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Association between selective serotonin reuptake inhibitors and mortality following COVID-19 among patients with Alzheimer's disease. 选择性血清素再摄取抑制剂与阿尔茨海默病患者服用 COVID-19 后的死亡率之间的关系。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-01 Epub Date: 2024-10-15 DOI: 10.1177/13872877241283820
Zhenxiang Gao, Ian Dorney, Pamela B Davis, David C Kaelber, Rong Xu

Background: Recent research suggests that selective serotonin reuptake inhibitors (SSRIs) may reduce mortality in COVID-19 patients; however, research into their benefits for elderly Alzheimer's disease (AD) patients remains limited.

Objective: To investigate the relationship between SSRIs therapy and the mortality risk after COVID-19 infection in elderly patients with and without AD.

Methods: This retrospective cohort study leveraged a large database containing over 100 million electronic health records in the US from the TriNetX platform to compare the hazard rates of mortality after COVID-19 infection in elderly AD patients prescribed SSRIs versus propensity-score matched individuals prescribed other antidepressants. This study was also conducted in separate cohorts of patients without AD to compare the findings.

Results: When compared with non-SSRI antidepressants, SSRIs were associated with lower risk for mortality after COVID-19 infection in elderly patients without AD over early, middle, and later stages of the pandemic with HRs of 0.84 (95% CI: 0.75-0.93), 0.86 (95% CI: 0.79-0.93), and 0.77 (95% CI: 0.71-0.33), respectively. When comparing SSRIs with non-SSRI antidepressants for mortality risk following COVID-19 among patients with AD, HRs of 0.95 (95% CI: 0.71-1.27), 0.80 (95% CI: 0.61-1.06), and 0.99 (95% CI: 0.75-1.32), were found respectively.

Conclusions: Our findings suggest that the use of SSRIs is significantly associated with reduced mortality risk following COVID-19 in elderly patients without AD compared to other antidepressants. While a lower mortality risk was also observed among AD patients, the association was not statistically significant.

背景:最近的研究表明,选择性5-羟色胺再摄取抑制剂(SSRIs)可降低COVID-19患者的死亡率;然而,有关其对老年阿尔茨海默病(AD)患者益处的研究仍然有限:目的:探讨SSRIs疗法与患有或不患有AD的老年患者感染COVID-19后的死亡风险之间的关系:这项回顾性队列研究利用了美国 TriNetX 平台包含 1 亿多份电子健康记录的大型数据库,比较了开具 SSRIs 的老年 AD 患者与开具其他抗抑郁药的倾向分数匹配者感染 COVID-19 后的死亡率。这项研究还在无AD患者的单独组群中进行,以比较研究结果:与非SSRI抗抑郁药相比,在大流行的早期、中期和后期,SSRI与无AD的老年患者感染COVID-19后较低的死亡风险相关,HR值分别为0.84(95% CI:0.75-0.93)、0.86(95% CI:0.79-0.93)和0.77(95% CI:0.71-0.33)。当比较SSRI与非SSRI抗抑郁药在AD患者COVID-19后的死亡风险时,发现HR值分别为0.95(95% CI:0.71-1.27)、0.80(95% CI:0.61-1.06)和0.99(95% CI:0.75-1.32):我们的研究结果表明,与其他抗抑郁药物相比,使用 SSRIs 可显著降低无 AD 老年患者 COVID-19 后的死亡风险。虽然在注意力缺失症患者中也观察到了较低的死亡风险,但这种关联在统计学上并不显著。
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引用次数: 0
Perceptions of key informant neurologists before implementing anti-amyloid drugs in the Spanish departments of neurology. 西班牙神经内科在使用抗淀粉样蛋白药物前主要信息提供者神经内科医生的看法。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-01 DOI: 10.1177/13872877241284312
Jordi A Matias-Guiu, José Álvarez-Sabín, Enrique Botia, Ignacio Casado-Naranjo, Mar Castellanos, Ana Frank, Cristina Íñiguez, María Dolores Jiménez-Hernández, Félix Javier Jiménez-Jiménez, José-Miguel Láinez, Ester Moral, David A Pérez-Martínez, Alfredo Rodríguez-Antigüedad, Nuria Ruiz-Lavilla, Tomás Segura, Pedro J Serrano-Castro, Jorge Matias-Guiu

Background: A deep knowledge of the healthcare system and the organization of neurology departments is important for planning and optimizing changes to facilitate the successful implementation of anti-amyloid antibodies treatments.

Objective: We aimed to assess the necessary changes prior to introducing these therapies in our setting.

Methods: We conducted a key informant survey among heads of departments of neurology from 16 hospitals in Spain. The questionnaire comprised questions about changes in the organization and functioning of the departments of neurology with the introduction of anti-amyloid drugs, changes in diagnosis and patient care, use of diagnostic techniques, patients, families and public information, resources allocation, and research.

Results: Sixteen key informants completed the survey. They strongly agreed that the introduction of anti-amyloid drugs will impact the functioning of neurology services, especially in hospitals with dementia units. Consensus was reached regarding referring all Alzheimer's disease patients eligible for therapy to dementia units. There was also agreement on the need to expand the neurology services, day hospital units, extend visit durations, and hire more professionals, especially neurologists, neuropsychologists, and nuclear medicine physicians. Furthermore, consensus was achieved on increasing the use of MRI, amyloid PET, cerebrospinal fluid biomarkers, APOE genotyping, and the necessity of advancing blood biomarkers and tau tracers.

Conclusions: Our study highlights the need for extensive changes within Spanish neurological departments to effectively integrate anti-amyloid antibodies. Implementing these changes is essential for the timely and equitable adoption of novel therapies.

背景:对医疗系统和神经内科组织的深入了解对于规划和优化改革以促进抗淀粉样蛋白抗体治疗的成功实施非常重要:我们旨在评估在我们的环境中引入这些疗法之前所需的变革:我们对西班牙 16 家医院的神经内科主任进行了关键信息调查。问卷内容包括:随着抗淀粉样蛋白药物的引入,神经内科的组织和职能发生了哪些变化;诊断和患者护理发生了哪些变化;诊断技术的使用情况;患者、家属和公众信息;资源分配和研究情况:16 位主要信息提供者完成了调查。他们强烈认为,抗淀粉样蛋白药物的引入将影响神经内科服务的运作,尤其是在设有痴呆症科室的医院。他们就将所有符合治疗条件的阿尔茨海默病患者转诊至痴呆症科室达成了共识。会议还就扩大神经病学服务、日间医院病房、延长就诊时间以及聘用更多专业人员(尤其是神经病学家、神经心理学家和核医学医生)的必要性达成了共识。此外,我们还就更多地使用核磁共振成像、淀粉样蛋白 PET、脑脊液生物标记物、APOE 基因分型以及改进血液生物标记物和 tau 示踪剂的必要性达成了共识:我们的研究强调,西班牙神经科需要进行广泛改革,以有效整合抗淀粉样蛋白抗体。实施这些变革对于及时、公平地采用新型疗法至关重要。
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引用次数: 0
Social isolation and social cognition: A cross-sectional analysis. 社会隔离与社会认知:横断面分析
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-01 Epub Date: 2024-10-17 DOI: 10.1177/13872877241284222
Jessica Grothe, Alexander Pabst, Susanne Röhr, Steffi G Riedel-Heller, Melanie Luppa

Background: The impact of social isolation on social cognition is not entirely clear.

Objective: The aim of the study is to investigate the association between social isolation and social cognition.

Methods: In a population-based sample of 83 individuals aged 50+ years without dementia, we assessed the relationship between social isolation (measured by the Lubben Social Network Scale - LSNS-6) and performance on emotional recognition (measured by the Emotion Recognition Task (ERT)) and on Theory of Mind (ToM) abilities (measured by the Reading the Mind in the Eyes Test (RMET)), two core aspects of social cognition.

Results: No significant association was found between social isolation and ToM abilities for both the unadjusted and adjusted models. Similarly, no significant association was observed between social isolation and emotion recognition.

Conclusions: Further research is needed to understand the complex correlation between social relationships and cognitive health, particularly in different cognitive domains, adopting a life course perspective.

背景:社会隔离对社会认知的影响尚不完全清楚:社会隔离对社会认知的影响尚不完全清楚:本研究旨在调查社会隔离与社会认知之间的关系:方法:在83名50岁以上无痴呆症的人群样本中,我们评估了社会隔离(通过卢本社会网络量表--LSNS-6测量)与情绪识别(通过情绪识别任务(ERT)测量)和心智理论(ToM)能力(通过读心测试(RMET)测量)之间的关系,这是社会认知的两个核心方面:结果:在未调整模型和调整模型中,均未发现社会隔离与心智理论能力之间存在明显联系。同样,社会隔离与情绪识别之间也没有发现明显的联系:需要从生命历程的角度进一步研究社会关系与认知健康之间复杂的相关性,特别是在不同的认知领域。
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引用次数: 0
The safety and effectiveness of 40 Hz γ-tACS in Alzheimer's disease: A meta-analysis. 40 Hz γ-tACS 对阿尔茨海默病的安全性和有效性:荟萃分析
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-01 Epub Date: 2024-10-29 DOI: 10.1177/13872877241289397
Xinyang Zhang, Renhua Lv, Yanqiu Sun, Timon Cheng-Yi Liu

Background: The efficacy and safety of 40 Hz gamma transcranial alternating current stimulation (γ-tACS) in Alzheimer's disease (AD) are still uncertain.

Objective: This meta-analysis was conducted to investigate the therapeutic potential and safety of 40 Hz γ-tACS for AD.

Methods: The meta-analysis was conducted by systematically searching four databases from their start to 28 December 2023. Subgroup analyses were performed to identify the intervention effects of γ-tACS.

Results: Of the 7 included studies, γ-tACS has a notable impact on improving overall cognition [standardized mean difference (SMD): 0.49, 95% CI: 0.09 to 0.89], memory (SMD: 0.79, 95% CI: 0.18 to 1.41), and cholinergic transmission (weighted mean difference: -0.40, 95% CI: -0.43 to -0.37). Furthermore, subgroup analysis revealed that γ-tACS treatment had a substantial impact on enhancing memory targeting the left angular gyrus in both home (SMD: 3.12, 95% CI: 1.54 to 4.70) and non-home settings (SMD: 0.53, 95% CI: 0.24 to 0.82). However, γ-tACS had a positive effect on overall cognition in non-home settings (SMD: 0.55, 95% CI 0.11 to 0.98), but not in home settings (SMD: 0.22, 95% CI -0.76 to 1.20). Additionally, targeting temporo-frontal or bitemporal γ-tACS treatment resulted in improvement in overall cognition (SMD: 0.61, 95% CI: 0.06 to 1.16), but not targeting the left angular gyrus (SMD: 0.22, 95% CI: -0.76 to 1.20).

Conclusions: γ-tACS could be beneficial in enhancing cognition, memory and restoring cholinergic dysfunction in AD. The different selection of stimulation sites plays distinct roles. Meanwhile, AD patients are recommended to receive γ-tACS treatment at home.

背景:40赫兹γ经颅交变电流刺激(γ-tACS)对阿尔茨海默病(AD)的疗效和安全性仍不确定:本荟萃分析旨在研究 40 赫兹γ-tACS 对阿尔茨海默病(AD)的治疗潜力和安全性:方法:荟萃分析通过系统检索四个数据库(从开始到 2023 年 12 月 28 日)进行。为了确定γ-tACS的干预效果,进行了分组分析:在纳入的 7 项研究中,γ-tACS 对改善整体认知[标准化平均差(SMD):0.49,95% CI:0.09 至 0.89]、记忆(SMD:0.79,95% CI:0.18 至 1.41)和胆碱能传递(加权平均差:-0.40,95% CI:-0.43 至 -0.37)有显著影响。此外,亚组分析表明,γ-tACS 治疗对增强家庭(SMD:3.12,95% CI:1.54 至 4.70)和非家庭环境(SMD:0.53,95% CI:0.24 至 0.82)中以左侧角回为目标的记忆有很大影响。然而,γ-tACS 对非居家环境中的总体认知能力有积极影响(SMD:0.55,95% CI 0.11 至 0.98),但对居家环境中的总体认知能力没有积极影响(SMD:0.22,95% CI -0.76 至 1.20)。此外,针对颞额叶或颞位的γ-tACS治疗可改善整体认知能力(SMD:0.61,95% CI:0.06至1.16),但针对左侧角回的治疗效果不佳(SMD:0.22,95% CI:-0.76至1.20)。结论:γ-tACS 对增强 AD 患者的认知、记忆和恢复胆碱能功能障碍有益,刺激部位的不同选择发挥着不同的作用。同时,建议 AD 患者在家中接受 γ-tACS 治疗。
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引用次数: 0
Amyloid-β positivity is less prevalent in cognitively unimpaired KLOTHO KL-VS heterozygotes. 在认知功能未受损的 KLOTHO KL-VS 杂合子中,淀粉样蛋白-β阳性率较低。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-01 Epub Date: 2024-11-11 DOI: 10.1177/13872877241289785
Noah Cook, Ira Driscoll, Julian M Gaitán, Matthew Glittenberg, Tobey J Betthauser, Cynthia M Carlsson, Sterling C Johnson, Sanjay Asthana, Henrik Zetterberg, Kaj Blennow, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Dena B Dubal, Ozioma C Okonkwo

Background: Klotho, encoded by the KLOTHO gene, is an anti-aging and neuroprotective protein. KLOTHO KL-VS heterozygosity (KL-VSHET) is hypothesized to be protective against the accumulation of Alzheimer's disease (AD) neuropathological hallmarks (amyloid-β (Aβ) and tau).

Objective: We examine whether being positive for Aβ (A+) or tau (T+), or A/T joint status [positive for Aβ (A + T-), tau (A-T+), both (A + T+) or neither (A-T-)] vary by KL-VS and whether serum klotho protein levels vary based on A+, T+, or A/T status in a cohort enriched for AD risk.

Methods: The sample consisted of 704 cognitively unimpaired, late middle-aged, and older adults; MeanAge(SD) = 64.9(8.3). Serum klotho was available for a sub-sample of 396 participants; MeanAge(SD) = 66.8(7.4). Covariate-adjusted logistic regression examined whether A + or T+, and multinomial regression examined whether A/T status, vary by KL-VS genotype. Covariate-adjusted linear regression examined whether serum klotho levels differ based on A+, T+, or A/T status.

Results: A+ prevalence was lower in KL-VSHET (p = 0.05), with no differences in T + prevalence (p = 0.52). KL-VSHET also had marginally lower odds of being A + T- (p = 0.07). Serum klotho levels did not differ based on A+, T+, or A/T status (all ps ≥ 0.40).

Conclusions: KL-VSHET is associated with lower odds of being positive for Aβ, regardless of whether one is also positive for tau. Conversely, the likelihood of being tau positive did not differ based on KL-VS genotype. Our findings add to the growing KLOTHO literature and suggests the need for further research focused on understanding the mechanisms underlying KL-VS-related putative resilience to AD.

背景由 KLOTHO 基因编码的 Klotho 是一种抗衰老和神经保护蛋白。KLOTHO KL-VS杂合度(KL-VSHET)被认为对阿尔茨海默病(AD)神经病理学标志物(淀粉样蛋白-β(Aβ)和tau)的积累具有保护作用:我们研究了Aβ(A+)或tau(T+)阳性或A/T联合状态[Aβ阳性(A+T-)、tau阳性(A-T+)、两者均阳性(A+T+)或两者均不阳性(A-T-)]是否因KL-VS而异,以及在富含AD风险的队列中,血清klotho蛋白水平是否因A+、T+或A/T状态而异:样本包括 704 名认知能力未受损的中老年人;平均年龄(标清)= 64.9(8.3)岁。396名参与者的血清中含有克罗托;平均年龄(标清)=66.8(7.4)岁。协变量调整的逻辑回归检验了A+或T+,多项式回归检验了A/T状态是否因KL-VS基因型而异。协变量调整的线性回归检验了血清 klotho 水平是否因 A+、T+ 或 A/T 状态而不同:结果:KL-VSHET 的 A+ 患病率较低(p = 0.05),T+ 患病率没有差异(p = 0.52)。KL-VSHET 中 A + T- 的几率也略低(p = 0.07)。血清 klotho 水平在 A+、T+ 或 A/T 状态下没有差异(所有 ps 均≥ 0.40):结论:KL-VSHET 与较低的 Aβ 阳性几率相关,无论是否同时为 tau 阳性。相反,tau 阳性的几率并不因 KL-VS 基因型的不同而不同。我们的研究结果为日益增多的 KLOTHO 文献增添了新的内容,并表明有必要开展进一步的研究,重点了解与 KL-VS 相关的假定抗病能力的内在机制。
{"title":"Amyloid-β positivity is less prevalent in cognitively unimpaired <i>KLOTHO</i> KL-VS heterozygotes.","authors":"Noah Cook, Ira Driscoll, Julian M Gaitán, Matthew Glittenberg, Tobey J Betthauser, Cynthia M Carlsson, Sterling C Johnson, Sanjay Asthana, Henrik Zetterberg, Kaj Blennow, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Dena B Dubal, Ozioma C Okonkwo","doi":"10.1177/13872877241289785","DOIUrl":"10.1177/13872877241289785","url":null,"abstract":"<p><strong>Background: </strong>Klotho, encoded by the <i>KLOTHO</i> gene, is an anti-aging and neuroprotective protein. <i>KLOTHO</i> KL-VS heterozygosity (KL-VS<sub>HET</sub>) is hypothesized to be protective against the accumulation of Alzheimer's disease (AD) neuropathological hallmarks (amyloid-β (Aβ) and tau).</p><p><strong>Objective: </strong>We examine whether being positive for Aβ (A+) or tau (T+), or A/T joint status [positive for Aβ (A + T-), tau (A-T+), both (A + T+) or neither (A-T-)] vary by KL-VS and whether serum klotho protein levels vary based on A+, T+, or A/T status in a cohort enriched for AD risk.</p><p><strong>Methods: </strong>The sample consisted of 704 cognitively unimpaired, late middle-aged, and older adults; Mean<sub>Age</sub>(SD) = 64.9(8.3). Serum klotho was available for a sub-sample of 396 participants; Mean<sub>Age</sub>(SD) = 66.8(7.4). Covariate-adjusted logistic regression examined whether A + or T+, and multinomial regression examined whether A/T status, vary by KL-VS genotype. Covariate-adjusted linear regression examined whether serum klotho levels differ based on A+, T+, or A/T status.</p><p><strong>Results: </strong>A+ prevalence was lower in KL-VS<sub>HET</sub> (<i>p </i>= 0.05), with no differences in T + prevalence (<i>p </i>= 0.52). KL-VS<sub>HET</sub> also had marginally lower odds of being A + T- (<i>p </i>= 0.07). Serum klotho levels did not differ based on A+, T+, or A/T status (all <i>ps </i>≥ 0.40).</p><p><strong>Conclusions: </strong>KL-VS<sub>HET</sub> is associated with lower odds of being positive for Aβ, regardless of whether one is also positive for tau. Conversely, the likelihood of being tau positive did not differ based on KL-VS genotype. Our findings add to the growing <i>KLOTHO</i> literature and suggests the need for further research focused on understanding the mechanisms underlying KL-VS-related putative resilience to AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"480-490"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Comparative accuracy of Mini-Linguistic State Examination, Addenbrooke's Cognitive Examination, and Depistage Cognitif de Quebec for the diagnosis of primary progressive aphasia. 比较迷你语言状态检查、Addenbrooke 认知检查和 Depistage Cognitif de Quebec 对诊断原发性进行性失语症的准确性。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-01 Epub Date: 2024-10-17 DOI: 10.1177/13872877241284199
Lucía Fernández-Romero, Florentina Morello-García, Robert Laforce, Cristina Delgado-Alonso, Alfonso Delgado-Álvarez, María José Gil-Moreno, Monica Lavoie, Jorge Matias-Guiu, Fernando Cuetos, Jordi A Matias-Guiu

Background: Clinical diagnosis in primary progressive aphasia (PPA) is challenging. Recently, emphasis has been placed on the importance of screening evaluation. Three different screening tests that use different strategies based on the assessment of language (Mini-Linguistic State Examination, MLSE) or different cognitive domains (Addenbrooke's Cognitive Examination, ACE-III and Dépistage Cognitif de Québec, DCQ) have been proposed and independently validated. These tests aim to detect PPA and classify into the three main variants (non-fluent (nfvPPA), semantic (svPPA) and logopenic (lvPPA)).

Objective: This study aims to evaluate and compare the diagnostic capacity of these three instruments in PPA.

Methods: A cross-sectional study including 43 patients with PPA (nfvPPA (n = 19), svPPA (n = 8), and lvPPA (n = 16)) and 21 cognitively unimpaired controls was conducted. Clinical diagnoses were established based on an extensive multidisciplinary assessment including neuropsychological assessment, fluorodeoxyglucose-positron emission tomography, MRI, and cerebrospinal fluid biomarkers. Both PPA patients and controls completed the three tests (MLSE, ACE-III, and DCQ).

Results: Internal consistency was excellent for the three tests. The area under the curve for the diagnosis of PPA was 0.950 for MLSE, 0.953 for ACE-III, and 0.933 for DCQ. Correlations between the three tests were high. The MLSE, ACE-III, and DCQ tests obtained adequate levels of discrimination between the variants of PPA, with accuracies between 76-79%.

Conclusions: This study confirms the validity of ACE-III, MLSE, and DCQ for the diagnosis of PPA and its variants. This suggests that detailed assessment of linguistic characteristics (MLSE) and non-linguistic features (DCQ, ACE-III) are relevant for the diagnosis and classification of PPA.

背景:原发性进行性失语症(PPA)的临床诊断具有挑战性。最近,人们开始强调筛查评估的重要性。目前已提出三种不同的筛查测试,这些测试采用不同的策略,分别基于语言评估(迷你语言状态检查,MLSE)或不同的认知领域(Addenbrooke 认知检查,ACE-III 和 Dépistage Cognitif de Québec, DCQ),并经过独立验证。这些测试旨在检测 PPA,并将其分为三种主要变体(非流利型(nfvPPA)、语义型(svPPA)和对数开放型(lvPPA)):本研究旨在评估和比较这三种工具对 PPA 的诊断能力:这项横断面研究包括 43 名 PPA 患者(nfvPPA(19 人)、svPPA(8 人)和 lvPPA(16 人))和 21 名认知功能未受损的对照组。临床诊断基于广泛的多学科评估,包括神经心理学评估、氟脱氧葡萄糖正电子发射断层扫描、核磁共振成像和脑脊液生物标志物。PPA 患者和对照组均完成了三项测试(MLSE、ACE-III 和 DCQ):结果:三项测试的内部一致性非常好。MLSE 的 PPA 诊断曲线下面积为 0.950,ACE-III 为 0.953,DCQ 为 0.933。三项测试之间的相关性很高。MLSE、ACE-III和DCQ测试对PPA变异体的鉴别能力足够高,准确率在76%-79%之间:本研究证实了 ACE-III、MLSE 和 DCQ 在诊断 PPA 及其变体方面的有效性。这表明,对语言特点(MLSE)和非语言特点(DCQ、ACE-III)的详细评估与 PPA 的诊断和分类相关。
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引用次数: 0
Discovery of novel metabolic biomarkers in blood serum for diagnosis of Alzheimer's disease. 发现用于诊断阿尔茨海默病的新型血清代谢生物标记物。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-01 Epub Date: 2024-10-25 DOI: 10.3233/JAD-240280
Yingxin Zhao, Alejandro Villasante-Tezanos, Ernesto G Miranda-Morales, Miguel A Pappolla, Xiang Fang

Background: Blood metabolites have emerged as promising candidates in the search for biomarkers for Alzheimer's disease (AD), as evidence shows that various metabolic derangements contribute to neurodegeneration in AD.

Objective: We aim to identify metabolic biomarkers for AD diagnosis.

Methods: We conducted an in-depth analysis of the serum metabolome of AD patients and age, sex-matched cognitively unimpaired older adults using ultra-high-performance liquid chromatography-high resolution mass spectrometry. The biomarkers associated with AD were identified using machine learning algorithms.

Results: Using the discovery dataset and support vector machine (SVM) algorithm, we identified a panel of 14 metabolites predicting AD with a 1.00 area under the curve (AUC) of receiver operating characteristic (ROC). The SVM model was tested against the verification dataset using an independent cohort and retained high predictive accuracy with a 0.97 AUC. Using the random forest (RF) algorithm, we identified a panel of 13 metabolites that predicted AD with a 0.96 AUC when tested against the verification dataset.

Conclusions: These findings pave the way for an efficient, blood-based diagnostic test for AD, holding promise for clinical screenings and diagnostic procedures.

背景:在寻找阿尔茨海默病(AD)生物标志物的过程中,血液代谢物已成为很有希望的候选物,因为有证据表明,各种代谢失调导致了AD的神经变性:我们的目的是找出诊断阿尔茨海默病的代谢生物标志物:我们采用超高效液相色谱-高分辨质谱法对AD患者和年龄、性别匹配的认知功能未受损的老年人的血清代谢组进行了深入分析。利用机器学习算法确定了与AD相关的生物标志物:利用发现数据集和支持向量机(SVM)算法,我们确定了一组 14 种代谢物,其曲线下面积(AUC)为 1.00 的接收器操作特征(ROC),可预测 AD。我们使用独立队列对 SVM 模型的验证数据集进行了测试,结果表明该模型具有很高的预测准确性,AUC 为 0.97。使用随机森林(RF)算法,我们确定了13种代谢物,在与验证数据集进行测试时,这些代谢物预测AD的AUC为0.96:这些发现为基于血液的高效AD诊断测试铺平了道路,为临床筛查和诊断程序带来了希望。
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引用次数: 0
Extra virgin olive oil beneficial effects on memory, synaptic function, and neuroinflammation in a mouse model of Down syndrome. 特级初榨橄榄油对唐氏综合症小鼠模型的记忆、突触功能和神经炎症有益处。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-01 Epub Date: 2024-10-04 DOI: 10.1177/13872877241283675
Jian-Guo Li, Alessandro Leone, Maurizio Servili, Domenico Praticò

Background: Clinical and preclinical studies have shown that extra virgin olive oil (EVOO), a major component of the Mediterranean diet, has beneficial effects on brain aging and cognition. Individuals with Down syndrome develop age-dependent cognitive decline and synaptic dysfunction. However, whether EVOO intake is beneficial in Down syndrome is not known.

Objective: In this study, by implementing a mouse model of Down syndrome, we aimed to investigate the effect that chronic administration of EVOO has on memory, synaptic function, and neuroinflammation.

Methods: Starting at 4 months of age Ts65dn mice were randomized to receive EVOO for 5 months in their diet, after which they were tested for learning and memory impairment. After euthanasia, synaptic function was measured in freshly obtained hippocampal slices, whereas brain tissues were assessed for inflammatory biomarkers.

Results: Compared with controls, mice receiving EVOO had a significant improvement in learning and spatial memory. Additionally, field potential recordings showed that treated mice had an improvement in synaptic function. Finally, array analysis showed that EVOO modulated the expression levels of several inflammatory biomarkers.

Conclusions: Chronic administration of EVOO to a mouse model of Down syndrome has beneficial effects on memory impairments, synaptic function deficits and neuroinflammation. Our findings provide additional support for the potential therapeutic effects of EVOO also in individuals with Down syndrome.

背景:临床和临床前研究表明,特级初榨橄榄油(EVOO)是地中海饮食的主要成分,对大脑衰老和认知能力有好处。唐氏综合征患者会出现年龄依赖性认知功能衰退和突触功能障碍。然而,唐氏综合征患者摄入特级初榨橄榄油是否有益尚不清楚:在本研究中,我们通过使用唐氏综合征小鼠模型,旨在研究长期服用乙烯烯酮对记忆力、突触功能和神经炎症的影响:从 4 个月大的 Ts65dn 小鼠开始,在其饮食中随机添加 5 个月的环氧乙烷,之后对其进行学习和记忆障碍测试。安乐死后,测量新鲜海马切片的突触功能,同时评估脑组织的炎症生物标志物:结果:与对照组相比,接受乙烯茴香油治疗的小鼠在学习和空间记忆方面有显著改善。此外,场电位记录显示,接受治疗的小鼠突触功能有所改善。最后,阵列分析表明,EVOO调节了几种炎症生物标志物的表达水平:结论:在唐氏综合症小鼠模型中长期服用乙烯茴香烯酮对记忆障碍、突触功能缺陷和神经炎症有好处。我们的研究结果进一步证明,EVOO 对唐氏综合症患者也有潜在的治疗作用。
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引用次数: 0
Is KIBRA polymorphism associated with memory performance and cognitive impairment in Alzheimer's disease? KIBRA 多态性与阿尔茨海默病的记忆表现和认知障碍有关吗?
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-01 Epub Date: 2024-10-15 DOI: 10.1177/13872877241284313
Vanesa Jurasova, Ross Andel, Alzbeta Katonova, Raena Nolan, Zuzana Lacinova, Tereza Kolarova, Vaclav Matoska, Martin Vyhnalek, Jakub Hort

Background: Genetic variations in a common single nucleotide polymorphism in the ninth intron of the KIBRA gene have been linked to memory performance and risk of Alzheimer's disease (AD).

Objective: We examined the risk of AD related to presence of KIBRA T allele (versus CC homozygote) and to memory performance. The role of established genetic risk factors APOE ε4 and BDNF Met was also considered.

Methods: Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory.

Results: KIBRA T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, p = 0.012) compared to KIBRA CC genotype. In APOE ε4 negative individuals, KIBRA T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, p = 0.038) and AD dementia (OR = 15.75, p = 0.009). In BDNF Met positive individuals, the KIBRA T allele was associated with a greater risk of AD dementia (OR = 10.98, p = 0.050). In AD dementia, the association between KIBRA T allele and better memory performance approached significance (β = 0.42; p = 0.062). The link between possessing the KIBRA T allele and better memory reached statistical significance only among BDNF Met carriers (β = 1.21, p = 0.027).

Conclusions: Findings suggest that KIBRA T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits.

背景:KIBRA 基因第九个内含子中一个常见单核苷酸多态性的遗传变异与记忆能力和阿尔茨海默病(AD)风险有关:KIBRA基因第九个内含子中一个常见单核苷酸多态性的遗传变异与记忆力和阿尔茨海默病(AD)的风险有关:我们研究了与 KIBRA T 等位基因(与 CC 同源物)的存在和记忆表现有关的阿尔茨海默病风险。我们还考虑了已确定的遗传风险因素 APOE ε4 和 BDNF Met 的作用:参与者包括认知能力健康的个体(n = 19)、AD 引起的失忆性轻度认知障碍(aMCI)患者(n = 99)以及捷克脑老化研究中的 AD 痴呆患者(n = 37)。二元和多叉逻辑回归比较了属于某一诊断类别的几率,多变量线性回归评估了与记忆的关联:与KIBRA CC基因型相比,KIBRA T等位基因与AD痴呆风险增加有关(几率比[OR] = 5.98,p = 0.012)。在APOE ε4阴性个体中,KIBRA T等位基因与AD导致的aMCI(OR = 6.68,p = 0.038)和AD痴呆(OR = 15.75,p = 0.009)的更高风险相关。在 BDNF Met 阳性个体中,KIBRA T 等位基因与更高的 AD 痴呆症风险相关(OR = 10.98,p = 0.050)。在 AD 痴呆症患者中,KIBRA T 等位基因与更好的记忆表现之间的关系接近显著性(β = 0.42;p = 0.062)。只有在BDNF Met携带者中,KIBRA T等位基因与更好的记忆力之间的联系才达到统计学意义(β = 1.21,p = 0.027):研究结果表明,KIBRA T等位基因可能无法完全预防AD痴呆症,但有可能延缓诊断后认知障碍的进展。
{"title":"Is KIBRA polymorphism associated with memory performance and cognitive impairment in Alzheimer's disease?","authors":"Vanesa Jurasova, Ross Andel, Alzbeta Katonova, Raena Nolan, Zuzana Lacinova, Tereza Kolarova, Vaclav Matoska, Martin Vyhnalek, Jakub Hort","doi":"10.1177/13872877241284313","DOIUrl":"https://doi.org/10.1177/13872877241284313","url":null,"abstract":"<p><strong>Background: </strong>Genetic variations in a common single nucleotide polymorphism in the ninth intron of the <i>KIBRA</i> gene have been linked to memory performance and risk of Alzheimer's disease (AD).</p><p><strong>Objective: </strong>We examined the risk of AD related to presence of <i>KIBRA</i> T allele (versus <i>CC</i> homozygote) and to memory performance. The role of established genetic risk factors <i>APOE</i> ε4 and <i>BDNF</i> Met was also considered.</p><p><strong>Methods: </strong>Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory.</p><p><strong>Results: </strong><i>KIBRA</i> T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, <i>p </i>= 0.012) compared to <i>KIBRA</i> CC genotype. In <i>APOE</i> ε4 negative individuals, <i>KIBRA</i> T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, <i>p </i>= 0.038) and AD dementia (OR = 15.75, <i>p </i>= 0.009). In <i>BDNF</i> Met positive individuals, the <i>KIBRA</i> T allele was associated with a greater risk of AD dementia (OR = 10.98, <i>p </i>= 0.050). In AD dementia, the association between <i>KIBRA</i> T allele and better memory performance approached significance (β = 0.42; <i>p </i>= 0.062). The link between possessing the <i>KIBRA</i> T allele and better memory reached statistical significance only among <i>BDNF</i> Met carriers (β = 1.21, <i>p </i>= 0.027).</p><p><strong>Conclusions: </strong>Findings suggest that <i>KIBRA</i> T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":"102 1","pages":"218-227"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Neurofilament light and cognition in community-dwelling non-Hispanic Blacks. 社区居住的非西班牙裔黑人的神经丝光和认知能力。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-01 Epub Date: 2024-10-20 DOI: 10.1177/13872877241283693
Lubnaa Abdullah, Fan Zhang, James Hall, Sid O'Bryant

Background: No large-scale characterizations of neurofilament light chain (NfL) and cognitive outcomes have been conducted in community-dwelling non-Hispanic Blacks.

Objective: This study aims to enhance the application of blood biomarkers, in particular NfL, to ethno-racially diverse communities. We assess the association of NfL with cognitive outcomes, hypothesizing that NfL can identify cognitive changes regardless of diagnostic category.

Methods: Baseline data were analyzed among n = 283 non-Hispanic Blacks (NHB) from the multi-ethnic Health and Aging Brain Study- Health Disparities (HABS-HD). Plasma NfL was measured on the Simoa platform. Linear regression models were conducted, covarying for age, gender, and education.

Results: The majority of study participants (72%) were cognitively unimpaired (CU), with 21% having mild cognitive impairment (MCI), and 6.7% with Alzheimer's disease (AD). In adjusted models among the entire sample, significant associations existed between NfL and Trails A (p < 0.0001), Trails B (p < 0.0001), phonemic (FAS) and semantic (Animals) fluency (p = 0.03), and Symbol Digit Substitution (p < 0.001). When separated by diagnostic classification, significant associations were removed for functions involving executive functions for all diagnostic groups. Higher levels of NfL were positively associated with cognitive diagnosis, older age, and less education.

Conclusions: Plasma NfL levels are significantly associated with measures of executive functioning, which elucidate NfL as a non-specific marker of neurodegeneration associated with efficiency of brain functions involving attention, processing, and generativity. NfL may be a sensitive measure for the detection of alterations in cognitive processing before the onset of phenotypic functional changes of neurodegeneration.

背景:神经丝蛋白轻链(NfL目前尚未在居住在社区的非西班牙裔黑人中对神经丝蛋白轻链(NfL)和认知结果进行大规模研究:本研究旨在加强血液生物标志物,尤其是神经丝蛋白轻链在不同种族社区的应用。我们评估了 NfL 与认知结果的关联,假设 NfL 可以识别认知变化,而与诊断类别无关:我们分析了多种族健康与老龄化脑研究--健康差异(HABS-HD)中 283 名非西班牙裔黑人(NHB)的基线数据。血浆 NfL 在 Simoa 平台上测量。在与年龄、性别和教育程度共线的基础上建立了线性回归模型:大多数研究参与者(72%)认知能力未受损(CU),21%患有轻度认知障碍(MCI),6.7%患有阿尔茨海默病(AD)。在整个样本的调整模型中,NfL 与轨迹 A(p p p = 0.03)和符号数字替换(p 结论:NfL 与轨迹 A 和符号数字替换之间存在显著关联:血浆 NfL 水平与执行功能的测量结果明显相关,这说明 NfL 是神经退化的非特异性标记,与涉及注意力、处理和生成的大脑功能的效率有关。在神经退行性病变的表型功能变化出现之前,NfL可能是检测认知处理改变的灵敏指标。
{"title":"Neurofilament light and cognition in community-dwelling non-Hispanic Blacks.","authors":"Lubnaa Abdullah, Fan Zhang, James Hall, Sid O'Bryant","doi":"10.1177/13872877241283693","DOIUrl":"https://doi.org/10.1177/13872877241283693","url":null,"abstract":"<p><strong>Background: </strong>No large-scale characterizations of neurofilament light chain (NfL) and cognitive outcomes have been conducted in community-dwelling non-Hispanic Blacks.</p><p><strong>Objective: </strong>This study aims to enhance the application of blood biomarkers, in particular NfL, to ethno-racially diverse communities. We assess the association of NfL with cognitive outcomes, hypothesizing that NfL can identify cognitive changes regardless of diagnostic category.</p><p><strong>Methods: </strong>Baseline data were analyzed among <i>n</i> = 283 non-Hispanic Blacks (NHB) from the multi-ethnic Health and Aging Brain Study- Health Disparities (HABS-HD). Plasma NfL was measured on the Simoa platform. Linear regression models were conducted, covarying for age, gender, and education.</p><p><strong>Results: </strong>The majority of study participants (72%) were cognitively unimpaired (CU), with 21% having mild cognitive impairment (MCI), and 6.7% with Alzheimer's disease (AD). In adjusted models among the entire sample, significant associations existed between NfL and Trails A (<i>p</i> < 0.0001), Trails B (<i>p</i> < 0.0001), phonemic (FAS) and semantic (Animals) fluency (<i>p</i> = 0.03), and Symbol Digit Substitution (<i>p</i> < 0.001). When separated by diagnostic classification, significant associations were removed for functions involving executive functions for all diagnostic groups. Higher levels of NfL were positively associated with cognitive diagnosis, older age, and less education.</p><p><strong>Conclusions: </strong>Plasma NfL levels are significantly associated with measures of executive functioning, which elucidate NfL as a non-specific marker of neurodegeneration associated with efficiency of brain functions involving attention, processing, and generativity. NfL may be a sensitive measure for the detection of alterations in cognitive processing before the onset of phenotypic functional changes of neurodegeneration.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":"102 1","pages":"60-66"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
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Journal of Alzheimer's Disease
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