Neurodegenerative Disorders

神经退行性疾病
  • 文章类型: Journal Article
    阿尔茨海默病代表了整个非洲的重大和不断升级的公共卫生威胁。阿尔茨海默病导致严重的认知障碍和记忆丧失,给受影响的个人及其家人带来沉重负担,朋友,和照顾者。它影响了非洲的267万人,大多数人生活在撒哈拉以南非洲。根据世界卫生组织的估计,到2050年,这种疾病的患病率预计将急剧上升到全球约1.5亿人。
    本文提供了非洲阿尔茨海默病的综合概况,跨越已知的遗传和可改变的风险,讨论了诊断和治疗中存在的挑战,到2050年,对患病率和残疾调整后的生命年负担的预测,以及重新平衡等式所需的优先政策对策。
    本文研究了现有文献,以总结当前关于风险因素的知识,诊断,治疗,以及非洲阿尔茨海默病的负担。收集流行病学评估,临床指南,和有关非洲老年痴呆症的评论。
    数据揭示了有关非洲阿尔茨海默病诊断和护理的现实。诊断基础设施缺陷,资源限制,知识差距是反复出现的障碍。正电子发射断层扫描,脑脊液化验,发达国家常见的其他主要检测方式显示出有限的可用性。
    解决非洲的阿尔茨海默病危机需要多管齐下的策略来提高诊断能力,治疗可用性,专业培训,公众意识,和协调的政策制定。优先考虑生物标志物和成像以确认早期神经变性是基础,除了扩大毒品准入。
    UNASSIGNED: Alzheimer\'s disease represents a substantial and escalating public health threat across Africa. Alzheimer\'s disease leads to substantial cognitive impairment and memory loss, placing a heavy burden on the affected individuals and their families, friends, and caregivers. It affects 2.67 million people in Africa, the majority of whom live in sub-Saharan Africa. The prevalence of this disease is expected to rise drastically to approximately 150 million individuals worldwide by 2050, as estimated by the WHO.
    UNASSIGNED: This paper offers an integrative profile of Alzheimer\'s disease in Africa, spanning known genetic and modifiable risks, discusses the existing challenges in diagnosis and treatment, projections on prevalence and disability-adjusted life year burden through 2050, and priority policy responses needed to rebalance the equation.
    UNASSIGNED: This paper examines available literature to summarize current knowledge on risk factors, diagnosis, treatments, and burden of Alzheimer\'s disease in Africa. Gather epidemiological assessments, clinical guidelines, and commentary related to Alzheimer\'s disease in Africa.
    UNASSIGNED: The data reveals concerning realities regarding Alzheimer\'s disease diagnosis and care in Africa. Diagnostic infrastructure shortcomings, resource limitations, and knowledge gaps emerge as recurring barriers. Positron emission tomography scans, cerebrospinal fluid assays, and other mainstay detection modalities common in developed countries show restricted availability.
    UNASSIGNED: Addressing Africa\'s Alzheimer\'s disease crisis demands a multipronged strategy to uplift diagnostic capacities, treatment availability, specialist training, public awareness, and coordinated policymaking. Prioritizing biomarkers and imaging to confirm early neurodegeneration is foundational, alongside drug access expansion.
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  • 文章类型: Journal Article
    “Hotcrossbun”标志是磁共振成像上罕见的放射学标志,可以帮助指导多系统萎缩的小脑亚型的诊断。它表明对横桥小脑纤维的损害,并且可以在其他病理中看到,包括脊髓小脑共济失调。此放射学标志的名称是1998年创造的,将成像时的十字形高强度比作带有十字架的英国五香面包,历史上是在基督教宗教节日耶稣受难日吃的。
    The \"hot cross bun\" sign is a rare radiologic sign seen on magnetic resonance imaging that can help direct the diagnosis of the cerebellar subtype of multiple system atrophy. It indicates damage to the transverse pontocerebellar fibers and can be seen in other pathologies including spinocerebellar ataxia. The name for this radiologic sign was coined in 1998, likening the cruciform hyperintensity on imaging to the English spiced bun marked with a cross and historically eaten on the Christian religious holiday Good Friday.
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  • 文章类型: Journal Article
    神经退行性疾病(NDD)是一类使蛋白质结构逐渐受损并导致神经系统神经功能障碍的衰弱疾病。在这些疾病中,阿尔茨海默病(AD),朊病毒疾病,如克雅氏病(CJD),和帕金森病(PD)是由细胞水平的蛋白质错误折叠和聚集引起的。近年来,过渡金属配合物因其在诊断中的潜在应用而受到广泛关注,成像,并治愈这些NDD。这些复合物由于其不同的配体系统和化学性质而具有作为治疗剂的有趣可能性,并且可以与生物系统相互作用而具有最小的有害作用。本文综述了过渡金属疗法的最新进展,作为对抗AD的新希望时代,CJD,和PD通过在体外和体内调节蛋白质聚集。它可能会提供革命性的见解,为研究人员开发基于金属的药物来对抗NDD提供新的机会。
    Neurodegenerative disorders (NDDs) are a class of debilitating diseases that progressively impair the protein structure and result in neurological dysfunction in the nervous system. Among these disorders, Alzheimer\'s disease (AD), prion diseases such as Creutzfeldt-Jakob disease (CJD), and Parkinson\'s disease (PD) are caused by protein misfolding and aggregation at the cellular level. In recent years, transition metal complexes have gained significant attention for their potential applications in diagnosing, imaging, and curing these NDDs. These complexes have intriguing possibilities as therapeutics due to their diverse ligand systems and chemical properties and can interact with biological systems with minimal detrimental effects. This review focuses on the recent progress in transition metal therapeutics as a new era of hope in the battle against AD, CJD, and PD by modulating protein aggregation in vitro and in vivo. It may shed revolutionary insights into unlocking new opportunities for researchers to develop metal-based drugs to combat NDDs.
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  • 文章类型: Journal Article
    与衰老相关的神经退行性疾病和神经重症护理疾病的发病率在世界范围内正在增加。小胶质细胞,大脑中的主要炎症细胞,可能是治疗神经系统疾病的潜在可行治疗靶点。有趣的是,线粒体功能,包括能量代谢,线粒体自噬和转移,裂变和聚变,和线粒体DNA表达,激活的小胶质细胞也发生变化。值得注意的是,线粒体在神经退行性疾病和神经危重病的病理生理学中起着积极而重要的作用。本文简要综述了神经退行性疾病和神经重症监护疾病中小胶质细胞线粒体功能障碍的最新知识,并全面讨论了线粒体在神经损伤防治靶点中的应用前景。
    The incidence of aging-related neurodegenerative disorders and neurocritical care diseases is increasing worldwide. Microglia, the main inflammatory cells in the brain, could be potential viable therapeutic targets for treating neurological diseases. Interestingly, mitochondrial functions, including energy metabolism, mitophagy and transfer, fission and fusion, and mitochondrial DNA expression, also change in activated microglia. Notably, mitochondria play an active and important role in the pathophysiology of neurodegenerative disorders and neurocritical care diseases. This review briefly summarizes the current knowledge on mitochondrial dysfunction in microglia in neurodegenerative disorders and neurocritical care diseases and comprehensively discusses the prospects of the application of neurological injury prevention and treatment targets by mitochondria.
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  • 文章类型: Journal Article
    在这项研究中,在四肢淋巴水肿管理取得重大进展的背景下,作者阐明了头颈部淋巴水肿(HNL)这一被低估的领域.尽管它的流行和影响,HNL长期以来一直被忽视,归因于其微妙的症状表现和初级保健提供者缺乏意识。该研究深入研究了与诊断和治疗HNL相关的独特挑战,强调内部肿胀优于外部表现。作者主张对结果测量进行细化和标准化,并整合创新技术,例如吲哚菁绿淋巴造影和患者报告的结果。
    In this study, the authors shed light on the underappreciated realm of head and neck lymphedema (HNL) amid the backdrop of significant advancements in extremity lymphedema management. Despite its prevalence and impact, HNL has long been overlooked, attributed to its subtle symptom presentation and lack of awareness among primary care providers. The study delves into the unique challenges associated with diagnosing and treating HNL, emphasizing the predominance of internal swelling over external manifestations. The authors advocate for the refinement and standardization of outcome measures and the integration of innovative techniques such as indocyanine green lymphography and patient-reported outcomes.
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  • 文章类型: Journal Article
    许多研究探索了神经退行性疾病(NDD)与白蛋白之间的联系,人血浆中的主要蛋白质。然而,结果不一致,强调进行详细系统分析的必要性。
    利用英国生物银行的数据,我们调查了血清和尿白蛋白的基线水平与常见NDD的发生之间的关系,包括帕金森病(PD),肌萎缩侧索硬化症(ALS)和痴呆,采用Cox比例风险回归分析。
    我们的结果表明,基线血清白蛋白水平升高与患痴呆症的风险降低有关(β=-0.024,SE=0.004,p<0.001)。亚组和相互作用分析强调了体重指数(BMI)等因素的影响,年龄,和饮酒对这种关系的影响。具体来说,BMI较高的参与者,年龄较小,或较低的酒精摄入量表现出更强的保护作用。另一方面,较高的尿微量白蛋白基线水平与痴呆风险略有增加有关(β=0.003,SE=3.30E-04,p<0.001).白蛋白水平与PD或ALS的风险之间没有发现显着关联。
    我们的研究强调了血清白蛋白作为降低痴呆风险的生物标志物的潜在作用。这些发现有助于理解白蛋白对NDD的影响,提示其在临床中作为痴呆的生物标志物的实用性,并在临床试验中为未来的治疗策略提供信息。
    UNASSIGNED: A number of studies have explored the link between neurodegenerative disorders (NDDs) and albumin, the main protein in human plasma. However, the results have been inconsistent, highlighting the necessity for a detailed systemic analysis.
    UNASSIGNED: Utilizing data from the United Kingdom Biobank, we investigated the relationship between baseline levels of serum and urine albumin and the occurrence of common NDDs, including Parkinson\'s disease (PD), amyotrophic lateral sclerosis (ALS) and dementia, employing Cox proportional hazards regression analysis.
    UNASSIGNED: Our results reveal that elevated baseline serum albumin levels are linked to a decreased risk of developing dementia (beta = -0.024, SE = 0.004, p < 0.001). Subgroup and interaction analyses highlighted the impact of factors like body mass index (BMI), age, and alcohol consumption on this relationship. Specifically, participants with higher BMI, younger age, or lower alcohol intake exhibited a stronger protective effect. On the other hand, a higher baseline level of urine microalbumin was connected to a slight increase in dementia risk (beta = 0.003, SE = 3.30E-04, p < 0.001). No significant associations were found between albumin levels and the risk of PD or ALS.
    UNASSIGNED: Our study underscores the potential role of serum albumin as a biomarker associated with reduced dementia risk. These findings contribute valuable insights into the understanding of albumin\'s impact on NDDs, suggesting its utility as a biomarker for dementia in clinical settings and informing future therapeutic strategies in clinical trials.
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  • 文章类型: Journal Article
    帕金森病是一种神经退行性疾病,表现为运动功能减退,姿势不稳定和步态障碍。在故障和/或响应有限的情况下,深部脑刺激已被确立为替代和有效的治疗方式。然而,一部分有步态障碍的PD患者代表了一种治疗挑战.使用PubMed进行了系统评价(2000-2023年),Embase,WebofScience,Scopus,和Cochrane图书馆数据库来确定疗效,刺激波形/参数,脊柱水平,在有和没有慢性疼痛的PD患者中使用不同波形进行脊髓刺激的结果测量。在预定义的随访期内评估三组的脊髓刺激反应性(短期随访=0-3个月;中期随访=3-12个月;长期随访=超过12个月)。此外,我们简要概述了替代神经刺激疗法以及与PD相关的闭环脊髓刺激的最新进展.总之,纳入18篇出版物和70例来自非对照观察性试验的患者,低质量的证据和相互矛盾的发现。首先,现有数据不支持使用脊髓刺激治疗PD相关步态障碍,但已证实其对PD相关慢性疼痛的有用性.
    Parkinson\'s Disease is a neurodegenerative disorder manifesting itself as a hypokinetic movement impairment with postural instability and gait disturbance. In case of failure and/or limited response, deep brain stimulation has been established as an alternative and effective treatment modality. However, a subset of PD patients with gait impairment represents a therapeutic challenge. A systematic review (2000-2023) was performed using PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases to determine the efficacy, stimulation waveform/parameters, spine level, and outcome measures of spinal cord stimulation using different waveforms in PD patients with and without chronic pain. Spinal cord stimulation responsiveness was assessed within the pre-defined follow-up period in three groups (short-term follow-up = 0-3 months; intermediate follow-up = 3-12 months; and long-term follow-up = more than 12 months). In addition, we briefly outline alternative neurostimulation therapies and the most recent developments in closed-loop spinal cord stimulation relevant to PD. In summary, 18 publications and 70 patients from uncontrolled observational trials were included, with low-quality evidence and conflicting findings. First and foremost, the currently available data do not support the use of spinal cord stimulation to treat PD-related gait disorders but have confirmed its usefulness for PD-associated chronic pain.
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  • 文章类型: Journal Article
    这项研究旨在评估Anadenantheracolubrina的乙醇提取物在实验性自身免疫性脑脊髓炎(EAE)模型中调节免疫应答的功效。通过ESI()Orbitrap-MS分析干燥树皮的乙醇提取物,以获得代谢物谱,展示了各种各样的多酚,如类黄酮和酚酸。评估了各种参数,如临床症状,细胞因子,细胞轮廓,和中枢神经系统(CNS)的组织病理学。Colubrina的乙醇提取物表现出显著的积极作用,减弱与EAE相关的临床体征和病理过程。提取物治疗的有益效果由降低的促炎细胞因子水平证明。如IL1β,IL-6,IL-12,TNF,IFN-γ,几个细胞分布显著减少,包括CD8+,CD4+,CD4+IFN-γ,CD4+IL-17+,CD11c+MHC-II+,CD11+CD80+,和CNS中的CD11+CD86+。此外,组织学分析显示,与对照模型组相比,用提取物处理的小鼠脊髓中的炎性浸润和脱髓鞘位点较少。这些结果表明,第一次,Colubrina的乙醇提取物对炎症过程有调节作用,改善EAE的临床体征,在疾病的急性期,可以进一步探索作为可能的治疗替代方案。
    This study aimed to evaluate the efficacy of the ethanolic extract of Anadenanthera colubrina in modulating the immune response in the Experimental Autoimmune Encephalomyelitis (EAE) model. The ethanolic extract of the dried bark was analyzed by ESI (+) Orbitrap-MS to obtain a metabolite profile, demonstrating a wide variety of polyphenols, such as flavonoids and phenolic acids. Various parameters were evaluated, such as clinical signs, cytokines, cellular profile, and histopathology in the central nervous system (CNS). The ethanolic extract of A. colubrina demonstrated significant positive effects attenuating the clinical signs and pathological processes associated with EAE. The beneficial effects of the extract treatment were evidenced by reduced levels of pro-inflammatory cytokines, such as IL1β, IL-6, IL-12, TNF, IFN-γ, and a notable decrease in several cell profiles, including CD8+, CD4+, CD4+IFN-γ, CD4+IL-17+, CD11c+MHC-II+, CD11+CD80+, and CD11+CD86+ in the CNS. In addition, histological analysis revealed fewer inflammatory infiltrates and demyelination sites in the spinal cord of mice treated with the extract compared to the control model group. These results showed, for the first time, that the ethanolic extract of A. colubrina exerts a modulatory effect on inflammatory processes, improving clinical signs in EAE, in the acute phase of the disease, which could be further explored as a possible therapeutic alternative.
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  • 文章类型: Journal Article
    肠道微生物群(GM)产生各种分子,这些分子通过肠-脑轴(GBA)调节大脑的生理功能。研究表明,GBA的改变可能导致各种神经功能障碍的发作和进展。此外,衰老是导致GBA改变的重要原因之一。随着年龄的增长,GM经历了种群规模和微生物区系种类的变化,导致其分泌的代谢物发生变化。这些变化也阻碍了HPA(下丘脑-垂体-肾上腺)之间的交流,ENS(肠神经系统),和ANS(自主神经系统)。最近在改善健康和维持肠道与大脑之间的沟通方面获得关注的治疗干预措施是卡路里限制(CR)。在自噬和神经发生过程中也起着关键作用。然而,其严格的制度和终身承诺构成了挑战。需要产生CR的类似有益效果而不具有其严格的依从性。这导致了对卡路里限制模拟物(CRM)的探索,该模拟物可以模仿CR的功能而不限制饮食,提供长期健康益处。CRM通过肠道细菌及其代谢物确保GBA的有效功能,即短链脂肪酸,胆汁酸,和神经递质。这对老年人尤其有利,随着年龄的增长和身体消化积累的有毒物质的能力下降。在这次审查中,我们已经探索了通过增强有益菌及其对代谢物产生的影响来延长寿命的CRM的有益作用,生理条件,和神经功能障碍,包括神经退行性疾病。
    The gut microbiota (GM) produces various molecules that regulate the physiological functionality of the brain through the gut-brain axis (GBA). Studies suggest that alteration in GBA may lead to the onset and progression of various neurological dysfunctions. Moreover, aging is one of the prominent causes that contribute to the alteration of GBA. With age, GM undergoes a shift in population size and species of microflora leading to changes in their secreted metabolites. These changes also hamper communications among the HPA (hypothalamic-pituitary-adrenal), ENS (enteric nervous system), and ANS (autonomic nervous system). A therapeutic intervention that has recently gained attention in improving health and maintaining communication between the gut and the brain is calorie restriction (CR), which also plays a critical role in autophagy and neurogenesis processes. However, its strict regime and lifelong commitment pose challenges. The need is to produce similar beneficial effects of CR without having its rigorous compliance. This led to an exploration of calorie restriction mimetics (CRMs) which could mimic CR\'s functions without limiting diet, providing long-term health benefits. CRMs ensure the efficient functioning of the GBA through gut bacteria and their metabolites i.e., short-chain fatty acids, bile acids, and neurotransmitters. This is particularly beneficial for elderly individuals, as the GM deteriorates with age and the body\'s ability to digest the toxic accumulates declines. In this review, we have explored the beneficial effect of CRMs in extending lifespan by enhancing the beneficial bacteria and their effects on metabolite production, physiological conditions, and neurological dysfunctions including neurodegenerative disorders.
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  • 文章类型: Journal Article
    背景:诊断为亚急性硬化性全脑炎(SSPE)的儿童在疾病的不同阶段表现出一系列神经影像学异常,但其确切的临床意义尚不清楚.
    方法:在这项回顾性队列研究中,我们的目的是检查18岁以下亚急性硬化性全脑炎患者的脑部磁共振成像(MRI)异常.我们旨在将这些MRI异常与临床严重程度相关联,社会人口统计学变量,脑电图(EEG)异常,和脑脊液抗麻疹抗体滴度。
    结果:本研究包括112例亚急性硬化性全脑炎(平均年龄8.9±2.6岁)。表现时的MRI分析显示以下异常:皮质下白质信号改变(n=95),脑室周围白质信号改变(n=76),call体受累(n=39),弥漫性call体受累(n=27),脑萎缩(n=35),基底神经节受累(n=10),和脑干受累(n=2)。值得注意的是,皮层下白质受累,脑室周围白质受累,弥漫性call体受累,在III期和IV期亚急性硬化性全脑炎患者中,基底节受累更为普遍(P<0.05)。与IV期亚急性硬化性全脑炎患者相比,III期患者的脑萎缩也更为常见(P<0.0001)。然而,在MRI检查结果和EEG异常之间没有发现实质性的阳性或阴性关联。其他社会人口统计学/临床变量,脑脊液麻疹特异性抗体滴度(P>.05)。
    结论:亚急性硬化性全脑炎的疾病进展早期,皮质下白质的颞顶和顶枕区域受到影响。神经影像学异常与Jabbour的临床分期有更强的相关性,但与其他临床没有显著关联,社会人口统计学,和脑电图特征。
    BACKGROUND: Children diagnosed with subacute sclerosing panencephalitis (SSPE) display a range of neuroimaging abnormalities during different stages of the disease, but their exact clinical significance remains unclear.
    METHODS: In this retrospective cohort study, our objective was to examine magnetic resonance imaging (MRI) abnormalities in the brains of patients aged 18 years or younger with subacute sclerosing panencephalitis. We aimed to correlate these MRI abnormalities with clinical severity, sociodemographic variables, electroencephalographic (EEG) abnormalities, and cerebrospinal anti-measles antibody titers.
    RESULTS: The study included 112 cases of subacute sclerosing panencephalitis (mean age at onset: 8.9 ± 2.6 years). MRI analysis at the time of presentation revealed the following abnormalities: subcortical white matter signal changes (n = 95), periventricular white matter signal changes (n = 76), splenium of corpus callosum involvement (n = 39), diffuse corpus callosum involvement (n = 27), cerebral atrophy (n = 35), basal ganglia involvement (n = 10), and brain stem involvement (n = 2). Notably, subcortical white matter involvement, periventricular white matter involvement, diffuse corpus callosum involvement, and basal ganglia involvement were more prevalent in patients with stage III and IV subacute sclerosing panencephalitis (P < .05 for all). Cerebral atrophy was also significantly more common in patients with stage III compared to those with stage IV subacute sclerosing panencephalitis (P < .0001). However, no substantial positive or negative associations were found between MRI findings and EEG abnormalities, other sociodemographic/clinical variables, and cerebrospinal fluid measles-specific antibody titers (P > .05).
    CONCLUSIONS: Early in the disease progression of subacute sclerosing panencephalitis, the temporoparietal and parietooccipital regions of the subcortical white matter are affected. Neuroimaging abnormalities exhibit a stronger association with Jabbour\'s clinical staging, but do not show significant associations with other clinical, sociodemographic, and EEG features.
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