D Neffa-Creech, R Aggarwal, C Stowell, U Menon, S George, A Plant, J B Langbaum
{"title":"Understanding Barriers and Facilitators to Signing Up for a Mobile-Responsive Registry to Recruit Healthy Volunteers and Members of Underrepresented Communities for Alzheimer's Disease Prevention Studies.","authors":"D Neffa-Creech, R Aggarwal, C Stowell, U Menon, S George, A Plant, J B Langbaum","doi":"10.14283/jpad.2023.67","DOIUrl":"10.14283/jpad.2023.67","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) disproportionately affects Black/African American and Hispanic/Latino adults, yet they are underrepresented in AD studies. Recruitment challenges for these populations limit generalizability of findings.</p><p><strong>Objectives: </strong>This study explores barriers and facilitators to signing up for an AD participant recruitment registry website intended to optimize recruitment of these adults. The registry is geared toward recruitment on smartphones and tablets (mobile devices), as research suggests that mobile-first approaches may be more successful within these populations.</p><p><strong>Design: </strong>In 2020, we conducted four focus groups (n = 39) and an online survey (n = 1010) with Black/African American and Hispanic/Latino adults. The survey also included Whites as a comparison group.</p><p><strong>Setting: </strong>Focus groups were in-person at research facilities in New Orleans, Louisiana, and Los Angeles, California. The online survey was distributed by a survey panel company to participants nationwide.</p><p><strong>Participants: </strong>Black/African American (n = 360), Hispanic/Latino (n = 359), or White (n = 330) individuals, 45-75 years old, who self-reported not having mild cognitive impairment (MCI), dementia, or AD.</p><p><strong>Measurements: </strong>Barriers and facilitators explored in the focus groups and survey were related to health and AD (e.g., AD-related concerns and past participation/willingness to participate in health or AD studies); current use of mobile devices (e.g., comfort using devices and receptivity to the AD recruitment registry); and participant characteristics and beliefs (e.g., demographics, health literacy level, and trust in government and the scientific community).</p><p><strong>Results: </strong>The focus groups and survey revealed similar findings. Participants commonly use mobile devices to go online and perform health-related activities. They were aware of AD, expressed concerns with developing it, and were willing to participate in AD-related studies (motivated by personal connection to AD, altruism, and compensation). When presented with the AD recruitment registry, most provided positive feedback (e.g., easy to use and informative) and shared an interest in joining. Barriers to joining the registry with a mobile device included complex or multistep enrollment processes, beliefs that studies are primarily for those with a specific disease, and confusion about how studies can prevent AD among those low-risk for AD. The focus groups also revealed that Black/African American participants expressed more hesitation than Hispanic/Latinos in joining the registry due to greater distrust in the government and scientific community.</p><p><strong>Conclusions: </strong>Recruiting more Black/African American and Hispanic/Latino participants into AD studies is vitally important. This mixed methods study suggests that adults in these underrepres","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"865-874"},"PeriodicalIF":8.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10884139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66894094","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 D Howe, K J Britton, H E Joyce, G J Pappas, M A Faust, B C Dawson, M C Riddle, S P Salloway
{"title":"Initial Experiences with Amyloid-Related Imaging Abnormalities in Patients Receiving Aducanumab Following Accelerated Approval.","authors":"M D Howe, K J Britton, H E Joyce, G J Pappas, M A Faust, B C Dawson, M C Riddle, S P Salloway","doi":"10.14283/jpad.2023.96","DOIUrl":"10.14283/jpad.2023.96","url":null,"abstract":"<p><p>Aducanumab is the first FDA-approved amyloid-lowering immunotherapy for Alzheimer's disease. There is little real-world data to guide management of amyloid-related imaging abnormalities (ARIA), a potentially serious side-effect which requires surveillance with magnetic resonance imaging. We report our experiences in managing ARIA in patients receiving aducanumab at the Butler Hospital Memory and Aging Program during the year following FDA approval. We followed the Appropriate Use Recommendations for aducanumab to guide patient selection, detection, and management of ARIA (1). ARIA-E occurred in 6 out of 24 participants treated; all APOE-ε4 carriers. Treatment was discontinued in 4 cases of moderate-severe ARIA-E, temporarily held in 1 moderate case, and dosed through in 1 mild case (mean duration = 3 months, range, 1-6 months). No participants required hospitalization or high dose corticosteroids. Participants on anticoagulation were excluded and no macrohemorrhages occurred. These data support the measured approaches to treatment outlined in the Appropriate Use Recommendations.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"765-770"},"PeriodicalIF":8.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66895032","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}
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
{"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":8.5,"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}
{"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":7.8,"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
{"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":8.5,"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
{"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}
{"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
{"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
{"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}