Alzheimer''s and Dementia: Translational Research and Clinical Interventions最新文献

{"title":"Sex, gender, sexual orientation, and more: Sexual diversity in Alzheimer's research needs a new lens to achieve inclusive research and generalizable results","authors":"Shana D. Stites,&nbsp;Beans Velocci","doi":"10.1002/trc2.12476","DOIUrl":"10.1002/trc2.12476","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Diversity, Equity, and Inclusion (DEI) efforts in Alzheimer's disease and related dementia (ADRD) research are guiding the adoption of two-step self-report questions that capture research participants’ identity based on categories of sex, sexual orientation, and gender identity. The intent is to facilitate inclusion and representation of sexual and gender minoritized (SGM) communities in ADRD research. The data from using these questions are on a collision course with another National Institute of Aging initiative, which is aimed at understanding sex differences in ADRD mechanisms. Here, we critically analyze the goals and methods of the two initiatives. We propose that, in addition to being SGM focused, DEI efforts are needed to expand how scientists consider and measure sexual diversity itself.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Sex, sexual orientation, and gender identity (SSOGI) will be asked in ADRD studies.</li>\u0000 \u0000 <li>SSOGI data will expand representation of research participant identities.</li>\u0000 \u0000 <li>SSOGI data are on a collision course with sex differences research.</li>\u0000 \u0000 <li>Both emphasize sexual diversity (SD) largely as SSOGI identity categories.</li>\u0000 \u0000 <li>Diversity, Equity, and Inclusion efforts must develop SD methods in ADRD research.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using concept mapping to identify recruitment and engagement strategies for inclusion of LGBTQIA+ populations in Alzheimer's disease and related dementia research","authors":"Brittany Klenczar-Castro,&nbsp;Krystal R. Kittle,&nbsp;Joel G. Anderson,&nbsp;Whitney Wharton,&nbsp;Andrea Gilmore-Bykovskyi,&nbsp;N. Maritza Dowling,&nbsp;Jaime Perales-Puchalt,&nbsp;Jason D. Flatt","doi":"10.1002/trc2.12477","DOIUrl":"https://doi.org/10.1002/trc2.12477","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Past Alzheimer's disease and related dementias (ADRD) research has not considered ways to ensure the representation of diverse sexual and gender minorities. This study used concept mapping (CM) to identify strategies for engaging and recruiting LGBTQIA+ older adults living with memory loss and their caregivers into ADRD research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>CM, involving brainstorming, thematic analysis, and rating of strategies, was conducted with 46 members from one national and three local community advisory boards. Data was analyzed using The Concept Systems Global MAX™ web platform.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>One hundred twenty-two solutions were identified from June through December 2022, and represented five key themes: aging focused, LGBTQIA+ specific, memory loss and caregiving support focused, physical advertisements, and other media. Promising strategies included partnering with LGBTQIA+ health centers, attending social groups for older adults, and increasing community representation in marketing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Tailored strategies, building trust, and community involvement are essential for engaging LGBTQIA+ individuals living with memory loss or ADRD and their caregivers in ADRD-focused research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Innovative ways to ensure the inclusion of LGBTQIA+ older adults in Alzheimer's disease and related dementias (ADRD) research can be bolstered through collaboration with key community stakeholders.</li>\u0000 \u0000 <li>Promising strategies for recruitment and engagement include partnering with LGBTQIA+ centers, attending social groups for older adults, and ensuring diverse representation in marketing.</li>\u0000 \u0000 <li>Tailored recruitment and engagement strategies are crucial for building trust with LGBTQIA+ populations to increase participation in ADRD research.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hearing loss and cognitive decline: Prioritizing equity in a world in which hearing health matters","authors":"Carrie L. Nieman,&nbsp;Roland J. Thorpe Jr.,&nbsp;Esther S. Oh","doi":"10.1002/trc2.12484","DOIUrl":"https://doi.org/10.1002/trc2.12484","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Alzheimer's disease and related dementias (ADRDs) and age-related hearing loss are the intersection of two major public health challenges. With age as the primary risk factor for both disease processes, the burden of ADRDs and age-related hearing loss is growing, and each field maintains significant barriers to broadscale identification and management that is affordable and accessible. With the disproportionate burden of ADRDs among racial and ethnic minority older adults and existing disparities within hearing care, both areas face challenges in achieving equitable access and outcomes across diverse populations. The publication of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) trial in July 2023 marked a significant moment in the fields of brain and hearing health. The ACHIEVE trial was the first randomized controlled trial to examine whether providing hearing intervention, specifically provision of hearing aids, compared to an education control, would reduce cognitive changes over 3 years. The participants most at risk for cognitive decline, with lower education, lower income, more likely to identify as Black, and have more cardiovascular risk factors, were the participants who benefited most from the hearing intervention and are also the least likely to be represented in research and the least likely to obtain hearing care. With growing evidence of the interconnection between cognitive and sensory health, we have an opportunity to prioritize equity, from purposeful inclusion of diverse participants in trials to influencing the emerging market of over-the-counter hearing aids to supporting expanded models of hearing care that reach those who have traditionally gone unserved. No longer can hearing go unrecognized by clinicians, researchers, and advocates for brain health. At the same time, the fields of brain and hearing health must center equity if we are going to meet the needs of diverse older adults in a world in which hearing health matters.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12484","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141439619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A service-oriented approach to clinical trial recruitment for dementia and brain health: Methods and case examples of MyAlliance for Brain Health","authors":"Eric D. Vidoni,&nbsp;Emma Swinford,&nbsp;Kelli Barton,&nbsp;Jaime Perales-Puchalt,&nbsp;C. Michelle Niedens,&nbsp;Tina Lewandowski,&nbsp;Tiffany Schwasinger-Schmidt,&nbsp;Jill Peltzer,&nbsp;JoEllen Wurth,&nbsp;Jannette Berkley-Patton,&nbsp;Ryan A. Townley,&nbsp;W. Todd Moore,&nbsp;Ashley R. Shaw,&nbsp;Mickeal N. Key,&nbsp;Erica Andrade,&nbsp;Melissa Robinson,&nbsp;Susan Sprague,&nbsp;Aiden Bondurant,&nbsp;Debra Brook,&nbsp;Jennifer Freund,&nbsp;Jeffrey M. Burns","doi":"10.1002/trc2.12475","DOIUrl":"10.1002/trc2.12475","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Recruitment of sufficient and diverse participants into clinical research for Alzheimer's disease and related dementias remains a formidable challenge. The primary goal of this manuscript is to provide an overview of an approach to diversifying research recruitment and to provide case examples of several methods for achieving greater diversity in clinical research enrollment.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The University of Kansas Alzheimer's Disease Research Center (KU ADRC) developed MyAlliance for Brain Health (MyAlliance), a service-oriented recruitment model. MyAlliance comprises a Primary Care Provider Network, a Patient and Family Network, and a Community Organization Network, each delivering tailored value to relevant parties while facilitating research referrals.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We review three methods for encouraging increased diversity in clinical research participation. Initial outcomes reveal an increase in underrepresented participants from 17% to 27% in a research registry. Enrollments into studies supported by the research registry experienced a 51% increase in proportion of participants from underrepresented communities.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;MyAlliance shifts power, resources, and knowledge to community advocates, promoting brain health awareness and research participation, and demands substantial financial investment and administrative commitment. MyAlliance offers valuable lessons for building sustainable, community-centered research recruitment infrastructure, emphasizing the importance of localized engagement and cultural understanding.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;MyAlliance led to a significant increase in the representation of underrepresented racial and ethnic groups and individuals from rural areas.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The service-oriented approach facilitated long-term community engagement and trust-building, extending partnerships between an academic medical center and community organizations.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;While effective, MyAlliance required substantial financial investment, with costs including infrastructure development, staff support, partner organization compensation, and promotional activities, underscoring the resource-intensive nature of i","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discrepancies between self- and proxy-rated quality of life in people living with dementia","authors":"Maresa Buchholz,&nbsp;Lidia Engel,&nbsp;Fabian Kleinke,&nbsp;Franka Mühlichen,&nbsp;Michelle Pfaff,&nbsp;Moritz Platen,&nbsp;Anika Rädke,&nbsp;Annelie Scharf,&nbsp;Niklas Weber,&nbsp;Neeltje van den Berg,&nbsp;Wolfgang Hoffmann,&nbsp;Bernhard Michalowsky","doi":"10.1002/trc2.12486","DOIUrl":"10.1002/trc2.12486","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The aim of this study was to analyze discrepancies between self- and proxy-rated health-related quality of life (HRQoL), measured with the EuroQol 5 Dimension 5 Level survey (EQ-5D-5L), in people living with dementia (PlwD) and their caregivers on an individual response level.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;EQ-5D-5L, sociodemographic and clinical data were obtained from baseline data of &lt;i&gt;n&lt;/i&gt; = 174 dyads of a cluster-randomized, controlled intervention trial. Self- and proxy-rated EQ-5D-5L health profiles were evaluated in terms of response distribution and agreement (weighted Kappa), and discrepancies in individual dimension level were analyzed using the Paretian Classification of Health Change (PCHC) as well as the presence and degree of inconsistencies between ratings.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;PlwD had a mean age of 80.1, nearly the half were female and 82.3% were mildly to moderately cognitively impaired. PlwD reported a higher utility index than caregiver proxies (mean 0.75 vs. 0.68, 83% of PlwD &gt; 0.5). According to the PCHC and inconsistency approach, 95% of PlwD rated their health differently compared to proxies; 66% with divergent responses in at least three EQ-5D-5L dimensions. Nine dyads (5%) showed identical ratings. Discrepancies of one higher or lower EQ-5D-5L response represented the most frequent discrepancy (35.4%). Caregivers were two times more likely to report “moderate problems,” representing the middle of the 5-point Likert scale. &lt;i&gt;Usual activities&lt;/i&gt; had the lowest agreement between ratings (weighted kappa = 0.23). In PlwD reporting no or some problems in EQ-5D-5L-dimensions, proxies were more likely to report more problems and vice versa, especially in the more observable dimension &lt;i&gt;usual activities&lt;/i&gt; and less likely in the less observable domains &lt;i&gt;pain/discomfort&lt;/i&gt; and &lt;i&gt;anxiety/depression&lt;/i&gt;.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The central tendency bias observed in proxy-ratings could be associated with assessment uncertainties, resulting in an underestimation (overestimation) in PlwD reporting better (worse) health. This diverging trend extends the knowledge from previous studies and underlines the need for more methodological research in this area.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;People living with dementia (PlwD) rate their ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Communicating Alzheimer's biomarker results to cognitively unimpaired research participants: Satisfaction, utility, and impact on research attitudes","authors":"Claire M. Erickson,&nbsp;Fred B. Ketchum,&nbsp;Kristin E. Basche,&nbsp;Nathaniel A. Chin,&nbsp;Marcella L. Eveler,&nbsp;Lindsay R. Clark","doi":"10.1002/trc2.12483","DOIUrl":"https://doi.org/10.1002/trc2.12483","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Introduction&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Recruitment and retention pose a significant challenge to Alzheimer's disease (AD) research. Returning AD biomarker results to participants has been proposed as a means to improve recruitment and retention. We present findings related to participant satisfaction, utility, and impact on research attitudes from the amyloid positron emission tomography (PET) disclosure sub-study within the Wisconsin Registry for Alzheimer's Prevention (WRAP).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Ninety-nine cognitively unimpaired WRAP participants learned their amyloid PET results (mean age ± SD = 72.0 ± 4.8). Measures of reasons for wanting to learn results, study comprehension, result utility, visit satisfaction, research attitudes, and future study enrollment willingness were collected. Between-group, chi-squared analysis was conducted to determine differences by result type (elevated vs. not elevated amyloid PET result) in study comprehension, result utility, and visit satisfaction. Linear mixed-effects modeling was used to evaluate changes in research attitudes and enrollment willingness as a function of time, amyloid result type (elevated/not elevated), and their interaction.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The reasons most frequently endorsed for wanting to learn amyloid PET result was a “desire to contribute to research on Alzheimer's disease dementia” and “to inform preventative measures [one] might take (e.g., change diet, exercise, or other lifestyle changes).” Overall, participants reported understanding the results and found learning them useful. Satisfaction with the study visits was overwhelmingly high, with over 80% agreeing with visit usefulness and their satisfaction. Few differences were found between participants who learned an elevated and not elevated result. Over the course of the study, participants who learned an elevated amyloid PET result reported higher willingness to enroll in drug trials (beta: 0.12, &lt;i&gt;p&lt;/i&gt; = 0.01) and lifestyle interventions (beta: 0.10, &lt;i&gt;p&lt;/i&gt; = 0.02) compared to participants who learned a not elevated result.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Discussion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Formal incorporation of disclosure practices may encourage participant recruitment and retention within AD research.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Participants wanted to learn their amyloid results to contri","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12483","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141326679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing tilavonemab efficacy in early Alzheimer's disease via longitudinal item response theory modeling","authors":"Xiaoxiao Zhou,&nbsp;Haotian Zou,&nbsp;Michael W. Lutz,&nbsp;Konstantin Arbeev,&nbsp;Igor Akushevich,&nbsp;Anatoli Yashin,&nbsp;Kathleen A. Welsh-Bohmer,&nbsp;Sheng Luo","doi":"10.1002/trc2.12471","DOIUrl":"https://doi.org/10.1002/trc2.12471","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Alzheimer's disease (AD) is a neurodegenerative disorder characterized by declines in cognitive and functional severities. This research utilized the Clinical Dementia Rating (CDR) to assess the influence of tilavonemab on these deteriorations.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Longitudinal Item Response Theory (IRT) models were employed to analyze CDR domains in early-stage AD patients. Both unidimensional and multidimensional models were contrasted to elucidate the trajectories of cognitive and functional severities.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We observed significant temporal increases in both cognitive and functional severities, with the cognitive severity deteriorating at a quicker rate. Tilavonemab did not demonstrate a statistically significant effect on the progression in either severity. Furthermore, a significant positive association was identified between the baselines and progression rates of both severities.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;While tilavonemab failed to mitigate impairment progression, our multidimensional IRT analysis illuminated the interconnected progression of cognitive and functional declines in AD, suggesting a comprehensive perspective on disease trajectories.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ol&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;Utilized longitudinal Item Response Theory (IRT) models to analyze the Clinical Dementia Rating (CDR) domains in early-stage Alzheimer's disease (AD) patients, comparing unidimensional and multidimensional models.&lt;/p&gt;\u0000 &lt;/li&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;Observed significant temporal increases in both cognitive and functional severities, with cognitive severity deteriorating at a faster rate, while tilavonemab showed no statistically significant effect on either domain's progression.&lt;/p&gt;\u0000 &lt;/li&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;Found a significant positive association between the baseline severities and their progression rates, indicating interconnected progression patterns of cognitive and functional declines in AD.&lt;/p&gt;\u0000 &lt;/li&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;Introduced the application of multidimensional longitudinal IRT models t","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141245715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic associations with psychosis and affective disturbance in Alzheimer's disease","authors":"Inga Margret Antonsdottir,&nbsp;Byron Creese,&nbsp;Lambertus Klei,&nbsp;Mary Ann A. DeMichele-Sweet,&nbsp;Elise A. Weamer,&nbsp;Pablo Garcia-Gonzalez,&nbsp;Marta Marquie,&nbsp;Mercè Boada,&nbsp;Emilio Alarcón-Martín,&nbsp;Sergi Valero,&nbsp;NIA-LOAD Family Based Study Consortium, Alzheimer's Disease Genetics Consortium (ADGC), AddNeuroMed Consortium,&nbsp;Yushi Liu,&nbsp;Basavaraj Hooli,&nbsp;Dag Aarsland,&nbsp;Geir Selbaek,&nbsp;Sverre Bergh,&nbsp;Arvid Rongve,&nbsp;Ingvild Saltvedt,&nbsp;Håvard K. Skjellegrind,&nbsp;Bo Engdahl,&nbsp;Ole A. Andreassen,&nbsp;Barbara Borroni,&nbsp;Patrizia Mecocci,&nbsp;Yehani Wedatilake,&nbsp;Richard Mayeux,&nbsp;Tatiana Foroud,&nbsp;Agustín Ruiz,&nbsp;Oscar L. Lopez,&nbsp;M. Ilyas Kamboh,&nbsp;Clive Ballard,&nbsp;Bernie Devlin,&nbsp;Constantine Lyketsos,&nbsp;Robert A. Sweet","doi":"10.1002/trc2.12472","DOIUrl":"10.1002/trc2.12472","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Individuals with Alzheimer's disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study's goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Genome-wide association meta-analysis of 9988 AD participants from six source studies with participants characterized for AD+P AD+A, and a joint phenotype (AD+A+P).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;AD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms. AD+A was positively correlated with anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereas AD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;It has long been known that psychotic and affective symptoms are often comorbid in individuals diagnosed with Alzheimer's disease. Here we examined for the first time the genetic architecture underlying this clinical observation, determining that psychotic and affective phenotypes in Alzheimer's disease are genetically correlated.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Nevertheless, psychotic and affective phenotypes in Alzheimer's disease diverged in their genetic correlations with psychiatric phenotypes assessed in individuals without Alzheimer's disease. Psychosis in Alzheimer's disease was negatively genetically correlated with bipolar disorder and positively with depressive symptoms, whereas the affective phenotypes in Alzheimer's disease were positively correlated with anxiety disorder and more strongly correlated than psychosis with depressive symptoms.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Psychosis in A","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11114588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative systems pharmacology-based exploration of relevant anti-amyloid therapy challenges in clinical practice","authors":"Hugo Geerts,&nbsp;Silke Bergeler,&nbsp;Mike Walker,&nbsp;Rachel H. Rose,&nbsp;Piet H. van der Graaf","doi":"10.1002/trc2.12474","DOIUrl":"https://doi.org/10.1002/trc2.12474","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Addressing practical challenges in clinical practice after the recent approvals of amyloid antibodies in Alzheimer's disease (AD) will benefit more patients. However, generating these answers using clinical trials or real-world evidence is not practical, nor feasible.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Here we use a Quantitative Systems Pharmacology (QSP) computational model of amyloid aggregation dynamics, well validated with clinical data on biomarkers and amyloid-related imaging abnormality–edema (ARIA-E) liability of six amyloid antibodies in clinical trials to explore various clinical practice challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Treatment duration to reach amyloid negativity ranges from 12 to 44, 16 to 40, and 6 to 20 months for lecanemab, aducanumab, and donanemab, respectively, for baseline central amyloid values between 50 and 200 Centiloids (CL). Changes in plasma cerebrospinal fluid Aβ42 and the plasma Aβ42/ Aβ40 ratio—fluid biomarkers to detect central amyloid negativity—is greater for lecanemab than for aducanumab and donanemab, indicating that these fluid amyloid biomarkers are only suitable for lecanemab. After reaching amyloid negativity an optimal maintenance schedule consists of a 24-month, 48-month and 64-month interval for 10 mg/kg (mpk) lecanemab, 10 mpk aducanumab, and 20 mpk donanemab, respectively, to keep central amyloid negative for 10 years. Cumulative ARIA-E liability could be reduced to almost half by introducing a drug holiday in the first months. For patients experiencing ARIA-E, restarting treatment with a conservative titration strategy resulted in an additional delay ranging between 3 and 4 months (donanemab), 5 months (lecanemab), and up to 7 months (aducanumab) for reaching amyloid negativity, depending upon the timing of the incident. Clinical trial designs for Down syndrome patients suggested the same rank order for central amyloid reduction, but higher ARIA-E liability especially for donanemab, which can be significantly mitigated by adopting a longer titration period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This QSP platform could support clinical practice challenges to optimize real-world treatment paradigms for new and existing amyloid drugs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141073768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recruiting a prospective community cohort to study Alzheimer's disease and structural and social determinants of health among adults racialized as Black: The ARCHES cohort","authors":"Alexis I. B. Walker,&nbsp;Jean-Francois Trani,&nbsp;Christian F. Banks,&nbsp;Samantha A. Murphy,&nbsp;Wenqing Zha,&nbsp;Monique M. Williams,&nbsp;Gregory S. Day,&nbsp;Yiqi Zhu,&nbsp;Beau M. Ances,&nbsp;Carl V. Hill,&nbsp;Darrell L. Hudson,&nbsp;Ganesh M. Babulal","doi":"10.1002/trc2.12473","DOIUrl":"https://doi.org/10.1002/trc2.12473","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This ongoing, prospective study examines the effectiveness of methods used to successfully recruit and retain 238 Black older adults in a longitudinal, observational Alzheimer's disease (AD) study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Recruitment strategies included traditional media, established research registries, speaking engagements, community events, and snowball sampling. Participants were asked to complete an annual office testing session, blood-based biomarker collection, optional one-time magnetic resonance imaging (MRI) scan, and community workshop.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Within the first 22 months of active recruitment, 629 individuals expressed interest in participating, and 238 enrolled in the ongoing study. Of the recruitment methods used, snowball sampling, community events, and speaking engagements were the most effective.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The systemic underrepresentation of Black participants in AD research impacts the ability to generalize research findings and determine the effectiveness and safety of disease-modifying treatments. Research to slow, stop, or prevent AD remains a top priority but requires diversity in sample representation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Provide flexible appointments in the evening or weekends, offering transportation assistance, and allowing participants to complete study visits at alternative locations, such as senior centers or community centers.</li>\u0000 \u0000 <li>Continuously monitor and analyze recruitment data to identify trends, challenges, and opportunities for improvement.</li>\u0000 \u0000 <li>Implement targeted strategies to recruit participants who are underrepresented based on sex, gender, or education to increase representation.</li>\u0000 \u0000 <li>Diversify the research team to include members who reflect the racial and cultural backgrounds of the target population, to enhance trust and rapport with prospective participants.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140949315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}