FeizpourA, DoréV, DoeckeJ D, SaadZ S, Triana-BaltzerG, SlemmonR, MaruffP, KrishnadasN, BourgeatP, HuangK, FowlerC, Rainey-SmithS R, BushA I, WardL, RobertsonJ, MartinsR N, MastersC L, VillemagneV L, FrippJ, KolbH C, RoweC C
Background: Plasma p217+tau has shown high concordance with cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of amyloid-β (Aβ) and tau in Alzheimer's Disease (AD). However, its association with longitudinal cognition and comparative performance to PET Aβ and tau in predicting cognitive decline are unknown.
Objectives: To evaluate whether p217+tau can predict the rate of cognitive decline observed over two-year average follow-up and compare this to prediction based on Aβ (18F-NAV4694) and tau (18F-MK6240) PET. We also explored the sample size required to detect a 30% slowing in cognitive decline in a 2-year trial and selection test cost using p217+tau (pT+) as compared to PET Aβ (A+) and tau (T+) with and without p217+tau pre-screening.
Design: A prospective observational cohort study.
Setting: Participants of the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) and Australian Dementia Network (ADNeT).
Measurements: Baseline p217+tau Simoa® assay, 18F-MK6240 tau-PET and 18F-NAV4694 Aβ-PET with neuropsychological follow-up (MMSE, CDR-SB, AIBL-PACC) over 2.4 ± 0.8 years.
Results: In CI, p217+tau was a significant predictor of change in MMSE (β = -0.55, p < 0.001) and CDR-SB (β =0.61, p < 0.001) with an effect size similar to Aβ Centiloid (MMSE β = -0.48, p = 0.002; CDR-SB β = 0.43, p = 0.004) and meta-temporal (MetaT) tau SUVR (MMSE: β = -0.62, p < 0.001; CDR-SB: β = 0.65, p < 0.001). In CU, only MetaT tau SUVR was significantly associated with change in AIBL-PACC (β = -0.22, p = 0.008). Screening pT+ CI participants into a trial could lead to 24% reduction in sample size compared to screening with PET for A+ and 6-13% compared to screening with PET for T+ (different regions). This would translate to an 81-83% biomarker test cost-saving assuming the p217+tau test cost one-fifth of a PET scan. In a trial requiring PET A+ or T+, p217+tau pre-screening followed by PET in those who were pT+ would cost more in the CI group, compared to 26-38% biomarker test cost-saving in the CU.
Conclusions: Substantial cost reduction can be achieved using p217+tau alone to select participants with MCI or mild dementia for a clinical trial designed to slow cognitive decline over two years, compared to participant selection by PET. In pre-clinical AD trials, p217+tau provides significant cost-saving if used as a pre-screening measure for PET A+ or T+ but in MCI/mild dementia trials this may add to cost both in testing and in the increased number of participants needed for testing.
血浆p217+tau与脑脊液(CSF)和正电子发射断层扫描(PET)测量的淀粉样蛋白-β (Aβ)和tau在阿尔茨海默病(AD)中显示高度一致性。然而，它与纵向认知的关系以及PET Aβ和tau在预测认知能力下降方面的比较表现尚不清楚。评估p217+tau是否可以预测两年平均随访期间观察到的认知衰退率，并将其与基于Aβ (18F-NAV4694)和tau (18F-MK6240) PET的预测进行比较。我们还探讨了在2年试验中检测认知衰退减缓30%所需的样本量，以及使用p217+tau (pT+)与PET a β (a +)和tau (T+)进行p217+tau预筛选和不进行p217+tau预筛选时的选择测试成本。一项前瞻性观察队列研究。澳大利亚衰老成像、生物标志物和生活方式旗舰研究(AIBL)和澳大利亚痴呆症网络(ADNeT)的参与者。153名认知未受损(CU)和50名认知受损(CI)个体。基线p217+tau Simoa®检测18F-MK6240 tau- pet和18F-NAV4694 a - β- pet，神经心理学随访(MMSE, CDR-SB, AIBL-PACC)超过2.4±0.8年。在CI中，p217+tau是MMSE (β = - 0.55, p < 0.001)和CDR-SB (β =0.61, p < 0.001)变化的显著预测因子，其效应大小与a β Centiloid (MMSE β = - 0.48, p = 0.002;CDR-SB β = 0.43, p = 0.004)和meta-temporal (MetaT) tau SUVR (MMSE: β = - 0.62, p < 0.001);CDR-SB: β = 0.65, p < 0.001)。在CU中，只有MetaT tau SUVR与AIBL-PACC变化显著相关(β = - 0.22, p = 0.008)。将pT+ CI参与者筛选到试验中，与PET筛选a +相比可减少24%的样本量，与PET筛选T+相比可减少6-13%(不同地区)。假设p217+tau测试的成本是PET扫描的五分之一，这将转化为节省81-83%的生物标志物测试成本。在一项需要PET a +或T+的试验中，在pT+的患者中进行p217+tau预筛选后再进行PET，与CU中生物标志物测试成本节省26-38%相比，CI组的成本更高。与PET选择参与者相比，单独使用p217+tau来选择MCI或轻度痴呆患者进行为期两年的临床试验，可以显著降低成本，旨在减缓认知能力下降。在临床前AD试验中，如果将p217+tau用作PET a +或T+的预筛选措施，则可以显著节省成本，但在MCI/轻度痴呆试验中，这可能会增加测试成本和测试所需参与者数量的增加。
{"title":"Two-Year Prognostic Utility of Plasma p217+tau across the Alzheimer's Continuum.","authors":"FeizpourA, DoréV, DoeckeJ D, SaadZ S, Triana-BaltzerG, SlemmonR, MaruffP, KrishnadasN, BourgeatP, HuangK, FowlerC, Rainey-SmithS R, BushA I, WardL, RobertsonJ, MartinsR N, MastersC L, VillemagneV L, FrippJ, KolbH C, RoweC C","doi":"10.14283/jpad.2023.83","DOIUrl":"10.14283/jpad.2023.83","url":null,"abstract":"<p><strong>Background: </strong>Plasma p217+tau has shown high concordance with cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of amyloid-β (Aβ) and tau in Alzheimer's Disease (AD). However, its association with longitudinal cognition and comparative performance to PET Aβ and tau in predicting cognitive decline are unknown.</p><p><strong>Objectives: </strong>To evaluate whether p217+tau can predict the rate of cognitive decline observed over two-year average follow-up and compare this to prediction based on Aβ (18F-NAV4694) and tau (18F-MK6240) PET. We also explored the sample size required to detect a 30% slowing in cognitive decline in a 2-year trial and selection test cost using p217+tau (pT+) as compared to PET Aβ (A+) and tau (T+) with and without p217+tau pre-screening.</p><p><strong>Design: </strong>A prospective observational cohort study.</p><p><strong>Setting: </strong>Participants of the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) and Australian Dementia Network (ADNeT).</p><p><strong>Participants: </strong>153 cognitively unimpaired (CU) and 50 cognitively impaired (CI) individuals.</p><p><strong>Measurements: </strong>Baseline p217+tau Simoa® assay, 18F-MK6240 tau-PET and 18F-NAV4694 Aβ-PET with neuropsychological follow-up (MMSE, CDR-SB, AIBL-PACC) over 2.4 ± 0.8 years.</p><p><strong>Results: </strong>In CI, p217+tau was a significant predictor of change in MMSE (β = -0.55, p < 0.001) and CDR-SB (β =0.61, p < 0.001) with an effect size similar to Aβ Centiloid (MMSE β = -0.48, p = 0.002; CDR-SB β = 0.43, p = 0.004) and meta-temporal (MetaT) tau SUVR (MMSE: β = -0.62, p < 0.001; CDR-SB: β = 0.65, p < 0.001). In CU, only MetaT tau SUVR was significantly associated with change in AIBL-PACC (β = -0.22, p = 0.008). Screening pT+ CI participants into a trial could lead to 24% reduction in sample size compared to screening with PET for A+ and 6-13% compared to screening with PET for T+ (different regions). This would translate to an 81-83% biomarker test cost-saving assuming the p217+tau test cost one-fifth of a PET scan. In a trial requiring PET A+ or T+, p217+tau pre-screening followed by PET in those who were pT+ would cost more in the CI group, compared to 26-38% biomarker test cost-saving in the CU.</p><p><strong>Conclusions: </strong>Substantial cost reduction can be achieved using p217+tau alone to select participants with MCI or mild dementia for a clinical trial designed to slow cognitive decline over two years, compared to participant selection by PET. In pre-clinical AD trials, p217+tau provides significant cost-saving if used as a pre-screening measure for PET A+ or T+ but in MCI/mild dementia trials this may add to cost both in testing and in the increased number of participants needed for testing.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"828-836"},"PeriodicalIF":6.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66894526","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}
R Aggarwal, E Sidnam-Mauch, D Neffa-Creech, A Plant, E Williams, E Shami, U Menon, S George, J B Langbaum
Background: Web-based participant recruitment registries can be useful tools for accelerating enrollment into studies, but existing Alzheimer's disease (AD)-focused recruitment registries have had limited success enrolling individuals from underrepresented racial and ethnic groups. Designing these registries to meet the needs of individuals from these communities, including designing mobile-first, may facilitate improvement in the enrollment of underrepresented groups.
Objectives: Evaluate the usability of a prototype mobile-first participant recruitment registry for AD prevention studies; assess users' perceptions of and willingness to sign up for the registry.
Design and setting: Quantitative usability testing and an online survey; online setting.
Participants: We recruited 1,358 adults ages 45-75 who self-reported not having a diagnosis of mild cognitive impairment, AD, or other forms of dementia (Study 1: n=589, Study 2: n=769). Black/African American and Hispanic/Latino participants were specifically recruited, including those with lower health literacy.
Methods and measurements: Study 1 measures the prototype's usability through observed task success rates, task completion times, and responses to the System Usability Scale. Study 2 uses an online survey to collect data on perceptions of and willingness to sign up for the mobile-first registry.
Results: Study 1 findings show the prototype mobile-first recruitment registry website demonstrates high usability and is equally usable for Black / African American, Hispanic/Latino, and White user groups. Survey results from Study 2 indicate that users from underrepresented communities understand the registry's purpose and content and express willingness to sign up for the registry on a mobile device.
Conclusions: Designing mobile-first participant recruitment registries based on feedback from underrepresented communities may result in more sign-ups by individuals from minoritized communities.
{"title":"Development of a Mobile-First Registry to Recruit Healthy Volunteers and Members of Underrepresented Communities for Alzheimer's Disease Prevention Studies.","authors":"R Aggarwal, E Sidnam-Mauch, D Neffa-Creech, A Plant, E Williams, E Shami, U Menon, S George, J B Langbaum","doi":"10.14283/jpad.2023.86","DOIUrl":"10.14283/jpad.2023.86","url":null,"abstract":"<p><strong>Background: </strong>Web-based participant recruitment registries can be useful tools for accelerating enrollment into studies, but existing Alzheimer's disease (AD)-focused recruitment registries have had limited success enrolling individuals from underrepresented racial and ethnic groups. Designing these registries to meet the needs of individuals from these communities, including designing mobile-first, may facilitate improvement in the enrollment of underrepresented groups.</p><p><strong>Objectives: </strong>Evaluate the usability of a prototype mobile-first participant recruitment registry for AD prevention studies; assess users' perceptions of and willingness to sign up for the registry.</p><p><strong>Design and setting: </strong>Quantitative usability testing and an online survey; online setting.</p><p><strong>Participants: </strong>We recruited 1,358 adults ages 45-75 who self-reported not having a diagnosis of mild cognitive impairment, AD, or other forms of dementia (Study 1: n=589, Study 2: n=769). Black/African American and Hispanic/Latino participants were specifically recruited, including those with lower health literacy.</p><p><strong>Methods and measurements: </strong>Study 1 measures the prototype's usability through observed task success rates, task completion times, and responses to the System Usability Scale. Study 2 uses an online survey to collect data on perceptions of and willingness to sign up for the mobile-first registry.</p><p><strong>Results: </strong>Study 1 findings show the prototype mobile-first recruitment registry website demonstrates high usability and is equally usable for Black / African American, Hispanic/Latino, and White user groups. Survey results from Study 2 indicate that users from underrepresented communities understand the registry's purpose and content and express willingness to sign up for the registry on a mobile device.</p><p><strong>Conclusions: </strong>Designing mobile-first participant recruitment registries based on feedback from underrepresented communities may result in more sign-ups by individuals from minoritized communities.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"857-864"},"PeriodicalIF":6.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10884078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66894734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M R Mindt, M T Ashford, D Zhu, H Cham, A Aaronson, C Conti, X Deng, R Alaniz, J Sorce, C Cypress, P Griffin, D Flenniken, M Camacho, J Fockler, D Truran, R S Mackin, C Hill, M W Weiner, D Byrd, R W Turner Ii, R L Nosheny
<p><strong>Background: </strong>Although Black/African American older adults bear significant inequities in prevalence, incidence, and outcomes of Alzheimer's disease and related dementias, they are profoundly under-included in Alzheimer's Disease research. Community-Engaged Research (e.g., equitable community/science partnerships) is an evidence-based approach for improving engagement of underrepresented populations into Alzheimer's Disease research, but has lacked scalability to the national level. As internet use among older adults from underrepresented populations continues to grow, internet-based research shows promise as a feasible, valid approach to engagement and longitudinal assessment. The Community Engaged Digital Alzheimer's Research (CEDAR) study utilizes a community-engaged research approach to increase the engagement and research participation of Black/African American adults in the Brain Health Registry (BHR) and Alzheimer Disease clinical research.</p><p><strong>Objectives: </strong>To describe the methods and evaluate the feasibility of the CEDAR culturally-informed digital platform within BHR.</p><p><strong>Design: </strong>All Black/African American participants in BHR were invited to enroll in CEDAR and to consider serving on a newly convened Community-Scientific Partnership Board to guide the study. The community board guided the development a culturally-informed cadre of engagement materials and strategies to increase research participation. Engagement strategies included incentives for study task completion, culturally-informed communications (e.g., landing page, emails and social media), resources about brain health, and video and written testimonials by CEDAR participants.</p><p><strong>Setting: </strong>BHR, an Internet-based registry and cohort.</p><p><strong>Participants: </strong>BHR participants self-identifying as Black/African American were invited to enroll. All participants who signed an online informed consent document were enrolled.</p><p><strong>Measurements: </strong>We report the number of participants invited, enrolled, completed tasks, and volunteered to join the community board. We compared the demographics, cognitive profile, and baseline BHR task completion rates between CEDAR participants and all those invited to join the study.</p><p><strong>Results: </strong>Of 3738 invited, 349 (9.34%) enrolled in CEDAR. 134 (37% of CEDAR participants) volunteered to join the community board, of which 19 were selected for the community board. Compared to those invited, the CEDAR cohort had a higher percentage of female participants (84.5%) and a lower percentage of participants who identify as belonging to more than one ethnocultural group (21.8%). Compared to those did not enroll in CEDAR, those enrolled in CEDAR had a higher percentage of participants completing all BHR tasks (22%) and a higher percentage of participants completing at least one cognitive test (76%). Those enrolled in CEDAR also had a higher perce
背景：尽管美国黑人/非洲裔老年人在阿尔茨海默病及相关痴呆症的患病率、发病率和结果方面存在严重的不平等，但他们在阿尔茨海默病研究中的参与度却远远不够。社区参与式研究（如公平的社区/科学合作伙伴关系）是一种基于证据的方法，可提高代表性不足人群参与阿尔茨海默病研究的程度，但在全国范围内缺乏可扩展性。随着来自代表性不足人群的老年人使用互联网的人数不断增加，基于互联网的研究有望成为一种可行、有效的参与和纵向评估方法。社区参与的数字阿尔茨海默氏症研究（CEDAR）利用社区参与的研究方法来提高黑人/非裔美国成年人在脑健康登记（BHR）和阿尔茨海默氏症临床研究中的参与度和研究参与度：描述 CEDAR 方法并评估 BHR 中以文化为基础的数字平台的可行性：设计：邀请BHR的所有黑人/非裔美国人参与者加入CEDAR，并考虑加入新成立的社区-科学合作委员会，以指导该研究。社区委员会指导开发了一批有文化背景的参与材料和策略，以提高研究参与度。参与策略包括对完成研究任务的奖励、有文化背景的交流（如登陆页面、电子邮件和社交媒体）、有关大脑健康的资源以及 CEDAR 参与者的视频和书面感言：BHR 是一个基于互联网的登记和队列：邀请自称为黑人/非裔美国人的 BHR 参与者参加。所有签署了在线知情同意书的参与者都被纳入其中：我们报告了受邀、注册、完成任务和自愿加入社区委员会的参与者人数。我们比较了 CEDAR 参与者和所有受邀参加研究者的人口统计学、认知概况和基线 BHR 任务完成率：在3738名受邀者中，有349人（9.34%）加入了CEDAR。134人（占CEDAR参与者的37%）自愿加入社区委员会，其中19人被选入社区委员会。与受邀者相比，CEDAR 的参与者中女性比例较高（84.5%），自认为属于一个以上种族文化群体的参与者比例较低（21.8%）。与未参加 CEDAR 的参与者相比，参加 CEDAR 的参与者完成所有 BHR 任务的比例更高（22%），完成至少一项认知测试的比例更高（76%）。参加 CEDAR 的参与者中，有研究伙伴的比例也更高（18%）：结论：采用文化信息社区参与研究的方法，包括远程召集社区委员会，让黑人/非裔美国人参与者参与在线研究注册是可行的。这种方法可用于各种临床研究和其他场合。未来的研究将评估参与策略的有效性。
{"title":"The Community Engaged Digital Alzheimer's Research (CEDAR) Study: A Digital Intervention to Increase Research Participation of Black American Participants in the Brain Health Registry.","authors":"M R Mindt, M T Ashford, D Zhu, H Cham, A Aaronson, C Conti, X Deng, R Alaniz, J Sorce, C Cypress, P Griffin, D Flenniken, M Camacho, J Fockler, D Truran, R S Mackin, C Hill, M W Weiner, D Byrd, R W Turner Ii, R L Nosheny","doi":"10.14283/jpad.2023.32","DOIUrl":"10.14283/jpad.2023.32","url":null,"abstract":"<p><strong>Background: </strong>Although Black/African American older adults bear significant inequities in prevalence, incidence, and outcomes of Alzheimer's disease and related dementias, they are profoundly under-included in Alzheimer's Disease research. Community-Engaged Research (e.g., equitable community/science partnerships) is an evidence-based approach for improving engagement of underrepresented populations into Alzheimer's Disease research, but has lacked scalability to the national level. As internet use among older adults from underrepresented populations continues to grow, internet-based research shows promise as a feasible, valid approach to engagement and longitudinal assessment. The Community Engaged Digital Alzheimer's Research (CEDAR) study utilizes a community-engaged research approach to increase the engagement and research participation of Black/African American adults in the Brain Health Registry (BHR) and Alzheimer Disease clinical research.</p><p><strong>Objectives: </strong>To describe the methods and evaluate the feasibility of the CEDAR culturally-informed digital platform within BHR.</p><p><strong>Design: </strong>All Black/African American participants in BHR were invited to enroll in CEDAR and to consider serving on a newly convened Community-Scientific Partnership Board to guide the study. The community board guided the development a culturally-informed cadre of engagement materials and strategies to increase research participation. Engagement strategies included incentives for study task completion, culturally-informed communications (e.g., landing page, emails and social media), resources about brain health, and video and written testimonials by CEDAR participants.</p><p><strong>Setting: </strong>BHR, an Internet-based registry and cohort.</p><p><strong>Participants: </strong>BHR participants self-identifying as Black/African American were invited to enroll. All participants who signed an online informed consent document were enrolled.</p><p><strong>Measurements: </strong>We report the number of participants invited, enrolled, completed tasks, and volunteered to join the community board. We compared the demographics, cognitive profile, and baseline BHR task completion rates between CEDAR participants and all those invited to join the study.</p><p><strong>Results: </strong>Of 3738 invited, 349 (9.34%) enrolled in CEDAR. 134 (37% of CEDAR participants) volunteered to join the community board, of which 19 were selected for the community board. Compared to those invited, the CEDAR cohort had a higher percentage of female participants (84.5%) and a lower percentage of participants who identify as belonging to more than one ethnocultural group (21.8%). Compared to those did not enroll in CEDAR, those enrolled in CEDAR had a higher percentage of participants completing all BHR tasks (22%) and a higher percentage of participants completing at least one cognitive test (76%). Those enrolled in CEDAR also had a higher perce","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"847-856"},"PeriodicalIF":6.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Observational studies suggest psychosocial factors such as social support and loneliness are associated with vulnerability for cognitive decline in older adults. However, because of racial/ethnic homogeneity in prior studies focused on identifying these associations in predominantly White cohorts, less is known about the generalizability of these putative psychosocial mechanisms in a diverse population. Thus, we evaluated whether lower levels of loneliness were associated with better cognitive performance in our sample.
Methods: We conducted a cross-sectional study using 541 participants from (Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa) Dementia Cohort. Participants' self-reported loneliness as exposure. Cognitive performance is measured using a neuropsychological battery as the outcome. Raw scores were converted into Z scores, and global cognitive function was created. Generalized estimated equation and robust regression analysis).
Results: Better global cognitive function is associated with a lower level of loneliness at (β = -0.0131, 95 % CI -0.1990, -0.0071) after adjustment for age, gender, and education. Lower levels of loneliness were associated with varying cognitive domains after adjustment for age, gender, and education; and persisted after additional adjustments of vascular risk factors.
Conclusions: Self-reported lower loneliness was associated with higher levels of cognitive performance in a rural South African cohort of Black older adults. Although these findings and the potential of reverse causality need to be further validated, our results suggest that an intervention study may be merited to assess whether reducing loneliness lessens vulnerability to cognitive decline.
引言观察性研究表明，社会支持和孤独感等社会心理因素与老年人认知能力下降的脆弱性有关。然而，由于之前的研究主要是在以白人为主的队列中发现这些关联的种族/民族同质性，因此对于这些假定的社会心理机制在不同人群中的普遍性知之甚少。因此，我们评估了在我们的样本中，较低水平的孤独感是否与较好的认知表现相关：我们对《非洲的健康与老龄化》（Health and Aging in Africa：南非 INDEPTH 社区纵向研究）痴呆症队列中的 541 名参与者进行了横断面研究。参与者自我报告的孤独感为暴露。认知表现以神经心理测试作为结果。原始分数被转换成 Z 分数，并创建了整体认知功能。结果：在对年龄、性别和教育程度进行调整后，较好的整体认知功能与较低的孤独感相关（β = -0.0131，95 % CI -0.1990，-0.0071）。在对年龄、性别和教育程度进行调整后，较低的孤独感与不同的认知领域相关；在对血管风险因素进行额外调整后，孤独感仍持续存在：结论：在南非农村黑人老年人群中，自我报告的较低孤独感与较高的认知能力水平相关。尽管这些发现和潜在的反向因果关系还需要进一步验证，但我们的研究结果表明，可能值得进行干预研究，以评估减少孤独感是否会降低认知能力下降的脆弱性。
{"title":"Association of Loneliness with Cognitive Functions.","authors":"K T Kyaw, A Levine","doi":"10.14283/jpad.2023.60","DOIUrl":"10.14283/jpad.2023.60","url":null,"abstract":"<p><strong>Introduction: </strong>Observational studies suggest psychosocial factors such as social support and loneliness are associated with vulnerability for cognitive decline in older adults. However, because of racial/ethnic homogeneity in prior studies focused on identifying these associations in predominantly White cohorts, less is known about the generalizability of these putative psychosocial mechanisms in a diverse population. Thus, we evaluated whether lower levels of loneliness were associated with better cognitive performance in our sample.</p><p><strong>Methods: </strong>We conducted a cross-sectional study using 541 participants from (Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa) Dementia Cohort. Participants' self-reported loneliness as exposure. Cognitive performance is measured using a neuropsychological battery as the outcome. Raw scores were converted into Z scores, and global cognitive function was created. Generalized estimated equation and robust regression analysis).</p><p><strong>Results: </strong>Better global cognitive function is associated with a lower level of loneliness at (β = -0.0131, 95 % CI -0.1990, -0.0071) after adjustment for age, gender, and education. Lower levels of loneliness were associated with varying cognitive domains after adjustment for age, gender, and education; and persisted after additional adjustments of vascular risk factors.</p><p><strong>Conclusions: </strong>Self-reported lower loneliness was associated with higher levels of cognitive performance in a rural South African cohort of Black older adults. Although these findings and the potential of reverse causality need to be further validated, our results suggest that an intervention study may be merited to assess whether reducing loneliness lessens vulnerability to cognitive decline.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"903-908"},"PeriodicalIF":8.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893511","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}
H H Feldman, S Belleville, H B Nygaard, M Montero-Odasso, J Durant, J-L Lupo, C Revta, S Chan, M Cuesta, P J Slack, S Winer, P W H Brewster, S M Hofer, A Lim, A Centen, D M Jacobs, N D Anderson, J D Walker, M R Speechley, G Y Zou, H Chertkow
<p><strong>Background/objectives: </strong>CAN-THUMBS UP is designed as a comprehensive and innovative fully remote program to 1) develop an interactive and compelling online Brain Health Support Program intervention, with potential to positively influence dementia literacy, self-efficacy and lifestyle risk factors; 2) enroll and retain a community-dwelling Platform Trial Cohort of individuals at risk of dementia who will participate in the intervention; 3) support an open platform trial to test a variety of multidomain interventions that might further benefit individuals at risk of dementia. This manuscript presents the Brain Health Support Program Study protocol.</p><p><strong>Design/setting: </strong>Twelve-month prospective multi-center longitudinal study to evaluate a fully remote web-based educational intervention. Participants will subsequently be part of a Platform Trial Cohort and may be eligible to participate in further dementia prevention clinical trials.</p><p><strong>Participants: </strong>Three hundred fifty older adults who are cognitively unimpaired or have mild cognitive impairment, with at least 1 well established dementia risk factor.</p><p><strong>Intervention: </strong>Participants engage in the Brain Health Support Program intervention for 45-weeks and complete pre/post intervention measures. This intervention is designed to convey best available evidence for dementia prevention, consists of 181 chapters within 8 modules that are progressively delivered, and is available online in English and French. The program has been developed as a collaborative effort by investigators with recognized expertise in the program's content areas, along with input from older-adult citizen advisors.</p><p><strong>Measurements: </strong>This study utilizes adapted remote assessments with accessible technologies (e.g. videoconferencing, cognitive testing via computer and mobile phone, wearable devices to track physical activity and sleep, self-administered saliva sample collection). The primary outcome is change in dementia literacy, as measured by the Alzheimer's Disease Knowledge Scale. Secondary outcomes include change in self-efficacy; engagement using the online program; user satisfaction ratings; and evaluation of usability and acceptance. Exploratory outcomes include changes in attitudes toward dementia, modifiable risk factors, performance on the Neuropsychological Test Battery, performance on self-administered online cognitive assessments, and levels of physical activity and sleep; success of the national recruitment plan; and the distribution of age adjusted polygenic hazard scores.</p><p><strong>Conclusions: </strong>This fully remote study provides an accessible approach to research with all study activities being completed in the participants' home environment. This approach may reduce barriers to participation, provide an easier and less demanding participant experience, and reach a broader geography with recruitment from all regi
{"title":"Protocol for the Brain Health Support Program Study of the Canadian Therapeutic Platform Trial for Multidomain Interventions to Prevent Dementia (CAN-THUMBS UP): A Prospective 12-Month Intervention Study.","authors":"H H Feldman, S Belleville, H B Nygaard, M Montero-Odasso, J Durant, J-L Lupo, C Revta, S Chan, M Cuesta, P J Slack, S Winer, P W H Brewster, S M Hofer, A Lim, A Centen, D M Jacobs, N D Anderson, J D Walker, M R Speechley, G Y Zou, H Chertkow","doi":"10.14283/jpad.2023.65","DOIUrl":"10.14283/jpad.2023.65","url":null,"abstract":"<p><strong>Background/objectives: </strong>CAN-THUMBS UP is designed as a comprehensive and innovative fully remote program to 1) develop an interactive and compelling online Brain Health Support Program intervention, with potential to positively influence dementia literacy, self-efficacy and lifestyle risk factors; 2) enroll and retain a community-dwelling Platform Trial Cohort of individuals at risk of dementia who will participate in the intervention; 3) support an open platform trial to test a variety of multidomain interventions that might further benefit individuals at risk of dementia. This manuscript presents the Brain Health Support Program Study protocol.</p><p><strong>Design/setting: </strong>Twelve-month prospective multi-center longitudinal study to evaluate a fully remote web-based educational intervention. Participants will subsequently be part of a Platform Trial Cohort and may be eligible to participate in further dementia prevention clinical trials.</p><p><strong>Participants: </strong>Three hundred fifty older adults who are cognitively unimpaired or have mild cognitive impairment, with at least 1 well established dementia risk factor.</p><p><strong>Intervention: </strong>Participants engage in the Brain Health Support Program intervention for 45-weeks and complete pre/post intervention measures. This intervention is designed to convey best available evidence for dementia prevention, consists of 181 chapters within 8 modules that are progressively delivered, and is available online in English and French. The program has been developed as a collaborative effort by investigators with recognized expertise in the program's content areas, along with input from older-adult citizen advisors.</p><p><strong>Measurements: </strong>This study utilizes adapted remote assessments with accessible technologies (e.g. videoconferencing, cognitive testing via computer and mobile phone, wearable devices to track physical activity and sleep, self-administered saliva sample collection). The primary outcome is change in dementia literacy, as measured by the Alzheimer's Disease Knowledge Scale. Secondary outcomes include change in self-efficacy; engagement using the online program; user satisfaction ratings; and evaluation of usability and acceptance. Exploratory outcomes include changes in attitudes toward dementia, modifiable risk factors, performance on the Neuropsychological Test Battery, performance on self-administered online cognitive assessments, and levels of physical activity and sleep; success of the national recruitment plan; and the distribution of age adjusted polygenic hazard scores.</p><p><strong>Conclusions: </strong>This fully remote study provides an accessible approach to research with all study activities being completed in the participants' home environment. This approach may reduce barriers to participation, provide an easier and less demanding participant experience, and reach a broader geography with recruitment from all regi","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"1 1","pages":"875-885"},"PeriodicalIF":6.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44577434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Souchet, M. Audrain, Y. Gu, M. Lindberg, N. S. Orefice, E. Rey, N. Cartier, N. Janel, L. Meijer, J. Braudeau
The authors would like to draw the reader’s attention to the error in the following article.
作者想提请读者注意下面文章中的错误。
{"title":"Erratum to: Cerebral Phospho-Tau Acts Synergistically with Soluble Aβ42 Leading to Mild Cognitive Impairment in AAV-AD Rats","authors":"B. Souchet, M. Audrain, Y. Gu, M. Lindberg, N. S. Orefice, E. Rey, N. Cartier, N. Janel, L. Meijer, J. Braudeau","doi":"10.14283/jpad.2022.74","DOIUrl":"https://doi.org/10.14283/jpad.2022.74","url":null,"abstract":"The authors would like to draw the reader’s attention to the error in the following article.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"150 - 150"},"PeriodicalIF":6.4,"publicationDate":"2022-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47664281","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}
Budd Haeberlein and colleagues presented the data from the two randomized Phase 3 studies of aducanumab in early Alzheimer’s disease (AD) recently in JPAD (1). The data have been carefully evaluated by the field over the past few years and are now finally reported for closer scrutiny. Essentially, the two studies involved 3,285 participants with mild cognitive impairment or mild dementia due to underlying AD as documented by amyloid positivity. One study, EMERGE, demonstrated statistically significant findings on the primary outcome measure, three secondary measures and a tertiary measure. The parallel study, ENGAGE, failed to replicate these results. The sponsor did post hoc analyses on the ENGAGE study to rationalize its failure to replicate the EMERGE results and suggested several plausible hypotheses. Central to this discussion was the implementation of protocol amendments during the conduct of the study that may have differentially influenced the outcomes of the two studies. The studies were stopped for futility in March of 2019 according to predetermined guidelines. The sponsor, however, evaluated an expanded dataset beyond the data available to the iDMC and concluded that EMERGE demonstrated positive results while ENGAGE did not. The socio-political fallout of these studies has been enormous. From the original termination of the studies due to futility through the subsequent analyses of additional double-blinded data, the FDA’s willingness to entertain a filing, the FDA Advisory Committee’s recommendations, the accelerated approval by the FDA on June 7, 2021, and the subsequent consideration for coverage by CMS have resulted in a firestorm. As such, it may be time to step back from the media circus and look at the implications of these studies for the field and, most importantly, our patients. An interpretation of these data could conclude that there is a positive effect of aducanumab on clinical progression of AD, but the effect is modest. The combination of the positive results from the EMERGE study would be statistically quite unlikely to have happened by chance. However, these data need to be interpreted in the context of the negative results from the parallel study, ENGAGE. This may reflect reality. The impact of intervention on amyloid at the stage of plaque development, along with the symptoms of mild cognitive impairment or mild dementia, may be minimal. If one accepts the putative explanation of the development of AD pathophysiology with amyloid accumulation occurring over years to decades subsequently leading to tau hyperphosphorylation, synaptic dysfunction and cognitive impairment, then results of these types of amyloid interventions may be comprehensible. That is, if amyloid has built up over decades and if one is able to successfully reduce the plaque burden over the course of 12 to 18 months, what might be a reasonable clinical manifestation of that intervention? One could argue that the expectations should be quite modest b
{"title":"Where Do We Go from Here?","authors":"R. C. Petersen","doi":"10.14283/jpad.2022.35","DOIUrl":"https://doi.org/10.14283/jpad.2022.35","url":null,"abstract":"Budd Haeberlein and colleagues presented the data from the two randomized Phase 3 studies of aducanumab in early Alzheimer’s disease (AD) recently in JPAD (1). The data have been carefully evaluated by the field over the past few years and are now finally reported for closer scrutiny. Essentially, the two studies involved 3,285 participants with mild cognitive impairment or mild dementia due to underlying AD as documented by amyloid positivity. One study, EMERGE, demonstrated statistically significant findings on the primary outcome measure, three secondary measures and a tertiary measure. The parallel study, ENGAGE, failed to replicate these results. The sponsor did post hoc analyses on the ENGAGE study to rationalize its failure to replicate the EMERGE results and suggested several plausible hypotheses. Central to this discussion was the implementation of protocol amendments during the conduct of the study that may have differentially influenced the outcomes of the two studies. The studies were stopped for futility in March of 2019 according to predetermined guidelines. The sponsor, however, evaluated an expanded dataset beyond the data available to the iDMC and concluded that EMERGE demonstrated positive results while ENGAGE did not. The socio-political fallout of these studies has been enormous. From the original termination of the studies due to futility through the subsequent analyses of additional double-blinded data, the FDA’s willingness to entertain a filing, the FDA Advisory Committee’s recommendations, the accelerated approval by the FDA on June 7, 2021, and the subsequent consideration for coverage by CMS have resulted in a firestorm. As such, it may be time to step back from the media circus and look at the implications of these studies for the field and, most importantly, our patients. An interpretation of these data could conclude that there is a positive effect of aducanumab on clinical progression of AD, but the effect is modest. The combination of the positive results from the EMERGE study would be statistically quite unlikely to have happened by chance. However, these data need to be interpreted in the context of the negative results from the parallel study, ENGAGE. This may reflect reality. The impact of intervention on amyloid at the stage of plaque development, along with the symptoms of mild cognitive impairment or mild dementia, may be minimal. If one accepts the putative explanation of the development of AD pathophysiology with amyloid accumulation occurring over years to decades subsequently leading to tau hyperphosphorylation, synaptic dysfunction and cognitive impairment, then results of these types of amyloid interventions may be comprehensible. That is, if amyloid has built up over decades and if one is able to successfully reduce the plaque burden over the course of 12 to 18 months, what might be a reasonable clinical manifestation of that intervention? One could argue that the expectations should be quite modest b","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"9 1","pages":"188 - 189"},"PeriodicalIF":6.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47443804","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}
{"title":"Digital Therapeutics for MCI and Alzheimer’s disease: A Regulatory Perspective — Highlights From The Clinical Trials on Alzheimer’s Disease conference (CTAD)","authors":"J. Shuren, P. Doraiswamy","doi":"10.14283/jpad.2022.28","DOIUrl":"https://doi.org/10.14283/jpad.2022.28","url":null,"abstract":"","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"9 1","pages":"236 - 240"},"PeriodicalIF":6.4,"publicationDate":"2022-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43231002","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}
K. Papp, H. Rofael, A. Veroff, M. Donohue, S. Wang, C. Randolph, E. Grober, H. Brashear, G. Novak, K. Ernstrom, R. Raman, P. Aisen, R. Sperling, G. Romano, D. Henley
Cognitive composites commonly serve as primary outcomes in Alzheimer’s disease (AD) secondary prevention trials. To evaluate the association between amyloid (Aβ) burden level (+/−) and performance on three separate composite endpoints: Preclinical Alzheimer’s Cognitive Composite (PACC), PACC+Semantic Fluency (PACC5), and Repeatable Battery for Neuropsychological Status (RBANS). Screening data from the randomized, double-blind, placebo-controlled, phase 2b/3 atabecestat EARLY study in preclinical AD participants were used in this analysis. The EARLY study was conducted at 143 centers across 14 countries. 3,569 cognitively unimpaired older adults (Clinical Dementia Rating of 0; aged 60–85 years) screened for inclusion in the EARLY study with Aβ status and at least PACC or RBANS at screening were included. Participants were categorized as those with non-pathological Aβ levels (Aβ−, n=2,824) and those with pathological Aβ levels (Aβ+, n=745) based on florbetapir uptake or levels of cerebrospinal fluid Aβ1–42. Analysis of Covariance models controlling for age, sex, and education were used to examine the difference in PACC, PACC5, and RBANS between Aβ groups. Nonparametric bootstrap was used to compare sensitivity of composites to differentiate between Aβ status. Of 3,569 participants, 2,116 were women (59%); 3,006 were Caucasian (84%); mean (SD) age was 68.98 (5.28) years. Aβ+ participants performed worse versus Aβ− participants on all cognitive composites though the magnitude of the Aβ effect was generally small. The Aβ+/− effect size for the PACC (Cohen’s d=−0.15) was significantly greater than the RBANS (d=−0.097) while the PACC5 effect size (d=−0.139) was numerically larger than the RBANS. When examining subscores from the composites, memory tests (i.e., Free and Cued Selective Reminding Test, Figure Recall) and speed of processing (i.e., Digit-Symbol/Coding on the PACC/RBANS) exhibited the largest Aβ+/− effect sizes. Cross-sectional relationships between Aβ and cognition among clinically unimpaired older adults are detectable on multi-domain cognitive composites but are relatively small in magnitude. The Aβ+/− group effect was statistically larger for PACC and marginally larger for PACC5 versus RBANS. However, interpretation of composite sensitivity to Aβ status cross-sectionally cannot be generalized to sensitivity to change over time.
{"title":"Sensitivity of the Preclinical Alzheimer’s Cognitive Composite (PACC), PACC5, and Repeatable Battery for Neuropsychological Status (RBANS) to Amyloid Status in Preclinical Alzheimer’s Disease -Atabecestat Phase 2b/3 EARLY Clinical Trial","authors":"K. Papp, H. Rofael, A. Veroff, M. Donohue, S. Wang, C. Randolph, E. Grober, H. Brashear, G. Novak, K. Ernstrom, R. Raman, P. Aisen, R. Sperling, G. Romano, D. Henley","doi":"10.14283/jpad.2022.17","DOIUrl":"https://doi.org/10.14283/jpad.2022.17","url":null,"abstract":"Cognitive composites commonly serve as primary outcomes in Alzheimer’s disease (AD) secondary prevention trials. To evaluate the association between amyloid (Aβ) burden level (+/−) and performance on three separate composite endpoints: Preclinical Alzheimer’s Cognitive Composite (PACC), PACC+Semantic Fluency (PACC5), and Repeatable Battery for Neuropsychological Status (RBANS). Screening data from the randomized, double-blind, placebo-controlled, phase 2b/3 atabecestat EARLY study in preclinical AD participants were used in this analysis. The EARLY study was conducted at 143 centers across 14 countries. 3,569 cognitively unimpaired older adults (Clinical Dementia Rating of 0; aged 60–85 years) screened for inclusion in the EARLY study with Aβ status and at least PACC or RBANS at screening were included. Participants were categorized as those with non-pathological Aβ levels (Aβ−, n=2,824) and those with pathological Aβ levels (Aβ+, n=745) based on florbetapir uptake or levels of cerebrospinal fluid Aβ1–42. Analysis of Covariance models controlling for age, sex, and education were used to examine the difference in PACC, PACC5, and RBANS between Aβ groups. Nonparametric bootstrap was used to compare sensitivity of composites to differentiate between Aβ status. Of 3,569 participants, 2,116 were women (59%); 3,006 were Caucasian (84%); mean (SD) age was 68.98 (5.28) years. Aβ+ participants performed worse versus Aβ− participants on all cognitive composites though the magnitude of the Aβ effect was generally small. The Aβ+/− effect size for the PACC (Cohen’s d=−0.15) was significantly greater than the RBANS (d=−0.097) while the PACC5 effect size (d=−0.139) was numerically larger than the RBANS. When examining subscores from the composites, memory tests (i.e., Free and Cued Selective Reminding Test, Figure Recall) and speed of processing (i.e., Digit-Symbol/Coding on the PACC/RBANS) exhibited the largest Aβ+/− effect sizes. Cross-sectional relationships between Aβ and cognition among clinically unimpaired older adults are detectable on multi-domain cognitive composites but are relatively small in magnitude. The Aβ+/− group effect was statistically larger for PACC and marginally larger for PACC5 versus RBANS. However, interpretation of composite sensitivity to Aβ status cross-sectionally cannot be generalized to sensitivity to change over time.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"9 1","pages":"255 - 261"},"PeriodicalIF":6.4,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42097536","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}
J. Barakos, D. Purcell, J. Suhy, S. Chalkias, P. Burkett, C. M. Grassi, C. Castrillo‐Viguera, I. Rubino, E. Vijverberg
Amyloid-related imaging abnormalities (ARIA) are adverse events reported in Alzheimer’s disease trials of anti-amyloid beta (Aβ) therapies. This review summarizes the existing literature on ARIA, including bapineuzumab, gantenerumab, donanemab, lecanemab, and aducanumab studies, with regard to potential risk factors, detection, and management. The pathophysiology of ARIA is unclear, but it may be related to binding of antibodies to accumulated Aβ in both the cerebral parenchyma and vasculature, resulting in loss of vessel wall integrity and increased leakage into surrounding tissues. Radiographically, ARIA-E is identified as vasogenic edema in the brain parenchyma or sulcal effusions in the leptomeninges/ sulci, while ARIA-H is hemosiderin deposits presenting as microhemorrhages or superficial siderosis. ARIA tends to be transient and asymptomatic in most cases, typically occurring early in the course of treatment, with the risk decreasing later in treatment. Limited data are available on continued dosing following radiographic findings of ARIA; hence, in the event of ARIA, treatment should be continued with caution and regular monitoring. Clinical trials have implemented management approaches such as temporary suspension of treatment until symptoms or radiographic signs of ARIA have resolved or permanent discontinuation of treatment. ARIA largely resolves without concomitant treatment, and there are no systematic data on potential treatments for ARIA. Given the availability of an anti-Aβ therapy, ARIA monitoring will now be implemented in routine clinical practice. The simple magnetic resonance imaging sequences used in clinical trials are likely sufficient for effective detection of cases. Increased awareness and education of ARIA among clinicians and radiologists is vital.
{"title":"Detection and Management of Amyloid-Related Imaging Abnormalities in Patients with Alzheimer’s Disease Treated with Anti-Amyloid Beta Therapy","authors":"J. Barakos, D. Purcell, J. Suhy, S. Chalkias, P. Burkett, C. M. Grassi, C. Castrillo‐Viguera, I. Rubino, E. Vijverberg","doi":"10.14283/jpad.2022.21","DOIUrl":"https://doi.org/10.14283/jpad.2022.21","url":null,"abstract":"Amyloid-related imaging abnormalities (ARIA) are adverse events reported in Alzheimer’s disease trials of anti-amyloid beta (Aβ) therapies. This review summarizes the existing literature on ARIA, including bapineuzumab, gantenerumab, donanemab, lecanemab, and aducanumab studies, with regard to potential risk factors, detection, and management. The pathophysiology of ARIA is unclear, but it may be related to binding of antibodies to accumulated Aβ in both the cerebral parenchyma and vasculature, resulting in loss of vessel wall integrity and increased leakage into surrounding tissues. Radiographically, ARIA-E is identified as vasogenic edema in the brain parenchyma or sulcal effusions in the leptomeninges/ sulci, while ARIA-H is hemosiderin deposits presenting as microhemorrhages or superficial siderosis. ARIA tends to be transient and asymptomatic in most cases, typically occurring early in the course of treatment, with the risk decreasing later in treatment. Limited data are available on continued dosing following radiographic findings of ARIA; hence, in the event of ARIA, treatment should be continued with caution and regular monitoring. Clinical trials have implemented management approaches such as temporary suspension of treatment until symptoms or radiographic signs of ARIA have resolved or permanent discontinuation of treatment. ARIA largely resolves without concomitant treatment, and there are no systematic data on potential treatments for ARIA. Given the availability of an anti-Aβ therapy, ARIA monitoring will now be implemented in routine clinical practice. The simple magnetic resonance imaging sequences used in clinical trials are likely sufficient for effective detection of cases. Increased awareness and education of ARIA among clinicians and radiologists is vital.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"9 1","pages":"211 - 220"},"PeriodicalIF":6.4,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43934024","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}
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