infrastructure(CNKI),Wanfang,VIP,and SinoMed,as well as English databases PubMed,the Cochrane Library,Web of Sciences,and Embase.Articles published from January 1980 to December 2024 were identified.Rogers’conceptual analysis of evolution was used for this concept analysis,including six steps:identifying the concept and its context,selecting appropriate databases,determining relevant literature,identifying the concept’s attributes,antecedents,and consequences,choosing a concept exemplar if appropriate,and defininghypotheses and implications for further concept development.Results:Thirty-one articles were included.This conceptual analysis revealed the evolution of in-home respite care service content over time and summarized three key attributes.The antecedents included factors related to people with dementia,family caregivers,and the social environment(aging society,government support).The consequences of in-home respite services include delayed institutional placement and reduced security risk events for people with dementia.For family caregivers,consequences include reduced caregiving stress,improved quality of life,and perceived benefitsfrom rest periods.Conclusion:In-home respite care can be interpreted as family-centered home care that provides temporary relief from family caregivers’responsibilities in caring for people with dementia to reduce caregiver burden.The trend of service specialization and attention on dementia families’needs in service provision are future research focus.展开更多
Dementia is a group of diseases,including Alzheimer's disease(AD),vascular dementia,Lewy body dementia,frontotemporal dementia,Parkinson's disease dementia,metabolic dementia and toxic dementia.The treatment o...Dementia is a group of diseases,including Alzheimer's disease(AD),vascular dementia,Lewy body dementia,frontotemporal dementia,Parkinson's disease dementia,metabolic dementia and toxic dementia.The treatment of dementia mainly includes symptomatic treatment by controlling the primary disease and accompanying symptoms,nutritional support therapy for repairing nerve cells,psychological auxiliary treatment,and treatment that improves cognitive function through drugs.Among them,drug therapy to improve cognitive function is important.This review focuses on introducing and commenting on some recent progress in exploring drugs to improve cognitive function,especially the new progress in drug treatment for AD.We mainly discuss the opportunities and challenges in finding and developing new therapeutic drugs from the aspects of acetylcholinesterase,N-methyl-D-aspartate glutamate receptor,amyloid protein,tau protein and chronic immune inflammation.展开更多
Dementias such as Alzheimer disease(AD)and mild cognitive impairment(MCI)lead to problems with memory,language,and daily activities resulting from damage to neurons in the brain.Given the irreversibility of this neuro...Dementias such as Alzheimer disease(AD)and mild cognitive impairment(MCI)lead to problems with memory,language,and daily activities resulting from damage to neurons in the brain.Given the irreversibility of this neuronal damage,it is crucial to find a biomarker to distinguish individuals with these diseases from healthy people.In this study,we construct a brain function network based on electroencephalography data to study changes in AD and MCI patients.Using a graph-theoretical approach,we examine connectivity features and explore their contributions to dementia recognition at edge,node,and network levels.We find that connectivity is reduced in AD and MCI patients compared with healthy controls.We also find that the edge-level features give the best performance when machine learning models are used to recognize dementia.The results of feature selection identify the top 50 ranked edge-level features constituting an optimal subset,which is mainly connected with the frontal nodes.A threshold analysis reveals that the performance of edge-level features is more sensitive to the threshold for the connection strength than that of node-and network-level features.In addition,edge-level features with a threshold of 0 provide the most effective dementia recognition.The K-nearest neighbors(KNN)machine learning model achieves the highest accuracy of 0.978 with the optimal subset when the threshold is 0.Visualization of edge-level features suggests that there are more long connections linking the frontal region with the occipital and parietal regions in AD and MCI patients compared with healthy controls.Our codes are publicly available at https://github.com/Debbie-85/eeg-connectivity.展开更多
Background Physical frailty and depression may share common pathophysiological pathways associated with dementia and thus interact with each other.However,previous studies have primarily focused on the individual impa...Background Physical frailty and depression may share common pathophysiological pathways associated with dementia and thus interact with each other.However,previous studies have primarily focused on the individual impact of these factors on dementia.Aims To examine the joint effect and interaction of physical frailty and depression on the risk of all-cause dementia.Methods We conducted prospective analyses among participants aged≥60 years from three cohorts:the UK Biobank(UKB),the English Longitudinal Study of Ageing(ELSA)and the Health and Retirement Study(HRS).Physical frailty was assessed using modified versions of the Fried frailty phenotype.Depression was evaluated through mental health questionnaires or combined with hospital admission records.The primary outcome was incident all-cause dementia,identified via active follow-up and passive surveillance.Cox proportional hazards models were used to estimate the hazard ratios(HRs)and 95%confidence intervals(CIs).Results A total of 220947 participants(mean age:64.5 years;53.3%female)were included.Over 2832696 person-years of follow-up,9088 participants(7605 in UKB,1207 in HRS and 276 in ELSA)developed incident all-cause dementia.Compared with robust individuals,frail participants faced a 155%increased risk of dementia(pooled HR:2.55,95%CI 2.36 to 2.76;I2=72.3%).Depression conferred a 1.59-fold excess risk for dementia(pooled HR:1.59,95%CI 1.50 to 1.69;I2=56.8%).Adding physical frailty and depression to a traditional dementia risk model significantly improved prediction accuracy(all p-Δarea under the curve<0.05).Jointly,participants with both physical frailty and depression exhibited the highest dementia risk(pooled HR:3.23,95%CI 2.86 to 3.65;I2=41.6%)compared with those without physical frailty and depression.Moreover,a significant additive interaction between physical frailty and depression was observed(pooled relative excess risk due to interaction:0.38,95%CI 0.13 to 0.63),with 17.1%(95%CI 6.0%to 28.3%)of dementia risk attributed to their interactive effects.Conclusions Individuals with both physical frailty and depression had the highest risk of dementia.More importantly,these two factors interact in an additive manner,further amplifying dementia risk.展开更多
Objective Observational studies have found associations between inflammatory bowel disease(IBD)and the risk of dementia,including Alzheimer’s dementia(AD)and vascular dementia(VD);however,these findings are inconsist...Objective Observational studies have found associations between inflammatory bowel disease(IBD)and the risk of dementia,including Alzheimer’s dementia(AD)and vascular dementia(VD);however,these findings are inconsistent.It remains unclear whether these associations are causal.Methods We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia.Mendelian randomization(MR)analysis based on summary genome-wide association studies(GWASs)was performed.Genetic correlation and Bayesian colocalization analyses were used to provide robust genetic evidence.Results Ten observational studies involving 80,565,688 participants were included in this metaanalysis.IBD was significantly associated with dementia(risk ratio[RR]=1.36,95%CI=1.04-1.78;I2=84.8%)and VD(RR=2.60,95%CI=1.18-5.70;only one study),but not with AD(RR=2.00,95%CI=0.96-4.13;I^(2)=99.8%).MR analyses did not supported significant causal associations of IBD with dementia(dementia:odds ratio[OR]=1.01,95%CI=0.98-1.03;AD:OR=0.98,95%CI=0.95-1.01;VD:OR=1.02,95%CI=0.97-1.07).In addition,genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia.Conclusion Our study did not provide genetic evidence for a causal association between IBD and dementia risk.The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.展开更多
Background(1)To investigate the association between age at diabetes diagnosis and the incidence of all-cause dementia(ACD),Alzheimer’s disease(AD),and vascular dementia(VD)in individuals with diabetes.(2)To assess th...Background(1)To investigate the association between age at diabetes diagnosis and the incidence of all-cause dementia(ACD),Alzheimer’s disease(AD),and vascular dementia(VD)in individuals with diabetes.(2)To assess the relationship among age at diabetes diagnosis,dementia polygenic risk score(PRS),APOEε4 carrier status,and risk of ACD.Methods In a large,population-based cohort with a median follow-up of 13.4 years,participants were stratified by age at diabetes diagnosis(<50,50–60,and>60 years).Cox proportional hazards models were used,adjusted for multiple covariates.Genetic risk was assessed using dementia PRS,and APOEε4 carrier status was considered in the analysis.Results(1)Individuals diagnosed at ages 50–60(hazard ratio(HR)=0.71,95%CI:0.55–0.93,P=0.0117)and>60 years(HR=0.59,95%CI:0.44–0.79,P<0.001)had significantly lower ACD risk compared to those diagnosed at age<50 years.(2)Genetic risk stratification:among participants with intermediate and high dementia PRS,diabetes diagnosis at age>60 years was associated with reduced ACD risk(intermediate PRS:HR=0.66,95%CI:0.44–0.97,P=0.0035;high PRS:HR=0.46,95%CI:0.26–0.83,P=0.009).(3)APOEε4 carrier analysis:in APOEε4 carriers,diagnosis of diabetes at>60 years(HR=0.43,95%CI:0.29–0.64,P<0.001)and at 50–60 years(HR=0.69,95%CI:0.40–0.85,P=0.005)was associated with a significantly reduced risk of ACD compared to diagnosis at age<50 years.Conclusion Later onset of diabetes(age≥50)is associated with a lower risk of ACD,particularly among individuals with higher genetic susceptibility to dementia,including APOEε4 carriers.These findings highlight the importance of early diabetes management and targeted lifestyle interventions in high-risk populations to potentially reduce dementia risk.展开更多
Objective To investigate the effects of WenFei JiangZhuo Formula on cognitive function,serum neurofactors,and cerebral blood flow status in patients with mild-to-moderate vascular dementia(VaD),providing evidence for ...Objective To investigate the effects of WenFei JiangZhuo Formula on cognitive function,serum neurofactors,and cerebral blood flow status in patients with mild-to-moderate vascular dementia(VaD),providing evidence for clinical treatment.Methods A total of 80 patients with mild-to-moderate VaD admitted to our hospital from January 2022 to December 2023 were randomly divided into a control group(40 cases)and an observation group(40 cases)using a random number table.The control group received oral administration of butylphenidyl soft capsules,while the observation group received WenFei JiangZhuo Formula decoction as adjunct therapy.Both groups underwent continuous treatment for 12 weeks.Clinical outcomes were compared including cognitive function scores(MMSE,MoCA),serum neurofactors[brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)],and cerebral hemodynamics parameters[peak systolic velocity(Vs),end-diastolic velocity(Vd),mean velocity(Vm)of the middle cerebral artery(MCA)and anterior cerebral artery(ACA)].Clinical efficacy and adverse reactions were statistically analyzed.Results:After treatment,both groups showed significantly improved MMSE and MoCA scores compared to baseline levels(P<0.05),with the observation group demonstrating greater improvement than the control group(P<0.05).Serum BDNF and NGF levels increased significantly in both groups(P<0.05),while TNF-αand IL-6 levels decreased markedly(P<0.05),with the observation group showing better improvement than the control group(P<0.05).Both groups showed significant increases in MCA,ACA,Vs,Vd,and Vm compared to baseline levels(P<0.05),with the observation group outperforming the control group(P<0.05).The overall effective rate in the observation group was 87.50%,significantly higher than the control group's 67.50%(P<0.05).No statistically significant differences were observed in adverse reaction rates between the groups(P>0.05).Conclusion:WenFei JiangZhuo Formula can effectively improve cognitive function in patients with mild-to-moderate VaD.This mechanism may involve upregulating neurotrophic factors,suppressing inflammatory responses,and enhancing cerebral blood flow perfusion,with demonstrated safety profile.展开更多
Evidence on the association between osteoporosis and dementia is not fully clear.This study aimed to investigate the potential association between osteoporosis and the subsequent risk of dementia among older adults.We...Evidence on the association between osteoporosis and dementia is not fully clear.This study aimed to investigate the potential association between osteoporosis and the subsequent risk of dementia among older adults.We performed a cohort study of176150 community-dwelling older adults aged≥65 years and free of cognitive impairment between 2018 and 2022 using integrated healthcare data from Shenzhen,China.Diagnoses of osteoporosis,osteoporotic fractures,and dementia were identified through linked outpatient and inpatient medical records and death registration records.Multivariate Cox proportional hazards models were used to estimate the adjusted hazard ratios(HRs)and 95%confidence intervals(CIs)of incident dementia associated with osteoporosis and osteoporotic fractures.The mean(SD)age of the total study population was 70.7(5.4)years,and 9605 had a previous diagnosis of osteoporosis.Over a median follow-up of 2.2(IQR:1.8–4.3,maximum:5.5)years,corresponding to 505423person-years at risk,1367 incident all-cause dementia cases,including 617 Alzheimer's disease and 298 vascular dementia cases,occurred.Physician-diagnosed osteoporosis was associated with a higher risk of all-cause dementia(HR:1.80,95%CI:1.53–2.12).The increased dementia risk tended to be more prominent among patients with osteoporotic fractures(HR:2.43,95%CI:1.83–3.23)than those without(HR:1.63,95%CI:1.35–1.97).Results were similar for Alzheimer's disease and vascular dementia.This study provides evidence that older adults with osteoporosis,especially those with osteoporotic fractures,have an elevated risk of incident dementia.Effective prevention and management of osteoporosis among the older population may be promising to mitigate the dual burden of osteoporosis and dementia.展开更多
Alzheimer’s dementia(AD)and type 2 diabetes(T2D)are interrelated global public health problems,and the current epidemics of both AD and T2D are insulin resistance diseases.Thus,AD and T2D may share common risk factor...Alzheimer’s dementia(AD)and type 2 diabetes(T2D)are interrelated global public health problems,and the current epidemics of both AD and T2D are insulin resistance diseases.Thus,AD and T2D may share common risk factors such as an unhealthy diet,lifestyle,and obesity.Meat products is an important part of the diet of consumers worldwide.This systematic review and meta-analysis aims to assess and estimate the effect of meat products consumption on AD and T2D in humans.Web of Science,MEDLINE,PubMed,Cochrane Library,and Embase were searched from January 2012 to April 2024.29 articles reported 32 cohort studies with 1785769 subjects,with 3546 AD cases and 91092 T2D cases that met the inclusion criteria and were included in our analysis.Consumption of various meat products increased the risk of T2D(hazard ratios(HR)=1.19,95%confidence intervals(CI):1.13−1.26,P=0.000;I2=88.5%),consumption of smoked,grilled/roasted and fried meat products was more likely to induce T2D(HR=1.24,95%CI:1.18−1.30,P=0.000;I2=76.1%),but was borderline significant for the risk of AD(HR=1.11,95%CI:0.98−1.25,P=0.094;I2=58.8%),with consumption of mainly livestock and poultry products increasing the risk(HR=1.21,95%CI:1.03−1.42,P=0.017;I2=66.8%).The association between meat products consumption and AD risk was influenced by meat type and sample size,while the risk of T2D was influenced by meat type,follow-up and sex.A daily intake of 27,123 and 170 g of livestock products increased the risk of T2D by 10%,51%and 70%respectively,whereas the risk of T2D was reduced when the intake of various meat products was less than 23 g/day.展开更多
文摘The rising incidence of dementia and associated neurodegenerative disorders poses a growing public health challenge.These conditions have traditionally been studied as isolated central nervous system disorders;however,emerging evidence suggests that broader systemic factors,including chronic inflammation,immune dysregulation,metabolic dysfunction,and genetic susceptibility,may also play a role.This review ex-amines the interconnection between autoimmune diseases and metabolic syndromes in the pathogenesis and exacerbation of neurodegeneration.Conditions such as rheu-matoid arthritis,systemic lupus erythematosus,and type 1 diabetes mellitus have been associated with a heightened risk of developing dementia through chronic immune activation,blood-brain barrier disruption,and neuroinflammatory signaling.Similarly,metabolic disorders such as diabesity promote insulin resistance and oxidative stress,accelerating cognitive decline.The review also discusses glaucoma as a neurodegenera-tive condition with autoimmune features,underscoring the need for expanded classifi-cation and treatment strategies.A key focus is the utilization of the Collaborative Cross(CC)mouse model,which enables the study of gene-environment interactions across genetically diverse backgrounds.Findings from CC mice reveal strain-dependent sus-ceptibility to inflammation,cognitive impairment,and gut-brain axis dysfunction,pro-viding a translational bridge to human variability.This review highlights the importance of integrating precision-based approaches to dementia research that consider systemic influences.Advancing our understanding of these multiorgan interactions holds po-tential for designing precision-based therapeutic approaches to postpone the onset or reduce the incidence of neurodegenerative conditions.
基金supported by the Natural Science Foundation of Beijing,No.7232279(to XW)the National Natural Science Foundation of China,No.U21A20400(to QW)Key Project of Beijing University of Chinese Medicine,Nos.2022-JYB-JBZR-004(to XW),2024-JYB-JBZD-043(to CL).
文摘Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an important factor influencing the onset and progression of vascular dementia.The myelin sheath is a critical component of white matter,and damage and repair of the white matter are closely linked to myelin sheath integrity.This article reviews the role of microglia in vascular dementia,focusing on their effects on myelin sheaths and the potential therapeutic implications.The findings suggest that ischemia and hypoxia cause disruption of the blood-brain barrier and activate microglia,which may worsen blood-brain barrier damage through the release of matrix-degrading enzymes.Microglia-mediated metabolic reprogramming is recognized as an important driver of inflammation.Damage to the blood-brain barrier and subsequent inflammation can lead to myelin injury and accelerate the progression of vascular dementia.Early activation of microglia is a protective response that contributes to the maintenance of blood-brain barrier integrity through sensing,debris-clearing,and defensive mechanisms.However,prolonged activation can trigger a shift in microglia toward the pro-inflammatory M1 phenotype,resulting in myelin damage and cognitive impairment.Triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells 1 have been identified as potential biomarkers for vascular dementia,as both are closely linked to cognitive decline.Although effective clinical treatments for myelin damage in the central nervous system are currently lacking,researchers are actively working to develop targeted therapies.Several drugs,including nimodipine,dopaminergic agents,simvastatin,biotin,and quetiapine,have been evaluated for clinical use in treating microglial and myelin damage.Future research will face challenges in developing targeted therapeutic strategies for vascular dementia,requiring further investigation into the timing,duration,and specific mechanisms of microglial activation,as well as the exploration of new drug combinations and additional therapeutic targets.
基金supported by the Research Cultivation Project of Beijing Municipal Hospital(北京市属医院科研培育课题,No.PZ2022015).
文摘Objective:To observe the efficacy of acupuncture combined with traditional Chinese herbs in the treatment of poststroke vascular dementia(VD)and the effects on serum interleukin(IL)-6 and superoxide dismutase(SOD).Methods:A total of 240 patients with poststroke VD were selected and randomly divided into two groups according to the random number table method,with 120 cases in each group.Both groups received Hua Tan Tong Luo(phlegmresolving and collateral-activating)formula,once daily;the observation group was additionally treated with Yi Shen Tiao Du(kidney-tonifying and Governor Vessel-regulating)acupuncture once daily for 6 consecutive days,followed by 1 d of rest.Both groups were treated for 15 d as one course,for a total of 2 courses.After treatment,the total effective rate was compared.Changes in scores of traditional Chinese medicine(TCM)symptoms,clinical dementia rating(CDR),National Institutes of Health stroke scale(NIHSS),and Chinese version of mini-mental state examination(MMSE),and serum levels of IL-6 and SOD were observed in both groups.Results:The total effective rate in the observation group was higher than that in the control group(P<0.05).After treatment,TCM symptom,CDR,and NIHSS scores,and serum IL-6 levels in both groups were lower than those before treatment(P<0.05),while MMSE scores and serum SOD levels were higher than those before treatment(P<0.05).After treatment,the observation group showed lower TCM symptom,CDR,and NIHSS scores,and serum IL-6 levels than the control group(P<0.05),and higher MMSE scores and serum SOD levels than the control group(P<0.05).Conclusion:Compared to Hua Tan Tong Luo formula alone,Yi Shen Tiao Du acupuncture combined with Hua Tan Tong Luo formula demonstrates better efficacy in reducing dementia severity,improving cognitive and neurological function,and inhibiting inflammation in patients with poststroke VD.
基金supported by the Beijing Nova Program,Nos.20230484436,Z211100002121038the Chinese Institutes for Medical Research,No.CX23YQ01+1 种基金the NationalNatural Science Foundation of China,Nos.32100925,82027802Beijing-Tianjin-Hebei Basic Research Cooperation Project,No.22JCZXJC00190(all to XJand JL).
文摘Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.
文摘Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2500 g),normal birth weight(2500-3999 g),and macrosomia(≥4000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.
文摘Objective:To translate and adapt the dementia knowledge assessment scale(DKAS)into Sinhala version and to evaluate its psychometric properties among nursing students.Methods:A cross-sectional validation study was conducted in two phases:(i)translation and adaptation and(ii)evaluating psychometric properties(N=394 nursing students).Results:The DKAS was adapted to the Sinhala(Si-DKAS)version,and the content validity index(CVI=0.9)was satisfactory.Exploratory factor analysis(EFA)and confirmatory factor analysis(CFA)resulted in an 18-item Si-DKAS with a four-factor model:“care considerations,”“causes and characteristics of dementia,”“health promotion,”and“misconceptions about dementia.”The model fit indices were suboptimal(comparative fix index[CFI]=0.809 and Turker-Lewis index[TLI]=0.773),and some indices were acceptable(standardized root-mean-squared residual[SRMR]=0.040 and root-mean-squared error of approximation[RMSEA]=0.053).Internal consistency(0.7)and test-retest correlation(0.9)were acceptable.Discriminant validity was confirmed by knowledge score differences based on academic years.Conclusions:This is a valid and reliable tool for assessing knowledge of dementia among Sinhala-speaking nursing students.
文摘Background Depression is a common comorbidity in Parkinson's disease(PD)and Lewy body dementia(LBD).However,studies examining the rate of incident depression in the period preceding and following the diagnosis of PD and LBD are lacki ng in the literature.Aims To quantify the incidence of depression in the period preceding and following the diagnosis of PD and LBD.Methods We conducted a retrospective case-control study.Specifically,we used Danish registers to identify all patients with a diagnosis of PD or LBD in the period from 2007 to 2019.These patients were matched by age,calendar year of diagnosis and sex with up to three patients diagnosed with rheumatoid arthritis(RA),chronic kidney disease(CKD)or osteoporosis,respectively.The outcome was incident depression.The incidence of depression was assessed for up to 10 years before and up to 10 years after the diagnosis of PD or LBD.Hazard rates of incident depression for patients with PD or LBD,both before and after diagnosis,were compared with those for patients with RA,CKD or osteoporosis using a Coxproportional hazards model.Results We identified 17711 patients with PD or LBD.Their median age was 74.98(68.10-80.85)years,and39.92%were females.These patients were matched to 19556,40842 and 47809 patients with RA,CKD and osteoporosis,respectively.From 7 to 8 years before diagnosis to 5 years after diagnosis,patients with PD and LBD consistently had higher hazard rates of incident depression than all comparator groups.Conclusions These findings are compatible with depression being an early manifestation of the neurodegenerative changes eventually leading to PD and LBD and imply that incident depression at a late age should raise awareness of potential PD and LBD.
基金supported by UKResearch and Innovation(MR/S03546X/1)National BrainAppeal,Economic and Social ResearchCouncil(ES/S010467/1)+4 种基金Wellcome Trust(221915/Z/20/Z),ESRC(ES/W006014/1)Royal National Institute for Deaf People-Dunhill Medical Trust Pauline Ashley(204841/Z/16/Z,PA23)London Hospitals Biomedical Research Centre(221915/Z/20/Z)Bloomsbury and East London Doctoral Training Partnership(ES/P000592/1)National Institute for Health Research.
文摘Rarer dementias are associated with atypical symptoms and younger onset,which result in a higher burden of care.We provide a review of the global literature on longitudinal decline in activities of daily living(ADLs)in dementias that account for less than 10%of dementia diagnoses.Published studies were identified through searches conducted in Medical Literature Analysis and Retrieval System Online(MEDLINE),Excerpta Medica Database(Embase),Excerpta Medica Care(Emcare),PsycINFO,and Cumulative Index in Nursing and Allied Health Literature(CINAHL).The search criteria included terms related to‘rarer dementias’,‘activities of daily living’and‘longitudinal or cross-sectional studies’following a predefined protocol registered.Studies were screened,and those that met the criteria were citation searched.Quality assessments were performed,and relevant data were extracted.20 articles were selected,of which 19 focused on dementias within the frontotemporal dementia/primary progressive aphasia spectrum,while one addressed posterior cortical atrophy.Four studies were cross-sectional and 16 studies were longitudinal,with a median duration of 2.2 years.The Disability Assessment for Dementia was used to measure decline in 8 of the 20 studies.The varied sequences of ADL decline reported in the literature reflect variation in diagnostic specificity between studies and within-syndrome heterogeneity.Most studies used Alzheimer’s disease staging scales to measure decline,which cannot capture variant-specific symptoms.To enhance care provision in dementia,ADL scales could be deployed postdiagnosis to aid treatment and planning.This necessitates staging scales that are variant-specific and span the disease course from diagnosis to end of life.
基金supported by the National Key R&D Program of China,No.2019YFE0121200(to LQZ)the National Natural Science Foundation of China,Nos.82325017(to LQZ),82030032(to LQZ),82261138555(to DL)+2 种基金the Natural Science Foundation of Hubei Province,No.2022CFA004(to LQZ)the Natural Science Foundation of Jiangxi Province,No.20224BAB206040(to XZ)Research Project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province,No.RZYB202201(to XZ).
文摘With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.
文摘Dementia is a contemporary global health issue with far reaching consequences, not only for affected individuals and their families, but for national and global socio-economic conditions. The hallmark feature of dementia is that of irreversible cognitive decline, usually affecting memory, and impaired activities of daily living. Advances in healthcare worldwide have facilitated longer life spans, increasing the risks of developing cognitive decline and dementia in late life. Dementia remains a clinical diagnosis. The role of structural and molecular neuroimaging in patients with dementia is primarily supportive role rather than diagnostic, American and European guidelines recommending imaging to exclude treatable causes of dementia, such as tumor, hydrocephalus or intracranial haemorrhage, but also to distinguish between different dementia subtypes, the commonest of which is Alzheimer’s disease. However, this depends on the availability of these imaging techniques at individual centres. Advanced magnetic resonance imaging (MRI) techniques, such as functional connectivity MRI, diffusion tensor imaging and magnetic resonance spectroscopy, and molecular imaging techniques, such as 18F fluoro-deoxy glucose positron emission tomography (PET), amyloid PET, tau PET, are currently within the realm of dementia research but are available for clinical use. Increasingly the research focus is on earlier identification of at risk preclinical individuals, for example due to family history. Intervention at the preclinical stages before irreversible brain damage occurs is currently the best hope of reducing the impact of dementia.
基金Supported by The National Natural Science Foundation of China Young Scientists Fund:82004480。
文摘Objective:This study aimed to observe the effects of xiusanzhen acupuncture(olfactory three-needling therapy)on the behavior,hippocampal histopathology and microglial(MG)activation of rats with vascular dementia(VD),and to assess the role of the trigeminal nerve.Methods:Sprague-Dawley(SD)rats were randomly assigned to the sham-operation,model,xiusanzhen,and trigeminal neurotomy groups(n=15 per group).Bilateral common carotid artery ligation was performed to prepare the VD models.Models of trigeminal neurotomy were prepared through the excision of the frontal nerve and infraorbital nerve.Xiusanzhen acupuncture was delivered via electric stimulation.The acupoints selected were bilateral“Yingxiang(LI20)”and“Yintang(EX-HN3)”,and the stimulation parameters were as follows:disperse-dense wave,at a frequency of 2/15HZ and intensity of 1 mA.The course of treatment was once daily,with one course lasting five days,followed by an interval of two days,yielding a total of four courses.Behavioral changes were detected using the Morris water maze,changes in histomorphology in the hippocampal CA1 region were determined with hematoxylin and eosin(HE)staining,and MG activation in the hippocampal CA1 region was detected using immunofluorescence.Results:The escape latency:From days 3 to 5,the escape latency was higher in the model group compared to the sham-operation group(P<0.05),but was lower in the xiusanzhen group compared to the model and trigeminal neurotomy groups(P<0.05).The frequency for platform crossing and swimming distance:both were reduced in the model group compared to the sham-operation group(P<0.01);and were elevated in the xiusanzhen group compared to the model group and trigeminal neurotomy group(P<0.01).Hippocampal pathomorphological changes:In the sham-operation group,the morphological structure and nucleoli were well-defined;in the model group and the trigeminal neurotomy group,cell numbers were reduced and karyopyknosis increased;while in the xiusanzhen group,the cell numbers were elevated and karyopyknosis was reduced compared with the model group.MG:the positive rate was higher in the model group compared to the sham-operation group(P<0.05);lower in the xiusanzhen group compared to the model group(P<0.05);and higher in the trigeminal neurotomy group compared to the xiusanzhen group(P<0.05).Conclusion:Xiusanzhen acupuncture attenuates cognitive impairment in VD rats,inhibits MG activation,and reduces hippocampal tissue damage.Its effects depend on the structural integrity of the trigeminal nerve.
基金supported by the Fundamental Research Funds for the Central Universities(lzujbky-2022-it36)。
文摘Objective:To clarify the concept of in-home respite care in dementia care and identify changes in the service content over time to help providers and users better understand this sustainable service.Method:A literature search was conducted through Chinese databases China National Knowledge Infrastructure(CNKI),Wanfang,VIP,and SinoMed,as well as English databases PubMed,the Cochrane Library,Web of Sciences,and Embase.Articles published from January 1980 to December 2024 were identified.Rogers’conceptual analysis of evolution was used for this concept analysis,including six steps:identifying the concept and its context,selecting appropriate databases,determining relevant literature,identifying the concept’s attributes,antecedents,and consequences,choosing a concept exemplar if appropriate,and defininghypotheses and implications for further concept development.Results:Thirty-one articles were included.This conceptual analysis revealed the evolution of in-home respite care service content over time and summarized three key attributes.The antecedents included factors related to people with dementia,family caregivers,and the social environment(aging society,government support).The consequences of in-home respite services include delayed institutional placement and reduced security risk events for people with dementia.For family caregivers,consequences include reduced caregiving stress,improved quality of life,and perceived benefitsfrom rest periods.Conclusion:In-home respite care can be interpreted as family-centered home care that provides temporary relief from family caregivers’responsibilities in caring for people with dementia to reduce caregiver burden.The trend of service specialization and attention on dementia families’needs in service provision are future research focus.
基金Supported by National Natural Science Foundation of China (General Program),No.32060182Qiannan Prefecture Science and Technology Plan Project in China,No.Qiannan Kehe She Zi[2022]No.1.
文摘Dementia is a group of diseases,including Alzheimer's disease(AD),vascular dementia,Lewy body dementia,frontotemporal dementia,Parkinson's disease dementia,metabolic dementia and toxic dementia.The treatment of dementia mainly includes symptomatic treatment by controlling the primary disease and accompanying symptoms,nutritional support therapy for repairing nerve cells,psychological auxiliary treatment,and treatment that improves cognitive function through drugs.Among them,drug therapy to improve cognitive function is important.This review focuses on introducing and commenting on some recent progress in exploring drugs to improve cognitive function,especially the new progress in drug treatment for AD.We mainly discuss the opportunities and challenges in finding and developing new therapeutic drugs from the aspects of acetylcholinesterase,N-methyl-D-aspartate glutamate receptor,amyloid protein,tau protein and chronic immune inflammation.
基金supported by the National Natural Science Foundation of China(Grant Nos.62071451,62331025,and U21A20447)the National Key Research and Development Project(Grant No.2021YFC3002204)the CAMS Innovation Fund for Medical Sciences(Grant No.2019-I2M-5-019).
文摘Dementias such as Alzheimer disease(AD)and mild cognitive impairment(MCI)lead to problems with memory,language,and daily activities resulting from damage to neurons in the brain.Given the irreversibility of this neuronal damage,it is crucial to find a biomarker to distinguish individuals with these diseases from healthy people.In this study,we construct a brain function network based on electroencephalography data to study changes in AD and MCI patients.Using a graph-theoretical approach,we examine connectivity features and explore their contributions to dementia recognition at edge,node,and network levels.We find that connectivity is reduced in AD and MCI patients compared with healthy controls.We also find that the edge-level features give the best performance when machine learning models are used to recognize dementia.The results of feature selection identify the top 50 ranked edge-level features constituting an optimal subset,which is mainly connected with the frontal nodes.A threshold analysis reveals that the performance of edge-level features is more sensitive to the threshold for the connection strength than that of node-and network-level features.In addition,edge-level features with a threshold of 0 provide the most effective dementia recognition.The K-nearest neighbors(KNN)machine learning model achieves the highest accuracy of 0.978 with the optimal subset when the threshold is 0.Visualization of edge-level features suggests that there are more long connections linking the frontal region with the occipital and parietal regions in AD and MCI patients compared with healthy controls.Our codes are publicly available at https://github.com/Debbie-85/eeg-connectivity.
基金supported by the National Key Research and Development Program of China(2017YFC0907004 to YZ)。
文摘Background Physical frailty and depression may share common pathophysiological pathways associated with dementia and thus interact with each other.However,previous studies have primarily focused on the individual impact of these factors on dementia.Aims To examine the joint effect and interaction of physical frailty and depression on the risk of all-cause dementia.Methods We conducted prospective analyses among participants aged≥60 years from three cohorts:the UK Biobank(UKB),the English Longitudinal Study of Ageing(ELSA)and the Health and Retirement Study(HRS).Physical frailty was assessed using modified versions of the Fried frailty phenotype.Depression was evaluated through mental health questionnaires or combined with hospital admission records.The primary outcome was incident all-cause dementia,identified via active follow-up and passive surveillance.Cox proportional hazards models were used to estimate the hazard ratios(HRs)and 95%confidence intervals(CIs).Results A total of 220947 participants(mean age:64.5 years;53.3%female)were included.Over 2832696 person-years of follow-up,9088 participants(7605 in UKB,1207 in HRS and 276 in ELSA)developed incident all-cause dementia.Compared with robust individuals,frail participants faced a 155%increased risk of dementia(pooled HR:2.55,95%CI 2.36 to 2.76;I2=72.3%).Depression conferred a 1.59-fold excess risk for dementia(pooled HR:1.59,95%CI 1.50 to 1.69;I2=56.8%).Adding physical frailty and depression to a traditional dementia risk model significantly improved prediction accuracy(all p-Δarea under the curve<0.05).Jointly,participants with both physical frailty and depression exhibited the highest dementia risk(pooled HR:3.23,95%CI 2.86 to 3.65;I2=41.6%)compared with those without physical frailty and depression.Moreover,a significant additive interaction between physical frailty and depression was observed(pooled relative excess risk due to interaction:0.38,95%CI 0.13 to 0.63),with 17.1%(95%CI 6.0%to 28.3%)of dementia risk attributed to their interactive effects.Conclusions Individuals with both physical frailty and depression had the highest risk of dementia.More importantly,these two factors interact in an additive manner,further amplifying dementia risk.
基金supported by the China Postdoctoral Science Foundation(Grant No.2021M703366)Shenzhen Science and Technology Program(Grant No.KQTD20190929172835662).
文摘Objective Observational studies have found associations between inflammatory bowel disease(IBD)and the risk of dementia,including Alzheimer’s dementia(AD)and vascular dementia(VD);however,these findings are inconsistent.It remains unclear whether these associations are causal.Methods We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia.Mendelian randomization(MR)analysis based on summary genome-wide association studies(GWASs)was performed.Genetic correlation and Bayesian colocalization analyses were used to provide robust genetic evidence.Results Ten observational studies involving 80,565,688 participants were included in this metaanalysis.IBD was significantly associated with dementia(risk ratio[RR]=1.36,95%CI=1.04-1.78;I2=84.8%)and VD(RR=2.60,95%CI=1.18-5.70;only one study),but not with AD(RR=2.00,95%CI=0.96-4.13;I^(2)=99.8%).MR analyses did not supported significant causal associations of IBD with dementia(dementia:odds ratio[OR]=1.01,95%CI=0.98-1.03;AD:OR=0.98,95%CI=0.95-1.01;VD:OR=1.02,95%CI=0.97-1.07).In addition,genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia.Conclusion Our study did not provide genetic evidence for a causal association between IBD and dementia risk.The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
基金supported by Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization(2021B1212040007)Special Projects for Scientific and Technological Research in Chinese Medicine and Ethnomedicine(QZYY-2024-035)+3 种基金Scientific and Technological Innovation 2030(2023ZD0505804,2023ZD0505800,and 2024YFF0507500)the National Key Research and Development Program of China(2021YFC2500100 and 2021YFC2500103)the National Natural Science Foundation of China(82471212,82071187,82360387,and 81870821)Key Project of Yunnan Provincial Department of Science and Technology(202301AS070037 and 202305AK340001).
文摘Background(1)To investigate the association between age at diabetes diagnosis and the incidence of all-cause dementia(ACD),Alzheimer’s disease(AD),and vascular dementia(VD)in individuals with diabetes.(2)To assess the relationship among age at diabetes diagnosis,dementia polygenic risk score(PRS),APOEε4 carrier status,and risk of ACD.Methods In a large,population-based cohort with a median follow-up of 13.4 years,participants were stratified by age at diabetes diagnosis(<50,50–60,and>60 years).Cox proportional hazards models were used,adjusted for multiple covariates.Genetic risk was assessed using dementia PRS,and APOEε4 carrier status was considered in the analysis.Results(1)Individuals diagnosed at ages 50–60(hazard ratio(HR)=0.71,95%CI:0.55–0.93,P=0.0117)and>60 years(HR=0.59,95%CI:0.44–0.79,P<0.001)had significantly lower ACD risk compared to those diagnosed at age<50 years.(2)Genetic risk stratification:among participants with intermediate and high dementia PRS,diabetes diagnosis at age>60 years was associated with reduced ACD risk(intermediate PRS:HR=0.66,95%CI:0.44–0.97,P=0.0035;high PRS:HR=0.46,95%CI:0.26–0.83,P=0.009).(3)APOEε4 carrier analysis:in APOEε4 carriers,diagnosis of diabetes at>60 years(HR=0.43,95%CI:0.29–0.64,P<0.001)and at 50–60 years(HR=0.69,95%CI:0.40–0.85,P=0.005)was associated with a significantly reduced risk of ACD compared to diagnosis at age<50 years.Conclusion Later onset of diabetes(age≥50)is associated with a lower risk of ACD,particularly among individuals with higher genetic susceptibility to dementia,including APOEε4 carriers.These findings highlight the importance of early diabetes management and targeted lifestyle interventions in high-risk populations to potentially reduce dementia risk.
文摘Objective To investigate the effects of WenFei JiangZhuo Formula on cognitive function,serum neurofactors,and cerebral blood flow status in patients with mild-to-moderate vascular dementia(VaD),providing evidence for clinical treatment.Methods A total of 80 patients with mild-to-moderate VaD admitted to our hospital from January 2022 to December 2023 were randomly divided into a control group(40 cases)and an observation group(40 cases)using a random number table.The control group received oral administration of butylphenidyl soft capsules,while the observation group received WenFei JiangZhuo Formula decoction as adjunct therapy.Both groups underwent continuous treatment for 12 weeks.Clinical outcomes were compared including cognitive function scores(MMSE,MoCA),serum neurofactors[brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)],and cerebral hemodynamics parameters[peak systolic velocity(Vs),end-diastolic velocity(Vd),mean velocity(Vm)of the middle cerebral artery(MCA)and anterior cerebral artery(ACA)].Clinical efficacy and adverse reactions were statistically analyzed.Results:After treatment,both groups showed significantly improved MMSE and MoCA scores compared to baseline levels(P<0.05),with the observation group demonstrating greater improvement than the control group(P<0.05).Serum BDNF and NGF levels increased significantly in both groups(P<0.05),while TNF-αand IL-6 levels decreased markedly(P<0.05),with the observation group showing better improvement than the control group(P<0.05).Both groups showed significant increases in MCA,ACA,Vs,Vd,and Vm compared to baseline levels(P<0.05),with the observation group outperforming the control group(P<0.05).The overall effective rate in the observation group was 87.50%,significantly higher than the control group's 67.50%(P<0.05).No statistically significant differences were observed in adverse reaction rates between the groups(P>0.05).Conclusion:WenFei JiangZhuo Formula can effectively improve cognitive function in patients with mild-to-moderate VaD.This mechanism may involve upregulating neurotrophic factors,suppressing inflammatory responses,and enhancing cerebral blood flow perfusion,with demonstrated safety profile.
基金supported by the Shenzhen Medical Academy of Research and Translation(Grant C2302001)the Noncommunicable Chronic Diseases-National Science and Technology Major Project(Grant 2023ZD0503500)+5 种基金the National Natural Science Foundation of China(Grants 82030102,12126602)the Shenzhen Science and Technology Innovation Committee(No.ZDSYS20200810171403013)the Talents enlisted in major talent programs of Guangdong Province(20210N020921)the Shenzhen Development and Reform Committee(No.XMHT20230108022)the Medical Research Innovation Project(Grant G030410001)the Shenzhen Medical Research Funds(Grant A2402041)。
文摘Evidence on the association between osteoporosis and dementia is not fully clear.This study aimed to investigate the potential association between osteoporosis and the subsequent risk of dementia among older adults.We performed a cohort study of176150 community-dwelling older adults aged≥65 years and free of cognitive impairment between 2018 and 2022 using integrated healthcare data from Shenzhen,China.Diagnoses of osteoporosis,osteoporotic fractures,and dementia were identified through linked outpatient and inpatient medical records and death registration records.Multivariate Cox proportional hazards models were used to estimate the adjusted hazard ratios(HRs)and 95%confidence intervals(CIs)of incident dementia associated with osteoporosis and osteoporotic fractures.The mean(SD)age of the total study population was 70.7(5.4)years,and 9605 had a previous diagnosis of osteoporosis.Over a median follow-up of 2.2(IQR:1.8–4.3,maximum:5.5)years,corresponding to 505423person-years at risk,1367 incident all-cause dementia cases,including 617 Alzheimer's disease and 298 vascular dementia cases,occurred.Physician-diagnosed osteoporosis was associated with a higher risk of all-cause dementia(HR:1.80,95%CI:1.53–2.12).The increased dementia risk tended to be more prominent among patients with osteoporotic fractures(HR:2.43,95%CI:1.83–3.23)than those without(HR:1.63,95%CI:1.35–1.97).Results were similar for Alzheimer's disease and vascular dementia.This study provides evidence that older adults with osteoporosis,especially those with osteoporotic fractures,have an elevated risk of incident dementia.Effective prevention and management of osteoporosis among the older population may be promising to mitigate the dual burden of osteoporosis and dementia.
基金supported by the Agricultural Science and Technology Innovation Program,Institute of Food Science and Technology,Chinese Academy of Agricultural Sciences under Grant CAAS-ASTIP-2023-IFSTGuangdong Provincial Key R&D Programme(2023B0202080003).
文摘Alzheimer’s dementia(AD)and type 2 diabetes(T2D)are interrelated global public health problems,and the current epidemics of both AD and T2D are insulin resistance diseases.Thus,AD and T2D may share common risk factors such as an unhealthy diet,lifestyle,and obesity.Meat products is an important part of the diet of consumers worldwide.This systematic review and meta-analysis aims to assess and estimate the effect of meat products consumption on AD and T2D in humans.Web of Science,MEDLINE,PubMed,Cochrane Library,and Embase were searched from January 2012 to April 2024.29 articles reported 32 cohort studies with 1785769 subjects,with 3546 AD cases and 91092 T2D cases that met the inclusion criteria and were included in our analysis.Consumption of various meat products increased the risk of T2D(hazard ratios(HR)=1.19,95%confidence intervals(CI):1.13−1.26,P=0.000;I2=88.5%),consumption of smoked,grilled/roasted and fried meat products was more likely to induce T2D(HR=1.24,95%CI:1.18−1.30,P=0.000;I2=76.1%),but was borderline significant for the risk of AD(HR=1.11,95%CI:0.98−1.25,P=0.094;I2=58.8%),with consumption of mainly livestock and poultry products increasing the risk(HR=1.21,95%CI:1.03−1.42,P=0.017;I2=66.8%).The association between meat products consumption and AD risk was influenced by meat type and sample size,while the risk of T2D was influenced by meat type,follow-up and sex.A daily intake of 27,123 and 170 g of livestock products increased the risk of T2D by 10%,51%and 70%respectively,whereas the risk of T2D was reduced when the intake of various meat products was less than 23 g/day.
