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.

Effectiveness of Music-Based Therapeutic Intervention on People with Dementia: A Rapid Review

Background: Dementia is a condition with progressive cognitive dysfunction and manifestation of both behavioral and psychosocial symptoms. Non-pharmacological measures such as music therapy are gaining importance since efficacy and safety of people with dementia have been questionable for pharmacological measures. Patient’s response to music is persistent even in the later stage of dementia. Aim: This rapid review aims to identify, analyze, evaluate, and summarize the best available evidence on the effectiveness of music-based therapeutic interventions among people with dementia. Method: CINAHL Cochrane Library, internet websites of rapid review producers, and reference lists were searched to identify articles for inclusion. Two reviewers independently screened the literature search results. Effectiveness, music-based therapeutic intervention, dementia, Alzheimer’s disease, systematic review and systematic review with meta-analysis terms were used to abstract data from included studies. Main Findings: 11 SRs and SRs with meta-analysis were reviewed which revealed positive effect of music therapy on five major outcomes with 9 studies effect on behavioral outcome, 6 studies with positive effect on psychosocial outcome reducing anxiety, 6 with improved cognition, 1 study revealed with improved quality of life and 1 study revealed effect on physiological outcomes. Conclusion: Music therapy has positive effect on treatment of dementia but further studies with larger sample size and specified to single intervention should be conducted to provide generalisable and precise results on this topic.

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.

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.

An Innovative Person-Centered Model for Provision of Mental, Social and Medical Care for People Living with Dementia

Globally there is an increased digitalization going on with an increasing number of people having access to the internet, having smartphones and now also in many countries being expected to access health-related information and schedule appointments through websites, apps or web-based portals. Healthcare providers have also adopted this with an increasing number of public or private organizations providing web-based portals as well as app interfaces to some of the largest electronic healthcare systems. The benefit of this is easier access, more efficient provision of services, increased transparency and improved workflows. This may increase the population’s capability to manage their conditions and reduce the contacts to, thereby burdening healthcare professionals. But not all will be able to benefit from this digital (r)evolution. Those who will not be able to include people with dementia. For people with dementia to also be able to take advantage of digital health tools and services, it will require planning and involvement of caregivers. In 2017, we presented the Epital Care Model as a framework to organize an efficient people-centered cross-disciplinary and cross-sectoral way to organize activities, roles, responsibilities and describe geographical locations and used technologies in response to individuals’ specific diagnoses and everyday changes in their condition. In 2021, an EU-funded project was initiated to investigate how living labs and scaling up could be done building upon the ECM. One of the living labs was organized around an organization providing care to PWD in Netherlands. In the period 2021 to 2024, we have tried to identify ways for how the ECM could be used to digitally enable the services provided by the organization. In 2022, the care organization tanteLouise started a project originally named Daycare Centre2.0 (now called “Van Thuis Uit” meaning “From Home”), together with healthcare insurance company CZ, and developed a model for onboarding people with dementia and introducing them to specific interventions based on their personal goals and needs. We here present how the ECM and the “Van Thuis Uit” can be mapped within each other to create synergy in creating a healthcare setting for people with dementia. This work may serve as a model for other conditions, where individuals are likely to need more intensive support from their informal caregivers due to a relatively rapid progression of the condition or development of severe impairments. Examples here can be neurologic conditions such as multiple sclerosis and amyotrophic lateral sclerosis or the final stage of conditions that require palliation.

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.

Searching for new drugs to treat Alzheimer’s disease dementia through multiple pathways

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.

Mendelian Randomization Study of Causal Relationship between Inflammatory Factors and Vascular Dementia and Chinese Herbal Medicines Screening for Prevention and Treatment

Objective: This study aims to examine the causal relationship between inflammatory factors and the probability of developing vascular dementia (VD) using Mendelian Randomization (MR) and Chinese herbal medicine prediction method, and to screen potential Chinese herbal medicines for the prevention and treatment of VD. Methods: Single nucleotide polymorphisms (SNPs) that exhibit a strong association with vascular dementia (VD) were identified as instrumental variables from the summary statistics of genome-wide association studies (GWAS). The primary analytical method employed was inverse variance weighting (IVW), while auxiliary analyses included the MR-Egger method, weighted median method, simple model, and weighted model. A two-way Mendelian randomization analysis was conducted to assess the causal relationship between inflammatory factors and the risk of VD, thereby identifying the key inflammatory factors involved. The MR-Egger intercept test and Cochran’s Q test were employed to assess the horizontal polymorphism and heterogeneity of instrumental variables. A sensitivity analysis was conducted by excluding one method at a time. Ultimately, based on key inflammatory factors, predictions for the prevention and treatment using traditional Chinese medicine were made, along with the screening of homologous herbal remedies. Results: Based on the results of the forward MR, the probability of developing VD was elevated when the inflammatory factors CXCL10 and CXCL5 were expressed at higher levels, whereas the probability of developing VD decreased as the expression levels of IL-13 and IL-20RA increased. These findings were supported by the assessment of pleiotropy, heterogeneity, and sensitivity. The results of the reverse MR analysis showed that there was no causal relationship between VD, as an exposure dataset, and these four inflammatory factors. According to the key inflammatory factors, 37 Chinese herbal medicines such as Siraitia grosvenorii were selected. Their characteristics including four natures, five flavors, channel tropism and treatment efficiency were cold, warm, neutral, pungent, sweet, bitter, lung meridian, spleen meridian, liver meridian, kidney meridian and clearing heat. Among them, Siraitia grosvenorii, Poria with hostwood, Perilla frutescens, and Radix Platycodi were all medicine and food homologous Chinese herbal medicines. Conclusions: The increase of CXCL10 and CXCL5 expression levels can increase the risk of VD, and the increase of IL-13 and IL-20 RA expression levels can reduce the risk of VD. Siraitia grosvenorii and other Chinese herbal medicines might be potential sources of therapeutic drugs for the treatment of VD. Medicine and food homologous Chinese herbal medicines, such as Siraitia grosvenorii, Poria with hostwood, Perilla frutescens, and Radix Platycodi, may help the elderly population with corresponding Traditional Chinese Medicine (TCM) constitutions to prevent VD.

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.

Caregivers'awareness regarding the care of dementia and the coping strategies among the caregivers of people with dementia:a cross-sectional study in Udupi District,Karnataka

Objectives:To assess the awareness and coping skills of the informal and formal caregivers of people living with dementia(PLWD).Dementia is a condition,which leads to memory loss and gradual deterioration of cognitive abilities in the affected person.The lack of awareness regarding the care of people with dementia and the caregivers'poor coping strategies can negatively impact caregivers'experiences.Methods:A cross-sectional survey was conducted among the 80 caregivers of PLWD from the psychiatric units of the selected hospitals of Udupi district,Karnataka,India.The baseline data were collected by a self-reported sociodemographic questionnaire.The“Dementia Knowledge Assessment Scale”was used to gauge participants'awareness of the care of people with dementia,while the“Brief COPE inventory,”a 28-item questionnaire,was used to gauge carers'coping mechanisms.Descriptive and inferential statistics were used for the data analysis using Jamovi(2.3.24),a graphical user interface for R programming,and Microsoft Excel.Results:Most of the caregivers(n=68,85%)had lesser awareness regarding the care of people with dementia.The mean coping strategies score was 60.9±7.71.There was a positive correlation between the awareness and the coping strategies scores among the caregivers(r=0.659,P<0.05).Conclusions:The caregivers of people with dementia often lack awareness about dementia and hence experience poor coping due to their high workload and stress.The frontline healthcare professionals and nurses need to provide appropriate interventions to the caregivers to improve their awareness about dementia and its care.

Coping review of dementia fear studies among middle-aged and elderly people in the community

This study used Arksey and O’Malley’s scoping review methodology as a framework and searched the following databases:PubMed,Embase,EBSCO,CINAHL,Web of Science,Cochrane Library,Scopus,CNKI,Wanfang,VIP,and the Chinese Biomedical Literature Database.The database is open to December 20,2023,and documents related to the fear of dementia among the elderly in the community are described and analyzed to provide a reference for future research in this field.At the same time,we screened,extracted,and summarized relevant information from 21 included documents(16 in English and 5 in Chinese),which consisted of 16 cross-sectional studies,2 quasi-experimental studies,2 randomized controlled studies,and 1 longitudinal study.Sixteen of the included documents mentioned the incidence or level of dementia fear among the elderly in the community,2 addressed the adverse effects of dementia fear,and 4 reported prevention and intervention measures for dementia fear.In total,there are 8 assessment tools,and the influencing factors are categorized into sociodemographic characteristics,psychological and behavioral characteristics,sociocultural background factors,and health and dementia-related factors.The final conclusion is that the fear of dementia is common among the elderly in the community.In the future,the application of research tools should be expanded among middle-aged individuals,with considerations for other types of dementia in mind.It is recommended to conduct large-scale,multi-center randomized controlled trials while confirming the intervention’s effect on different types of middle-aged and elderly individuals,focusing on the long-term impact of these intervention measures to promote healthy aging.

Clinical Study on the Treatment of Senile Alzheimer’s Dementia with Sodium Oligomannate Combined with Memantine Hydrochloride

Objective:To analyze the clinical effects of sodium oligomannate combined with memantine hydrochloride in the treatment of senile Alzheimer’s dementia.Methods:Sixty-eight cases of Alzheimer’s dementia treated at the Second People’s Hospital of Fujian University of Traditional Chinese Medicine from March 2020 to March 2022 were selected as the study subjects.The patients were divided into two groups based on different treatment methods:the control group(treated with memantine hydrochloride,34 cases)and the treatment group(treated with sodium oligomannate+memantine hydrochloride,34 cases).Cognitive function,activities of daily living,neurotransmitters,serum intestinal flora metabolic markers,inflammatory factors,neurotrophic factors,and adverse reactions were compared between the two groups.Results:The treatment group showed better cognitive function,quality of life scores,and levels of relevant metabolic markers in the body compared to the control group,with statistically significant differences(P<0.05).The incidence of adverse reactions between the two groups(treatment group:2%;control group:4%)was not statistically significant(χ^(2)=0.731,P=0.393).Conclusion:Sodium oligomannate combined with memantine hydrochloride has better efficacy than the control group for treating senile Alzheimer’s dementia.It significantly improves and restores cognitive function and daily living abilities,benefits neurotransmitter secretion and internal regulation,upregulates the expression of neurotrophic factors,and has fewer adverse reactions,making it a treatment worthy of further clinical promotion and application.

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.

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.

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.

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.

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.

MRI应用于阿尔茨海默病、血管性痴呆、混合型痴呆患者中血管损伤与脑萎缩评估的研究

目的对比血管损伤与脑萎缩在阿尔茨海默病(AD)、血管性痴呆(VD)或混合性痴呆(MD)患者中的分布,探究MRI在AD、VD、MD鉴别诊断中的价值。方法76例患者分别诊断为AD34例、VD31例和MD 22例。分别对三组通过分析MRI图像进行独立视觉评分量表和Evans's指数评估。结果与AD相比,MD的脑室周围白质病变PVL(P=0.002)、深部白质病变DWML(P=0.006)、皮质下微出血Juxtacortical MB(P=0.007)、深部白质微出血Deep MB(P=0.003)评分更高,VD的深部灰质病变DGML(p=0.016)、血管周围间隙PVS BG-CS(P=0.005)明显更多。VD与MD比较,血管性病变视觉评分结果无统计学差异,但VD患者内侧颞叶萎缩MTA(P<0.001)评分显著高于MD。脑皮层萎缩和Evans's指数的分布在组间无显著差异。结论MRI在痴呆患者的评估中可以更准确地检测血管病变及评估脑萎缩情况。研究证实血管病变在VD或MD患者中比AD更多,其中MD以深部和皮层旁微出血为主,这表明淀粉样脑血管病(CAA)可能是其主要的潜在病理机制。

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.