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Meaningful patient and public engagement in dissemination-embedding co-production in dementia research. 患者和公众有意义地参与传播--在痴呆症研究中纳入共同生产。
Pub Date : 2024-09-16 eCollection Date: 2024-01-01 DOI: 10.3389/frdem.2024.1426019
Susanne de Wolf-Linder, Iris Kramer, Martina Hersperger, Maria Schubert, Sonja Bächi, Monika Stolz, Emma Wolverson, Christina Ramsenthaler

Background: Patient and Public Involvement and Engagement (PPIE) is still underutilised in both dementia research and corresponding dissemination activities.

Aim: To describe the methods, format, and lessons learned in co-creating and co-producing a dissemination strategy for a research project focused on establishing patient-centred outcome measures into routine palliative community care for persons living with dementia (PLWD) and their informal carers.

Materials and methods: A participatory, hybrid-format workshop was conducted to co-create the dissemination strategy with a PPIE group. A video presentation of findings and a list of prompts shared prior to the workshop were used to elicit views on dissemination strategies and knowledge translation. The workshop was followed up with a survey to consolidate the dissemination strategy. Workshop minutes and survey responses were analysed using qualitative thematic analysis.

Results: 22 participants from our diverse PPIE group attended the workshop. Two major themes emerged: (a) Knowledge translation: building bridges between research and practise, and (b) Collaboration and dissemination: everyone's voice is needed. Participants suggested critical changes to dissemination methods and materials. Successful knowledge translation depends on a strong evidence base. For this, materials need to be tailored to specific audiences. Everyone's voice needs to be integrated through co-production in dissemination activities by PPIE members to influence societal change. Tailored dissemination activities within a dissemination strategy were co-created spanning all phases of the research cycle.

Discussion: Informing and educating the public and policymakers about the needs of PLWD relies on disseminating and fostering knowledge translation throughout all phases of the research cycle.

背景:目的:描述为一个研究项目共同创建和共同制定传播策略的方法、形式和经验教训,该项目侧重于为痴呆症患者及其非正式护理者在常规社区姑息治疗中建立以患者为中心的结果测量:举办了一次参与式混合形式研讨会,与一个PPIE小组共同制定传播策略。在研讨会之前,通过视频介绍研究结果并分享一份提示清单,以征求对传播策略和知识转化的意见。研讨会后进行了一次调查,以巩固传播战略。我们采用定性专题分析法对研讨会会议记录和调查答复进行了分析。出现了两大主题:(a) 知识转化:在研究与实践之间架起桥梁,(b) 合作与传播:需要每个人的声音。与会者建议对传播方法和材料进行重大改革。成功的知识转化取决于强大的证据基础。为此,需要为特定受众量身定制材料。需要通过 PPIE 成员在传播活动中的共同制作,整合每个人的声音,以影响社会变革。在传播战略的框架内,共同开展有针对性的传播活动,跨越研究周期的各个阶段:讨论:向公众和政策制定者宣传和教育残疾人的需求,有赖于在研究周期的各个阶段传播和促进知识转化。
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引用次数: 0
The use of audio-biographical cues in dementia care: a four-year evaluation in Swiss hospitals, care, and domestic homes. 在痴呆症护理中使用音频传记线索:在瑞士医院、护理机构和家庭护理院进行的为期四年的评估。
Pub Date : 2024-08-30 eCollection Date: 2024-01-01 DOI: 10.3389/frdem.2024.1429290
Heather Edwards, Sandra Oppikofer, Damaris Aschwanden

Introduction: In dementia care, the integration of innovative interventions is essential to enhancing the wellbeing and quality of life of people with dementia. Among these interventions, the Music Mirror intervention has emerged as a promising tool to provide personalized audio-biographical cues aimed at soothing, motivating, and engaging people with dementia. This study examined the effects of a Music Mirror intervention on the (a) wellbeing, emotions, and behavioral and psychological symptoms of 155 individuals with dementia, (b) perceived burden, relationship quality, and gains of their informal/formal caregivers, and (c) momentary closeness, wellbeing and stress of caregivers.

Methods: This four-year study employed a quasi-experimental waiting-control group design, utilizing before-after measurements in Swiss hospitals, care homes, and domestic homes. For four 6-week intervention phases, Music Mirrors, i.e., brief written resources of acoustic material, associated with practical activities of daily life, were applied at least twice a week by the caregivers during critical moments such as staff handover. Repeated measures' analysis of variance and other tests were used to analyze the data.

Results: Individuals with dementia had a higher wellbeing after the Music Mirror use across different care situations. While the Music Mirrors were played, individuals with dementia showed more positive than negative emotions at each measurement occasion, but emotion scores did not significantly change over time. After the MM use, caregivers felt better, closer to the person with dementia, and less stressed. Caregivers also reported significant gains at the end of the intervention. However, there were no significant changes in the frequency of the behavioral and psychological symptoms of dementia, care-related burden and relationship quality over time, regardless of the treatment condition.

Discussion: By incorporating personalized audio-biographical cues into their care routines, the wellbeing of people with dementia was improved as well as it had positive momentary effects on their caregivers. The Music Mirror intervention addresses the preferences and needs of people with dementia and helps build bonds between care-recipients and caregivers. Therefore, Music Mirrors can be seen as a highly adaptive and individualized instrument to improve momentary wellbeing of people with dementia in various care situations during daily life.

介绍:在痴呆症护理中,整合创新干预措施对于提高痴呆症患者的福祉和生活质量至关重要。在这些干预措施中,"音乐镜像 "干预措施已成为一种很有前途的工具,它能提供个性化的音频传记提示,旨在舒缓、激励和吸引痴呆症患者。本研究探讨了音乐魔镜干预对以下方面的影响:(a)155 名痴呆症患者的福祉、情绪、行为和心理症状;(b)其非正式/正式护理人员的感知负担、关系质量和收益;以及(c)护理人员的瞬间亲近感、福祉和压力:这项为期四年的研究采用了准实验性的等待-对照组设计,在瑞士的医院、护理院和家庭中进行了前后测量。在为期 6 周的四个干预阶段中,护理人员每周至少两次在员工交接等关键时刻使用 "音乐镜像",即与日常生活实际活动相关的简短书面声学材料资源。数据分析采用了重复测量方差分析和其他检验方法:结果:在不同的护理情况下,痴呆症患者在使用音乐镜后都有较高的幸福感。在播放音乐镜的过程中,痴呆症患者在每次测量中表现出的积极情绪多于消极情绪,但情绪得分并没有随着时间的推移而发生显著变化。使用音乐镜后,护理人员感觉更好,与痴呆症患者更亲近,压力更小。在干预结束时,照护者也报告了明显的收获。然而,无论治疗条件如何,随着时间的推移,痴呆症的行为和心理症状频率、护理相关负担和关系质量都没有明显变化:讨论:通过在日常护理中加入个性化的音频-传记提示,痴呆症患者的福祉得到了改善,同时也对其护理人员产生了积极的瞬间效应。音乐镜像干预满足了痴呆症患者的喜好和需求,有助于在护理对象和护理人员之间建立联系。因此,音乐镜可以被视为一种高度适应性和个性化的工具,在日常生活中的各种护理情况下改善痴呆症患者的瞬间幸福感。
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引用次数: 0
Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes. 酪氨酸激酶:多种神经退行性疾病相关过程交叉点上的多面受体。
Pub Date : 2024-08-16 eCollection Date: 2024-01-01 DOI: 10.3389/frdem.2024.1458038
Max Stevenson, Norah K Algarzae, Charbel Moussa

Tyrosine kinases (TKs) are catalytic enzymes activated by auto-phosphorylation that function by phosphorylating tyrosine residues on downstream substrates. Tyrosine kinase inhibitors (TKIs) have been heavily exploited as cancer therapeutics, primarily due to their role in autophagy, blood vessel remodeling and inflammation. This suggests tyrosine kinase inhibition as an appealing therapeutic target for exploiting convergent mechanisms across several neurodegenerative disease (NDD) pathologies. The overlapping mechanisms of action between neurodegeneration and cancer suggest that TKIs may play a pivotal role in attenuating neurodegenerative processes, including degradation of misfolded or toxic proteins, reduction of inflammation and prevention of fibrotic events of blood vessels in the brain. In this review, we will discuss the distinct roles that select TKs have been shown to play in various disease-associated processes, as well as identify TKs that have been explored as targets for therapeutic intervention and associated pharmacological agents being investigated as treatments for NDDs.

酪氨酸激酶(TKs)是一种通过自动磷酸化激活的催化酶,其功能是使下游底物上的酪氨酸残基磷酸化。酪氨酸激酶抑制剂(TKIs)已被大量用作癌症疗法,这主要是由于它们在自噬、血管重塑和炎症中的作用。这表明,酪氨酸激酶抑制剂是一种很有吸引力的治疗靶点,可以利用几种神经退行性疾病(NDD)病理的趋同机制。神经退行性疾病和癌症的作用机制相互重叠,这表明酪氨酸激酶抑制剂可能在减轻神经退行性疾病过程中发挥关键作用,包括降解折叠错误或有毒的蛋白质、减轻炎症反应和预防脑血管纤维化事件。在本综述中,我们将讨论已被证明在各种疾病相关过程中发挥独特作用的特定 TKs,并确定已被探索作为治疗干预靶点的 TKs 以及正在研究作为 NDDs 治疗方法的相关药剂。
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引用次数: 0
The psychological effects of research participation on people with dementia: findings from a German exploratory interview study. 参与研究对痴呆症患者的心理影响:德国探索性访谈研究的结果。
Pub Date : 2024-08-07 eCollection Date: 2024-01-01 DOI: 10.3389/frdem.2024.1421541
Katja Seidel, Claudia Winiarski, Jochen René Thyrian, Julia Haberstroh

The German National Dementia Strategy aims to engage people with dementia in research projects. However, the effects of such research participation on experience and behavior have been insufficiently explored. This study aimed to investigate the psychological effect of research participation on people living with dementia. In a qualitative, exploratory approach, guideline-based interviews were conducted with four persons with dementia who had served as co-researchers on an advisory board in a health services research study for 8 months at that time. The analysis revealed predominantly positive effects of research participation at all levels of experience and behavior. Most effects were reported by the co-researchers on a cognitive level. Both the perception of being competent and of making a positive contribution to oneself and/or others are key effects of research participation. The main effects on an emotional level were joy and wellbeing and on a behavioral level were positive social contacts and social communication. Sadness and insecurity represent the sole negative effects. Nuanced focal points of effects among the individual interviews were found. The results align with existing research highlighting the positive effects of participation on people with dementia. Through advancing an interdisciplinary perspective on their research involvement, we advocate for heightened attention to this topic within the realm of psychology.

德国国家痴呆症战略旨在让痴呆症患者参与研究项目。然而,这种研究参与对体验和行为的影响还没有得到充分的探讨。本研究旨在调查研究参与对痴呆症患者的心理影响。研究采用定性、探索性的方法,对四名痴呆症患者进行了基于指南的访谈,他们当时作为共同研究者参与了一项医疗服务研究的咨询委员会,为期 8 个月。分析结果显示,参与研究在经验和行为的各个层面上都产生了积极的影响。共同研究人员报告的大多数效果都体现在认知层面。认为自己有能力以及为自己和/或他人做出积极贡献是参与研究的主要影响。情绪层面的主要影响是快乐和幸福,行为层面的主要影响是积极的社会接触和社会交流。悲伤和不安全感是唯一的负面影响。在个别访谈中发现了不同的影响焦点。研究结果与现有研究一致,都强调了参与对痴呆症患者的积极影响。通过从跨学科的角度推进他们的研究参与,我们提倡在心理学领域内加强对这一主题的关注。
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引用次数: 0
Editorial: Cognitive assessment in facilitating early detection of dementia. 社论:认知评估有助于早期发现痴呆症。
Pub Date : 2024-08-01 eCollection Date: 2024-01-01 DOI: 10.3389/frdem.2024.1441582
Pai-Yi Chiu, Chi-Cheng Yang, Mohammad H Mahoor, Hsin-Te Chang
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引用次数: 0
Traffic-related air pollution and APOE4 can synergistically affect hippocampal volume in older women: new findings from UK Biobank. 交通相关空气污染和 APOE4 可协同影响老年妇女的海马体积:英国生物数据库的新发现。
Pub Date : 2024-07-29 eCollection Date: 2024-01-01 DOI: 10.3389/frdem.2024.1402091
Vladimir A Popov, Svetlana V Ukraintseva, Hongzhe Duan, Anatoliy I Yashin, Konstantin G Arbeev

A growing research body supports the connection between neurodegenerative disorders, including Alzheimer's disease (AD), and traffic-related air pollution (TRAP). However, the underlying mechanisms are not well understood. A deeper investigation of TRAP effects on hippocampal volume (HV), a major biomarker of neurodegeneration, may help clarify these mechanisms. Here, we explored TRAP associations with the HV in older participants of the UK Biobank (UKB), taking into account the presence of APOE e4 allele (APOE4), the strongest genetic risk factor for AD. Exposure to TRAP was approximated by the distance of the participant's main residence to the nearest major road (DNMR). The left/right HV was measured by magnetic resonance imaging (MRI) in cubic millimeters (mm3). Analysis of variance (ANOVA), Welch test, and regression were used to examine statistical significance. We found significant interactions between DNMR and APOE4 that influenced HV. Specifically, DNMR <50m (equivalent of a chronically high exposure to TRAP), and carrying APOE4 were synergistically associated with a significant (P = 0.01) reduction in the right HV by about 2.5% in women aged 60-75 years (results for men didn't reach a statistical significance). Results of our study suggest that TRAP and APOE4 jointly promote neurodegeneration in women. Living farther from major roads may help reduce the risks of neurodegenerative disorders, including AD, in female APOE4 carriers.

越来越多的研究表明,包括阿尔茨海默病(AD)在内的神经退行性疾病与交通相关空气污染(TRAP)之间存在联系。然而,人们对其潜在机制还不甚了解。深入研究交通相关空气污染对海马体积(HV)(神经退行性疾病的主要生物标志物)的影响可能有助于阐明这些机制。在此,我们探讨了TRAP与英国生物库(UKB)老年参与者海马体积的关系,同时考虑了APOE e4等位基因(APOE4)的存在,APOE4是AD的最强遗传风险因素。与TRAP的接触程度根据参与者主要住所到最近主干道(DNMR)的距离来估算。左/右HV通过磁共振成像(MRI)测量,单位为立方毫米(mm3)。方差分析(ANOVA)、韦尔奇检验(Welch test)和回归分析用于检验统计学意义。我们发现 DNMR 和 APOE4 之间存在明显的交互作用,对 HV 有影响。具体来说,在 60-75 岁的女性中,DNMR APOE4 与右侧 HV 显著降低约 2.5%(P = 0.01)协同相关(男性的结果未达到统计学意义)。我们的研究结果表明,TRAP 和 APOE4 共同促进了女性的神经退行性变。居住地离主干道较远可能有助于降低女性 APOE4 携带者罹患神经退行性疾病(包括注意力缺失症)的风险。
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引用次数: 0
A critical reflection on using the Patient Engagement In Research Scale (PEIRS) to evaluate patient and family partners' engagement in dementia research. 使用 "患者参与研究量表"(PEIRS)评估患者和家庭合作伙伴参与痴呆症研究的批判性思考。
Pub Date : 2024-06-24 eCollection Date: 2024-01-01 DOI: 10.3389/frdem.2024.1422820
Joey Wong, Lillian Hung, Cates Bayabay, Karen Lok Yi Wong, Annette Berndt, Jim Mann, Lily Wong, Lynn Jackson, Mario Gregorio

Introduction: Research involvement of people with lived experiences is increasing. Few tools are designed to evaluate their engagement in research. The Patient Engagement In Research Scale (PEIRS) is one of the few validated tools. Our team employed the PEIRS with patient and family partners with lived experiences of dementia every 6 months in a two-year telepresence robot project. This reflection paper reports our self-study on key learnings and proposes practical tips on using the PEIRS to evaluate patient and family partners' engagement in dementia research. It is the first to document a case using the PEIRS multiple times in a dementia research project.

Methods: Guided by Rolfe et al.'s reflective model, we conducted three team reflective sessions to examine the team's experiences using the PEIRS to improve and evaluate patient and family partners' engagement in the research. We also reviewed our meeting notes and fieldnotes documented in the research journal. A reflexive thematic analysis was performed.

Results: The team identified three key learnings: the values of using the PEIRS survey, the adaptations, and the factors influencing its implementation as an evaluation tool. Using the PEIRS provided significant benefits to the project, although some patient and family partners felt it was burdensome. The evaluation tool was enhanced with emojis and comment boxes based on suggestions from patient partners. The emojis introduced an element of fun, while the comment boxes allowed for personalized responses. Several factors influenced the PEIRS tool's effectiveness: the interviewer's identity, the confidentiality of responses and follow-ups, the timing and frequency of using the tool, and the presentation of the evaluations. These learnings led to the development of six practical tips,-"ENGAGE": Enjoyable and fun process, Never impose, Get prepared early, Adapt to the team's needs, Give people options, and Engage and reflect.

Conclusion: With the emerging trend of including people with lived experiences in dementia research, there is a need for ongoing assessment of engagement from both patient and family partners and the research team strategies. Future research can further explore survey logistics, co-development of evaluation tools, and the use of tools with people living with dementia.

导言:有生活经历的人越来越多地参与研究。但很少有工具可用于评估他们参与研究的情况。患者参与研究量表 (PEIRS) 是为数不多的经过验证的工具之一。在一个为期两年的远程呈现机器人项目中,我们的团队每 6 个月对有痴呆症生活经历的患者和家庭伙伴使用 PEIRS。这篇反思论文报告了我们对主要学习成果的自我研究,并提出了使用 PEIRS 评估患者和家庭合作伙伴参与痴呆症研究的实用技巧。这是首次记录在痴呆症研究项目中多次使用 PEIRS 的案例:在 Rolfe 等人的反思模型指导下,我们进行了三次团队反思会议,以检查团队使用 PEIRS 改善和评估患者及家庭合作伙伴参与研究的经验。我们还回顾了研究日志中记录的会议记录和现场笔记。结果:研究小组确定了三条主要经验:使用 PEIRS 调查的价值、调整以及影响其作为评估工具实施的因素。使用 PEIRS 为项目带来了显著的益处,尽管一些患者和家庭合作伙伴认为这是一种负担。根据患者合作伙伴的建议,评估工具增加了表情符号和评论框。表情符号引入了趣味元素,而评论框则允许个性化回复。有几个因素影响了 PEIRS 工具的有效性:访谈者的身份、回复和跟踪的保密性、使用工具的时间和频率以及评估的呈现方式。根据这些经验,我们提出了六条实用建议--"参与":ENGAGE":愉快和有趣的过程、绝不强人所难、及早准备、适应团队需要、给人选择、参与和反思:随着将有生活经验的人纳入痴呆症研究的新兴趋势,有必要对患者和家庭伙伴以及研究团队的参与策略进行持续评估。未来的研究可以进一步探索调查的后勤工作、共同开发评估工具以及与痴呆症患者共同使用工具。
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引用次数: 0
Cerebrovascular lesion loads and accelerated brain aging: insights into the cognitive spectrum. 脑血管病损负荷与大脑加速衰老:认知谱系的启示。
Pub Date : 2024-06-21 eCollection Date: 2024-01-01 DOI: 10.3389/frdem.2024.1380015
Iman Beheshti, Olivier Potvin, Mahsa Dadar, Simon Duchesne

Introduction: White matter hyperintensities (WMHs) and cerebral microbleeds are widespread among aging population and linked with cognitive deficits in mild cognitive impairment (MCI), vascular MCI (V-MCI), and Alzheimer's disease without (AD) or with a vascular component (V-AD). In this study, we aimed to investigate the association between brain age, which reflects global brain health, and cerebrovascular lesion load in the context of pathological aging in diverse forms of clinically-defined neurodegenerative conditions.

Methods: We computed brain-predicted age difference (brain-PAD: predicted brain age minus chronological age) in the Comprehensive Assessment of Neurodegeneration and Dementia cohort of the Canadian Consortium on Neurodegeneration in Aging including 70 cognitively intact elderly (CIE), 173 MCI, 88 V-MCI, 50 AD, and 47 V-AD using T1-weighted magnetic resonance imaging (MRI) scans. We used a well-established automated methodology that leveraged fluid attenuated inversion recovery MRIs for precise quantification of WMH burden. Additionally, cerebral microbleeds were detected utilizing a validated segmentation tool based on the ResNet50 network, utilizing routine T1-weighted, T2-weighted, and T2* MRI scans.

Results: The mean brain-PAD in the CIE cohort was around zero, whereas the four categories showed a significantly higher mean brain-PAD compared to CIE, except MCI group. A notable association trend between brain-PAD and WMH loads was observed in aging and across the spectrum of cognitive impairment due to AD, but not between brain-PAD and microbleed loads.

Discussion: WMHs were associated with faster brain aging and should be considered as a risk factor which imperils brain health in aging and exacerbate brain abnormalities in the context of neurodegeneration of presumed AD origin. Our findings underscore the significance of novel research endeavors aimed at elucidating the etiology, prevention, and treatment of WMH in the area of brain aging.

导言:白质高密度(WMHs)和脑微出血广泛存在于老龄人口中,并与轻度认知障碍(MCI)、血管性 MCI(V-MCI)、无血管性阿尔茨海默病(AD)或有血管性成分的阿尔茨海默病(V-AD)中的认知障碍有关。在这项研究中,我们旨在调查反映大脑整体健康的脑年龄与临床定义的各种神经退行性疾病病理衰老背景下脑血管病变负荷之间的关联:我们使用 T1 加权磁共振成像(MRI)扫描计算了加拿大老龄化神经退行性病变联盟(Canadian Consortium on Neurodegeneration in Aging)的神经退行性病变和痴呆综合评估队列(Comprehensive Assessment of Neurodegeneration and Dementia cohort)中的脑预测年龄差(brain-PAD:预测脑年龄减去计时年龄),其中包括 70 名认知功能完好的老年人(CIE)、173 名 MCI、88 名 V-MCI、50 名 AD 和 47 名 V-AD。我们采用了一种成熟的自动化方法,利用流体衰减反转恢复 MRI 对 WMH 负荷进行精确量化。此外,我们还利用经过验证的基于 ResNet50 网络的分割工具,利用常规 T1 加权、T2 加权和 T2* MRI 扫描检测脑微出血:CIE组群的平均脑PAD值约为零,而与CIE相比,除MCI组外,其他四个组群的平均脑PAD值均显著高于CIE。在老年期和AD引起的认知障碍的各个阶段,都观察到脑PAD与WMH负荷之间有明显的关联趋势,但脑PAD与微出血负荷之间没有关联:讨论:WMH 与大脑加速衰老有关,应将其视为在衰老过程中危及大脑健康的风险因素,并在推测为 AD 的神经变性过程中加剧大脑异常。我们的研究结果表明,在脑衰老领域开展旨在阐明 WMH 病因、预防和治疗的新型研究工作意义重大。
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引用次数: 0
Cultural adaptation of the brain health assessment for early detection of cognitive impairment in Southeast Nigeria. 在尼日利亚东南部对大脑健康评估进行文化适应性调整,以早期发现认知障碍。
Pub Date : 2024-06-18 eCollection Date: 2024-01-01 DOI: 10.3389/frdem.2024.1423957
Chukwuanugo Ogbuagu, Ekenechukwu Ogbuagu, Obiageli Emelumadu, Uzoma Okereke, Irene Okeke, Godswill Chigbo, Katherine L Possin, Isabel E Allen, Elena Tsoy, Richard Uwakwe

Objective: The aging population in developing countries demands parallel improvements in brain health assessment services to mitigate stigma, promote healthy aging, and diagnose cognitive impairments including dementia in primary health care (PHC) facilities. The lack of culturally appropriate cognitive assessment tools in PHC facilities delays early detection. This study aims to culturally adapt a brief digital cognitive assessment tool for PHC professionals in Southeast Nigeria.

Method: A total of 30 participants (15 healthcare workers HCW and 15 community members) were selected to be culturally representative of the community. We completed focus groups and pilot testing to evaluate and refine the Brain Health Assessment (BHA) a subset of tools from the Tablet-based Cognitive Assessment Tool (TabCAT) known to be sensitive to cognitive impairment in other settings. We examined BHA subtests across local languages (Pidgin and Igbo) spoken at two geriatric clinics in Anambra State Southeast Nigeria.

Results: Following structured approaches in focus groups, adaptations were made to the Favorites (memory) and Line Length (visuospatial) subtests based on their input. Participants found the new adaptations to have good construct validity for the region.

Conclusions: The BHA subtests showed content validity for future work needed to validate the tool for detecting early cognitive changes associated with dementia and Alzheimer's disease in PHC settings. The use of culturally adapted and concise digital cognitive assessment tools relevant to healthcare professionals in Southeast Nigeria's PHCs is advocated.

目的:发展中国家的人口老龄化要求同时改善脑健康评估服务,以减轻耻辱感,促进健康老龄化,并在初级卫生保健(PHC)设施中诊断包括痴呆症在内的认知障碍。由于初级卫生保健机构缺乏与文化相适应的认知评估工具,延误了早期检测。本研究旨在为尼日利亚东南部的初级卫生保健专业人员从文化角度调整简短的数字认知评估工具:方法:我们共挑选了 30 名参与者(15 名医护人员和 15 名社区成员),以在文化上代表该社区。我们完成了焦点小组和试点测试,以评估和改进脑健康评估(BHA),这是基于平板电脑的认知评估工具(TabCAT)的子工具集,已知在其他环境中对认知障碍很敏感。我们对尼日利亚东南部阿南布拉州两家老年病诊所使用的当地语言(皮金语和伊博语)进行了脑健康评估子测试:根据焦点小组的结构化方法,我们根据他们的意见对 Favorites(记忆)和 Line Length(视觉空间)子测试进行了调整。参与者认为新的改编对该地区具有良好的建构效度:BHA分测验显示出了内容效度,未来的工作需要对该工具进行验证,以便在初级保健机构中检测与痴呆症和阿尔茨海默氏症相关的早期认知变化。我们提倡在尼日利亚东南部的初级保健中心使用经过文化调整的简明数字认知评估工具。
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引用次数: 0
Evidence for prodromal changes in neuronal excitability and neuroinflammation in the hippocampus in young alpha-synuclein (A30P) transgenic mice. 幼年α-突触核蛋白(A30P)转基因小鼠海马神经元兴奋性和神经炎症前驱变化的证据。
Pub Date : 2024-06-17 eCollection Date: 2024-01-01 DOI: 10.3389/frdem.2024.1404841
Ibtisam Al-Musawi, Bethany H Dennis, Gavin J Clowry, Fiona E N LeBeau

Introduction: Neuronal hyperexcitability and neuroinflammation are thought to occur at early stages in a range of neurodegenerative diseases. Neuroinflammation, notably activation of microglia, has been identified as a potential prodromal marker of dementia with Lewy bodies (DLB). Using a transgenic mouse model of DLB that over-expresses human mutant (A30P) alpha-synuclein (hα-syn) we have investigated whether early neuroinflammation is evident in the hippocampus in young pre-symptomatic animals.

Methods: Previous studies have shown early hyperexcitability in the hippocampal CA3 region in male A30P mice at 2-4 months of age, therefore, in the current study we have immunostained this region for markers of neuronal activity (c-Fos), reactive astrocytes (glial fibrillary acidic protein, GFAP), microglia (ionizing calcium binding adapter protein 1, Iba-1) and reactive microglia (inducible nitric oxide synthase, iNOS).

Results: We found an interesting biphasic change in the expression of c-Fos in A30P mice with high expression at 1 month, consistent with early onset of hyperexcitability, but lower expression from 2-4 months in male A30P mice compared to wild-type (WT) controls, possibly indicating chronic hyperexcitability. Neuroinflammation was indicated by significant increases in the % area of GFAP and the number of Iba-1+ cells that expressed iNOS immunoreactivity in the CA3 region in 2-4 months A30P male mice compared to WT controls. A similar increase in % area of GFAP was observed in female A30P mice, however, the Iba-1 count was not different between female WT and A30P mice. In WT mice aged 2-4 months only 4.6% of Iba-1+ cells co-expressed iNOS. In contrast, in age matched A30P mice 87% of cells co-expressed Iba-1 and iNOS. Although there was no difference in GFAP immunoreactivity at 1 month, Iba-1/iNOS co-expression was also increased in a cohort of 1 month old A30P mice.

Discussion: Abnormal hα-syn expression in A30P mice caused early changes in network excitability, as indicated by c-Fos expression, and neuroinflammation which might contribute to disease progression.

导言:神经元过度兴奋和神经炎症被认为发生在一系列神经退行性疾病的早期阶段。神经炎症,尤其是小胶质细胞的激活,已被确定为路易体痴呆(DLB)的潜在前驱标志。利用过度表达人类突变型(A30P)α-突触核蛋白(hα-syn)的DLB转基因小鼠模型,我们研究了早期神经炎症在年轻的症状前动物的海马中是否明显:先前的研究表明,雄性 A30P 小鼠在 2-4 个月大时海马 CA3 区会出现早期过度兴奋,因此,在本研究中,我们对该区域的神经元活性标记物(c-Fos)、反应性星形胶质细胞(胶质纤维酸性蛋白,GFAP)、小胶质细胞(电离钙结合适配蛋白 1,Iba-1)和反应性小胶质细胞(诱导型一氧化氮合酶,iNOS)进行了免疫染色:我们发现 A30P 小鼠中 c-Fos 的表达呈有趣的双相变化,1 个月时表达量较高,这与兴奋性过高的早期症状一致,但与野生型(WT)对照组相比,雄性 A30P 小鼠 2-4 个月时的表达量较低,这可能表明兴奋性长期过高。与 WT 对照组相比,2-4 个月的 A30P 雄性小鼠 CA3 区 GFAP 面积百分比和表达 iNOS 免疫反应的 Iba-1+ 细胞数量显著增加,这表明存在神经炎症。在雌性 A30P 小鼠中也观察到了类似的 GFAP 面积百分比的增加,但是,雌性 WT 小鼠和 A30P 小鼠的 Iba-1 数量没有差异。在 2-4 个月大的 WT 小鼠中,只有 4.6% 的 Iba-1+ 细胞同时表达 iNOS。相反,在年龄匹配的 A30P 小鼠中,87% 的细胞同时表达 Iba-1 和 iNOS。虽然 1 个月大的 A30P 小鼠的 GFAP 免疫反应没有差异,但在 1 个月大的 A30P 小鼠群中,Iba-1/iNOS 的共表达也有所增加:讨论:hα-syn在A30P小鼠中的异常表达导致了网络兴奋性的早期变化(如c-Fos表达所示)和神经炎症,这可能是疾病进展的原因之一。
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Frontiers in dementia
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