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.

New insights into the therapeutic approaches for the treatment of tauopathies

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.

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.

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

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 activity in the brain,CSF,and blood Aβ,as well as its implication for cognitive health.

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

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 process and its prognosis.Also,the effects of anti-amyloid-beta drugs,recently approved for the treatment of Alzheimer's disease,could be influenced by the APOE genotype.

Cognitive function among military veterans with STEM occupations

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.

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.

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.

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.

Cognitive impairment in cerebral small vessel disease induced by hypertension

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.

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

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.

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

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.

Predictors of prognosis in Alzheimer’s disease: The role of cognitive dysfunction, immune abnormalities, and advanced neuroimaging

Alzheimer’s disease(AD)is a grave illness that results in cognitive and social issues.A recent study examined the association between neuroimaging results,cognitive dysfunction,atypical cellular immune function,and poor prognostic factors in AD patients who demonstrated poor prognosis.Poor prognosis was associated with abnormal cellular immune function,extrapyramidal symptoms,altered consciousness,abnormal electroencephalogram,modified Rankin scale,increased neutrophil lymphocyte ratio,and severe pneumonia.The impaired cellular immune function characterized by a reduction in the blood T lym-phocytes’proportion predicted poor prognosis as an independent risk factor in AD.Early initiation and maintenance of AD medications is associated with better outcomes.

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.

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.

Alzheimer's disease with depressive symptoms: Clinical effect of intermittent theta burst stimulation repetitive transcranial magnetic stimulation

BACKGROUND Alzheimer's disease(AD),characterized by the ongoing deterioration of neural function,often presents alongside depressive features and greatly affects the quality of life of individuals living with the condition.Although several treatment methods exist,their efficacy is limited.In recent years,repetitive transcranial magnetic stimulation(rTMS)utilizing the theta burst stimulation(TBS)mode,specifically the intermittent TBS(iTBS),has demonstrated promising therapeutic potential in the management of neuropsychiatric disorders.AIM To examine the therapeutic efficacy of iTBS mode of rTMS for treating depressive symptoms in patients with AD.METHODS This retrospective study enrolled 105 individuals diagnosed with AD with depressive symptoms at Huzhou Third Municipal Hospital,affiliated with Huzhou University,between January 2020 and December 2023.Participants received standard pharmacological interventions and were categorized into control(n=53)and observation(n=52)groups based on treatment protocols.The observation group received iTBS mode of rTMS,while the control group received pseudo-stimulation.A comparative analysis evaluated psychological well-being,adverse events,and therapeutic at initiation of hospitalization(T0)and 15 days post-treatment(T1).RESULTS At T1,both groups exhibited a marked reduction in self-rating depression scale and Hamilton depression scale scores compared to T0.Furthermore,the observa-tion group showed a more pronounced decrease than the control group.By T1,the Mini-mental state examination scores for both groups had increased markedly from their initial T0 assessments.Importantly,the increase was particularly more substantial in the observation group than in the control group.Fourteen patients in the control group had ineffective treatment effects,while five patients in the observation group experienced the same.Additionally,the observation group experienced a substantially reduced incidence of ineffective treatment as compared to the control group(both P<0.05);there were no recorded serious adverse events in either group.CONCLUSION The iTBS model of rTMS effectively treated AD with depression,improving depressive symptoms and cognitive function in patients without serious adverse reactions,warranting clinical consideration.

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.

How Music Intervention Lowered Participants’ Morning Cortisol—Qualitative Case Stories

Non-pharmacological interventions for improved home care of persons with dementia and their family caregiver are and will be increasingly important for society. A music intervention study was performed on persons with persons with dementia and family caregiver. The persons with dementia and family caregiver were instructed to choose a daily routine for joint listening to recorded music. They selected the music they were interested in from a menu. The intervention period lasted for two months. Both persons with dementia and family caregiver provided daily saliva samples for the assessment of stress-related steroid hormones. In previous reports we have reported that the morning cortisol levels decreased significantly among the family caregiver when the intervention group was compared to a control group. In the present study we report narratives from four dyads, two of whom with beneficial effects of the music intervention, one dyad with no clear beneficial effects and one dyad with mixed results. The narratives illustrate the strong cohesive effect that the joint music listening could have, leading to improved social functioning paralleled by decreased morning cortisol levels particularly in the family caregiver. The narratives also illustrate reasons for failed effects.

重视老年听力损失的研究强化主动健康工作的推进

全球老龄化程度不断加剧,中国人口老龄化程度也在不断加深。2020年国家统计局《第七次人口普查统计公报》发布数据显示,60岁及以上人口比重上升5.44%,65岁及以上人口比重上升4.63%[1]。据国家卫生健康委员会老龄司预计:“十四五”时期,60岁及以上的老年人口总量将突破3亿,占比将超过20%,进入中度老龄化阶段。2035年左右,60岁及以上老年人口将突破4亿。

年龄相关性听力损失与认知功能障碍的关联机制

年龄相关性听力损失以双侧对称性和渐进性的听力损失为特征,高频区域的听力损失更为明显。横断面和纵向研究均表明,年龄相关性听力损失与认知功能障碍之间存在关联性。听力损失对痴呆的可改变风险因素高于其他已知的因素,包括抑郁、社会隔离、吸烟、高血压等,使其成为认知功能障碍和痴呆预防策略中新的目标。听力损失和认知功能障碍的关联机制可分为因果机制假说和共同病因假说两个类别。其中因果机制包括信息退化、听觉剥夺和社会孤立三种假说,均可解释为听力损失通过中间变量造成认知功能下降。共同病因假说指存在同时造成听力损失和认知功能障碍的混杂因素。当前针对老年人群进行的认知和听力损失的研究在评估方法上存在一些限制,未来应结合纯音测听、言语测试以及中枢听觉测试等技术开展研究。听觉以外的感觉功能,如视觉、嗅觉和本体感觉,也可能与认知功能障碍有关,应结合不同感觉功能障碍开展认知功能障碍的关联研究。