Pub Date : 2024-11-01Epub Date: 2024-10-15DOI: 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.
{"title":"Association between selective serotonin reuptake inhibitors and mortality following COVID-19 among patients with Alzheimer's disease.","authors":"Zhenxiang Gao, Ian Dorney, Pamela B Davis, David C Kaelber, Rong Xu","doi":"10.1177/13872877241283820","DOIUrl":"https://doi.org/10.1177/13872877241283820","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>To investigate the relationship between SSRIs therapy and the mortality risk after COVID-19 infection in elderly patients with and without AD.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":"102 1","pages":"99-109"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576149","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}
Pub Date : 2024-11-01DOI: 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。
{"title":"Perceptions of key informant neurologists before implementing anti-amyloid drugs in the Spanish departments of neurology.","authors":"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","doi":"10.1177/13872877241284312","DOIUrl":"https://doi.org/10.1177/13872877241284312","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>We aimed to assess the necessary changes prior to introducing these therapies in our setting.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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, <i>APOE</i> genotyping, and the necessity of advancing blood biomarkers and tau tracers.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":"102 1","pages":"207-217"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576235","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}
Pub Date : 2024-11-01Epub Date: 2024-10-17DOI: 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.
{"title":"Social isolation and social cognition: A cross-sectional analysis.","authors":"Jessica Grothe, Alexander Pabst, Susanne Röhr, Steffi G Riedel-Heller, Melanie Luppa","doi":"10.1177/13872877241284222","DOIUrl":"https://doi.org/10.1177/13872877241284222","url":null,"abstract":"<p><strong>Background: </strong>The impact of social isolation on social cognition is not entirely clear.</p><p><strong>Objective: </strong>The aim of the study is to investigate the association between social isolation and social cognition.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":"102 1","pages":"53-59"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576242","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}
Pub Date : 2024-11-01Epub Date: 2024-10-29DOI: 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.
{"title":"The safety and effectiveness of 40 Hz γ-tACS in Alzheimer's disease: A meta-analysis.","authors":"Xinyang Zhang, Renhua Lv, Yanqiu Sun, Timon Cheng-Yi Liu","doi":"10.1177/13872877241289397","DOIUrl":"10.1177/13872877241289397","url":null,"abstract":"<p><strong>Background: </strong>The efficacy and safety of 40 Hz gamma transcranial alternating current stimulation (γ-tACS) in Alzheimer's disease (AD) are still uncertain.</p><p><strong>Objective: </strong>This meta-analysis was conducted to investigate the therapeutic potential and safety of 40 Hz γ-tACS for AD.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":"102 2","pages":"295-307"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687013","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}
Pub Date : 2024-11-01Epub Date: 2024-11-11DOI: 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.
{"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}
Pub Date : 2024-11-01Epub Date: 2024-10-17DOI: 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.
{"title":"Comparative accuracy of Mini-Linguistic State Examination, Addenbrooke's Cognitive Examination, and Depistage Cognitif de Quebec for the diagnosis of primary progressive aphasia.","authors":"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","doi":"10.1177/13872877241284199","DOIUrl":"https://doi.org/10.1177/13872877241284199","url":null,"abstract":"<p><strong>Background: </strong>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)).</p><p><strong>Objective: </strong>This study aims to evaluate and compare the diagnostic capacity of these three instruments in PPA.</p><p><strong>Methods: </strong>A cross-sectional study including 43 patients with PPA (nfvPPA (<i>n</i> = 19), svPPA (<i>n</i> = 8), and lvPPA (<i>n</i> = 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).</p><p><strong>Results: </strong>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%.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":"102 1","pages":"67-76"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576137","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}
Pub Date : 2024-11-01Epub Date: 2024-10-25DOI: 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.
{"title":"Discovery of novel metabolic biomarkers in blood serum for diagnosis of Alzheimer's disease.","authors":"Yingxin Zhao, Alejandro Villasante-Tezanos, Ernesto G Miranda-Morales, Miguel A Pappolla, Xiang Fang","doi":"10.3233/JAD-240280","DOIUrl":"https://doi.org/10.3233/JAD-240280","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>We aim to identify metabolic biomarkers for AD diagnosis.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>These findings pave the way for an efficient, blood-based diagnostic test for AD, holding promise for clinical screenings and diagnostic procedures.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":"102 1","pages":"237-253"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576157","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}
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.
{"title":"Extra virgin olive oil beneficial effects on memory, synaptic function, and neuroinflammation in a mouse model of Down syndrome.","authors":"Jian-Guo Li, Alessandro Leone, Maurizio Servili, Domenico Praticò","doi":"10.1177/13872877241283675","DOIUrl":"https://doi.org/10.1177/13872877241283675","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":"102 1","pages":"35-43"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576205","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}
Pub Date : 2024-11-01Epub Date: 2024-10-15DOI: 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}
Pub Date : 2024-11-01Epub Date: 2024-10-20DOI: 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}