Neurocognitive disorder

神经认知障碍
  • 文章类型: Journal Article
    背景:抑郁症和痴呆症是老年人面临的重大健康挑战。尽管指南推荐抗抑郁药,它们在抑郁症痴呆患者中的疗效仍不确定。
    目的:这篇综述,在遵循一种生动的系统审查方法时,主要目的是确定任何类型的抗抑郁药对老年痴呆症患者抑郁症状水平的影响,其次,如果任何类型的抗抑郁药对认知状态有影响,生活质量,以及老年痴呆症患者的功能。
    方法:来自Medline,Embase,和Cochrane注册。参与者≥65岁,患有抑郁症和任何类型的痴呆症。通过Cochrane偏差风险工具和等级评估证据的确定性。分析涉及标准化均值差异,95%置信区间(CI)。
    结果:在27,771篇筛选的文章中,8项研究(617名参与者),用SSRI治疗,SSNRI,非典型的,和三环抗抑郁药被保留用于定量合成。没有发现效果的证据(SMD-0.10[-0.26,0.07]),当根据抑郁严重程度或痴呆程度分组时,也不是次要结果。
    结论:本综述没有发现抗抑郁药治疗老年痴呆患者抑郁症的临床效果的证据。方法上的挑战可能有助于这一发现。
    BACKGROUND: Depression and dementia represent significant health challenges in older adults. Despite guidelines recommending antidepressants, their efficacy in depressed patients with dementia remains undetermined.
    OBJECTIVE: This review, in following a living systematic review approach, primarily aims to determine the effect of any-type antidepressant on the level of depressive symptoms in older adults with dementia and secondly if there is an effect of any-type antidepressants on cognitive state, quality of life, and functionality in the old-age population with dementia.
    METHODS: Systematic review and meta-analysis of RCTs from Medline, Embase, and Cochrane Register. Participants were ≥65 years, with both depression and any type of dementia. Certainty-of-Evidence was assessed through the Cochrane Risk-of-Bias tool and GRADE. Analysis involved standardized mean difference, with 95 % confidence-intervals (CIs).
    RESULTS: Of the 27,771 screened articles, 8 studies (617 participants), treated with SSRI, SSNRI, atypical, and tricyclic antidepressants were retained for quantitative synthesis. No evidence for an effect was found (SMD -0.10 [-0.26, 0.07]), nor when subgrouped based on depression severity or dementia level, nor for secondary outcomes.
    CONCLUSIONS: This review did not find evidence of a clinical effect of antidepressants for treating depression in older adults with dementia. Methodological challenges might contribute to this finding.
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  • 文章类型: Journal Article
    背景:为了绘制有关长期护理中患有神经认知障碍的老年人使用技术的当前知识状态,以促进互动,健康,和刺激。
    方法:护理和相关健康文献的累积指数(CINAHLPlus);MEDLINE;PsycINFO;Embase和WebofScience在符合条件的文献中搜索,没有时间限制,描述长期护理中患有神经认知障碍的老年人目前对技术的使用情况。考虑了所有类型的文献,除了论文,社论,社交媒体。这项范围审查是围绕Peters等人的建议而建立的。(2020年版)。三名研究人员合作选择文章,并独立审查论文,根据资格标准和审查问题。
    结果:搜索产生了3,605项研究,其中包括39个。报道的大多数技术类型是机器人技术。纳入的研究报告了对使用这种技术的不同积极影响,如增加参与度和积极作用。
    结论:该研究强调了技术对患有神经认知障碍的长期护理居民的不同类型和潜在益处,强调迫切需要更多的研究来完善干预措施及其使用。
    BACKGROUND: To map the current state of knowledge about the use of technology with seniors with neurocognitive disorders in long-term care to foster interactions, wellness, and stimulation.
    METHODS: Cumulative Index to Nursing and Allied Health Literature (CINAHL Plus); MEDLINE; PsycINFO; Embase and Web of Science were searched in eligible literature, with no limit of time, to describe the current use of technology by seniors with neurocognitive disorders in long-term care. All types of literature were considered except for theses, editorial, social media. This scoping review was built around the recommendations of Peters et al. (2020 version). Three researchers collaborated on the selection of articles and independently reviewed the papers, based on the eligibility criteria and review questions.
    RESULTS: The search yielded 3,605 studies, of which 39 were included. Most technology type reported was robotics. Included studies reports different positive effects on the use of such technology such as increase of engagement and positive.
    CONCLUSIONS: The study highlights different types and potential benefits of technology for long-term care residents with neurocognitive disorders, emphasizing the crucial need for additional research to refine interventions and their use.
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  • 文章类型: Journal Article
    介绍轻度和重度神经认知障碍(NCDs)的患病率,也被称为轻度认知障碍和痴呆,正在全球崛起。预防非传染性疾病是一项重大的全球公共卫生利益。我们试图综合有关非传染性疾病潜在可改变的危险因素的文献。方法我们在多个数据库中进行了系统检索,以确定相关的系统评价和荟萃分析。符合条件的审查检查了轻度或主要非传染性疾病的潜在可改变的危险因素。我们使用随机效应多级荟萃分析方法来综合每个风险因素的风险比,同时考虑到评论中的重叠。我们进一步研究了由于两种常见病因导致的主要NCD的危险因素:阿尔茨海默病和血管性痴呆。结果共纳入45篇综述和212项荟萃分析。我们确定了14种与这些疾病显着相关的广泛定义的可改变的风险因素:饮酒,体重,抑郁症,糖尿病,饮食,高血压,少受教育,缺乏身体活动,感官损失,睡眠障碍,吸烟,社会孤立,创伤性脑损伤,维生素D缺乏。所有14个因素都与主要NCD的风险相关,5例伴有轻度NCD。我们发现对血管性痴呆和轻度NCD的研究相当少。结论我们的综述量化了与轻度和主要非传染性疾病的14种潜在可改变的危险因素相关的风险。包括痴呆症行动计划中很少包含的几个因素。预防策略应考虑通过促进健康来降低这些危险因素的发生率和严重程度的方法。identification,早期管理。
    BACKGROUND: The prevalence of mild and major neurocognitive disorders (NCDs), also referred to as mild cognitive impairment and dementia, is rising globally. The prevention of NCDs is a major global public health interest. We sought to synthesize the literature on potentially modifiable risk factors for NCDs.
    METHODS: We conducted an umbrella review using a systematic search across multiple databases to identify relevant systematic reviews and meta-analyses. Eligible reviews examined potentially modifiable risk factors for mild or major NCDs. We used a random-effects multi-level meta-analytic approach to synthesize risk ratios for each risk factor while accounting for overlap in the reviews. We further examined risk factors for major NCD due to two common etiologies: Alzheimer\'s disease and vascular dementia.
    RESULTS: A total of 45 reviews with 212 meta-analyses were synthesized. We identified fourteen broadly defined modifiable risk factors that were significantly associated with these disorders: alcohol consumption, body weight, depression, diabetes mellitus, diet, hypertension, less education, physical inactivity, sensory loss, sleep disturbance, smoking, social isolation, traumatic brain injury, and vitamin D deficiency. All 14 factors were associated with the risk of major NCD, and five were associated with mild NCD. We found considerably less research for vascular dementia and mild NCD.
    CONCLUSIONS: Our review quantifies the risk associated with 14 potentially modifiable risk factors for mild and major NCDs, including several factors infrequently included in dementia action plans. Prevention strategies should consider approaches that reduce the incidence and severity of these risk factors through health promotion, identification, and early management.
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  • 文章类型: Meta-Analysis
    神经血管疾病,如症状性中风,无症状性脑梗塞和血管性认知障碍是镰状细胞病(SCD)的常见并发症,可对生活质量造成破坏性后果,employment,和社会功能。神经血管疾病的早期识别是及时优化医疗护理并将患者与适应性资源联系起来的前提。虽然认知障碍已经在儿童中得到了很好的描述,目前可用的数据仅限于成年人。因此,关于成人最佳认知筛查策略的指导很少。我们进行了系统评价,以确定已在SCD中评估的不同筛查工具。进行荟萃分析以估计该人群中疑似认知障碍的患病率。在这个定性综合中,我们提出了8项研究,评估了6种不同的筛选工具.影响认知筛查表现的患者特征包括年龄,教育水平,和以前的中风史。我们报告的合并患病率为38%[14-62%]的可疑认知障碍。我们讨论了不同筛查工具的相对益处和局限性,以帮助临床医生选择适合其特定患者需求的适应性方法。需要进一步的研究来建立和验证具有不同文化和教育背景的患者的认知筛查策略。
    Neurovascular disease such as symptomatic stroke, silent brain infarcts and vascular cognitive impairment are common complications of sickle cell disease (SCD) that can have devastating consequences on quality of life, employment, and social functioning.  Early recognition of neurovascular disease is a prerequisite for the timely optimization of medical care and to connect patients to adaptive resources. While cognitive impairment has been well described in children, currently available data are limited in adults. As a result, guidance on the optimal cognitive screening strategies in adults is scarce. We conducted a systematic review to identify the different screening tools that have been evaluated in SCD. A meta-analysis was performed to estimate the prevalence of suspected cognitive impairment in this population. In this qualitative synthesis, we present 8 studies that evaluated 6 different screening tools. Patient characteristics that impacted on cognitive screening performance included age, education level, and a prior history of stroke. We report a pooled prevalence of 38% [14-62%] of suspected cognitive impairment. We discuss the relative benefits and limitations of the different screening tools to help clinicians select an adapted approach tailored to their specific patients\' needs. Further studies are needed to establish and validate cognitive screening strategies in patients with diverse cultural and educational backgrounds.
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  • 文章类型: Systematic Review
    背景:人口老龄化的加剧带来了神经认知障碍(NCD)发病率的增加以及产生依赖性的各种情况。
    目的:通过系统评价分析老年人NCD和依赖与死亡风险的关系。
    方法:对发表在Pubmed和Scopus上的纵向研究进行了文献检索,这些研究涉及1995年至2021年之间发表的NCI,对日常生活基本活动(ADL)的依赖性和死亡率之间的关系。在发现的1040篇文章中,选择了10项研究。
    结果:观察到患有NCI的老年人群的死亡风险与ABVD损害(Barthel检验)和迷你精神状态检查评分呈显著线性趋势。与死亡风险相关的其他因素是教育水平低,独自生活,和脆弱。
    结论:结果强调了使用经过验证的量表进行认知和功能状态评估的重要性,因为这两个领域都与死亡率相关。搜索这项工作中使用的三个术语之间的联系很清楚,但值得注意的是,很少有纵向研究将它们一起分析。在研究和临床实践中都应考虑评估老年人的依赖性和认知功能,因为这将提供有关其与死亡率可能关系的信息。
    BACKGROUND: The increasing aging of the population brings with it an increase in the incidence of neurocognitive disorder (NCD) as well as various situations that generate dependence.
    OBJECTIVE: To analyze by means of a systematic review the relationship between NCD and dependence with the risk of mortality in the elderly.
    METHODS: A bibliographic search of longitudinal studies published in Pubmed and Scopus addressing the relationship between NCI, dependence for basic activities of daily living (ADL) and mortality published between 1995 and 2021 was performed. Of the 1040 articles found, 10 studies were selected.
    RESULTS: It was observed that cohorts of elderly people with NCI presented mortality risk associated with ABVD impairment (Barthel test) and Mini-Mental State Examination scores following a significant linear trend. Other factors associated with mortality risk were low levels of education, living alone, and frailty.
    CONCLUSIONS: The results underline the importance of performing assessments of cognitive and functional status using validated scales, since both areas are associated with mortality. The link between the three terms used in the search for this work is clear, but it is noteworthy that there are few longitudinal studies that analyze them together. The assessment of dependence and cognitive function in older adults should be considered in both research and clinical practice as it would provide information on their possible relationship with mortality.
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  • 文章类型: Journal Article
    随着普通人口老龄化,越来越多的患者出现令人烦恼的勃起功能障碍,压力性尿失禁和膀胱过度活动症,泌尿外科对三种常见的交互式植入物的需求可能会更高,阴茎假体,人工尿道括约肌(AUS)和骶神经调节(SNM)。Further,轻度和主要神经认知障碍(也称为轻度认知障碍和痴呆,分别)预计会增加。虽然上述泌尿外科植入物具有出色的短期和长期结果,还存在可能需要手术移除和/或翻修的已知装置问题,例如故障或误用。这篇叙述性综述的目的是描述认知障碍和泌尿外科植入物的关联。
    我们在1975-2023年间在PubMed上进行了搜索,以查找有关认知障碍的任何类型或严重程度及其与阴茎假体的关联的英语文章,AUS和/或SNM。虽然同行评审的出版手稿被优先考虑,符合我们搜索标准的摘要也包括在内。
    评估接受泌尿外科植入物放置的认知障碍患者预后的数据有限。AUS失败或误用与认知障碍之间存在关联。SNM在短期内在该群体中是有效的。在发展为痴呆的患者中,充气阴茎假体可以通过办公室内的针头穿刺放气,AUS可以停用。内存改变测试,轻度认知障碍的快速筛查和圣路易斯大学精神状态检查是相对快速的筛查测试,对轻度认知障碍具有良好的敏感性和特异性。
    虽然泌尿系统植入物与认知障碍之间的关联数据很少,泌尿科医师可以使用一些工具来筛查患者的认知障碍。通过筛选,泌尿科医师可以提供适当的术前咨询(包括建议反对植入),并可以提供更密切的术后监测。需要进一步的研究来评估哪些患者应被排除在设备植入之外,以及如何以对患者有益且对泌尿科医生方便有效的方式正确评估认知障碍。
    UNASSIGNED: With the general population aging and thus more patients developing bothersome erectile dysfunction, stress urinary incontinence and overactive bladder, there will likely be a higher demand for three common interactive implants in urology, the penile prosthesis, artificial urinary sphincter (AUS) and sacral neuromodulation (SNM). Further, the prevalence of mild and major neurocognitive disorders (also known as mild cognitive impairment and dementia, respectively) is expected to increase. While the aforementioned urologic implants have excellent short and long term outcomes, there are also known device issues such as malfunction or misuse that may require surgical removal and/or revision. The objective of this narrative review is to describe the association of cognitive impairment and urologic implants.
    UNASSIGNED: We performed a search on PubMed between the years 1975-2023 for English language articles that reported on any type or severity of cognitive impairment and its association with penile prosthesis, AUS and/or SNM. While peer-reviewed published manuscripts were prioritized, abstracts that fit our search criteria were also included.
    UNASSIGNED: Data assessing outcomes of patients with cognitive impairment who undergo placement of a urologic implant are limited. There is an association between AUS failure or misuse with cognitive impairment. SNM is efficacious in this population in the short term. In patients who develop dementia, an inflatable penile prosthesis can be deflated via in-office needle puncture and an AUS can be deactivated. The Memory Alteration Test, Quick Screen for Mild Cognitive Impairment and the Saint Louis University Mental Status Examination are relatively quick screening tests with good sensitivity and specificity for mild cognitive impairment.
    UNASSIGNED: While data on the association between urologic implants and cognitive impairment are sparse, there are tools that urologists can use to screen patients for cognitive impairment. With screening, urologists can provide appropriate preoperative counseling (including recommending against implantation) and can provide closer postoperative monitoring. Further study is required to assess which patients should be excluded from device implantation and how to properly assess for cognitive impairment in a manner that is both beneficial for the patient and convenient and efficient for a urologist.
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  • 文章类型: Journal Article
    认知障碍,脆弱,营养不良是人口老龄化所面临的三种最具影响力的疾病,在医疗和干预的几乎所有方面对发病率和死亡率都有显著影响。世界卫生组织估计,到2050年,全世界60岁以上的人口将增加近一倍,这些人口结构变化所造成的公共卫生损失不可低估。随着人口结构的变化,需要更加重视对这一弱势群体的护理和管理。接受手术的患者平均年龄越来越大,这就需要临床医生了解这些病理对他们当前的医疗护理需求以及适当的手术选择和手术结果预测的影响.我们认为临床医生有责任考虑脆弱,营养状况,以及每个患者在提供手术干预时的认知功能,以及考虑可能延缓这些疾病进展的干预措施。不幸的是,尽管有极好的证据支持常规的术前虚弱筛查和营养优化,许多特别有利于该人群的干预措施仍未纳入常规实践。在这次审查中,我们将综合有关这些主题的现有文献,为面对这种复杂人群的麻醉师和重症医师提供务实的方法和理解。
    Cognitive impairment, frailty, and malnutrition are three of the most impactful pathologies facing an aging population, having dramatic effects on morbidity and mortality across nearly all facets of medical care and intervention. By 2050, the World Health Organization estimates that the population of individuals over the age of sixty worldwide will nearly double, and the public health toll of these demographic changes cannot be understated. With these changing demographics comes a need for a sharpened focus on the care and management of this vulnerable population. The average patient presenting for surgery is getting older, and this necessitates that clinicians understand the implications of these pathologies for both their immediate medical care needs and for appropriate procedural selection and prognostication of surgical outcomes. We believe it is incumbent on clinicians to consider the frailty, nutritional status, and cognitive function of each individual patient when offering a surgical intervention, as well as consider interventions that may delay the progression of these pathologies. Unfortunately, despite excellent evidence supporting things like routine pre-operative frailty screening and nutritional optimization, many interventions that would specifically benefit this population still have not been integrated into routine practice. In this review, we will synthesize the existing literature on these topics to provide a pragmatic approach and understanding for anesthesiologists and intensivists faced with this complex population.
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  • 文章类型: Journal Article
    本综述的目的是研究右美托咪定对重大非心脏手术后延迟神经认知恢复(dNCR;术后认知功能障碍≥1周)的影响。
    右美托咪定(DEX)可有效减少重症监护病房的谵妄,据报道可减轻重大非心脏手术后的认知功能下降。确定对术后认知的真正影响是困难的,因为研究受到认知评估工具的次优选择的限制。测试时间,以及定义显著认知能力下降的标准。
    前瞻性随机试验比较围手术期DEX与安慰剂用于非心脏大手术评估术后≥1周的认知功能。儿科,非人类,和非英语试验,执行功能未被评估的被排除在外.数据由3名审阅者根据PRISMA指南独立和并行地提取。先验二元主要结果是dNCR定义为认知功能下降的最小临床重要差异或接受的替代措施(例如,可靠变化指数≥1.96)。使用Cochrane协作工具评估偏差。使用随机效应模型汇集数据。
    在确定的287个引用中,26(9%)符合全文检索标准。纳入11项随机试验(1233名参与者)进行定性分析,纳入7项试验(616名参与者)进行dNCR的荟萃分析。与安慰剂相比,右美托咪定并没有显着降低dNCR的发生率(OR0.57,95%CI0.30-1.10,P=0.09)。谵妄发生率无差异(OR0.94,95%CI0.55-1.63,P=0.83),血流动力学不稳定发生率较高(OR2.11,95%CI1.22-3.65,P=0.008)。
    右美托咪定不降低非心脏大手术后1周的dNCR。该荟萃分析目前尚不支持使用围手术期DEX来改善短期认知结果;正在进行的试验可能会改变这一结论,而需要更大的试验来完善效应点估计并检查长期认知结果。
    UNASSIGNED: The purpose of this review is to examine the effect of dexmedetomidine on delayed neurocognitive recovery (dNCR; cognitive dysfunction ≥1 week postoperative) after major noncardiac surgery.
    UNASSIGNED: Dexmedetomidine (DEX) effectively reduces delirium in the intensive care unit and reportedly attenuates cognitive decline following major noncardiac surgery. Ascertaining the true effect on postoperative cognition is difficult because studies are limited by suboptimal selection of cognitive assessment tools, timing of testing, and criteria for defining significant cognitive decline.
    UNASSIGNED: Prospective randomized trials comparing perioperative DEX to placebo for major noncardiac surgery assessing cognitive function ≥1 week postoperative were included. Pediatric, nonhuman, and non-English trials, and those where executive function was not assessed were excluded. Data were abstracted by 3 reviewers independently and in parallel according to PRISMA guidelines. The a priori binary primary outcome is dNCR defined as cognitive function declining by the minimal clinically important difference or accepted alternate measure (eg, Reliable Change Index ≥1.96). Bias was assessed with the Cochrane Collaboration tool. Data were pooled using a random effects model.
    UNASSIGNED: Among 287 citations identified, 26 (9%) met criteria for full-text retrieval. Eleven randomized trials (1233 participants) were included for qualitative analysis, and 7 trials (616 participants) were included for meta-analysis of dNCR. Dexmedetomidine did not reduce the incidence of dNCR significantly (OR 0.57, 95% CI 0.30-1.10, P = 0.09) compared with placebo. There was no difference in the incidence of delirium (OR 0.94, 95% CI 0.55-1.63, P = 0.83) and a higher incidence of hemodynamic instability (OR 2.11, 95% CI 1.22-3.65, P = 0.008).
    UNASSIGNED: Dexmedetomidine does not reduce dNCR 1 week after major noncardiac surgery. This meta-analysis does not yet support the use of perioperative DEX to improve short term cognitive outcomes at this time; trials underway may yet change this conclusion while larger trials are needed to refine the point estimate of effect and examine long-term cognitive outcomes.
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  • 文章类型: Systematic Review
    背景:疗养院(NH)工作人员提到患有神经认知障碍(NCD)的居民对痴呆的行为和心理症状(BPSD)的管理知识不足。因此,工作人员培训似乎是必要的,然而,关于最佳培训实践及其结果的现有证据仍然分散。本系统综述旨在:1)确定NHsBPSD管理员工培训干预措施的最佳临床实践和理论基础,和2)总结这些干预措施对居民和工作人员结果的影响。
    方法:进行混合方法系统评价。两名护士研究人员独立搜索了九个电子数据库,以确定针对NHsBPSD管理的员工培训干预措施的有效性研究,关于各种居民和工作人员的结果。该搜索是针对1996年至2022年之间发表的文章进行的,使用选定的关键字,MeSH术语,和预定义的资格标准。使用JBI检查表评估检索到的研究的方法学质量。
    结果:总体而言,包括47篇文章中的39项研究。确定了十类培训,其中三个对居民和工作人员都表现出最有希望的结果:1)结构化的协议和模型,2)以人为中心的沐浴,3)通信技术。检索到的研究的方法学质量普遍较弱。还注意到干预可行性和可重复性的问题。
    结论:结合结构化协议和模型的培训干预措施,以人为中心的沐浴和沟通技术与更好的员工和居民结果相关。然而,迫切需要高质量的研究来加强现有的证据,确保可行性和可重复性。
    Nursing home (NH) staff mention knowledge deficits regarding the management of behavioural and psychological symptoms of dementia (BPSDs) in residents with neurocognitive disorders (NCDs). Staff training therefore appears to be necessary. However, existing evidence on best training practices and their outcomes remains scattered. This systematic review aimed to (1) identify the best clinical practices and theoretical bases of staff training interventions on BPSD management in NHs and (2) summarize the effects of these interventions on resident and staff outcomes.
    A mixed methods systematic review was conducted. Two nurse researchers independently searched nine electronic databases to identify studies on the efficacy of staff training interventions aimed at BPSD management in NHs, on a variety of resident and staff outcomes. The search was conducted for articles published between 1996 and 2022, using selected keywords, MeSH terms, and predefined eligibility criteria. The methodological quality of the retrieved studies was assessed using JBI checklists.
    Overall, 39 studies in 47 articles were included. Ten categories of trainings were identified, of which three demonstrated the most promising results on both residents and staff: (1) structured protocols and models, (2) person-centred bathing, and (3) communication techniques. The methodological quality of the retrieved studies was generally weak. Issues with intervention feasibility and reproducibility were also noted.
    Training interventions incorporating structured protocols and models, person-centred bathing, and communication techniques are associated with better staff and resident outcomes. However, there is a strong need for high-quality research to strengthen existing evidence and ensure feasibility and reproducibility.
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  • 文章类型: Systematic Review
    认知下降被认为与神经退行性过程有关,涉及兴奋性毒性。氧化损伤,炎症,微血管和血脑屏障功能障碍。有趣的是,研究证据表明,脂质信号分子的上调合成是一种内源性的尝试,以对比这种神经变性相关的病理生理机制,恢复稳态平衡,并防止进一步的损害。在这些天然存在的分子中,棕榈酰乙醇胺(PEA)与神经保护和抗炎特性独立相关,这引起了人们的兴趣,即它的补充可能代表了一种新的治疗方法,可以支持身体自身调节许多可能导致神经认知障碍的病理生理过程。这里,我们系统地回顾了所有人类和动物研究,研究PEA及其在神经认知障碍中的生物行为相关性,发现33个合格产出。在神经变性动物模型中进行的研究表明,PEA改善神经行为功能,包括记忆和学习,通过减少氧化应激和促炎和星形胶质细胞标志物表达以及重新平衡谷氨酸能传递。发现PEA促进神经发生,尤其是在海马区,神经元的生存力和存活率,和微管相关蛋白2和脑源性神经营养因子的表达,同时抑制肥大细胞浸润/脱颗粒和星形胶质细胞活化。它还证明可以减轻β-淀粉样蛋白诱导的星形胶质细胞增生,通过调节脂质过氧化,蛋白质正糖基化,诱导型一氧化氮合酶诱导,活性氧的产生,caspase3激活,淀粉样蛋白生成,和tau蛋白过度磷酸化。这种作用与PEA间接激活大麻素受体和调节增殖物激活受体-α(PPAR-α)活性的能力有关。重要的是,临床前证据表明,PEA可能在神经认知障碍的早期阶段作为改善疾病的药物,而其在弗兰克障碍中的保护作用可能不太相关。有限的人体研究表明,补充PEA可以减少疲劳和认知障碍,后者在3项符合条件的研究中也得到了荟萃分析证实.PEA改善了全球执行功能,工作记忆,语言障碍,日常生活活动,可能通过调节皮质振荡活动和GABA能传递。目前没有确定的神经认知障碍的治疗方法,只有暂时减轻症状严重程度的治疗方法。在寻找能够预防导致神经认知障碍的病理生理机制的化合物时,PEA可以代表预防神经变性和支持内源性修复过程对抗疾病进展的有效治疗选择。
    Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and blood-brain barrier dysfunction. Interestingly, research evidence suggests upregulated synthesis of lipid signaling molecules as an endogenous attempt to contrast such neurodegeneration-related pathophysiological mechanisms, restore homeostatic balance, and prevent further damage. Among these naturally occurring molecules, palmitoylethanolamide (PEA) has been independently associated with neuroprotective and anti-inflammatory properties, raising interest into the possibility that its supplementation might represent a novel therapeutic approach in supporting the body-own regulation of many pathophysiological processes potentially contributing to neurocognitive disorders. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in neurocognitive disorders, finding 33 eligible outputs. Studies conducted in animal models of neurodegeneration indicate that PEA improves neurobehavioral functions, including memory and learning, by reducing oxidative stress and pro-inflammatory and astrocyte marker expression as well as rebalancing glutamatergic transmission. PEA was found to promote neurogenesis, especially in the hippocampus, neuronal viability and survival, and microtubule-associated protein 2 and brain-derived neurotrophic factor expression, while inhibiting mast cell infiltration/degranulation and astrocyte activation. It also demonstrated to mitigate β-amyloid-induced astrogliosis, by modulating lipid peroxidation, protein nytrosylation, inducible nitric oxide synthase induction, reactive oxygen species production, caspase3 activation, amyloidogenesis, and tau protein hyperphosphorylation. Such effects were related to PEA ability to indirectly activate cannabinoid receptors and modulate proliferator-activated receptor-α (PPAR-α) activity. Importantly, preclinical evidence suggests that PEA may act as a disease-modifying-drug in the early stage of a neurocognitive disorder, while its protective effect in the frank disorder may be less relevant. Limited human research suggests that PEA supplementation reduces fatigue and cognitive impairment, the latter being also meta-analytically confirmed in 3 eligible studies. PEA improved global executive function, working memory, language deficits, daily living activities, possibly by modulating cortical oscillatory activity and GABAergic transmission. There is currently no established cure for neurocognitive disorders but only treatments to temporarily reduce symptom severity. In the search for compounds able to protect against the pathophysiological mechanisms leading to neurocognitive disorders, PEA may represent a valid therapeutic option to prevent neurodegeneration and support endogenous repair processes against disease progression.
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