Causal relationships between gut microbiota and dementia:A twosample,bidirectional,Mendelian randomization study

BACKGROUND Existing evidence suggests that gut microbiota represent a significant environmental risk factor for various forms of dementia,including Alzheimer's dementia,vascular dementia,and dementia in other diseases classified elsewhere.However,the exact causal relationships between gut microbiota and the different forms of dementia or their subtypes remain unclear.AIM To investigate putative causal relationships between gut microbiota and dementia or its subtypes using Mendelian randomization(MR)analysis.METHODS A bidirectional,two-sample,MR analysis was conducted utilizing publicly available gut microbiota-related genome-wide association study(GWAS)summary data from the MiBioGen consortium alongside GWAS summary statistics for dementia and its subtypes from the FinnGen consortium.Instrumental variables were selected according to the fundamental tenets of MR and their strengths were evaluated using the F-statistic.Five MR methods were employed,and the robustness of our findings was validated.To account for multiple comparisons,we applied the Bonferroni method for P-value adjustment.RESULTS We identified several gut microbiota taxa exhibiting putative causal relationships with dementia or its subtypes,potentially serving as risk or protective factors for the disease.In addition,reverse MR analysis indicated that the relative abundance of several gut microbiota taxa might be influenced by dementia or its subtypes.An exhaustive sensitivity analysis confirmed the absence of heterogeneity and horizontal pleiotropy.After applying correction for multiple testing,we observed that the order Bacillales(odds ratio:0.830,95%confidence interval:0.740-0.932,P=0.00155,Padjust=0.0311)exhibited a strong association with Alzheimer’s disease-related dementia.CONCLUSION The results suggest that gut microbiota is causally associated with dementia.Our findings provide novel insights into the pathophysiology of dementia and have important implications for its treatment and prevention.

Human immunodeficiency virus-associated dementia complex with positive 14-3-3 protein in cerebrospinal fluid:A case report

BACKGROUND Human immunodeficiency virus(HIV)-associated dementia(HAD)is a subcortical form of dementia characterized by memory deficits and psychomotor slowing.However,HAD often presents with symptoms similar to those of Creutzfeldt-Jakob disease(CJD),particularly in patients with acquired immune deficiency syndrome(AIDS).CASE SUMMARY We report the case of a 54-year-old male who exhibited cognitive dysfunction and secondary behavioral changes following HIV infection and suspected prion exposure.The patient was diagnosed with HIV during hospitalization and his cerebrospinal fluid tested positive for 14-3-3 proteins.His electroencephalogram showed a borderline-abnormal periodic triphasic wave pattern.Contrast-enhanced magnetic resonance imaging revealed moderate encephalatrophy and demyelination.Initially,symptomatic treatment and administration of amantadine were pursued for presumed CJD,but the patient’s condition continued to deteriorate.By contrast,the patient’s condition improved following anti-HIV therapy.This individual is also the only patient with this prognosis to have survived over 4 years.Thus,the diagnosis was revised to HAD.CONCLUSION In the diagnostic process of rapidly progressive dementia,it is crucial to rule out as many potential causes as possible and to consider an autopsy to diminish diagnostic uncertainty.The 14-3-3 protein should not be regarded as the definitive marker for CJD.Comprehensive laboratory screening for infectious diseases is essential to enhance diagnostic precision,especially in AIDS patients with potential CJD.Ultimately,a trial of diagnostic treatment may be considered when additional testing is not feasible.

Strategies for translating proteomics discoveries into drug discovery for dementia

Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

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.

Association between inflammatory bowel disease and all-cause dementia:A two-sample Mendelian randomization study

BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization(MR)method.METHODS Genetic variants extracted from the large genome-wide association study(GWAS)for IBD(the International IBD Genetics Consortium,n=34652)were used to identify the causal link between IBD and dementia(FinnGen,n=306102).The results of the study were validated via another IBD GWAS(United Kingdom Biobank,n=463372).Moreover,MR egger intercept,MR pleiotropy residual sum and outlier,and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity.Finally,multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia,with the inverse variance weighted approach adopted as the primary analysis.RESULTS The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS.No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted[odds ratio(OR)=0.980,95%CI:0.942-1.020,P value=0.325],weighted median(OR=0.964,95%CI:0.914-1.017,P value=0.180),and MR-Egger(OR=0.963,95%CI:0.867-1.070,P value=0.492)approaches.Consistent results were observed in validation analyses.Reverse MR analysis also showed no effect of dementia on the development of IBD.Furthermore,MR analysis suggested that IBD and its subtypes did not causally affect allcause dementia and its four subtypes,including dementia in Alzheimer's disease,vascular dementia,dementia in other diseases classified elsewhere,and unspecified dementia.CONCLUSION Taken together,our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes.Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.

The Alzheimer’s Dementia Patients’ Observed Illness Course and Experience in Ghana and Care Lessons to Be Learnt: A Mental Health Professional’s Perspective

Alzheimer’s disease (AD) and associated dementia patient numbers continue to increase globally with associated economic costs to healthcare systems. Of note is the increase in numbers in lower and middle-income countries (LMICs) including Sub-Saharan African (SSA) countries, which already face challenges with their health budgets from communicable and non-communicable diseases. Ghana, an SSA country, faces the problem of healthcare budgetary difficulties and the additional impact of AD as a consequence of increasing population strata of old aged persons (OAPs) due to the demographic transition effect. This article uses examples of known patients’ illness courses to give a perspective on the lived experience of patients with dementia (PWD) in Ghana, living amongst a populace with a culture of stigmatization of PWD, and a relatively fragile public mental health system (PMHS) for those with mental illness, including AD. The lived experience of AD patients is characterised by stigmatisation, discrimination, non-inclusiveness, diminished dignity and human rights abuses in the face of their mental disability, and eventually death. This article is an advocacy article giving voice to the voiceless and all persons suffering from AD and other dementias in Ghana, whilst pleading for a call to action from healthcare professionals and responsible state agencies.

A pancreatic player in dementia:pathological role for islet amyloid polypeptide accumulation in the brain

Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia.While multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid polypeptide,that accompanies the pathophysiology of type 2 diabetes mellitus.Islet amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia,including Alzheimer’s disease and vascular dementia,but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are unclear.In this review,we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage,ultimately leading to the clinical symptoms of dementia.We discuss the evidence for islet amyloid polypeptide deposition in the brain,islet amyloid polypeptide interaction with other amyloids implicated in neurodegeneration,neuroinflammation caused by islet amyloid polypeptide deposition,vascular damage induced by islet amyloid polypeptide accumulation,and islet amyloid polypeptide-induced cytotoxicity.There are very few therapies approved for the treatment of dementia,and of these,clinical responses have been controversial at best.Therefore,investigating new,targetable pathways is vital for identifying novel therapeutic strategies for treating dementia.As such,we conclude this review by discussing islet amyloid polypeptide accumulation as a potential therapeutic target not only in treating type 2 diabetes mellitus but as a future target in treating or even preventing dementia associated with type 2 diabetes mellitus.

Replacement of leisure-time sedentary behavior with various physical activities and the risk of dementia incidence and mortality:A prospective cohort study

Background:Whether or not there is targeted pharmacotherapy for dementia,an active and healthy lifestyle that includes physical activity(PA)may be a better option than medication for preventing dementia.We examined the association between leisure-time sedentary behavior(SB)and the risk of dementia incidence and mortality.We further quantified the effect on dementia risk of replacing sedentary time with an equal amount of time spent on different physical activities.Methods:In the UK Biobank,484,169 participants(mean age=56.5 years;45.2%men)free of dementia were followed from baseline(2006-2010)through July 30,2021.A standard questionnaire measured individual leisure-time SB(watching TV,computer use,and driving)and PA(walking for pleasure,light and heavy do-it-yourself activity,strenuous sports,and other exercise)frequency and duration in the 4 weeks prior to evaluation.Apolipoprotein E(APOE)genotype data were available for a subset of 397,519(82.1%)individuals.A Cox proportional hazard model and an isotemporal substitution model were used in this study.Results:During a median 12.4 years of follow-up,6904 all-cause dementia cases and 2115 deaths from dementia were recorded.In comparison to participants with leisure-time SB<5 h/day,the hazard ratio((HR),95%confidence interval(95%CI))of dementia incidence was 1.07(1.02-1.13)for 5-8 h/day and 1.25(1.13-1.38)for>8 h/day,and the HR of dementia mortality was 1.35(1.12-1.61)for>8 h/day.A 1 standard deviation increment of sedentary time(2.33 h/day)was strongly associated with a higher incidence of dementia and mortality(HR=1.06,95%CI:1.03-1.08 and HR=1.07,95%CI:1.03-1.12,respectively).The association between sedentary time and the risk of developing dementia was more profound in subjects<60 years than in those>60 years(HR=1.26,95%CI:1.00-1.58 vs.HR=1.21,95%CI:1.08-1.35 in>8 h/day,p for interaction=0.013).Replacing 30 min/day of leisure sedentary time with an equal time spent in total PA was associated with a6%decreased risk and 9%decreased mortality from dementia,with exercise(e.g.,swimming,cycling,aerobics,bowling)showing the strongest benefit(HR=0.82,95%CI:0.78-0.86 and HR=0.79,95%CI:0.72-0.86).Compared with APOEε4 noncarriers,APOEε4 carriers are more likely to see a decrease in Alzheimer’s disease incidence and mortality when PA is substituted for SB.Conclusion:Leisure-time SB was positively associated with the risk of dementia incidence and mortality.Replacing sedentary time with equal time spent doing PA may be associated with a significant reduction in dementia incidence and mortality risk.

Predicting Dementia Risk Factors Based on Feature Selection and Neural Networks

Dementia is a disorder with high societal impact and severe consequences for its patients who suffer from a progressive cognitive decline that leads to increased morbidity,mortality,and disabilities.Since there is a consensus that dementia is a multifactorial disorder,which portrays changes in the brain of the affected individual as early as 15 years before its onset,prediction models that aim at its early detection and risk identification should consider these characteristics.This study aims at presenting a novel method for ten years prediction of dementia using on multifactorial data,which comprised 75 variables.There are two automated diagnostic systems developed that use genetic algorithms for feature selection,while artificial neural network and deep neural network are used for dementia classification.The proposed model based on genetic algorithm and deep neural network had achieved the best accuracy of 93.36%,sensitivity of 93.15%,specificity of 91.59%,MCC of 0.4788,and performed superior to other 11 machine learning techniques which were presented in the past for dementia prediction.The identified best predictors were:age,past smoking habit,history of infarct,depression,hip fracture,single leg standing test with right leg,score in the physical component summary and history of TIA/RIND.The identification of risk factors is imperative in the dementia research as an effort to prevent or delay its onset.

Brain Functional Network Generation Using Distribution-Regularized Adversarial Graph Autoencoder with Transformer for Dementia Diagnosis

The topological connectivity information derived from the brain functional network can bring new insights for diagnosing and analyzing dementia disorders.The brain functional network is suitable to bridge the correlation between abnormal connectivities and dementia disorders.However,it is challenging to access considerable amounts of brain functional network data,which hinders the widespread application of data-driven models in dementia diagnosis.In this study,a novel distribution-regularized adversarial graph auto-Encoder(DAGAE)with transformer is proposed to generate new fake brain functional networks to augment the brain functional network dataset,improving the dementia diagnosis accuracy of data-driven models.Specifically,the label distribution is estimated to regularize the latent space learned by the graph encoder,which canmake the learning process stable and the learned representation robust.Also,the transformer generator is devised to map the node representations into node-to-node connections by exploring the long-term dependence of highly-correlated distant brain regions.The typical topological properties and discriminative features can be preserved entirely.Furthermore,the generated brain functional networks improve the prediction performance using different classifiers,which can be applied to analyze other cognitive diseases.Attempts on the Alzheimer’s Disease Neuroimaging Initiative(ADNI)dataset demonstrate that the proposed model can generate good brain functional networks.The classification results show adding generated data can achieve the best accuracy value of 85.33%,sensitivity value of 84.00%,specificity value of 86.67%.The proposed model also achieves superior performance compared with other related augmentedmodels.Overall,the proposedmodel effectively improves cognitive disease diagnosis by generating diverse brain functional networks.

Reduced risk of dementia in patients with type 2 diabetes mellitus using Chinese herbal medicine:A nested case-control study

BACKGROUND Dementia is a prevalent condition in type 2 diabetes mellitus(T2DM)patients.While Chinese herbal medicine(CHM)is often employed as complementary therapy for glycemic control,its effect in controlling likelihood of dementia has not yet been fully elucidated.AIM To compare the risk of dementia between T2DM patients with and without CHM treatment.METHODS We undertook a nested case-control study and obtained data on patients 20-70 years of age who received medical care for T2DM between 2001 and 2010 from the National Health Insurance Research database in Taiwan.Cases,defined as those with dementia that occurred at least one year after the diagnosis of T2DM,were randomly matched to controls without dementia from the study cohort at a 1:1 ratio.We applied conditional logistic regression to explore the associations between CHM treatment and dementia.RESULTS A total of 11699 dementia cases were matched to 11699 non-dementia controls.We found that adding CHM to conventional care was related to a lower risk of dementia[adjusted odds ratio(OR)=0.51],and high-intensity CHM treatment was associated with an adjusted OR of 0.22.CONCLUSION This study shows that the cumulative CHM exposure was inversely associated with dementia risk in an exposureresponse manner,implying that CHM treatment may be embraced as a disease management approach for diabetic patients to prevent dementia.

Long-Term Active and Passive Horticultural Therapy Intervention for Elderly Patients with Moderate Dementia and AI Analysis of Medical Records and Care Documents

Background: Previous studies have shown that Hand Care Treatment, a form of passive horticultural therapy, is effective in preventing dementia and MCI and reducing the rate of progression. Due to the Covid-19 pandemic, various activity restrictions were implemented in Japan from March 2020, and the number of elderly people without care and rehabilitation will the number of elderly people without care and rehabilitation has been increasing. Purpose: Progression of cognitive, physical, and mental disability was examined for long-term horticultural therapy study subjects by level of care required. Methods: One subject who had been diagnosed with dementia and was residing in an elderly care facility and consented to a long-term study was selected. In addition to assessments using various evaluation forms, data recorded from time to time, including changes in care plans, were analyzed using text mining methods. Results: This subject tended to progress slowly from 1 to 2 care needs, but progressed from 3 to 5 care needs over a 2-year period. The results of the assessment chart test showed that cognitive impairment and IADL decreased with each increase in the level of care required, but DBD remained the same at the time of admission, even at 5 years of care required. A comparison of HCT and aroma intervention with and without aroma intervention during the nursing care level 1 showed that the improvement in physical, mental, and cognitive function was expected to be higher at the time of intervention. Text-mining inspections have revealed that during the period of nursing care level 1 - 5, active horticultural therapy techniques, and passive horticultural therapy techniques such as HCT and brain rejuvenation aromatherapy were found to betweenness centrality with each other. Conclusion: From the results of mean score of DBD, although the nursing care level has progressed from 1 to a maximum of 5, it can be concluded that the burden of care has not become heavier. There was no tendency for the progression of cognitive impairment in this subject to be faster than in the general AD population, despite the influences of Covid-19. The results indicated that caregiving techniques and active and passive horticultural therapy techniques in Japanese welfare facilities for the elderly are expected to be effective in preventing the progression of cognitive impairment.

Factors influencing quality of life in Chinese patients with dementia: a systematic review

Background:Dementia is a group of nervous system diseases characterized by progressive cognitive decline,leading to a loss of self-care ability and a decline in well-being.This places a significant burden on the global healthcare system,with Chinese patients accounting for approximately one-quarter of the world’s dementia cases.Therefore,it is crucial to identify factors that impact the quality of life(QOL)among elderly Chinese individuals with dementia.Method:To achieve this,we conducted a comprehensive search of several databases,including PubMed,Embase,Web of Science,the Cochrane Library,China National Knowledge Infrastructure,Wanfang Data,China VIP Database and China Biomedical Literature Database.We reviewed cross-sectional studies from the inception of these databases until March 27,2022.QOL outcomes were assessed using standardized scales in the studies included in this review.Results:The search yielded a total of 1,235 relevant articles,from which we finally included 21 cross-sectional studies and one longitudinal study after rigorous quality assessment.Among these,10 studies were classified as high quality,while 12 were classified as fair quality.Through our analysis,we identified 28 patient-rated QOL factors and 14 caregiver-rated QOL factors.These factors were categorized into three groups:patient,disease-related and caregiver.Factors commonly found to influence patient-rated QOL included age,education,marital status,depression,self-care ability,dementia severity,cognitive function,behavioral and psychological symptoms of dementia and caregiver burden.Similarly,factors commonly influencing caregiver-rated QOL included economic status,depression,self-care ability,dementia severity,cognitive function,behavioral and psychological symptoms of dementia and caregiving time.Conclusion:This review clarifies the factors that influence the QOL of Chinese individuals with dementia.When implementing interventions,it is crucial to consider the differences between patient-rated QOL and caregiver-proxy-rated QOL,as well as their respective influencing factors.

Preliminary Results of Dementia Prevalence among Elderly People at Home by Cognitive Disorder Adapted Test of Niamey (Niger)

Introduction: Neurocognitive disorders are frequent with aging and are often seen at advancing stages in our context. It is really difficult to evaluate rapidly Nigerien elderly persons according to tools available on cognitive status while there is a great number of uneducated elderly people who suffer from cognitive deficiency. The purpose was to determine neurocognitive disorders prevalence in uneducated groups and Muslim elderly people by using the cognitive disorder examination (Codex) test adopted in the population living at home in Niamey (Niger). Materials and Methods: These are the results of a preliminary prospective study with simple three (3) random sampling concerning elderly people aged 60 and over living at home in whom the codex test adapted to Niamey was administered in uneducated Muslim elderly people for a total duration of four (4) minutes. This screen-adapted test should be completed by the mini-mental test of Senegal which is adapted globally to uneducated people in hospitals. The basic Codex test was developed in France for educated people, so we used this basic test in our educated people in the same study. Results: A total of 198 patients had been collected, of which 51.5% were female with an average age of 68 years with extremes of 60 to 84 years. 40 were educated. Among educated persons, 62.5% had a very low probability of dementia and 5% had a very high probability of dementia in the first step of the Codex. In the second step, 12.5% had a low probability of dementia and 20% had a high probability in the same group, while 51.3% had a very low probability of dementia and 21.3% had a very high probability of dementia in the first step of CODEX in uneducated elderly. In the second step in the same group, 12.6% had a low probability and 14.5% had a high probability of dementia. Conclusion: The adapted codex test of Niamey is simple and could be rapidly used to screen dementia among uneducated elderly Muslim prayers, and then could confirm it by complementary cognitive status test validated in the same population. However, it should be confirmed by using a large sample.

Pathogenesis, Rehabilitation Assessment, Treatment Status, and Research Progress of Vascular Dementia

Given the global trends in population aging,the prevalence of vascular dementia(VD)is increasing year by year.VD has become the second most common type of dementia and can seriously threaten the quality of life of patients.Since VD is preventable,it is important to study VD clinically in order to improve the prognosis of patients.In recent years,a large number of studies have been carried out at home and abroad,focusing on the pathogenesis,rehabilitation assessment,and treatment of VD.This article is a concise overview of these studies.

A meta-analysis of Chinese herbal medicines for vascular dementia

OBJECTIVE： To investigate the efficacy and safety of Chinese herbal medicines in the treatment of patients with vascular dementia. DATA RETRIEVAL： We retrieved publications from Cochrane Library （2004 to July 2011）, PubMed （1966 to July 2011）, the Chinese Science and Technique Journals Database （1977 to July 2011）, the China National Knowledge Infrastructure （1979 to July 2011）, Google Scholar （July 2011）, and the Chinese Biomedical Database （1977 to July 2011） using the key words ＂Chinese medicine OR Chinese herbal medicine＂ and ＂vascular dementia OR mild cognition impair OR multi-infarct dementia OR small-vessel dementia OR strategic infarct dementia OR hypoperfusion dementia OR hemorrhagic dementia OR hereditary vascular dementia＂. SELECTION CRITERIA： Randomized controlled trials comparing Chinese herbal medicines with placebo/western medicine in the treatment of patients with vascular dementia were included. Diagnostic standards included Diagnostic and Statistical Manual of Mental Disorders-IV, and National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et I＇Enseignement en Neurosciences. Two participants independently conducted literature screening, quality evaluation and data extraction. The quality of each trial was assessed according to the Cochrane Reviewers＇ Handbook 5.0. MAIN OUTCOME MEASURES： Effective rate, Mini-Mental State Examination scores, Hasegawa Dementia Scale scores, and incidence of adverse reactions. RESULTS： We identified 1 143 articles discussing the effects of Chinese medicine on vascular dementia. Thirty-one of these were included in the analysis. These studies involved a total of 2 868 participants （1 605 patients took Chinese medicine decoctions （treatment group）; 1 263 patients took western medicine or placebo）. The results of our meta-analysis revealed that Chinese herbal remedies in the treatment group were more efficacious than the control intervention （relative risk （RR） = 1.27; 95% confidence interval （C/）： 1.18-1.38, P 〈 0.01）. Mini-Mental State Examination scores were higher in patients taking Chinese herbal medicines than in those in the control group （weighted mean difference （WMD） = 2.83; 95%CI： 2.55-3.12, P 〈 0.01）. Patients in the treatment group showed better disease amelioration than those in the control group （Hasegawa Dementia Scale scores; WMD = 2.41, 95%CI： 1.48-3.34, P 〈 0.01）. There were also considerably fewer adverse reactions among those in the treatment group compared with those in the control group （RR = 0.20, 95%CI： 0.08-0.47, P 〈 0.01）. CONCLUSION： Chinese herbal medicine appears to be safer and more effective than control measures in the treatment of vascular dementia. However, the included trials were generally low in quality. More well-designed, high-quality trials are needed to provide better evidence for the assessment of the efficacy and safety of Chinese medicines for vascular dementia.

Mortality of Dementia and Its Major Subtypes in Urban and Rural Communities of Beijing

Objective To identify the mortality and epidemiological pattern of dementia and its various major subtypes among urban and rural senior residents in Beijing.Methods Based on Beijing＇s dementia prevalence survey among residents aged 55 years and above in 1997,respondents were selected by stratified multiple‐stage cluster sampling and 12 urban communities and 17 rural village communities were randomly sampled then follow‐up in 2001.COX regression was used to analyze relative risks controllingconfounding factors on deaths of dementia cases.Results The mortality of dement patients in the 55‐64 age‐group was 0.82/100 person‐year.The age‐standardized mortality of dement cases was 0.90/100 person‐year.The mortality in the 65 and above age‐group was 1.44/100 person‐year,and the age‐standardized mortality was 1.56/100 person‐year.Among AD cases,the above two mortalities were 0.35/100 and 0.42/100 person‐year respectively,and among VaD cases,0.34/100 and 0.36/100 person‐year respectively.For both AD and VaD cases,their mortality increased with age.Region,gender and age were more significant to survival of AD cases.Conclusion One major subtype of dementia,AD,among elderly urban and rural residents in Beijing,has a different mortality and epidemiological pattern from VaD.

Prevalence of cerebrospinal fluid Alzheimer disease-like pattern in atypical dementias

BACKGROUND: Differential diagnosis between Frontotemporal Dementia (FTD), Corticobasal Syndrome (CBS), Progressive Supranuclear Palsy Syndrome (PSP), FTD with motor neuron disease (FTD-MND) is often challenging, because of the occurrence of atypical cases. Autopsy series have identified Alzheimer Disease (AD) pathology in a consistent percentage of patients with atypical dementias. It has been demonstrated that Cerebrospinal Fluid (CSF) Tau/Aβ42 dosage is a reliable marker for AD. OBJECTIVE: To evaluate the presence and percentage of CSF AD-like patterns (high CSF tau/Aβ42 ratio) in patients with atypical dementias in order to identify an ongoing AD neurodegenerative process. METHODS: One hundred seventy two consecutive patients fulfilling current clinical criteria for behavioural variant FTD (bvFTD, n = 73), agrammatic variant of Primary Progressive Aphasia (avPPA, n = 19), semantic variant of PPA (svPPA, n = 12), FTD-MND (n = 5), CBS (n = 42), PSP (n = 21) were recruited and underwent CSF analysis. CSF AD-like and non AD (nAD-like) patterns were identified. RESULTS: CSF AD-like pattern was reported in 6 out of 73 cases (8.2%) in the bvFTD group, in 3 out of 19 (15.8%) in the avPPA group, and in 7 out of 42 (16.7%) in the CBS group. One out of 12 (8.3%) of svPPA had CSF AD-like pattern. None of patients FTD-MND and PSP had CSF AD-like pattern. No differences in demographic characteristics were detected between subgroups in each phenotype. CONCLUSIONS: Our findings convey that the CSF tau/ Aβ42 ratio could be found in a proportion of cases with clinical bvFTD, avPPA and CBD. Detecting anon-going AD pathological process in atypical dementias has several implications for defining distinctive therapeutic approaches, guiding genetic screening and helping in patients’ selection in future clinical trials.

Neuropsychological features of progranulin-associated frontotemporal dementia: a nested case-control study

The distinction between sporadic and genetic behavioural-variant frontotemporal dementia(bvFTD)regarding some neuropsychological(NP)features remains challenging.Specifically,progranulin(GRN)-associated bvFTD frequently presents with early episodic memory impairment and some degree of parietal dysfunction which are supporters of Alzheimer’s disease(AD)diagnosis.In this context,we aimed to characterize the NP profile of GRN-bvFTD as compared to sporadic-bvFTD and AD in patients with mild dementia(Mini-Mental State Examination score≥17 and Clinical Dementia Rating Scale score≤1.We identified 21 patients at Centro Hospitalar e Universitário de Coimbra,Portugal with GRN mutations belonging to fifteen different families.As our focus was bvFTD variants,FTD-related aphasic forms(3 patients)were excluded.The remaining 18 GRN-bvFTD were further matched with 18 sporadic-bvFTD and 18 AD patients according to disease staging,age and education.All patients completed the Mini-Mental State Examination,Montreal Cognitive Assessment(MoCA)and a comprehensive NP assessment battery.Results were converted into z-scores.Differences between groups in individual NP measures and NP domains were assessed through non-parametric tests(Kruskal-Wallis test analysis)and eta squared(ŋ2)was calculated as a measure of effect size.Group comparisons show that GRN patients have worse performances on verbal retrieval processes(P=0.039,ŋ2=0.110)and visuoconstructive abilities(P=0.039,ŋ2=0.190)than sporadic bvFTD forms.When compared to AD,GRN patients present a higher impairment in frontal(P=0.001,ŋ2=0.211)and parietal(P=0.041,ŋ2=0.129)measures and a better performance in memory tasks(P=0.020,ŋ2=0.120).Sporadic-bvFTD forms are worse than AD in frontal measures(P=0.032,ŋ2=0.200),being better in both memory(P=0.010,ŋ2=0.131)and visuospatial skills(P=0.023,ŋ2=0.231).Considering these results,we conclude that GRN-bvFTD patients present a NP profile that associates the typical patterns of FTD and AD deficits.This is particularly expressive in visuoconstructive abilities,which was the more discriminative feature between groups,followed by episodic verbal memory.This study was approved by the Institutional Ethics Committee of Centro Hospitalar e Universitário de Coimbra,Portugal(CE-029/2019)on June 24,2019.

Associated mortality risk of atypical antipsychotic medication in individuals with dementia

BACKGROUND Antipsychotic medications such as risperidone,olanzapine and aripiprazole are used to treat psychological and behavioural symptoms among dementia patients.Current evidence indicate prescription rates for antipsychotics vary and wider consensus to evaluate clinical epidemiological outcomes is limited.AIM To investigate the potential impact of atypical antipsychotics on the mortality of patients with dementia.METHODS A retrospective clinical cohort study was developed to review United Kingdom Clinical Record Interactive Search system based data between January 1,2013 to December 31,2017.A descriptive statistical method was used to analyse the data.Mini Mental State Examination(MMSE)scores were used to assess the severity and stage of disease progression.A cox proportional hazards model was developed to evaluate the relationship between survival following diagnosis and other variables.RESULTS A total of 1692 patients were identified using natural language processing of which,587 were prescribed olanzapine,quetiapine or risperidone(common group)whilst 893(control group)were not prescribed any antipsychotics.Patients prescribed olanzapine showed an increased risk of death[hazard ratio(HR)=1.32;95%confidence interval(CI):1.08-1.60;P<0.01],as did those with risperidone(HR=1.35;95%CI:1.18-1.54;P<0.001).Patients prescribed quetiapine showed no significant association(HR=1.09;95%CI:0.90-1.34;P=0.38).Factors associated with a lower risk of death were:High MMSE score at diagnosis(HR=0.72;95%CI:0.62-0.83;P<0.001),identifying as female(HR=0.73;95%CI:0.64-0.82;P<0.001),and being of a White-British ethnic group(HR=0.82;95%CI:0.72-0.94;P<0.01).CONCLUSION A significant mortality risk was identified among those prescribed olanzapine and risperidone which contradicts previous findings although the study designs used were different.Comprehensive research should be conducted to better assess clinical epidemiological outcomes associated with diagnosis and therapies to improve clinical management of these patients.