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Sleep Characteristics in Older Adults with Different Levels of Risk for Dementia: A Cross-sectional Study. 不同痴呆症风险水平的老年人的睡眠特征:一项横断面研究
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-03-03 DOI: 10.2174/1567205020666230303110244
Xiuxiu Huang, Shifang Zhang, Yuxi Fang, Xiaoyan Zhao, Ting Cao, Yongan Sun, Qiaoqin Wan

Background: Sleep problems are very prevalent in older adults, especially in those at risk for dementia. But the relationships between sleep parameters and subjective or objective cognitive decline are still inconclusive.

Aim: The study aimed to investigate the self-reported and objectively measured sleep characteristics in older adults with mild cognitive impairment (MCI) and subjective cognitive decline (SCD).

Methods: This study adopted a cross-sectional design. We included older adults with SCD or MCI. Sleep quality was measured separately by the Pittsburgh sleep quality index (PSQI) and ActiGraph. Participants with SCD were divided into low, moderate, and high levels of SCD groups. Independent samples T-tests, one-way ANOVA, or nonparametric tests were used to compare the sleep parameters across groups. Covariance analyses were also performed to control the covariates.

Results: Around half of the participants (45.9%) reported poor sleep quality (PSQI<7), and 71.3% of participants slept less than 7 hours per night, as measured by ActiGraph. Participants with MCI showed shorter time in bed (TIB) (p<0.05), a tendency of shorter total sleep time (TST) at night (p = 0.074) and for each 24-hour cycle (p = 0.069), compared to those with SCD. The high SCD group reported the highest PSQI total score and longest sleep latency than all the other three groups (p<0.05). Both the MCI and high SCD groups had shorter TIB and TST for each 24-hour cycle than the low or moderate SCD groups. Besides, participants with multiple-domain SCD reported poorer sleep quality than those with single-domain SCD (p<0.05).

Conclusion: Sleep dysregulation is prevalent in older adults with a risk for dementia. Our findings revealed that objectively measured sleep duration might be an early sign of MCI. Individuals with high levels of SCD demonstrated poorerself-perceived sleep quality and deserved more attention. Improving sleep quality might be a potential target to prevent cognitive decline for people with a risk for dementia.

背景:睡眠问题在老年人中非常普遍,尤其是在有痴呆风险的老年人中。目的:本研究旨在调查患有轻度认知障碍(MCI)和主观认知能力下降(SCD)的老年人自我报告和客观测量的睡眠特征:本研究采用横断面设计。我们纳入了患有 SCD 或 MCI 的老年人。睡眠质量分别通过匹兹堡睡眠质量指数(PSQI)和 ActiGraph 进行测量。患有 SCD 的参与者被分为低度、中度和高度 SCD 组。采用独立样本 T 检验、单因素方差分析或非参数检验来比较各组的睡眠参数。此外,还进行了协方差分析以控制协变量:约半数参与者(45.9%)表示睡眠质量差(PSQI<7),71.3%的参与者每晚睡眠时间少于7小时(由ActiGraph测量)。与 SCD 患者相比,MCI 患者的卧床时间(TIB)较短(p<0.05),夜间总睡眠时间(TST)有缩短的趋势(p = 0.074),每个 24 小时周期的总睡眠时间(TST)也有缩短的趋势(p = 0.069)。与其他三组相比,高 SCD 组的 PSQI 总分最高,睡眠潜伏期最长(p<0.05)。与低度或中度 SCD 组相比,MCI 组和高度 SCD 组每个 24 小时周期的 TIB 和 TST 都更短。此外,多领域SCD参与者的睡眠质量比单领域SCD参与者差(P<0.05):结论:睡眠失调在有痴呆风险的老年人中很普遍。我们的研究结果表明,客观测量的睡眠时间可能是 MCI 的早期征兆。SCD水平较高的人自我感觉睡眠质量较差,值得更多关注。改善睡眠质量可能是预防痴呆症高危人群认知能力下降的一个潜在目标。
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引用次数: 0
The Characteristics of Entorhinal Cortex Functional Connectivity in Alzheimer's Disease Patients with Depression. 抑郁症阿尔茨海默病患者大脑内皮层功能连接的特征
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-03-03 DOI: 10.2174/1567205020666230303093112
Haokai Zhu, Hong Zhu, Xiaozheng Liu, Fuquan Wei, Huichao Li, Zhongwei Guo

Background: Depression is one of the most common neuropsychiatric symptoms of Alzheimer's disease (AD) which decreases the life quality of both patients and caregivers. There are currently no effective drugs. It is therefore important to explore the pathogenesis of depression in AD patients.

Objective: The present study aimed to investigate the characteristics of the entorhinal cortex (EC) functional connectivity (FC) in the whole brain neural network of AD patients with depression (D-AD).

Methods: Twenty-four D-AD patients, 14 AD patients without depression (nD-AD), and 20 healthy controls underwent resting-state functional magnetic resonance imaging. We set the EC as the seed and used FC analysis. One-way analysis of variance was used to examine FC differences among the three groups.

Results: Using the left EC as the seed point, there were FC differences among the three groups in the left EC-inferior occipital gyrus. Using the right EC as the seed point, there were FC differences among the three groups in the right EC-middle frontal gyrus, -superior parietal gyrus, -superior medial frontal gyrus, and -precentral gyrus. Compared with the nD-AD group, the D-AD group had increased FC between the right EC and right postcentral gyrus.

Conclusion: Asymmetry of FC in the EC and increased FC between the EC and right postcentral gyrus may be important in the pathogenesis of depression in AD.

背景:抑郁症是阿尔茨海默病(AD)最常见的神经精神症状之一,会降低患者和护理者的生活质量。目前还没有有效的药物。因此,探索阿尔茨海默病患者抑郁症的发病机制非常重要:本研究旨在探讨抑郁症 AD 患者(D-AD)全脑神经网络中内侧皮层(EC)功能连接(FC)的特征:24名D-AD患者、14名未患抑郁症的AD患者(nD-AD)和20名健康对照者接受了静息态功能磁共振成像。我们以EC为种子,采用FC分析。我们采用单因素方差分析来研究三组患者的功能障碍差异:结果:以左侧EC为种子点,三组之间在左侧EC-枕骨下回存在FC差异。以右侧EC为种子点,三组在右侧EC-额叶中回、-顶叶上回、-额叶内上回和-中央前回存在FC差异。与 nD-AD 组相比,D-AD 组右侧 EC 和右侧中央后回之间的 FC 增加:结论:EC FC的不对称性以及EC与右侧中央后回之间FC的增加可能是AD抑郁症发病机制中的重要因素。
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引用次数: 0
Bloodborne Pancreatic Amylin, A Therapeutic Target for Alzheimer's Disease. 血源性胰淀粉样蛋白--阿尔茨海默病的治疗靶点
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-02-17 DOI: 10.2174/1567205020666230217091540
Florin Despa

Alzheimer Disease (AD) pathology has been linked to brain accumulation of β amyloid (Aβ) and neurofibrillary tau tangles. An intriguing question is whether targeting therapeutically factors independent of Aβ and tau pathologies could delay or even stop neurodegeneration. Amylin, a pancreatic hormone co-secreted with insulin, is believed to play a role in the central regulation of satiation and was shown to form pancreatic amyloid in persons with type-2 diabetes mellitus. Accumulating evidence demonstrates that amyloid-forming amylin secreted from the pancreas synergistically aggregates with vascular and parenchymal Aβ in the brain, in both sporadic and early-onset familial AD. Pancreatic expression of amyloid-forming human amylin in AD-model rats accelerates AD-like pathology, whereas genetically suppressed amylin secretion protects against AD effects. Thus, current data suggest a role of pancreatic amyloid-forming amylin in modifying AD; further research is required to test whether lowering circulating amylin levels early during AD pathogenesis may curb cognitive decline.

阿尔茨海默病(AD)的病理与大脑中β淀粉样蛋白(Aβ)和神经纤维tau缠结的积累有关。一个耐人寻味的问题是,针对独立于Aβ和tau病理学的因素进行治疗是否可以延缓甚至阻止神经退行性变。淀粉样蛋白是一种与胰岛素共同分泌的胰腺激素,被认为在饱腹感的中枢调节中发挥作用,并在2型糖尿病患者体内形成胰腺淀粉样蛋白。越来越多的证据表明,在散发性和早发性家族性注意力缺失症中,从胰腺分泌的淀粉样蛋白与大脑中的血管和实质Aβ协同聚集形成淀粉样蛋白。淀粉样蛋白形成的人淀粉样蛋白在AD模型大鼠胰腺中的表达会加速AD样病理变化,而基因抑制淀粉样蛋白的分泌则可防止AD的影响。因此,目前的数据表明,胰腺淀粉样蛋白形成的淀粉样蛋白在改变注意力缺失症方面发挥作用;还需要进一步的研究来检验在注意力缺失症发病早期降低循环中的淀粉样蛋白水平是否能抑制认知能力的下降。
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引用次数: 0
Digital Intervention For The Management Of Alzheimer's Disease. 管理阿尔茨海默病的数字化干预措施
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-02-06 DOI: 10.2174/1567205020666230206124155
Namish Manchanda, Akanksha Aggarwal, Sonal Setya, Sushama Talegaonkar

Alzheimer's disease (AD) is a progressive, multifactorial, chronic, neurodegenerative disease with high prevalence and limited therapeutic options, making it a global health crisis. Being the most common cause of dementia, AD erodes the cognitive, functional, and social abilities of the individual and causes escalating medical and psychosocial needs. As yet, this disorder has no cure and current treatment options are palliative in nature. There is an urgent need for novel therapy to address this pressing challenge. Digital therapeutics (Dtx) is one such novel therapy that is gaining popularity globally. Dtx provides evidence based therapeutic interventions driven by internet and software, employing tools such as mobile devices, computers, videogames, apps, sensors, virtual reality aiding in the prevention, management, and treatment of ailments like neurological abnormalities and chronic diseases. Dtx acts as a supportive tool for the optimization of patient care, individualized treatment and improved health outcomes. Dtx uses visual, sound and other non-invasive approaches for instance-consistent therapy, reminiscence therapy, computerised cognitive training, semantic and phonological assistance devices, wearables and computer-assisted rehabilitation environment to find applications in Alzheimer's disease for improving memory, cognition, functional abilities and managing motor symptom. A few of the Dtx-based tools employed in AD include "Memory Matters", "AlzSense", "Alzheimer Assistant", "smart robotic dog", "Immersive virtual reality (iVR)" and the most current gamma stimulation. The purpose of this review is to summarize the current trends in digital health in AD and explore the benefits, challenges, and impediments of using Dtx as an adjunctive therapy for the management of AD.

阿尔茨海默病(AD)是一种进展性、多因素、慢性、神经退行性疾病,发病率高,治疗手段有限,已成为全球性健康危机。作为痴呆症最常见的病因,阿兹海默症会侵蚀患者的认知、功能和社交能力,导致医疗和心理需求不断增加。到目前为止,这种疾病还没有治愈的方法,目前的治疗方案都是缓解性的。我们迫切需要新型疗法来应对这一紧迫挑战。数字疗法(Dtx)就是这样一种在全球范围内日益流行的新型疗法。Dtx 通过互联网和软件,利用移动设备、计算机、电子游戏、应用程序、传感器、虚拟现实等工具,提供循证治疗干预,帮助预防、管理和治疗神经异常和慢性疾病等疾病。Dtx 是优化病人护理、个性化治疗和改善健康状况的辅助工具。Dtx 采用视觉、声音和其他非侵入性方法,例如连贯疗法、回忆疗法、计算机化认知训练、语义和语音辅助设备、可穿戴设备和计算机辅助康复环境,可应用于阿尔茨海默病,以改善记忆、认知、功能能力和控制运动症状。在阿尔茨海默病中应用的基于 Dtx 的工具包括 "记忆事项"、"AlzSense"、"阿尔茨海默助手"、"智能机器狗"、"沉浸式虚拟现实(iVR)"和最新的伽马刺激。本综述旨在总结当前 AD 数字健康的发展趋势,并探讨使用 Dtx 作为辅助疗法治疗 AD 的益处、挑战和障碍。
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引用次数: 0
From Infection to Inoculation: Expanding the Microbial Hypothesis of Alzheimer's Disease. 从感染到接种:阿尔茨海默病微生物假说的扩展。
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230202155404
Jolanta Dorszewska, Mikołaj Hurła, Natalia Banaszek, Domink Kobylarek, Thomas Piekut, Wojciech Kozubski
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引用次数: 4
Amisulpride Decreases Tau Protein Hyperphosphorylation in the Brain of OXYS Rats. 氨硫pride降低OXYS大鼠脑内Tau蛋白过度磷酸化。
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230828144651
Camilla A Molobekova, Elena M Kondaurova, Tatiana V Ilchibaeva, Alexander Ya Rodnyy, Natalia A Stefanova, Nataliya G Kolosova, Vladimir S Naumenko

Aim: In this study, OXYS rats of three ages (1, 3, and 6 months), a proven model of Alzheimer's disease (AD), at various stages of disease progression were used to thoroughly study the effects of amisulpride on behavior and tau protein phosphorylation.

Background: With the growing number of patients with AD, the problem of finding a cure is very acute. Neurodegeneration in AD has various causes, one of which is hyperphosphorylation of tau protein.

Objective: This study aimed to investigate whether amisulpride would affect pathological tau phosphorylation in AD.

Methods: We assessed the influence of chronic administration of amisulpride (3 weeks, 3 mg/kg per day, intraperitoneally)-a 5-HT7 receptor inverse agonist-on behavior and tau hyperphosphorylation in OXYS rats (at ages of 1, 3, and 6 months).

Results: Chronic administration of amisulpride dramatically decreased tau phosphorylation in the frontal cortex and hippocampus of 3-month-old OXYS rats. Additionally, in 1- and 3-month-old rats' hippocampi, amisulpride diminished the mRNA level of the Cdk5 gene encoding one of the main tau kinases involved in the 5-HT7 receptor-induced effect on tau phosphorylation.

Conclusion: Thus, We found that chronic administration of amisulpride could reduce pathological tau hyperphosphorylation while reducing anxiety. We propose amisulpride to have therapeutic potential against AD and that it can be the most effective in the early stages of the disease.

目的:在本研究中,采用三龄(1、3和6个月)的OXYS大鼠(一种已证实的阿尔茨海默病(AD)模型),在疾病进展的不同阶段,深入研究氨硫pride对行为和tau蛋白磷酸化的影响。背景:随着AD患者数量的不断增加,寻找治疗方法的问题非常紧迫。阿尔茨海默病的神经退行性变有多种原因,其中之一是tau蛋白的过度磷酸化。目的:探讨氨硫pride对AD病理性tau蛋白磷酸化的影响。方法:我们评估了长期给药氨硫pride(3周,每天3mg /kg,腹腔注射)-一种5-HT7受体逆激动剂对OXYS大鼠(1、3和6个月大)行为和tau过度磷酸化的影响。结果:长期服用氨硫pride可显著降低3月龄OXYS大鼠额叶皮质和海马的tau磷酸化。此外,在1个月和3个月大鼠的海马中,氨硫pride降低了Cdk5基因的mRNA水平,Cdk5基因编码一种主要的tau激酶,参与5-HT7受体诱导的tau磷酸化作用。结论:因此,我们发现长期服用氨硫pride可以减少病理性tau过度磷酸化,同时减少焦虑。我们认为氨硫pride具有治疗AD的潜力,并且在疾病的早期阶段是最有效的。
{"title":"Amisulpride Decreases Tau Protein Hyperphosphorylation in the Brain of OXYS Rats.","authors":"Camilla A Molobekova, Elena M Kondaurova, Tatiana V Ilchibaeva, Alexander Ya Rodnyy, Natalia A Stefanova, Nataliya G Kolosova, Vladimir S Naumenko","doi":"10.2174/1567205020666230828144651","DOIUrl":"10.2174/1567205020666230828144651","url":null,"abstract":"<p><strong>Aim: </strong>In this study, OXYS rats of three ages (1, 3, and 6 months), a proven model of Alzheimer's disease (AD), at various stages of disease progression were used to thoroughly study the effects of amisulpride on behavior and tau protein phosphorylation.</p><p><strong>Background: </strong>With the growing number of patients with AD, the problem of finding a cure is very acute. Neurodegeneration in AD has various causes, one of which is hyperphosphorylation of tau protein.</p><p><strong>Objective: </strong>This study aimed to investigate whether amisulpride would affect pathological tau phosphorylation in AD.</p><p><strong>Methods: </strong>We assessed the influence of chronic administration of amisulpride (3 weeks, 3 mg/kg per day, intraperitoneally)-a 5-HT7 receptor inverse agonist-on behavior and tau hyperphosphorylation in OXYS rats (at ages of 1, 3, and 6 months).</p><p><strong>Results: </strong>Chronic administration of amisulpride dramatically decreased tau phosphorylation in the frontal cortex and hippocampus of 3-month-old OXYS rats. Additionally, in 1- and 3-month-old rats' hippocampi, amisulpride diminished the mRNA level of the Cdk5 gene encoding one of the main tau kinases involved in the 5-HT7 receptor-induced effect on tau phosphorylation.</p><p><strong>Conclusion: </strong>Thus, We found that chronic administration of amisulpride could reduce pathological tau hyperphosphorylation while reducing anxiety. We propose amisulpride to have therapeutic potential against AD and that it can be the most effective in the early stages of the disease.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"496-505"},"PeriodicalIF":2.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10485337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
BACE-1 Inhibitors Targeting Alzheimer's Disease. 靶向阿尔茨海默病的BACE-1抑制剂
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230612155953
Kadja Luana Chagas Monteiro, Marcone Gomes Dos Santos Alcântara, Nathalia Monteiro Lins Freire, Esaú Marques Brandão, Vanessa Lima do Nascimento, Líbni Maísa Dos Santos Viana, Thiago Mendonça de Aquino, Edeildo Ferreira da Silva-Júnior

The accumulation of amyloid-β (Aβ) is the main event related to Alzheimer's disease (AD) progression. Over the years, several disease-modulating approaches have been reported, but without clinical success. The amyloid cascade hypothesis evolved and proposed essential targets such as tau protein aggregation and modulation of β-secretase (β-site amyloid precursor protein cleaving enzyme 1 - BACE-1) and γ-secretase proteases. BACE-1 cuts the amyloid precursor protein (APP) to release the C99 fragment, giving rise to several Aβ peptide species during the subsequent γ-secretase cleavage. In this way, BACE-1 has emerged as a clinically validated and attractive target in medicinal chemistry, as it plays a crucial role in the rate of Aβ generation. In this review, we report the main results of candidates in clinical trials such as E2609, MK8931, and AZD-3293, in addition to highlighting the pharmacokinetic and pharmacodynamic-related effects of the inhibitors already reported. The current status of developing new peptidomimetic, non-peptidomimetic, naturally occurring, and other class inhibitors are demonstrated, considering their main limitations and lessons learned. The goal is to provide a broad and complete approach to the subject, exploring new chemical classes and perspectives.

淀粉样蛋白-β (Aβ)的积累是与阿尔茨海默病(AD)进展相关的主要事件。多年来,已经报道了几种疾病调节方法,但没有临床成功。淀粉样蛋白级联假说提出了tau蛋白聚集和β-分泌酶(β-位点淀粉样蛋白前体蛋白切割酶1 - base -1)和γ-分泌酶蛋白酶的调节等重要靶点。BACE-1切割淀粉样蛋白前体蛋白(APP)以释放C99片段,在随后的γ分泌酶切割过程中产生几种Aβ肽。通过这种方式,BACE-1已成为药物化学中临床验证和有吸引力的靶标,因为它在a β生成速率中起着至关重要的作用。在这篇综述中,我们报告了候选药物在临床试验中的主要结果,如E2609、MK8931和AZD-3293,以及已经报道的抑制剂的药代动力学和药效学相关作用。考虑到它们的主要局限性和经验教训,展示了开发新的拟肽、非拟肽、自然发生和其他类抑制剂的现状。目标是提供一个广泛和完整的方法来研究这个问题,探索新的化学类别和观点。
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引用次数: 1
Impact of COVID-19 Mandatory Lockdown Measures on Cognitive and Neuropsychiatric Symptoms in Persons with Alzheimer's Disease in Lima, Peru. 秘鲁利马COVID-19强制封锁措施对阿尔茨海默病患者认知和神经精神症状的影响
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230417103216
Nilton Custodio, Marco Malaga, Rosa Montesinos, Diego Chambergo, Fiorella Baca, Sheila Castro, Juan Carlos Carbajal, Eder Herrera, David Lira, Monica Diaz, Serggio Lanata

Background: Neuropsychiatric symptoms (NPS) in patients with Alzheimer's disease (AD) worsened during the COVID-19 lockdowns, but their progression thereafter is unknown. We present the first longitudinal study tracking them before, during, and after restrictions.

Objectives: To describe the effect of the COVID-19 mandatory lockdowns on Cognitive and Neuropsychiatric symptoms in patients with Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD).

Methods: Cohort of 48 patients with amnestic MCI and 38 with AD in Lima, Peru. They received three rounds of cognitive (RUDAS, CDR, M@T), behavioral (NPI), and functional (ADCS-ADL) assessments. We assessed the change in score means across the time points and for each domain of NPS and tracked the changes in individual patients.

Results: RUDAS declined 0.9 (SD 1.0) from baseline to lockdown and 0.7 (SD 1.0) after restrictions. M@T declined 1.0 (SD 1.5) from baseline to lockdown and 1.4 (SD 2.0) after restrictions. CDR worsened in 72 patients (83.72%) from baseline to post-lockdown. NPI worsened by 10 (SD 8.3) from baseline to lockdown but improved by 4.8 (SD 6.4) after restrictions. Proportionally, 81.3% of all patients had worsened NPS during the lockdowns, but only 10.7% saw an increase thereafter. Improvement was statistically significant for specific NPS domains except hallucinations, delusions, and appetite changes. Anxiety, irritability, apathy, and disinhibition returned to baseline levels.

Conclusion: Following confinement, cognition continued to decline, but NPS demonstrated either stability or improvement. This highlights the role modifiable risk factors may have on the progression of NPS.

背景:阿尔茨海默病(AD)患者的神经精神症状(NPS)在COVID-19封锁期间恶化,但此后的进展尚不清楚。我们提出了第一个纵向研究,在限制之前,期间和之后跟踪他们。目的:探讨COVID-19强制封锁对轻度认知障碍(MCI)和阿尔茨海默病(AD)患者认知和神经精神症状的影响。方法:对秘鲁利马48例遗忘型轻度认知损伤患者和38例AD患者进行队列研究。他们接受了三轮认知(RUDAS, CDR, M@T),行为(NPI)和功能(ADCS-ADL)评估。我们评估了不同时间点和每个NPS域的评分平均值的变化,并跟踪了个体患者的变化。结果:从基线到封锁,RUDAS下降了0.9 (SD 1.0),限制后下降了0.7 (SD 1.0)。M@T从基线到封锁下降了1.0 (SD 1.5),限制后下降了1.4 (SD 2.0)。从基线到封城后,72例(83.72%)患者CDR恶化。从基线到封锁,NPI恶化了10 (SD 8.3),但在限制后改善了4.8 (SD 6.4)。按比例计算,在封锁期间,81.3%的患者新冠肺炎病情恶化,但此后只有10.7%的患者新冠肺炎发病率上升。除幻觉、妄想和食欲改变外,特定NPS领域的改善在统计学上是显著的。焦虑、易怒、冷漠和去抑制恢复到基线水平。结论:禁闭后认知能力持续下降,但NPS表现出稳定或改善。这突出了可改变的风险因素可能对NPS进展的作用。
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引用次数: 0
Landmark Model-based Individual Dynamic Prediction of Conversion from Mild Cognitive Impairment to Alzheimer's Disease using Cognitive Screening. 基于里程碑模型的认知筛查从轻度认知障碍到阿尔茨海默病转化的个体动态预测
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230526101524
Jing Cui, Durong Chen, Jiajia Zhang, Yao Qin, Wenlin Bai, Yifei Ma, Rong Zhang, Hongmei Yu

Background: Identifying individuals with mild cognitive impairment (MCI) who are at increased risk of Alzheimer's Disease (AD) in cognitive screening is important for early diagnosis and prevention of AD.

Objective: This study aimed at proposing a screening strategy based on landmark models to provide dynamic predictive probabilities of MCI-to-AD conversion according to longitudinal neurocognitive tests.

Methods: Participants were 312 individuals who had MCI at baseline. The longitudinal neurocognitive tests were the Mini-Mental State Examination, Alzheimer Disease Assessment Scale-Cognitive 13 items, Rey Auditory Verbal Learning Test immediate, learning, and forgetting, and Functional Assessment Questionnaire. We constructed three types of landmark models and selected the optimal landmark model to dynamically predict 2-year probabilities of conversion. The dataset was randomly divided into training set and validation set at a ratio of 7:3.

Results: The FAQ, RAVLT-immediate, and RAVLT-forgetting were significant longitudinal neurocognitive tests for MCI-to-AD conversion in all three landmark models. We considered Model 3 as the final landmark model (C-index = 0.894, Brier score = 0.040) and selected Model 3c (FAQ and RAVLT-forgetting as neurocognitive tests) as the optimal landmark model (C-index = 0.898, Brier score = 0.027).

Conclusion: Our study shows that the optimal landmark model with a combination FAQ and RAVLTforgetting is feasible to identify the risk of MCI-to-AD conversion, which can be implemented in cognitive screening.

背景:在认知筛查中识别阿尔茨海默病(AD)风险增加的轻度认知障碍(MCI)个体对AD的早期诊断和预防具有重要意义。目的:本研究旨在提出一种基于里程碑模型的筛查策略,根据纵向神经认知测试提供mci到ad转换的动态预测概率。方法:参与者是312名基线时患有轻度认知障碍的个体。纵向神经认知测试包括简易精神状态测试、阿尔茨海默病评估量表-认知13项、Rey听觉语言学习测试即时、学习和遗忘以及功能评估问卷。我们构建了三种类型的地标模型,并选择了最优的地标模型来动态预测2年的转换概率。数据集按7:3的比例随机分为训练集和验证集。结果:在所有三个里程碑模型中,FAQ、RAVLT-immediate和ravlt -forget是显著的mci - ad转换纵向神经认知测试。我们将模型3作为最终的里程碑模型(C-index = 0.894, Brier评分= 0.040),选择模型3c (FAQ和RAVLT-forgetting作为神经认知测试)作为最优的里程碑模型(C-index = 0.898, Brier评分= 0.027)。结论:我们的研究表明,结合FAQ和RAVLTforgetting的最优地标模型可用于识别mci - ad转换风险,可用于认知筛查。
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引用次数: 0
Glial-derived Neuroinflammation induced with Amyloid-beta-peptide Plus Fibrinogen Injection in Rat Hippocampus. 淀粉样肽加纤维蛋白原注射诱导大鼠海马胶质源性神经炎症。
IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-01-01 DOI: 10.2174/1567205020666230912113501
James G McLarnon

Introduction: The present study has examined microglial and astrocyte activation in association with neuronal degeneration in an animal model using an injection of amyloid-beta peptide Aβ1-42 (Aβ42) plus fibrinogen into rat hippocampus.

Methods: The combination of stimuli is suggested as a novel and potent perturbation to induce gliosis and the production of glial-derived neurotoxic factors in an animal model exhibiting a leaky BBB (blood-brain barrier). Specifically, Aβ42 + fibrinogen stimulation elevated levels of COX-2 (cyclooxygenase-2) and iNOS (inducible nitric oxide synthase) with a considerable extent of neuronal loss associated with microglia and astrocyte activation.

Results: Treatment of injected rats with the broad spectrum anti-inflammatory agent, minocycline or the iNOS inhibitor, 1400 W inhibited gliosis, reduced levels of COX-2 and iNOS, and demonstrated efficacy for neuroprotection.

Conclusion: The findings suggest the utility of combining amyloid beta peptide plus fibrinogen as a potent and understudied neuroinflammatory stimulus for the induction of glial-derived neurotoxic factors in BBB-compromised AD brain.

本研究通过向大鼠海马注射淀粉样β肽Aβ1-42 (Aβ42)和纤维蛋白原,研究了小胶质细胞和星形胶质细胞的活化与神经元变性的关系。方法:在血脑屏障有渗漏的动物模型中,联合刺激被认为是一种新的和有效的扰动,可以诱导胶质细胞形成和胶质源性神经毒性因子的产生。具体来说,a - β42 +纤维蛋白原刺激提高了COX-2(环氧化酶-2)和iNOS(诱导型一氧化氮合酶)的水平,并在相当程度上导致与小胶质细胞和星形胶质细胞活化相关的神经元损失。结果:给大鼠注射广谱抗炎药米诺环素或iNOS抑制剂1400w,可抑制胶质细胞增生,降低COX-2和iNOS水平,显示出神经保护作用。结论:研究结果表明,淀粉样肽和纤维蛋白原结合作为一种有效的神经炎症刺激,可在血脑屏障受损的AD脑中诱导胶质源性神经毒性因子。
{"title":"Glial-derived Neuroinflammation induced with Amyloid-beta-peptide Plus Fibrinogen Injection in Rat Hippocampus.","authors":"James G McLarnon","doi":"10.2174/1567205020666230912113501","DOIUrl":"10.2174/1567205020666230912113501","url":null,"abstract":"<p><strong>Introduction: </strong>The present study has examined microglial and astrocyte activation in association with neuronal degeneration in an animal model using an injection of amyloid-beta peptide Aβ<sub>1-42</sub> (Aβ<sub>42</sub>) plus fibrinogen into rat hippocampus.</p><p><strong>Methods: </strong>The combination of stimuli is suggested as a novel and potent perturbation to induce gliosis and the production of glial-derived neurotoxic factors in an animal model exhibiting a leaky BBB (blood-brain barrier). Specifically, Aβ<sub>42</sub> + fibrinogen stimulation elevated levels of COX-2 (cyclooxygenase-2) and iNOS (inducible nitric oxide synthase) with a considerable extent of neuronal loss associated with microglia and astrocyte activation.</p><p><strong>Results: </strong>Treatment of injected rats with the broad spectrum anti-inflammatory agent, minocycline or the iNOS inhibitor, 1400 W inhibited gliosis, reduced levels of COX-2 and iNOS, and demonstrated efficacy for neuroprotection.</p><p><strong>Conclusion: </strong>The findings suggest the utility of combining amyloid beta peptide plus fibrinogen as a potent and understudied neuroinflammatory stimulus for the induction of glial-derived neurotoxic factors in BBB-compromised AD brain.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"515-522"},"PeriodicalIF":2.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10227399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Current Alzheimer research
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