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Assessment of cheese sign and its association with vascular risk factors: Data from PUMCH dementia cohort

中华医学杂志(英文版) 2024年第7期137卷 830-836页

作者： Huang Xinying Hou Bo Wang Jie Li Jie Shang Li Mao Chenhui Dong Liling Liu Caiyan Feng Feng Gao Jing Peng Bin Department of Neurology State Key Laboratory of Complex Severe and Rare Disease Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing 100730 China Department of Radiology Chinese Academy of Medical Sciences and Peking Union Medical College

Background: In the clinic, practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging (MRI) signal in the basal ganglia, a phenomenon known as "cheese sign". This sign is reported as common in cerebrovascular diseases, dementia, and old age. Recently, cheese sign has been speculated to consist of dense perivascular space (PVS). This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors.Methods: A total of 812 patients from Peking Union Medical College Hospital (PUMCH) dementia cohort were enrolled. We analyzed the relationship between cheese sign and vascular risk. For assessing cheese sign and defining its degree, the abnormal punctate signals were classified into basal ganglia hyperintensity (BGH), PVS, lacunae/infarctions and microbleeds, and counted separately. Each type of lesion was rated on a four-level scale, and then the sum was calculated; this total was defined as the cheese sign score. Fazekas and Age-Related White Matter Changes (ARWMC) scores were used to evaluate the paraventricular, deep, and subcortical gray/white matter hyperintensities.Results: A total of 118 patients (14.5%) in this dementia cohort were found to have cheese sign. Age (odds ratio [OR]: 1.090, 95% confidence interval [CI]: 1.064-1.120,P <0.001), hypertension (OR: 1.828, 95% CI: 1.123-2.983,P = 0.014), and stroke (OR: 1.901, 95% CI: 1.092-3.259,P = 0.025) were risk factors for cheese sign. There was no significant relationship between diabetes, hyperlipidemia, and cheese sign. The main components of cheese sign were BGH, PVS, and lacunae/infarction. The proportion of PVS increased with cheese sign severity.Conclusions: The risk factors for cheese sign were hypertension, age, and stroke. Cheese sign consists of BGH, PVS, and lacunae/infarction.

关键词： dementia Cerebrovascular disease Cheese sign Dense punctate lesions Basal ganglia Risk factor White matter

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

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World Journal of Clinical Cases 2024年第16期12卷 2780-2788页

作者： Zhao-Lin Ren Hai-Hong Zhou Chu-Pei Chen Hao He Duo-Lao Wang Zhou Liu Department of Neurology The Affiliated Hospital of Guangdong Medical UniversityZhanjiang 524000Guangdong ProvinceChina Department of Clinical Medicine Guangdong Medical UniversityZhanjiang 524000Guangdong ProvinceChina Department of Clinical Sciences Liverpool School of Tropical MedicineLiverpool L693BXUnited Kingdom

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.

关键词： Mendelian randomization FinnGen MiBioGen Gut microbiota dementia Alzheimer’s disease Vascular dementia

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

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Advances in Alzheimer's Disease 2024年第2期13卷 35-47页

作者： Shreejeet Shrestha Samikshya Karmacharya Yadav Prasad Joshi Prasa Shrestha Department of Public Health Asian College for Advance Studies Lalitpur Nepal Department of Operation Theatre Gosford Hospital New South Wales Health Gosford Australia Faculty of Science Health and Technology Nepal Open University Lalitpur Nepal Manmohan Memorial Institute of Health Sciences Kathmandu Nepal Department of General Practice and Emergency Medicine Chitwan Medical College Bharatpur Nepal

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.

关键词： dementia Rapid Review Music Therapy Behavioral Cognitive Quality of Life

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Physical activity and amyloid beta in middle-aged and older adults:A systematic review and meta-analysis

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Journal of Sport and Health Science 2024年第2期13卷 133-144页

作者： María Rodriguez-Ayllon Patricio Solis-Urra Cristina Arroyo-ávila Miriam álvarez-Ortega Pablo Molina-García Cristina Molina-Hidalgo Manuel Gómez-Río Belinda Brown Kirk I.Erickson Irene Esteban-Cornejo Department of Epidemiology Erasmus University Medical Center RotterdamRotterdamGD 3015the Netherlands Department of Physical Education and Sports Faculty of Sport SciencesSport and Health University Research Institute(iMUDS)University of GranadaGranada 18071Spain Faculty of Education and Social Sciences Universidad Andres BelloVina del Mar 2531015Chile Department of Nuclear Medicine Virgen de las Nieves University HospitalInstitute of Biosanitary Research of Granada(IBS)Granada 18014Spain Physical Medicine and Rehabilitation Service Virgen de las Nieves University HospitalInstitute of Biosanitary Research of Granada(IBS)Granada 18014Spain Department of Psychology University of PittsburghPittsburghPA 15260USA Centre for Healthy Ageing Health Futures InstituteMurdoch UniversityMurdochWA 6150Australia School of Medical and Health Sciences Edith Cowan UniversityJoondalupWA 6027Australia Advent Health Research Institute Neuroscience Institute OrlandoOrlandoFL 32803USA Physiopathology of Obesity and Nutrition Research Center(CIBERobn) Institute of Health Carlos Ⅲ(ISCⅢ)Madrid 28029Spain

Background:One of the pathological hallmarks distinguishing Alzheimer’s disease from other dementias is the accumulation of amyloid beta(Aβ).Higher physical activity is associated with decreased dementia risk,and one potential path could be through Aβlevels modulation.We aimed to explore the relationship between physical activity and Aβin middle-aged and older adults.Methods:A systematic search of PubMed,Web of Science,PsycINFO,Cochrane Central Register of Controlled Trials,and SPORTDiscus was performed from inception to April 28,2022.Studies were eligible if they included physical activity and Aβdata in adults aged 45 years or older.Multi-level metaanalyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβlevels.Results:In total,37 articles were included(8 randomized controlled trials,3 non-randomized controlled trials,4 prospective longitudinal studies,and 22 cross-sectional studies).The overall effect size of physical activity interventions on changes in blood Aβwas medium(pooled standardized mean difference=-0.69,95%confidence interval(95%CI):-1.41 to 0.03;I^(2)=74.6%).However,these results were not statistically significant,and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid(CSF)and brain Aβ.Data from observational studies were examined based on measurements of Aβin the brain using positron emission tomography scans,CSF,and blood.Higher physical activity was positively associated with Aβonly in the CSF(Estimate r=0.12;95%CI:0.05-0.18;I^(2)=38.00%).Conclusion:Physical activity might moderately reduce blood Aβin middle-aged and older adults.However,results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies.In observational studies,higher levels of physical activity were positively associated with Aβonly in CSF.Therefore,further research is needed to understand the modulating role of physical act

关键词： Aging Cognitive impairment dementia Exercise PET

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Soluble p75 neurotrophic receptor as a reliable biomarker in neurodegenerative diseases: what is the evidence?

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Neural Regeneration Research 2024年第3期19卷 536-541页

作者： Georges Jourdi Samuel Fleury Imane Boukhatem Marie Lordkipanidzé Research Center Montreal Heart InstituteMontrealQCCanada Faculty of Pharmacy Universitéde MontréalMontrealQCCanada UniversitéParis Cité INSERMInnovative Therapies in HaemostasisParisFrance Service d’Hématologie Biologique AP-HPHôpital LariboisièreParisFrance

Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and maturation.Its cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and urine.There is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic neuropathy.Whether p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open question.In this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases.We also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.

关键词： Alzheimer’s disease amyotrophic lateral sclerosis biomarker dementia diabetic neuropathy nerve growth factor receptor(NGFR) neurodegeneration p75^(NTR) schizophrenia

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New insights into the therapeutic approaches for the treatment of tauopathies

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Neural Regeneration Research 2024年第5期19卷 1020-1026页

作者： Himanshi Singh Asmita Das Mohammad Moshahid Khan Tayebeh Pourmotabbed Department of Microbiology Immunology and BiochemistryUniversity of Tennessee Health Science CenterMemphisTNUSA Department of Biotechnology Delhi Technological UniversityShahbad DaulatpurDelhiIndia Department of Neurology College of MedicineUniversity of Tennessee Health Science CenterMemphisTNUSA Neuroscience Institute University of Tennessee Health Science CenterMemphisTNUSA Center for Muscle Metabolism and NeuropathologyDivision of Regenerative and Rehabilitation Sciences and Department of Physical TherapyCollege of Health ProfessionsUniversity of Tennessee Health Science CenterMemphisTNUSA

Tauopathies are a group of neurological disorders,including Alzheimer’s disease and frontotemporal dementia,which involve progressive neurodegeneration,cognitive deficits,and aberrant tau protein accumulation.The development of tauopathies cannot currently be stopped or slowed down by treatment measures.Given the significant contribution of tau burden in primary tauopathies and the strong association between pathogenic tau accumulation and cognitive deficits,there has been a lot of interest in creating therapies that can alleviate tau pathology and render neuroprotective effects.Recently,small molecules,immunotherapies,and gene therapy have been used to reduce the pathological tau burden and prevent neurodegeneration in animal models of tauopathies.However,the major pitfall of the current therapeutic approach is the difficulty of drugs and gene-targeting modalities to cross the blood-brain barrier and their unintended side effects.In this review,the current therapeutic strategies used for tauopathies including the use of oligonucleotide-based gene therapy approaches that have shown a promising result for the treatment of tauopathies and Alzheimer’s disease in preclinical animal models,have been discussed.

关键词： dementia gene therapies immunotherapy neurodegeneration oligonucleotides tau tauopathies therapies

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Cognitive impairment in cerebral small vessel disease induced by hypertension

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Neural Regeneration Research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang Department of Pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing Geriatric Medical Research Center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

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Impact of apolipoprotein E isoforms on sporadic Alzheimer's disease:beyond the role of amyloid beta

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Neural Regeneration Research 2024年第1期19卷 80-83页

作者： Madia Lozupone Francesco Panza Neurodegenerative Disease Unit Department of Basic MedicineNeuroscienceand Sense OrgansUniversity of Bari Aldo MoroBariItaly Unit of Research Methodology and Data Sciences for Population Health National Institute of Gastroenterology“Saverio de Bellis”Research HospitalCastellana GrotteBariItaly

The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully understood.ApoE exists as three common isoforms(ApoE2,ApoE3,and ApoE4),which differ in two amino acid residues.Traditionally,ApoE binds cholesterol and phospholipids and ApoE isoforms display diffe rent affinities for their receptors,lipids transport and distribution in the brain and periphery.The role of ApoE in the human depends on ApoE isoforms,brain regions,aging,and neural injury.APOE E4 is the strongest genetic risk factor for sporadic Alzheimer's disease,considering its role in influencing amyloid-beta metabolism.The exact mechanisms by which APOE gene variants may increase or decrease Alzheimer's disease risk are not fully understood,but APOE was also known to affect directly and indirectly tau-mediated neurodegeneration,lipids metabolism,neurovascular unit,and microglial function.Consistent with the biological function of ApoE,ApoE4 isoform significantly alte red signaling pathways associated with cholesterol homeostasis,transport,and myelination.Also,the rare protective APOE variants confirm that ApoE plays an important role in Alzheimer's disease pathogenesis.The objectives of the present mini-review were to describe classical and new roles of various ApoE isoforms in Alzheimer's disease pathophysiology beyond the deposition of amyloid-beta and to establish a functional link between APOE,brain function,and memory,from a molecular to a clinical level.APOE genotype also exerted a heterogeneous effect on clinical Alzheimer's disease phenotype and its outcomes.Not only in learning and memory but also in neuro psychiatric symptoms that occur in a premorbid condition.Cla rifying the relationships between Alzheimer's disease-related pathology with neuropsychiatric symptoms,particularly suicidal ideation in Alzheimer's disease patients,may be useful for elucidating also the underlying pathophysiological pro

关键词： Alzheimer's disease amyloid-beta apolipoprotein E dementia glymphatic transport lipids neuropsychiatric symptoms neurovascular unit tau protein

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Cognitive function among military veterans with STEM occupations

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Military Medical Research 2024年第2期11卷 308-310页

作者： Justin T.McDaniel Kevin N.Hascup Erin R.Hascup Ugochukwu G.Ezigbo Amanda M.Weidhuner Harvey Henson David L.Albright Dale and Deborah Smith Center for Alzheimer's Research and trEatment(CARE) Southern Illinois University School of MedicineSpringfieldIL 62794USA STEM Education Research Center Southern Illinois UniversityCarbondaleIL 62901USA Department of Political Science The University of AlabamaTuscaloosaAL 35487USA

Dear Editor,There is limited research on the relationship between science,technology,engineering,and mathematics(STEM)occupational history and cognitive function in later life,especially among military veterans,who may be at greater risk for later-life cognitive decline.This study examines a nationally representative sample of military veterans to address this gap in knowledge.

关键词： Alzheimer's disease Veterans Science technology engineering and mathematics(STEM) Animal fluency test dementia

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Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

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Neural Regeneration Research 2025年第4期20卷 990-1008页

作者： Lan Zhang Jingge Wei Xilei Liu Dai Li Xiaoqi Pang Fanglian Chen Hailong Cao Ping Lei Haihe Laboratory of Cell Ecosystem Department of GeriatricsTianjin Medical University General HospitalTianjinChina Tianjin Geriatrics Institute Tianjin Medical University General HospitalTianjinChina Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalNational Key Clinical SpecialtyTianjin Institute of Digestive DiseasesTianjin Key Laboratory of Digestive DiseasesTianjinChina Department of Urology Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institution Tianjin Medical University General HospitalTianjinChina

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

关键词： age aging Alzheimer’s disease astrocytes cognitive decline dementia gut microbiota gut–brain axis microbial metabolites neuroinflammation Parkinson’s disease

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