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

{"title":"Designing and implementing the IDEAL Study: A randomized clinical trial of APOE genotype disclosure for late-onset Alzheimer's disease in an urban Latino population","authors":"John B. Wetmore, Sophia Rodriguez, Daniela Diaz Caro, María Cabán, Wendy Uhlmann, Jill Goldman, Cheng-Shiun Leu, Jonathan D. Godinez, Itzel A. Camarillo, Rebecca Ferber, Drew Blasco, Rafael A. Lantigua, Ana Abraído-Lanza, Wendy K. Chung, J. Scott Roberts, Karolynn Siegel, Ruth Ottman","doi":"10.1002/trc2.70016","DOIUrl":"https://doi.org/10.1002/trc2.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The <i>Información de la Enfermedad de Alzheimer para Latinos</i> (IDEAL) Study is a randomized clinical trial investigating the psychosocial, behavioral, and cognitive impacts of apolipoprotein E (<i>APOE</i>) genotype disclosure for late-onset Alzheimer's disease (AD) among Latinos.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We used address-based sampling to recruit English- and Spanish-speaking Latinos aged 40–64 living in northern Manhattan for a community-based Baseline Survey about their knowledge and opinions about AD. Participants eligible for the clinical trial were invited to complete an Introductory Session, including AD and genetics education and informed consent, before undergoing genotyping for <i>APOE</i>. Participants were then randomized to learn their risk of AD by age 85 (range: 21%–55%) based on either Latino ethnicity and family history alone, or the same factors and their <i>APOE</i> genotype. Risk information is provided in a semi-structured genetic counseling session. Psychological impacts, health-related behavioral changes, and cognitive performance are evaluated 6 weeks, 9 months, and 15 months later via surveys and qualitative interviews. To promote cultural competence, study materials were developed by a multidisciplinary team including bilingual and bicultural staff, Latinx content experts, and genetic counselors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We sent invitations to 91,433 households; 5542 (6.1%) responded, 2120 completed the Baseline Survey (78.5% online; 21.5% via computer-assisted telephone interview), and 2087 were deemed eligible, yielding a response rate of 2.3%. Many participants expressed appreciation for the opportunity to contribute to AD research. We randomized 374 participants for the clinical trial.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>We describe the study design, recruitment and retention strategies, and interventions employed in the IDEAL Study. Our design provides a framework for future studies using rigorous mixed methods. Our findings may facilitate the development of culturally-sensitive educational materials about AD and genetic testing, as well as genetic counseling protocols, to improve coping and adjustment in response to receiving risk information.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The <i>Información de la Enfermedad de Alzheimer para La","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 4","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759858","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":"Impacts of informant replacement in two industry-sponsored Alzheimer's disease clinical trials","authors":"Mikaela K. Nishida, Michelle M. Nuño, Joshua D. Grill, Daniel L. Gillen","doi":"10.1002/trc2.70009","DOIUrl":"https://doi.org/10.1002/trc2.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>In Alzheimer's disease (AD) clinical trials, participants must enroll with a study partner informant who completes validated study instruments. We hypothesized that mid-trial informant replacement impacts study data in industry-sponsored trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We conducted a retrospective analysis of two industry-sponsored AD clinical trials testing semagacestat in mild-to-moderate AD dementia. We assessed the relationships between informant replacement and Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scores. Using generalized estimating equations, we assessed bias and variability using mean (bias) and mean absolute (variance) change in ADCS-ADL between successive visits as outcomes. Both models adjusted for a priori–specified potential confounding variables including participant sex, age, informant type, trial, time, previous ADCS-ADL score, and region. To analyze the impact on end-of-study change-from-baseline results, we used an analysis of covariance model to estimate the association between replacement and end-of-study change-from-baseline in ADCS-ADL, in which we adjusted for participant sex, age, informant type, trial, baseline measurement, and region. We conducted an <i>F</i>-test to compare the variances of this change.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Among <i>N</i> = 2637 randomized participants, 69 participants (2.6%) experienced 78 occurrences of replacement. For visits standardized to be 3 months apart, the difference in mean between-visit change in ADCS-ADL was approximately −1.61 points (95% confidence interval [CI]: −3.79, 0.57; <i>P</i> = 0.147), comparing participants who experienced replacement to similar participants who had stable informants. The difference in the mean between-visit absolute change was approximately 2.02 points (95% CI: 0.34, 3.70; <i>P</i> = 0.019). We did not estimate a statistically significant difference in end-of-study change-from-baseline (Est. = −0.70 points; 95% CI: −5.88, 4.48; <i>P</i> = 0.790) or a significant ratio of variances (Est. = 1.13; 95% CI: 0.67, 2.28; <i>P</i> = 0.600) for participants with replacement compared to those with stable informants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Informant replacement was associated with increased between-visit variability but had limited impact on overall trial outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 4","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758117","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":"Alzheimer's disease drug development in an evolving therapeutic landscape","authors":"Stacie Weninger,&nbsp;Michael C. Irizarry,&nbsp;Adam S. Fleisher,&nbsp;Teresa León,&nbsp;Paul Maruff,&nbsp;David S. Miller,&nbsp;Sheila Seleri,&nbsp;Maria C. Carrillo,&nbsp;Christopher J. Weber","doi":"10.1002/trc2.70015","DOIUrl":"https://doi.org/10.1002/trc2.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The Alzheimer's disease (AD) research field has entered a new era, where our fundamental understanding of the pathophysiology of AD and advances in biomarkers have not only allowed for earlier, timely, and accurate detection and diagnosis of the disease, but that amyloid removal has been shown to be associated with signals of slowing cognitive and functional decline. Although recent FDA-approved amyloid plaque-lowering monoclonal antibody therapies have shifted the trajectory of AD, additional treatment options will be key to further slowing clinical decline or stopping disease progression. Thus, new and emerging therapies for AD have created an evolving therapeutic landscape. The Alzheimer's Association Research Roundtable (AARR) Spring meeting held on May 23–34, 2023, brought together a broad array of scientific leaders from the AARR membership, academia, industry, and government and regulatory agencies to discuss the future of clinical trials in an era of regulator-approved amyloid-targeting therapies. Participants discussed lessons learned from other neurological diseases where disease-modifying treatments were first approved and key considerations for future clinical trials, for example, trial population real-world representativeness, duration, biomarker screening, efficacy endpoints, combination therapy, as well as overall trial design and the ethical and equity concerns that clinicians, patients, and their families face when considering clinical trial participation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The Alzheimer's Association Research Roundtable (AARR) convened leaders from industry and academia, as well as patients, clinicians, and government and regulatory agency scientists to discuss the topic, “Alzheimer's Disease Drug Development in an Evolving Therapeutic Landscape.”</li>\u0000 \u0000 <li>While recently approved amyloid-targeting therapies show great promise in providing clinically meaningful outcomes for patients and families, additional treatments, and a better understanding of dosing and administration of these approved treatments, are needed to further slow and eventually prevent clinical decline in AD.</li>\u0000 \u0000 <li>Approved therapies will impact many aspects of clinical trial design including the use of placebo-controls, participant re-enrollment, safety monitoring, as well as biomarker selection.</li>\u0000 \u0000 <li>This exciting new era in AD research represents a hopeful future for clinicians, patients, and their care partners.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 4","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758090","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":"Adaptive measurement of cognitive function based on multidimensional item response theory","authors":"Robert D. Gibbons,&nbsp;Diane S. Lauderdale,&nbsp;Robert S. Wilson,&nbsp;David A. Bennett,&nbsp;Tesnim Arar,&nbsp;David A. Gallo","doi":"10.1002/trc2.70018","DOIUrl":"https://doi.org/10.1002/trc2.70018","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;Up to 20% of older adults in the United States have mild cognitive impairment (MCI), and about one-third of people with MCI are predicted to transition to Alzheimer's disease (AD) within 5 years. Standard cognitive assessments are long and require a trained technician to administer. We developed the first computerized adaptive test (CAT) based on multidimensional item response theory (MIRT) to more precisely, rapidly, and repeatedly assesses cognitive abilities across the adult lifespan. We present results for a prototype CAT (pCAT-COG) for assessment of global cognitive function.&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;We sampled items across five cognitive domains central to neuropsychological testing (episodic memory [EM], semantic memory/language [SM], working memory [WM], executive function/flexible thinking, and processing speed [PS]). The item bank consists of 54 items, with 9 items of varying difficulty drawn from six different cognitive tasks. Each of the 54 items has 3 response trials, yielding an ordinal score (0–3 trials correct). We also include three long-term memory items not designed for adaptive administration, for a total bank of 57 items. Calibration data were collected in-person and online, calibrated using a bifactor MIRT model, and pCAT-COG scores validated against a technician-administered neuropsychological battery.&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 bifactor MIRT model improved fit over a unidimensional IRT model (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001). The global pCAT-COG scores were inversely correlated with age (&lt;i&gt;r&lt;/i&gt; = –0.44, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001). Simulated adaptive administration of 11 items maintained a correlation of &lt;i&gt;r&lt;/i&gt; = 0.94 with the total item bank scores. Significant differences between mild and no cognitive impairment (NCI) were found (effect size of 1.08 SD units). The pCAT-COG correlated with clinician-based global measure (&lt;i&gt;r&lt;/i&gt; = 0.64).&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;MIRT-based CAT is feasible and valid for the assessment of global cognitive impairment, laying the foundation for the development of a full CAT-COG that will draw from a much larger item bank with both global and domain specific measures of cognitive impairment.&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;As Americans age, numbers at risk for developing cognitive impairment are increasing.&lt;/li","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 4","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758115","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":"An environmental scan of equity-related measures for the certified nursing assistant dementia care workforce","authors":"Jasmine L. Travers,&nbsp;Shivani Shenoy,&nbsp;Julia Tague-LaCrone,&nbsp;Hillary Leger","doi":"10.1002/trc2.70012","DOIUrl":"https://doi.org/10.1002/trc2.70012","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;Certified nursing assistants (CNAs) constitute the largest segment of the nursing home workforce, with over 50% of the dementia care workforce comprised of racial and ethnic minoritized individuals. Despite their critical role in dementia care, CNAs face significant inequities in terms of salary, treatment, and working conditions. To enhance equity and improve working conditions, valid and reliable measures are essential for nursing homes to assess their current environment, track progress, and refine strategies. This paper synthesizes existing measures and tools that assess equity-related constructs among CNAs.&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;We conducted an environmental scan to identify existing measures, tools, and instruments assessing equity-related constructs among CNAs in nursing homes. Our search focused on nine key equity-related constructs: training, job satisfaction, compensation, staffing/workload, burnout, working conditions/environment, role, leadership, and turnover.&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;Our environmental scan resulted in 15 measures, tools, or instruments relevant to CNA equity. These instruments focused on job satisfaction, retention and turnover, job commitment, leadership experiences, and work environment. Sixty percent of these tools lacked reported validity or reliability data. While the remaining 40% demonstrated strong psychometric properties, overall, the methodological rigor of available measures is inconsistent. A critical gap in the existing literature is the absence of tools measuring burnout or workload, among CNAs.&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 identified measures/tools offer potential for evaluating the effectiveness of interventions addressing CNA equity. However, it is imperative to establish the validity and reliability of these instruments across diverse populations, particularly among racial and ethnic minoritized groups, and develop or adapt tools that measure burnout and workload for CNAs. Furthermore, a deeper understanding of the underlying mechanisms driving these inequities through qualitative data is crucial for developing targeted and impactful interventions.&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;Measuring equity among CNAs is important to evaluate strategies intended to improve equity.&lt;/li&gt;\u0000 \u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 4","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758118","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":"Relationship between physical activity and biomarkers of pathology and neuroinflammation in preclinical autosomal-dominant Alzheimer's disease","authors":"Edmarie Guzmán-Vélez,&nbsp;Angelys Rivera-Hernández,&nbsp;Sofia Fabrega,&nbsp;Gabriel Oliveira,&nbsp;Jairo E. Martínez,&nbsp;Ana Baena,&nbsp;Glen Picard,&nbsp;Francisco Lopera,&nbsp;Steven E. Arnold,&nbsp;J Andrew Taylor,&nbsp;Yakeel T. Quiroz","doi":"10.1002/trc2.70003","DOIUrl":"https://doi.org/10.1002/trc2.70003","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Physical activity (PA) has been linked to reduced Alzheimer's disease (AD) risk. However, less is known about its effects in the AD preclinical stage. We aimed to investigate whether greater PA was associated with lower plasma biomarkers of AD pathology, neural injury, reactive astrocytes, and better cognition in individuals with autosomal-dominant AD due to the presenilin-1 E280A mutation who are virtually guaranteed to develop dementia.&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;Twenty-eight cognitively unimpaired mutation carriers (ages x̄ = 29.28) wore a FitBit Charge-4 for 14 days. We calculated their average steps to measure locomotion, and Training Impulse (TRIMP) to quantify the intensity and duration of PAs using heart rate. Plasma amyloid beta 42/40 ratio, phosphorylated tau 181, neurofilament light chain, and glial fibrillary acidic protein (GFAP) were measured. Cognition was assessed with the Consortium to Establish a Registry for Alzheimer's Disease word list learning and delayed recall, Trail Making Test Part A, and Wechsler Adult Intelligence Scale-version IV Digit Span Backward. We conducted multiple linear regressions controlling for age, sex, body mass index, and education.&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;There were no associations among steps or TRIMP with plasma biomarkers or cognition. Greater TRIMP was related to higher GFAP levels.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;PA was not associated with cognition or plasma biomarkers. However, greater intensity and duration of PAs were related to higher GFAP. Participants engaged very little in moderate to vigorous PA. Therefore, light PA may not exert a significant protective effect in preclinical AD. Future work with larger samples and longitudinal data is needed to elucidate further the potential impact of PA on AD progression in the preclinical stages.&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;Locomotion (average steps) was not associated with plasma biomarkers or cognition.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Greater training load (training impulse) was related to higher glial fibrillary acidic protein levels in mutation carriers.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Light physical activity may not suffice to exert a protective effect on Alzheimer's disease.&lt;/li&gt;\u0000 &lt;/ul&gt;\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 4","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748938","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":"Assessment of disease impact through health-related quality of life measurement in primary progressive aphasia","authors":"Thomas Hopkins,&nbsp;Eunbi Kwon,&nbsp;Allison Lapins,&nbsp;Nathan Gill,&nbsp;Angela Roberts,&nbsp;Emily Rogalski","doi":"10.1002/trc2.12499","DOIUrl":"https://doi.org/10.1002/trc2.12499","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Measurements of health-related quality of life (HRQoL) are important for capturing disease impact beyond physical health and relative to other diseases but have rarely been assessed in primary progressive aphasia (PPA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>HRQoL was characterized overall, by sex and subtype in PPA (<i>n</i> = 118) using the Health Utilities Index-2/3 (HUI2/3). Multiple linear regression assessed associations between HRQoL and language severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Multi-attribute HUI2/3 summary scores indicated moderate to severe impairment. Scores did not differ by sex and were more severe for semantic than non-semantic PPA. Language severity scores showed significant associations with HUI multi-attribute scores and select single-attribute measures (hearing, sensation, cognition, and speech) with less language impairment associated with better functional capacity related to HRQoL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study identified poor HRQoL in a relatively large PPA cohort. HRQoL measures aid in determining patient perspective, policy decision making, and resource allocation. Results may be used to advocate for PPA support.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Primary progressive aphasia (PPA) negatively impacts health-related quality of life.</li>\u0000 \u0000 <li>Health utilities index scores are associated with Western Aphasia Battery performance in PPA.</li>\u0000 \u0000 <li>Severity of language impairment in PPA is associated with poorer quality of life.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 4","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737542","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":"Understanding recent advances in non-amyloid/non-tau (NANT) biomarkers and therapeutic targets in Alzheimer's disease","authors":"Linda J. Van Eldik,&nbsp;Eric R. Siemers,&nbsp;Emily C. Collins,&nbsp;Michael Gold,&nbsp;David Henley,&nbsp;Peter Johannsen,&nbsp;Hans J. Möbius,&nbsp;Melanie Shulman,&nbsp;Jin Zhou,&nbsp;Maria Carrillo,&nbsp;Christopher Weber","doi":"10.1002/trc2.70014","DOIUrl":"https://doi.org/10.1002/trc2.70014","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The Alzheimer's disease (AD) research community continues to make great strides in expanding approaches for early detection and treatment of the disease, including recent advances in our understanding of fundamental AD pathophysiology beyond the classical targets: beta-amyloid and tau. Recent clinical trial readouts implicate a variety of non-amyloid/non-tau (NANT) approaches that show promise in slowing cognitive decline for people with AD. The Alzheimer's Association Research Roundtable (AARR) meeting held on December 13–14, 2022, reviewed the current state of NANT targets on underlying AD pathophysiology and their contribution to cognitive decline, the current data on a diverse range of NANT biomarkers and therapeutic targets, and the integration of NANT concepts in clinical trial designs. Participants also discussed the current definition of therapies that target underlying AD pathophysiology, what endpoints best define what is considered a meaningful change beyond the current approved definition for clinical efficacy, and how the recent NANT findings should inform the development of future guidelines for AD classification and personalized treatment strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The Alzheimer's Association Research Roundtable (AARR) convened leaders from industry, academia, and government to review the current state of non-beta amyloid and non-tau (NANT) targets on underlying Alzheimer's disease (AD) pathophysiology.</li>\u0000 \u0000 <li>The totality of scientific and clinical evidence supports the hypothesis that emerging NANT targets play a role in cognitive decline and neurodegeneration in AD.\u0000</li>\u0000 \u0000 <li>New biomarkers based on NANT targets must be globally developed and implemented with specific consideration of fluid biomarkers as a cost-effective clinical option, to ensure better, more equitable treatment options for AD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 4","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685272","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":"The African Initiative for Bioinformatics Online Training in Neurodegenerative Diseases (AI-BOND): Investing in the next generation of African neuroscientists","authors":"Bernard Fongang,&nbsp;Biniyam A. Ayele,&nbsp;Yannick N. Wadop,&nbsp;Emmanuel Epenge,&nbsp;Cyrille D. Nkouonlack,&nbsp;Wepnyu Y. Njamnshi,&nbsp;Xueqiu Jian,&nbsp;Murali Sargurupremraj,&nbsp;Alice B. S. Nono Djotsa,&nbsp;Paul F. Seke Etet,&nbsp;Rebecca Bernal,&nbsp;Abdon Atangana,&nbsp;Jose E. Cavazos,&nbsp;Jayandra Jung Himali,&nbsp;Alfred N. Fonteh,&nbsp;Gladys Maestre,&nbsp;Alfred K. Njamnshi,&nbsp;Sudha Seshadri","doi":"10.1002/trc2.70002","DOIUrl":"https://doi.org/10.1002/trc2.70002","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;Neurodegenerative disorders, including Alzheimer's disease and AD-related dementias (AD/ADRD), pose significant challenges to health care systems globally, particularly in Africa. With the advances in medical technology and research capabilities, especially in next-generation sequencing and imaging, vast amounts of data have been generated from AD/ADRD research. Given that the greatest increase in AD/ADRD prevalence is expected to occur in Africa, it is critical to establish comprehensive bioinformatics training programs to help African scientists leverage existing data and collect additional information to untangle AD/ADRD heterogeneity in African populations. The South Texas Alzheimer's Disease Research Center, with efforts from the National Institutes of Health and the Global Brain Health Institute, has partnered with the Brain Research Africa Initiative to develop the &lt;b&gt;A&lt;/b&gt;frican &lt;b&gt;I&lt;/b&gt;nitiative on &lt;b&gt;B&lt;/b&gt;ioinformatics &lt;b&gt;O&lt;/b&gt;nline Training in &lt;b&gt;N&lt;/b&gt;eurodegenerative &lt;b&gt;D&lt;/b&gt;isease (&lt;b&gt;AI-BOND&lt;/b&gt;). AI-BOND is a comprehensive and accessible training program, the aim of which is to advance biostatistics and bioinformatics expertise in Africa in studying neurodegenerative diseases. This expertise is essential to enable African scientists to utilize the extensive AD/ADRD data and enhance the continent's ability to contribute to global research efforts in this field. The training addresses the gap in analyzing neurodegenerative disease data by providing skills and knowledge in genetic epidemiology, biostatistics, and bioinformatics to African students and researchers. This innovative online training program will last 6 months and provide training in skill sets R, SAS, and Python programing, genome-wide association studies, genomics, transcriptomics, proteomics, metabolomics, microbiome analysis, and advanced statistical methods. Additional training will include study design and manuscript and grant writing. The first cohort of the AI-BOND program will graduate in June 2024. The AI-BOND program is expected to build research computational capacities in Africa that will improve the ability of graduates to conduct and utilize large-scale studies, with the goal of curbing the growing incidence of neurodegenerative diseases in Africa.&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;Alzheimer's disease (AD) and AD-related dementias (ADRD) pose significant health challenges globally, particularly in Africa.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The most significant AD/ADRD prevalence increase is predicted to occur in Africa.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;It is crucial to establish a bioinformatics training capacity in Africa to leverage the vast number","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 4","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561726","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":"Predicting regional tau accumulation with machine learning-based tau-PET and advanced radiomics","authors":"Saima Rathore,&nbsp;Ixavier A. Higgins,&nbsp;Jian Wang,&nbsp;Ian A. Kennedy,&nbsp;Leonardo Iaccarino,&nbsp;Samantha C. Burnham,&nbsp;Michael J. Pontecorvo,&nbsp;Sergey Shcherbinin","doi":"10.1002/trc2.70005","DOIUrl":"https://doi.org/10.1002/trc2.70005","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 is partially characterized by the progressive accumulation of aggregated tau-containing neurofibrillary tangles. Although the association between accumulated tau, neurodegeneration, and cognitive decline is critical for disease understanding and clinical trial design, we still lack robust tools to predict individualized trajectories of tau accumulation. Our objective was to assess whether brain imaging biomarkers of flortaucipir-positron emission tomography (PET), in combination with clinical and genomic measures, could predict future pathological tau accumulation.&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;We quantified the disease profile of participants (&lt;i&gt;N&lt;/i&gt; = 276) using a comprehensive set of descriptors, including clinical/demographic (age, diagnosis, amyloid status, sex, race, ethnicity), genetic (apolipoprotein E [APOE]-ε4), and flortaucipir-PET imaging measures (regional flortaucipir standardized uptake value ratio [SUVr] and comprehensive radiomic texture features extracted from Automated Anatomical Labeling template regions). We trained an AdaBoost machine learning algorithm in a 2:1 split train-test configuration to derive a prognostic index that (i) stratifies individualized brain regions including global (AD-signature region) and lobar regions (frontal, occipital, parietal, temporal) into stable/slow- and fast-progressors based on future tau accumulation, and (ii) forecasts individualized regional annualized-rate-of-change in flortaucipir-PET SUVr. Further, we developed an adaptive model incorporating flortaucipir-PET measurements from the baseline and intermediate timepoints to predict annualized-rate-of-change.&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;In binary classification for predicting stable/slow- versus fast-progressors, the area-under-the-receiver-operating-characteristic curve was 0.86 in the AD-signature region and 0.83, 0.82, 0.84, and 0.83 in frontal, occipital, parietal, and temporal regions, respectively. The trained models successfully predicted annualized-rate-of-change of flortaucipir-PET regional flortaucipir SUVr in AD-signature and lobar regions (Pearson-correlation [&lt;i&gt;R&lt;/i&gt;]: AD-signature = 0.73; frontal = 0.73; occipital = 0.71; parietal = 0.70; temporal = 0.69). The models’ performance in predicting annualized-rate-of-change slightly increased when imaging features from intermediate timepoints were used in the adaptive setting (&lt;i&gt;R&lt;/i&gt;: AD-signature = 0.79; frontal = 0.87; occipital = 0.83; parietal = 0.74; temporal = 0.82).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 4","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142525669","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}