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

{"title":"Incorporating individually defined brain health priorities in clinical trial outcomes: the electronic Person-Specific Outcome Measure approach in the United States","authors":"Stina Saunders, Ali Jannati, Shane Sheehan, Claudio Toro-Serey, Sean Tobyne, Killian McManus, David Bates, John Showalter, Álvaro Pascual-Leone","doi":"10.1002/trc2.70088","DOIUrl":"https://doi.org/10.1002/trc2.70088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>While a limited number of disease-modifying treatments for Alzheimer's disease (AD) have been approved in the United States, there is caution in adopting these treatments in clinical use. The electronic Person-Specific Outcome Measure (ePSOM) tool was recently developed to establish whether, besides modifying underlying AD pathology, new treatments exerted sufficient beneficial effects in areas that matter the most to an individual.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We conducted a study to understand how findings from the ePSOM UK study applied in the United States. The ePSOM US survey (May 2023 to January 2024) collected primarily free-text responses in personally defined brain health priorities, alongside self-reported confidence in managing these priorities. We used natural language processing (k-means clustering of GloVe vectors) and chi-squared tests to examine differences between the US and UK populations' answers. We used a Mann–Whitney <i>U</i> test to compare the confidence ratings between participants with and without a self-reported diagnosis of neurodegenerative disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Our analysis included 764 participants in the United States (68.8% female; 74.2% high educational attainment) with a total of 9010 free-text responses, of whom 53 individuals (6.90%) reported neurodegenerative disease diagnosis. The comparable sample from the UK survey included 4529 participants with a total of 38,056 responses. There were statistically significant differences in the proportion of responses between the US and UK populations. The diagnosis group showed a significant difference in average total scores of self-reported confidence compared with those without a diagnosis (median score 21, interquartile range [IQR] = 17 to 23 vs median score 24, IQR = 22 to 25, <i>U</i> = 8908, <i>p</i> < .01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our study demonstrates heterogeneity in individual-level brain health priorities in the US and differences between the US and UK populations. The diagnosis group was significantly less confident in managing personally meaningful priorities. These findings support our hypothesis that what constitutes meaningful treatment benefits should be determined at an individual rather than group level, and cultural context needs to be considered.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944469","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":"Clinical evaluation of medicines for patients with mild cognitive impairment and mild dementia due to Alzheimer's disease in Japan","authors":"Reiko Yanagihara","doi":"10.1002/trc2.70100","DOIUrl":"https://doi.org/10.1002/trc2.70100","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Lecanemab and donanemab were approved in Japan in September 2023 and September 2024, respectively, for the treatment of patients with mild cognitive impairment and mild dementia due to Alzheimer's disease. Evaluating the efficacy of these drugs requires demonstrating a clinically meaningful delay in symptom progression while ensuring an acceptable safety profile. This paper describes the efficacy assessment in the Pharmaceuticals and Medical Devices Agency's (PMDA) review, focusing on clinical endpoints, biomarker evaluations, and the role of minimal clinically important difference (MCID) in benefit–risk assessment. At present, the Clinical Dementia Rating Sum of Boxes (CDR-SB), which assesses both cognitive and functional decline, is one of the most recommended primary endpoints in confirmatory trials. Time-to-progression analysis should be also conducted to support clinical significance. Biomarker evaluations, particularly amyloid beta (Aβ) reduction, should be included as secondary endpoints to confirm the mechanism of action. Though biomarker assessments showed significant Aβ reduction for both anti-amyloid therapies, no direct correlation with clinical outcomes was observed, limiting their use as surrogate endpoints. Therefore, the MCID for clinical symptom progression suppression cannot be inferred based on Aβ reduction. Safety evaluation focused on amyloid-related imaging abnormalities (ARIAs), a key risk associated with anti-Aβ antibody treatments. Under the condition in which ARIA risk is managed through magnetic resonance imaging monitoring and predefined risk mitigation measures, PMDA considers the benefit–risk balance of these anti-amyloid therapies are favorable. While regulatory approval does not require meeting predefined MCID thresholds, it is based on a comprehensive benefit–risk assessment. For regulatory approval, future drugs will be required to demonstrate a benefit–risk balance equivalent to or more favorable than that of the approved anti-Aβ antibody drugs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Lecanemab and donanemab were approved in Japan for early Alzheimer's disease in 2023 and 2024, respectively.</li>\u0000 \u0000 <li>Drug efficacy was considered clinically meaningful after comprehensive evaluation.</li>\u0000 \u0000 <li>Biomarker evaluation, including amyloid beta (Aβ), is crucial to support the intended mechanism of action.</li>\u0000 \u0000 <li>Aβ reduction did not correlate with the suppression of clinical symptom progression in individual cases.</li>\u0000 \u0000 <li>No biomarker is validated as a surrogate, and minimal clinica","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944888","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":"Disentangling minimum clinically important difference for an individual and a population in the treatment of Alzheimer's disease","authors":"Changyu Shen,&nbsp;Robert W. Platt,&nbsp;Shibeshih Belachew,&nbsp;Hiroko H. Dodge","doi":"10.1002/trc2.70093","DOIUrl":"https://doi.org/10.1002/trc2.70093","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Recent accelerated and traditional approval of anti-amyloid therapies by the U.S. Food and Drug Administration for the treatment of patients with early Alzheimer's disease has stimulated heated debate on whether or not the benefits of these therapeutic agents achieve a minimum clinically important effect size, or minimum clinically important difference. We argue that these debates are rooted in the entanglement of two fundamentally different concepts, the minimum clinically important difference for an individual versus that of a population. At the core of the indiscrimination between the two concepts is the unrealistic requirement or expectation that a drug should provide the same clinically important effect for every patient in the target population to be considered achieving meaningful benefit for the population. We discuss the difference and connection between the two concepts to facilitate the communication about their difference and relatedness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Minimum clinically important difference (MCID) is defined for an individual and population-level mimimum clinically important difference (pMCID) is defined for a population.</li>\u0000 \u0000 <li>MCID and pMCID are fundamentally different measures.</li>\u0000 \u0000 <li>We established their connection and showed in general pMCID &lt; MCID.</li>\u0000 \u0000 <li>Discussion of effect size of Alzheimer's disease treatments should clearly distinguish the two measures.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944887","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":"Community-engaged efforts to increase retention of Black American online registry participants","authors":"Miriam T. Ashford,&nbsp;Anna Aaronson,&nbsp;Danqi Zhu,&nbsp;Xinyue Deng,&nbsp;Sandhya Kannan,&nbsp;Catherine Conti,&nbsp;Roxanne Alaniz,&nbsp;Jennefer Sorce,&nbsp;Carole Cypress,&nbsp;Derek Flenniken,&nbsp;Monica Camacho,&nbsp;Juliet Fockler,&nbsp;Diana Truran,&nbsp;R. Scott Mackin,&nbsp;Carl Hill,&nbsp;Michael W. Weiner,&nbsp;Desiree Byrd,&nbsp;Robert W. Turner II,&nbsp;Heining Cham,&nbsp;Monica Rivera Mindt,&nbsp;Rachel L. Nosheny","doi":"10.1002/trc2.70046","DOIUrl":"https://doi.org/10.1002/trc2.70046","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;Many longitudinal Alzheimer's disease studies fail to retain Black American adults once enrolled. This limits the generalizability of research findings.&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 Community-Engaged Digital Alzheimer's Research (CEDAR) study developed digital, culturally-informed, community-engaged efforts to increase longitudinal registry task completion of Black American Brain Health Registry (BHR) participants. Difference-in-differences analysis was conducted to compare longitudinal registry task completion rates within groups (before vs. after CEDAR referral) and between groups (enrolled in CEDAR vs. not enrolled).&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;Of 3888 invited Black American BHR participants, 420 (10.8%) enrolled in CEDAR. For CEDAR participants, we found significant increases in enrollment rate into referral studies and BHR timepoint completion rate after enrollment into CEDAR. Compared to those not enrolled, CEDAR participants had higher rates of: enrollment in referral studies, timepoint completion, initial questionnaire completion, and neuropsychological test completion.&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 results provide preliminary evidence that CEDAR's culturally-informed, community-engaged research efforts were effective at improving engagement of Black American adults in an online longitudinal study. This is evidenced by increased registry engagement before and after enrollment and in comparison to Black American BHR participants not enrolled in CEDAR. These results need to be interpreted cautiously due to selection biases. This strategy can be adapted to other studies and settings.&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;CEDAR is an online AD/ADRD registry engagement intervention for Black participants.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The intervention is community-engaged, digital, culturally-informed, and multifaceted.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Engagement rates increased before versus during the intervention for enrollees.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Engagement rates decreased over the same time period for non-enrolled participants.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Results need to be interpreted with caution due to selection biases.&lt;/li&gt;\u0000 &lt;/ul&gt;\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925880","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 relationship between neurofilament light chain and depressive symptoms according to cognitive status","authors":"Federico Bellelli,&nbsp;Jeremy Raffin,&nbsp;Davide Angioni,&nbsp;Julie Romana,&nbsp;Maria Soto,&nbsp;Julien Delrieu,&nbsp;Philipe De Souto Barreto,&nbsp;for the MAPT/DSA study group","doi":"10.1002/trc2.70048","DOIUrl":"https://doi.org/10.1002/trc2.70048","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;Although recent studies have suggested a positive association between plasma neurofilament light chain (NfL) and depressive symptoms, the moderating effect of cognitive performance on this relationship remains unclear. The aim of this study was to investigate the association between NfL and depressive symptoms in a population of community-dwelling older adults and to determine whether cognitive status could modify this relationship.&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;This is a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT), including 512 individuals (60.2% women) with a median age of 76 years (interquartile range [IQR]: 7) and with available data for plasmatic NfL levels. Depressive symptoms and cognitive status were assessed using the 15-item Geriatric Depression Scale (GDS-15) and the Clinical Dementia Rating (CDR) scale, respectively. Multivariable linear regression analyses were conducted to explore the cross-sectional association between GDS-15 (dependent variable) and plasma NfL levels (pg/mL). The interaction between CDR status (binary: 0 or 0.5) and NfL levels in relation to depressive symptoms was also examined, followed by exploratory simple-slope analyses according to CDR status.&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;No significant association was observed between GDS-15 scores and plasma NfL levels (&lt;i&gt;B&lt;/i&gt; = 0.002, standard error [SE] = 0.001, &lt;i&gt;p&lt;/i&gt; = 0.08) in the entire sample. Although the CDR–NfL interaction was not significant (&lt;i&gt;B&lt;/i&gt; = 0.003, SE = 0.002, &lt;i&gt;p&lt;/i&gt; = 0.17), exploratory simple-slope analyses revealed that elevated NfL levels were associated with GDS-15 scores (&lt;i&gt;N&lt;/i&gt; = 233, &lt;i&gt;B&lt;/i&gt; = 0.004, SE = 0.002, &lt;i&gt;p&lt;/i&gt; = 0.03) among individuals with a CDR 0.5, but not among those with a CDR 0 (&lt;i&gt;N&lt;/i&gt; = 186, &lt;i&gt;p&lt;/i&gt; = 0.81).&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;NfL levels were not significantly associated with GDS-15 in a population of community-dwelling older adults without dementia. Although no significant CDR–NfL interaction was detected, exploratory analyses suggest that plasma NfL might be associated with GDS-15 scores only among people with a CDR 0.5 (indicative of mild cognitive impairment). Further studies with larger sample sizes are needed to elucidate the potential biological differences in depressive symptoms across different cognitive statuses.&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 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925872","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":"Safety considerations of semaglutide in the potential treatment of Alzheimer's disease: A pooled analysis of semaglutide in adults aged ≥ 65 years","authors":"Marwan Sabbagh,&nbsp;Cristina Boschini,&nbsp;Sharon Cohen,&nbsp;Magnus Fugger,&nbsp;Frank Jessen,&nbsp;Sune Dandanell,&nbsp;Sue D. Pedersen,&nbsp;Luis Rafael Solís Tarazona,&nbsp;Vanita R. Aroda","doi":"10.1002/trc2.70076","DOIUrl":"https://doi.org/10.1002/trc2.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The evoke/evoke+ trials are investigating semaglutide in a population with early Alzheimer's disease (AD). Specific analyses of semaglutide safety data in older adults are limited; therefore, in the current analysis, we aimed to evaluate safety considerations with semaglutide in adults ≥ 65 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Adverse event (AE) data from three semaglutide phase 3a programs in participants ≥ 65 years with type 2 diabetes and/or overweight/obesity were pooled. Change in body weight was also assessed in a smaller subset of participants ≥ 65 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The analysis included 3529 participants ≥ 65 years. Baseline mean age and body mass index in participants ≥ 65 years were 69.3 to 70.2 years and 29.7 to 35.4 kg/m², respectively, compared to 47.8 to 58.5 years and 31.3 to 36.7 kg/m² in the overall population. AEs with semaglutide occurred in 73.6% to 92.4% of participants ≥ 65 years versus 73.2% to 90.8% of the overall population. AEs with semaglutide leading to permanent discontinuation appeared to be more frequent in participants ≥ 65 years (9.3%–12.4%) versus the overall population (5.7%–8.7%). Gastrointestinal disorders were the most frequently reported AEs with semaglutide in participants ≥ 65 years (44.6%–73.8%) and in the overall population (39.1%–73.4%). Participants aged ≥ 65 years receiving semaglutide had an estimated weight loss of 3.8% at week 52 compared to 0.1% with placebo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Age ≥ 65 years did not appear to affect the safety considerations of semaglutide. The ongoing evoke/evoke+ trials will elucidate the balance of efficacy and safety in the treatment of early AD with semaglutide.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>This was a post hoc analysis evaluating adverse event (AE) data of semaglutide in people ≥ 65 years.</li>\u0000 \u0000 <li>The most common AE with semaglutide was gastrointestinal (GI).</li>\u0000 \u0000 <li>GI event rates were similar in people ≥ 65 years and the overall study populations.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914374","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":"Constructive engagement in cognitive stimulation therapy groups among people with dementia: A mixed-methods study","authors":"Anna Yan Zhang,&nbsp;Gloria Hoi Yan Wong,&nbsp;Terry Yat Sang Lum,&nbsp;Bob Woods,&nbsp;Aimee Spector","doi":"10.1002/trc2.70075","DOIUrl":"https://doi.org/10.1002/trc2.70075","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;Clinical guidelines recommend personalized activities and group cognitive stimulation therapy (CST) for promoting cognition, independence, and well-being in persons with dementia. Constructive engagement (CE), the state of being occupied positively in purposeful activities, is theoretically an essential process in personalized activities and CST. However, whether CE develops over time and what contributes to it are unknown. We investigated changes in CE during CST and its contributors.&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;This is a mixed-methods study. We used time sampling to record the time proportion of persons with dementia (&lt;i&gt;n&lt;/i&gt; = 113) spent in constructive, passive, non–task-related engagement and non-engagement during early, middle, and late phases in a 14-session group CST. We tested changes in time proportion between phases using repeated analysis of variance (ANOVA). We analyzed qualitative interviews of CST facilitators (&lt;i&gt;n&lt;/i&gt; = 12) thematically to explore contributors to CE.&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;Persons with dementia spent 51% and 46% of their time in constructive and passive engagement, respectively. Time of engagement in non–task-related activities and non-engagement was minimal. CE remained stable at around 50% of activity time throughout the intervention course, except for a slight increase from the early to middle phase (48% to 55%, F (2224) = 3.779, &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Age (&lt;i&gt;r &lt;/i&gt;= −0.26, &lt;i&gt;p&lt;/i&gt; &lt; 0.01), cognitive function (&lt;i&gt;r &lt;/i&gt;= −0.29, &lt;i&gt;p&lt;/i&gt; &lt; 0.01), and activities of daily living (&lt;i&gt;r &lt;/i&gt;= 0.20, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) at baseline were significantly correlated with CE, but gender and education were not. Contributors to CE include (1) tailoring activities, (2) using group dynamics, and (3) promoting positive experiences.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Discussions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Group CST engages persons with dementia well, regardless of their differences in gender and literacy levels. CE remained relatively stable during CST, and younger, more physically and cognitively able people showed slightly greater CE. In group-based interventions, facilitators' skills and techniques could enhance CE. Future studies may focus on how CE as a plausible change mechanism further improves the intervention outcomes of persons with dementia.&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 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865827","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":"AI approaches for phenotyping Alzheimer's disease and related dementias using electronic health records","authors":"Sara Knox,&nbsp;Stephanie Aghamoosa,&nbsp;Paul M. Heider,&nbsp;Maxwell Cutty,&nbsp;Andrew Wright,&nbsp;Dmitry Scherbakov,&nbsp;Gabriel Hood,&nbsp;Sara A. Nolin,&nbsp;Jihad S. Obeid","doi":"10.1002/trc2.70089","DOIUrl":"https://doi.org/10.1002/trc2.70089","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 current standard electronic (e-)phenotype for identifying patients with Alzheimer's disease and related dementias (ADRD) from medical claims data yields suboptimal diagnostic accuracy. This study leveraged artificial intelligence (AI)–based text-classification methods to improve the identification of patients with dementia due to ADRD using clinical notes from electronic health records (EHRs).&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;EHR data for patients aged ≥ 64 (&lt;i&gt;N&lt;/i&gt; = 4000) from an academic medical center were used. The cohort included 1000 patients with ADRD per the Chronic Conditions Warehouse (CCW) algorithm for ADRD (i.e., at least one ADRD International Classification of Diseases, Tenth Revision codes [ICD-10 code]) and 3000 matched controls without ADRD (i.e., no CCW codes). We trained several AI-based text-classification models, including bag-of-words models, deep learning, and large language models (LLMs), to make ADRD determinations from clinical notes. The performance of each model was evaluated against “gold standard” manual chart review.&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;A foundational LLM derived from Llama 2 demonstrated superior performance in identifying patients with ADRD (area under the curve [AUC] = 0.9534, &lt;i&gt;F&lt;/i&gt;&lt;sub&gt;1&lt;/sub&gt; score 0.8571) compared to both the current standard CCW algorithm (AUC = 0.8482, &lt;i&gt;F&lt;/i&gt;&lt;sub&gt;1&lt;/sub&gt; score 0.8323, although only the AUC was statistically significantly different) and other AI-based models. Several of the AI-based models, including convolutional neural networks, also outperformed the CCW algorithm.&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;These findings highlight the potential of AI-based text-classification methods to optimize the automated identification of patients with ADRD using rich EHR data. However, the success of this approach depends on the quality of clinical notes, and more work is needed to refine and validate these methods across more diverse data sets.&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;The current e-phenotype for patients with Alzheimer's disease and related dementias (ADRD) in electronic health records has suboptimal diagnostic accuracy.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The study used artificial intelligence (AI)–based text classification methods to improve the detection of patients with A","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871605","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":"Supporting dementia caregivers: The role of “lived experience” and public health collaboration","authors":"Chelsea Kline,&nbsp;Elma Johnson,&nbsp;Ellen Tambor,&nbsp;Catherine Woodall Colcombe,&nbsp;Sam Fazio,&nbsp;Greg Woods,&nbsp;Dale Rivard,&nbsp;Gary Epstein-Lubow","doi":"10.1002/trc2.70087","DOIUrl":"https://doi.org/10.1002/trc2.70087","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Developing effective resources to support dementia caregivers requires collaboration between public health officials and those with lived experience of caregiving. This perspective highlights why this collaboration is so crucial to elevating public health practice and describes the unique efforts of the BOLD Public Health Center of Excellence on Dementia Caregiving to foster this collaboration through its Lived Experience Advisory Groups (LEAG). The LEAGs convene people living with dementia, family caregivers, and public health officials to guide the development of resources that state, local, and tribal public health departments can use to support dementia caregivers in their communities. Through these interactions, public health strategies become more responsive to the real-life needs of caregivers and people living with dementia. This approach not only enhances caregiver support but also strengthens and aligns public health initiatives with the lived experiences of the populations they serve, fostering health equity and community engagement. This paper highlights key activities, outcomes, and future directions for integrating lived experience and public health perspectives into practice, offering a new and innovative model for other organizations seeking to improve support for dementia caregivers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Public engagement enhances responsiveness and effectiveness of public health programs.</li>\u0000 \u0000 <li>LEAGs allow people with lived experience to help shape programs and facilitate collaboration with public health professionals.</li>\u0000 \u0000 <li>Local and state health agencies can improve engagement by implementing LEAGs.</li>\u0000 \u0000 <li>Increasing diversity of people with lived experience can improve outcomes for communities disproportionately impacted by dementia.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871606","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":"Machine learning–enhanced screening funnel for clinical trials in Alzheimer's disease","authors":"Scott Gladstein,&nbsp;Liuqing Yang,&nbsp;Dustin Wooten,&nbsp;Xin Huang,&nbsp;Robert Comley,&nbsp;Qi Guo,&nbsp;the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/trc2.70084","DOIUrl":"https://doi.org/10.1002/trc2.70084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) clinical trials with therapeutic interventions require hundreds of subjects to be studied over many months/years due to variable and slow disease progression. This article presents a novel screening paradigm integrating disease progression models to improve trial efficiency by identifying appropriate candidates for early phase clinical studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A traditional screening funnel is enhanced using machine learning models, including 3D convolutional neural networks and ensemble models, which integrate neuroimaging, demographic, genetic, and clinical data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>This approach predicts clinical progression (2-year Clinical Dementia Rating Sum of Boxes change &gt; 1) with an area under the curve of 0.836. Incorporating it into trials (with maximized sensitivity/specificity optimization) could reduce the number of subjects required by 55%, shorten recruitment by 13 months, and reduce screening amyloid positron emission tomography scans by 72%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>By reducing patient burden and shortening timelines in clinical trials, this enhanced screening funnel could accelerate the development of AD therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>An innovative screening funnel was developed to improve Alzheimer's disease clinical trial efficiency.</li>\u0000 \u0000 <li>The funnel incorporates machine learning (ML)–based disease progression models.</li>\u0000 \u0000 <li>The ML model identifies patients with progression rate optimal for clinical trials.</li>\u0000 \u0000 <li>Unsuitable patients would fail early in the funnel before burdensome imaging procedures.</li>\u0000 \u0000 <li>This screening funnel is customizable to specific study needs.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865894","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}