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Neuropsychiatric Symptoms and Trajectories of Dependence and Cognition in a Sample of Community-dwelling Older Adults with Dementia. 社区居住老年痴呆患者的神经精神症状、依赖和认知轨迹
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230908163414
Anton J Kociolek, Kayri K Fernandez, Michelle Hernandez, Zhezhen Jin, Stephanie Cosentino, Carolyn W Zhu, Yian Gu, Davangere P Devanand, Yaakov Stern

Background and objectives: Neuropsychiatric symptoms (NPS), including psychotic symptoms (hallucinations, illusions, delusions), agitation/aggression, and depressed mood, are common in individuals with Alzheimer's disease (AD) and predict poorer outcomes, including faster disease progression. We aimed to evaluate associations between NPS and cognition and dependence in a multi-ethnic sample of community-dwelling older adults with AD.

Methods: Predictors 3 (P3) is a cohort study of AD disease courses recruiting older adults aged 65 and above residing in upper Manhattan. A total of 138 of 293 participants had probable AD at the study baseline. We fit linear mixed models to examine longitudinal associations of time-varying NPS (psychotic symptoms, agitation/aggression, and depressed mood) with dependence and cognition, adjusted for race-ethnicity, sex, education, age, clinical dementia rating score, APOE-ε4, and comorbidity burden; separate interaction models were fit for age, Hispanic ethnicity, and sex.

Results: Psychotic symptoms were associated with faster rates of increasing dependence and declining cognition over time, agitation/aggression with faster rates of declining cognition, and depressed mood with faster rates of increasing dependence. Among psychotic symptoms, delusions, but not hallucinations or illusions, were associated with worse outcome trajectories. Depressed mood predicted an accelerated increase in dependence in males but not females.

Conclusion: Our results confirm and extend prior results in clinic-based samples. The presence of NPS was associated with worse trajectories of dependence and cognition in this muti-ethnic sample of older adults with AD. Importantly, sex modified the association between depressed mood and dependence. Our results on NPS as predictors of differential AD progression in a community-dwelling, ethnically diverse sample serve to better inform the clinical care of patients and the future development of AD therapies.

背景和目的:神经精神症状(NPS),包括精神病症状(幻觉、幻觉、妄想)、躁动/攻击和抑郁情绪,在阿尔茨海默病(AD)患者中很常见,并预示着较差的预后,包括更快的疾病进展。我们的目的是评估多种族社区老年AD患者NPS与认知和依赖之间的关系。方法:预测因子3 (P3)是一项针对老年痴呆症病程的队列研究,招募居住在曼哈顿上城区的65岁及以上老年人。293名参与者中有138人在研究基线时可能患有阿尔茨海默病。我们拟合线性混合模型来检验时变NPS(精神病症状、躁动/攻击和抑郁情绪)与依赖性和认知的纵向关联,并对种族、性别、教育程度、年龄、临床痴呆评分、APOE-ε4和合并症负担进行了调整;不同的交互模型适合年龄、西班牙种族和性别。结果:随着时间的推移,精神病性症状与依赖性增加和认知能力下降的速度加快有关,激动/攻击与认知能力下降的速度加快有关,抑郁情绪与依赖性增加的速度加快有关。在精神病症状中,妄想,而不是幻觉或幻觉,与更糟糕的结局轨迹相关。抑郁情绪预示着男性对伴侣的依赖会加速增加,而女性则不然。结论:我们的结果证实并扩展了先前在临床样本中的结果。在这个多民族老年AD患者样本中,NPS的存在与较差的依赖和认知轨迹相关。重要的是,性改变了抑郁情绪和依赖性之间的联系。我们的研究结果表明,在社区居住、种族多样化的样本中,NPS作为阿尔茨海默病差异进展的预测因子,有助于更好地为患者的临床护理和阿尔茨海默病治疗的未来发展提供信息。
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引用次数: 0
Roles of Microglia in AD Pathology. 小胶质细胞在阿尔茨海默病病理中的作用。
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230203112351
Gao Rong, Wu Hongrong, Li Qingqi, Zhao Jianfeng

Amyloid plaques and neurofibrillary tangles are two main characteristics of Alzheimer's disease (AD). As cerebral resident phagocytes, microglia have different roles in Aβ pathology and tau pathology. In this review, we discuss microglial functions in the formation, clearance, and spread of Aβ and tau. Many receptors and enzymes, which are related to microglia, participate in AD pathologies and thus are thought to be potential targets of AD. So, making use of microglia can be beneficial to confine AD pathologies. To sum up, this article review the roles of microglia in AD pathology and possible corresponding treatments.

淀粉样斑块和神经原纤维缠结是阿尔茨海默病(AD)的两个主要特征。小胶质细胞作为大脑常驻吞噬细胞,在Aβ病理和tau病理中具有不同的作用。在这篇综述中,我们讨论了小胶质细胞在Aβ和tau的形成、清除和扩散中的功能。许多与小胶质细胞相关的受体和酶参与阿尔茨海默病的病理,因此被认为是阿尔茨海默病的潜在靶点。因此,利用小胶质细胞有助于限制阿尔茨海默病的病理。综上所述,本文综述了小胶质细胞在阿尔茨海默病病理中的作用及可能的治疗方法。
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引用次数: 2
Imagine Yourself Dancing Waltz: The Effect of Imagination on Memory in Alzheimer's Disease. 想象自己跳华尔兹舞:阿尔茨海默病中想象力对记忆的影响。
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230523155845
Mohamad El Haj, Frédérique Robin, Ahmed A Moustafa, Karim Gallouj

Background: Self-imagination refers to a mnemonic strategy of imagining oneself at a scene related to a cue.

Objective: We tested the effect of self-imagination on memory recall in Alzheimer's disease (AD) Methods: Individuals with AD and healthy controls were invited to perform two conditions. In the control (i.e., semantic elaboration) condition, participants were asked to define to which semantic category (e.g., dance) words (e.g., waltz) belong. However, in a self-imagining condition, participants were asked to imagine themselves in a scene related to the stimuli (e.g., dancing waltz). Both conditions were followed by two free memory tests with two different intervals (20 seconds vs. 20 minutes).

Results: Analysis showed a beneficial effect of self-imagination for the 20-second but not for the 20- minute recall in AD participants and controls.

Conclusion: Clinicians can incorporate our findings when assessing, especially when trying to rehabilitate, episodic memory in AD.

背景:自我想象是一种记忆策略,即想象自己处于与线索相关的场景中。目的:探讨自我想象对阿尔茨海默病(AD)患者记忆回忆的影响。方法:邀请阿尔茨海默病(AD)患者和健康对照者进行两种条件的测试。在控制(即语义细化)条件下,参与者被要求定义哪个语义类别(如舞蹈)词(如华尔兹)属于。然而,在自我想象条件下,参与者被要求想象自己处于与刺激相关的场景中(例如,跳华尔兹舞)。在这两种情况下,都进行了两次自由记忆测试,间隔时间不同(20秒vs. 20分钟)。结果:分析显示,在AD参与者和对照组中,自我想象对20秒回忆有有益影响,而对20分钟回忆没有。结论:临床医生在评估阿尔茨海默病的情景记忆时,尤其是在试图恢复情景记忆时,可以纳入我们的研究结果。
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引用次数: 0
Climate Change and Global Warming: Are Individuals with Dementia - Including Alzheimer's Disease - At a Higher Risk? 气候变化和全球变暖:患有痴呆症(包括阿尔茨海默病)的人风险更高吗?
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230726112305
Alex Buoite Stella, Alessandra Galmonte, Manuela Deodato, Serefnur Ozturk, Jacques Reis, Paolo Manganotti
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引用次数: 0
Cogstim: A Shared Decision-making Model to Support Older Adults' Brain Health. Cogstim:支持老年人大脑健康的共享决策模型。
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230525110814
Raymond L Ownby, Drenna Waldrop

The lack of effective treatments for cognitive decline in older adults has led to an interest in the possibility that lifestyle interventions can help to prevent changes in mental functioning and reduce the risk for dementia. Multiple lifestyle factors have been related to risk for decline, and multicomponent intervention studies suggest that changing older adults' behaviors can have a positive impact on their cognition. How to translate these findings into a practical model for clinical use with older adults, however, is not clear. In this Commentary, we propose a shared decision-making model to support clinicians' efforts to promote brain health in older persons. The model organizes risk and protective factors into three broad groups based on their mechanism of action and provides older persons with basic information to allow them to make evidence- and preference-based choices in choosing goals for effective brain health programs. A final component includes basic instruction in behavior change strategies such as goal setting, self-monitoring, and problem-solving. The implementation of the model will support older persons' efforts to develop a personally relevant and effective brainhealthy lifestyle that may help to reduce their risk for cognitive decline.

由于缺乏针对老年人认知能力下降的有效治疗方法,人们开始关注生活方式干预是否有助于预防心理功能的变化,并降低患痴呆症的风险。多种生活方式因素与衰退风险有关,多组分干预研究表明,改变老年人的行为可以对他们的认知产生积极影响。然而,如何将这些发现转化为老年人临床应用的实际模型尚不清楚。在这篇评论中,我们提出了一个共同的决策模型,以支持临床医生努力促进老年人的大脑健康。该模型根据其作用机制将风险和保护因素分为三大类,并为老年人提供基本信息,使他们能够根据证据和偏好选择有效的大脑健康计划目标。最后一个组成部分包括行为改变策略的基本指导,如目标设定、自我监控和问题解决。该模型的实施将支持老年人努力发展一种与个人相关和有效的大脑健康生活方式,这可能有助于减少他们认知能力下降的风险。
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引用次数: 1
The Immunopathy of Alzheimer's Disease: Innate or Adaptive? 阿尔茨海默病的免疫病变:先天的还是适应性的?
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230517103312
Donald F Weaver

Beyond the time-honoured targeting of protein misfolding and aggregation, Alzheimer's disease needs new, innovative therapeutic directions. When exploring alternative druggable mechanisms, multifaceted in vitro and in vivo data demonstrate that immune system dysfunction is a pivotal driver of Alzheimer's disease progression. In pursuing neuroimmunological targets, a major but often under-discussed consideration regards the issue of whether innate or adaptive immunity (or both) within the neuroimmune network should be the centre of focus when devising immunotherapeutic approaches to Alzheimer's. This perspective article briefly reviews current data, concluding that while both innate and adaptive immunity contributes to the immunopathology of Alzheimer's, the proinflammatory microglia and cytokines of innate immunity will provide higher yield targets with a greater likelihood of efficacy. Although it seems paradoxical to focus on a rapid, short-lived aspect of immunity when seeking approaches to a quintessentially chronic brain disease, accumulating evidence affords ample data to support the target-rich cascade of innate immunity for the development of much-needed new diagnostics and therapeutics.

除了长期以来针对蛋白质错误折叠和聚集的靶向治疗之外,阿尔茨海默病还需要新的、创新的治疗方向。在探索其他可药物机制时,多方面的体外和体内数据表明,免疫系统功能障碍是阿尔茨海默病进展的关键驱动因素。在追求神经免疫靶点的过程中,在设计阿尔茨海默氏症的免疫治疗方法时,神经免疫网络中的先天免疫或适应性免疫(或两者兼而有之)是否应该成为关注的焦点,这是一个主要但经常被忽视的问题。这篇前瞻性的文章简要回顾了目前的数据,得出结论,虽然先天免疫和适应性免疫都有助于阿尔茨海默氏症的免疫病理,但先天免疫的促炎小胶质细胞和细胞因子将提供更高的产量靶点,更有可能有效。虽然在寻找治疗典型慢性脑部疾病的方法时,专注于免疫的快速、短期方面似乎是自相矛盾的,但积累的证据提供了充足的数据来支持先天免疫的丰富靶标级联,以开发急需的新诊断和治疗方法。
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引用次数: 0
Is Vitamin D Supplementation a Danger to Potential Treatments of Alzheimer's Disease Treatment? 补充维生素D对阿尔茨海默病的潜在治疗有危险吗?
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230530095421
Pei-Yun Shih, Su-Boon Yong, Chin-Ming Liu, James Cheng-Chung Wei
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引用次数: 0
Predicting Dementia Due to Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia Using Algorithms with the Addenbrooke's Cognitive Examination-Revised Subscores Combined with Sociodemographic Factors. 使用Addenbrooke认知检查修正子核与社会形态因素相结合的算法预测阿尔茨海默病和行为变异性额颞叶痴呆引起的痴呆。
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230816160700
Viviane Amaral-Carvalho, Thais Bento Lima-Silva, Luciano Inácio Mariano, Leonardo Cruz de Souza, Henrique Cerqueira Guimarães, Valeria Santoro Bahia, Ricardo Nitrini, Maira Tonidandel Barbosa, Mônica Sanches Yassuda, Paulo Caramelli

Background: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are important causes of dementia with challenging differential diagnoses in many cases. Addenbrooke's Cognitive Examination-Revised (ACE-R) is a cognitive battery that may be useful to differentiate the two disorders.

Objective: The objectibe of this study is to investigate the value of the ACE-R combined with sociodemographic factors in the differential diagnosis between AD and bvFTD.

Methods: The ACE-R was administered to 102 patients with mild dementia due to probable AD, 37 with mild bvFTD, and 135 controls. Performances of patients and controls were analyzed by logistic regression and by ROC curves to refine the diagnostic accuracy of the ACE-R in AD and bvFTD.

Results: The ACE-R subscores Attention and Orientation, Fluency, and Memory, in combination with schooling differentiated AD from controls with an area under the ROC curve (AUC) of 0.936 (86% sensitivity and 87% specificity). The ACE-R subscores Attention and Orientation, Fluency, and Language, in combination with sex (male), age, and schooling, discriminated bvFTD from controls with an AUC of 0.908 (81% sensitivity and 95% specificity). In the differentiation between AD and bvFTD, the ACE-R subscores Attention and Orientation, Fluency, and Language, together with age, displayed an AUC of 0.865 (78% sensitivity and 85% specificity).

Conclusion: The combination of ACE-R scores with sociodemographic data allowed good differentiation between AD and bvFTD in the study sample.

背景:阿尔茨海默病(AD)和行为变异性额颞叶痴呆(bvFTD)是痴呆的重要原因,在许多情况下具有挑战性的鉴别诊断。Addenbrooke的认知检查修订版(ACE-R)是一种认知电池,可能有助于区分这两种疾病。目的:本研究的目的是探讨ACE-R与社会人口学因素在AD和bvFTD鉴别诊断中的价值。通过逻辑回归和ROC曲线分析患者和对照组的表现,以提高ACE-R在AD和bvFTD中的诊断准确性。ACE-R分量表注意力和方向、流利程度和语言,结合性别(男性)、年龄和学校教育,将FTD与对照组区分开来,AUC为0.908(81%的敏感性和95%的特异性)。在AD和bvFTD之间的区分中,ACE-R分量表注意力和方向、流利度和语言以及年龄显示出0.865的AUC(78%的敏感性和85%的特异性)。结论:将ACE-R评分与社会人口学数据相结合,可以很好地区分研究样本中的AD和bfFTD。
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引用次数: 0
Synthesis and Biological Study of 4-Aminopyridine-Peptide Derivatives Designed for the Treatment of Neurodegenerative Disorders. 用于治疗神经退行性疾病的4-氨基吡啶肽衍生物的合成和生物学研究。
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230602142012
Lyubomir T Vezenkov, Daniela S Tsekova, Ivanka Kostadinova, Rositsa Mihaylova, Valentin Lozanov, Nikolay G Vassilev, Nikolai Danchev, Ivanka Tsakovska, Ilza Pajeva

Background: Alzheimer's disease (AD) and Multiple sclerosis (MS) lead to neurodegenerative processes negatively affecting millions of people worldwide. Their treatment is still difficult and practically incomplete. One of the most commonly used drugs against these neurodegenerative diseases is 4-aminopyridine. However, its use is confined by the high toxicity.

Objectives: The aim of this work is to obtain new peptide derivatives of 4-aminopyridine with decreased toxicity compared to 4-aminopyridine.

Methods: Synthesis was conducted in solution using a consecutive condensation approach. The new derivatives were characterized by melting points, NMR, and Mass spectra. Important ADME (absorption, distribution, metabolism, and excretion) properties have been studied in silico using ACD/Percepta v.2020.2.0 software. Acute toxicity was determined in mice according to a Standard protocol. All new derivatives were tested in vitro for cytotoxic activity in a panel of human (HEP-G2, BV-173) and murine (NEURO 2A) tumor cell lines via a standard MTT-based colorimetric method. β-secretase inhibitory activity was determined by applying the fluorescent method.

Results: New derivatives of 4-aminopyridine containing analogues of the β-secretase inhibitory peptide (Boc-Val-Asn-Leu-Ala-OH) were obtained. The in vivo toxicity of the tested compounds was found to be as high as 1500 mg/kg. Cell toxicity screening against tumor cell lines of different origins showed negligible growth-inhibitory effects of all investigated 4-aminopyridine analogues.

Conclusion: Synthesis of new peptide derivatives of 4-aminopyridine is reported. Acute toxicity studies revealed a ca. 150 times lower toxicity of the new compounds as compared to 4-aminopyridine that may be ascribed to their peptide fragment.

背景:阿尔茨海默病(AD)和多发性硬化症(MS)导致神经退行性过程对全世界数百万人产生负面影响。他们的治疗仍然很困难,而且实际上是不完整的。治疗这些神经退行性疾病最常用的药物之一是4-氨基吡啶。但由于其毒性大,限制了其使用。目的:制备毒性较4-氨基吡啶低的4-氨基吡啶肽衍生物。方法:采用连续缩合法在溶液中合成。用熔点、核磁共振和质谱对新衍生物进行了表征。使用ACD/Percepta v.2020.2.0软件在计算机上研究了重要的ADME(吸收、分布、代谢和排泄)特性。根据标准方案测定小鼠急性毒性。所有新衍生物通过标准的mtt比色法在体外对人(HEP-G2, BV-173)和小鼠(NEURO 2A)肿瘤细胞系进行细胞毒活性测试。采用荧光法测定β-分泌酶抑制活性。结果:获得了含有β-分泌酶抑制肽(Boc-Val-Asn-Leu-Ala-OH)类似物的4-氨基吡啶衍生物。试验化合物的体内毒性高达1500毫克/公斤。对不同来源肿瘤细胞系的细胞毒性筛选显示,所有研究的4-氨基吡啶类似物的生长抑制作用可以忽略不计。结论:合成了新的4-氨基吡啶肽衍生物。急性毒性研究表明,与4-氨基吡啶相比,新化合物的毒性低约150倍,这可能归因于它们的肽片段。
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引用次数: 0
Into the Next Sun: A Restart in Current Alzheimer Research 走进下一个太阳:当前阿尔茨海默病研究的重启
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/156720502001230623100847
J. G. Górriz Sáez
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引用次数: 0
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Current Alzheimer research
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