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

{"title":"Psychosocial behavioral phenotypes of racially/ethnically minoritized older adults enrolled in HABS-HD differ on neuroimaging measures of brain age gap, hippocampal volume, and cortical thickness","authors":"Alexandra L. Clark,&nbsp;Makenna B. McGill,&nbsp;Alexandra J. Weigand,&nbsp;Julie K. Wisch,&nbsp;Kalen Petersen,&nbsp;Beau Ances,&nbsp;Meredith N. Braskie,&nbsp;Sid O'Bryant,&nbsp;Kelsey R. Thomas,&nbsp;HABS-HD Study Team","doi":"10.1002/trc2.70109","DOIUrl":"https://doi.org/10.1002/trc2.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study examined whether previously identified psychosocial behavioral phenotypes differed on structural neuroimaging markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Latent profile analysis (LPA) employed in a sample of 1820 community-dwelling older adults (1118 Hispanic and 702 Black) replicated previous Low Resource/Low Distress, High Resource/Low Distress, and Low Resource/High Distress phenotype classifications. Analyses of covariance (ANCOVAs) adjusting for relevant factors examined phenotype differences on neuroimaging outcomes of predicted brain age gap (BAG) (DeepBrainNet <i>Predicted</i> Age – <i>Chronological</i> Age), hippocampal volume, and cortical thickness of a meta-temporal region of interest.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The Low Resource/Low Distress and Low Resource/High Distress phenotypes had significantly higher predicted BAGs relative to the High Resource/Low Distress phenotype, and the Low Resource/High Distress group displayed significantly lower hippocampal volumes and meta-temporal cortical thickness relative to High Resource/Low Distress phenotype.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Results highlight there are neurostructural variations across psychosocial behavioral phenotypes and indicate the Low Resource/High Distress group may be at risk for ADRD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Brain age gap (BAG), hippocampal volumes, and cortical thickness differences were tested.</li>\u0000 \u0000 <li>The High Resource/Low Distress phenotype had the most favorable imaging outcomes.</li>\u0000 \u0000 <li>The Low Resource/High Distress phenotype demonstrated the poorest imaging outcomes.</li>\u0000 \u0000 <li>Risk for Alzheimer's disease and related dementias (ADRD) may differ across psychosocial behavioral phenotypes.</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":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118098","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":"Correction to “Prophylactic evaluation of verubecestat on disease- and symptom-modifying effects in 5XFAD mice”","authors":"","doi":"10.1002/trc2.70026","DOIUrl":"https://doi.org/10.1002/trc2.70026","url":null,"abstract":"<p>Oblak AL, Cope ZA, Quinney SK, et al. Prophylactic evaluation of verubecestat on disease- and symptom-modifying effects in 5XFAD mice. <i>Alzheimers Dement</i>. 2022;8:e12317. doi: 10.1002/trc2.12317</p><p>In the submitted Supplementary Methods, we discovered a mistake where an image was duplicated in S1 and S2. This image is correctly labeled in S1, but the same image was accidentally included in S2. We have corrected this error in the attached file by replacing the image with the correct IBA1 immunohistochemistry image.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118183","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":"Association of allostatic load with all-cause and cause-specific dementia: A prospective cohort study","authors":"Yifan Gou,&nbsp;Xin Qi,&nbsp;Chen Liu,&nbsp;Jingni Hui,&nbsp;Ye Liu,&nbsp;Meijuan Kang,&nbsp;Ruixue Zhou,&nbsp;Bingyi Wang,&nbsp;Panxing Shi,&nbsp;Feng Zhang","doi":"10.1002/trc2.70108","DOIUrl":"https://doi.org/10.1002/trc2.70108","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;Allostatic load (AL) serves as a valuable tool for objectively assessing the biological impact of chronic stress and has been implicated in dementia risk. This study aims to investigate the association between AL and all-cause dementia, Alzheimer's disease (AD), vascular dementia (VaD), and non-Alzheimer non-vascular dementia (NAVD).&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 prospective study included 361,920 adults from the UK Biobank, with an observation period extending from March 13, 2006, to October 31, 2022, excluding participants with prior dementia diagnoses. AL was estimated through 10 biomarkers related to the dysregulation of metabolic, cardiovascular, and inflammatory systems. Diagnoses were based on the International Classification of Diseases, 10th Revision (ICD-10). We performed Cox proportional hazards models to assess the relationship between AL and dementia. Additionally, we conducted subgroup analyses for sex, Townsend Deprivation Index (TDI), and smoking, along with sensitivity analyses.&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 median follow-up period was 12.88 years. Over the follow-up period, 6155 (1.70%) participants developed all-cause dementia, 2762 (0.76%) developed AD, 1316 (0.36%) developed VaD, and 3790 (1.05%) developed NAVD. In the fully adjusted model, high AL was associated with an increased risk of all-cause dementia (hazard ratio [HR]: 1.269, 95% confidence interval [CI]: 1.159–1.390), VaD (HR: 1.934, 95% CI: 1.569–2.384), and NAVD (HR: 1.253, 95% CI: 1.116–1.408). Women and non-smoking individuals with high AL were vulnerable to VaD, and the associations between AL and all-cause dementia were stronger in people with high TDI.&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;AL is positively associated with an elevated risk of dementia, underscoring its effect as a risk factor in the neurodegenerative process that provokes 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 &lt;li&gt;This study estimated allostatic load (AL) index through 10 biomarkers.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The associations between AL and all-cause and cause-specific dementia were evaluated.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Elevated AL is a risk factor for all-cause dementia and vascular dementia.&lt;/li&gt;\u0000 &lt;/ul&gt;\u0000 &lt;/div&gt;\u0000 &lt;/sec","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108782","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":"Creatine monohydrate pilot in Alzheimer's: Feasibility, brain creatine, and cognition","authors":"Aaron N. Smith,&nbsp;In-Young Choi,&nbsp;Phil Lee,&nbsp;Debra K. Sullivan,&nbsp;Jeffrey M. Burns,&nbsp;Russell H. Swerdlow,&nbsp;Emma Kelly,&nbsp;Matthew K. Taylor","doi":"10.1002/trc2.70101","DOIUrl":"https://doi.org/10.1002/trc2.70101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>Preclinical studies suggest that creatine monohydrate (CrM) improves cognition and Alzheimer's disease (AD) biomarkers. However, there is currently no clinical evidence demonstrating the effects of CrM in patients with AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In this single-arm pilot trial, we investigated the feasibility of 20 g/day CrM for 8 weeks in 20 patients with AD. We measured compliance throughout; serum creatine at baseline, 4 weeks, and 8 weeks; and brain total creatine (tCr) and cognition (National Institutes of Health [NIH] Toolbox, Mini-Mental State Examination [MMSE]) at baseline and 8 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Nineteen participants achieved the target of ≥80% compliance with the CrM intervention. Serum Cr was elevated at 4 and 8 weeks (<i>p</i> &lt; .001) and brain tCr increased by 11% (<i>p</i> &lt; .001). Cognition improved on global (<i>p</i> = .02) and fluid (<i>p</i> = .004) composites, List Sorting (<i>p</i> = .001), Oral Reading (<i>p</i> &lt; .001), and Flanker (<i>p</i> = .05) tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our data suggest that CrM supplementation is feasible in AD and provides preliminary evidence for future efficacy and mechanism studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov, NCT05383833, registered on May 20, 2022.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Creatine monohydrate supplementation was feasible in patients with Alzheimer's disease.</li>\u0000 \u0000 <li>Creatine monohydrate was associated with increased brain total creatine.</li>\u0000 \u0000 <li>Creatine monohydrate was associated with improvements in cognition.</li>\u0000 \u0000 <li>Efficacy of creatine monohydrate in Alzheimer's disease should be studied further.</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":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091933","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":"Correction to Vietnamese Insights into Cognitive Aging Program (VIP): Objectives, study design, and cohort description","authors":"","doi":"10.1002/trc2.70030","DOIUrl":"https://doi.org/10.1002/trc2.70030","url":null,"abstract":"<p>We apologize for the error.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085050","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":"Dynamic neurocognitive adaptation: A follow-up exposome investigation in aging","authors":"Filippo Cieri,&nbsp;Chad Lee Cross,&nbsp;Giulia Di Francesco,&nbsp;Jessica Zoe Kirkland Caldwell","doi":"10.1002/trc2.70103","DOIUrl":"https://doi.org/10.1002/trc2.70103","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;Forty-five percent of Alzheimer's disease (AD) cases may be preventable. Validated tools for measuring environmental factors, with precision equal to that of current biological and genetic assessment tools, are currently lacking.&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 used the dynamic Neurocognitive Adaptation (dNA) scale, our validated tool to explore protective factors in AD, in 410 older adult participants (50% women). The dNA asks participants to recall cognitive, creative, physical, and social activities that they engaged in at seven different time periods in their lives. We examined associations among engagement in these domains using distance correlations and tested differences in domain engagement over time with repeated-measures analysis of variance. We calculated within-subjects comparisons for time and all interactions among time, sex, and education. We examined between-subjects factors for sex, education, and their interaction. From these models, we constructed visualizations of estimated marginal means against time to assess potential patterns of interest.&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;Physical and creative domain engagements were significantly correlated (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) in the full sample, and social engagement correlated with physical (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) and creative (&lt;i&gt;p&lt;/i&gt; = 0.047) domains among females. Cognitive engagement increased over time (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) for the full sample, while physical and creative engagement increased from childhood to adolescence, then decreased over time (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). In contrast, social engagement increased from childhood to adolescence, declined through the senior years, and then sharply increased in old age. Overall, women showed higher cognitive engagement (&lt;i&gt;p&lt;/i&gt; = 0.024) and men showed higher physical engagement (&lt;i&gt;p&lt;/i&gt; = 0.011). Education was positively related to higher scores in all domains.&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;Our scale provides new insight into the correlation of environmental factors with education, suggests areas for lifestyle intervention, and highlights the importance of sex differences and middle age as a potential transition stage.&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;Physical activity decreases and cognitive activity increases through time.&lt;/li&gt;\u0000 \u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085045","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":"Correction to “Statin therapy and risk of Alzheimer's and age-related neurodegenerative diseases”","authors":"","doi":"10.1002/trc2.70027","DOIUrl":"https://doi.org/10.1002/trc2.70027","url":null,"abstract":"<p>Torrandell-Haro G, Branigan GL, Vitali F, Geifman N, Zissimopoulos JM, Brinton RD. Statin therapy and risk of Alzheimer's and age-related neurodegenerative diseases. <i>Alzheimer's Dement</i>. 2020; 6:e12108.</p><p>In Figure 2B, there was an error in the table where the values for risk reduction (RR) (95% confidence interval [CI]) of simvastatin for dementia and multiple Sclerosis (MS) were mistakenly duplicated. The correct value for simvastatin and risk of dementia is 0.59 (0.56–0.62), whereas the risk of MS was correctly presented as 0.45 (0.33–0.61). The correction in the table within Figure 2B does not change the statistical significance. Figure 2B has been updated to reflect the correct RR (95% CI) value for dementia associated with simvastatin and to address a publication-related adjustment to the X axis of Figure 2B. We sincerely apologize for the error in the RR value for dementia in the table within Figure 2B.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085048","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":"Three approaches to determining clinically meaningful benefit on the Cohen-Mansfield Agitation Inventory in dementia clinical trials for agitation","authors":"Kathy Y. Liu,&nbsp;Chineze Ivenso,&nbsp;Rebecca Howard,&nbsp;Penny Rapaport,&nbsp;Suzanne Reeves,&nbsp;Sube Banerjee,&nbsp;Lon S. Schneider,&nbsp;Maria I. Lapid,&nbsp;Agitation MCID Study Group,&nbsp;Robert Howard","doi":"10.1002/trc2.70099","DOIUrl":"https://doi.org/10.1002/trc2.70099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>There is a need to understand the clinical meaningfulness of symptom score changes in treatment trials of dementia-related agitation. We estimated minimal clinically important differences (MCIDs) for commonly employed agitation scales and contextualized their clinical application.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We employed anchor- and distribution-based approaches to determine changes in scores corresponding to minimal symptom improvement. An opinion-based approach assessed expert clinicians’ agreement on the meaningfulness of score changes through three clinical vignettes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Minimal symptom improvement for Cohen-Mansfield Agitation Inventory total score ranged from −4 (over &lt;1 month) to −11 (over 1 to 3 months) points. Greater symptom severity correlated with higher MCID estimates. The clinical importance of score changes was influenced by treatment duration, pharmacological side effects, and impacts on caregiver distress/time resources.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The clinical meaningfulness of agitation scale MCIDs is influenced by trial-specific and clinical factors. Shorter trial durations and measuring caregiver distress/time resources enhance the clinical interpretation of agitation treatment outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>For the CMAI total score, the MCID was −4 points over shorter time scales and −11 points for longer time scales.</li>\u0000 \u0000 <li>Worse agitation severity was associated with higher MCID estimates.</li>\u0000 \u0000 <li>There was high expert consensus that a noticeable treatment benefit was not worthwhile if it occurred after 12 weeks or had no impact on caregiver/staff distress/time resources.</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":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949814","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":"How do we put meaning into meaningful benefit? Perspectives from the lived experience","authors":"Russ Paulsen,&nbsp;Carla (DeMuro) Romano,&nbsp;Terry Frangiosa,&nbsp;Margaret Mordin,&nbsp;Gabrielle J. Dardis,&nbsp;Dana DiBenedetti,&nbsp;Ronald C. Petersen,&nbsp;Jeffrey L. Cummings","doi":"10.1002/trc2.70095","DOIUrl":"https://doi.org/10.1002/trc2.70095","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Meaningful benefit is a much-debated concept in Alzheimer's disease (AD). Research to date has primarily focused on change thresholds that are anchored in clinicians’ or care partners’ impressions; however, these thresholds are not inherently meaningful to people living with AD (PLWAD) and may not take their perspectives into account. By overlaying the lived experience of AD through the eyes of individual PLWAD and their care partners with clinical outcomes, we offer an important framework in which to consider meaningful benefit in terms of symptoms, functioning, and outcomes. The PLWAD and care partner interviews and surveys of the What Matters Most (WMM) research program have identified treatment-related needs, preferences, and priorities of people at risk of or living with AD and their care partners across the AD continuum. A WMM conceptual model of disease—created and refined through interviews with PLWAD and care partners across the AD severity spectrum—includes 50 concepts across six domains (social life/activities, thought processing, communication, daily activities, mood/emotion, and general independence) considered important to all PLWAD and care partners. From the PLWAD and care partner perspectives, an increase in time to the onset, development, or worsening of the symptoms in any of these meaningful concepts was considered a meaningful benefit. No single commonly used clinical outcome assessment captures all concepts of importance, nor the importance of time in AD; considering the lived experience and priorities of individuals affected by AD is crucial to put the “meaning” in “meaningful.”</p>\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":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949954","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":"Incorporating individually defined brain health priorities in clinical trial outcomes: the electronic Person-Specific Outcome Measure approach in the United States","authors":"Stina Saunders,&nbsp;Ali Jannati,&nbsp;Shane Sheehan,&nbsp;Claudio Toro-Serey,&nbsp;Sean Tobyne,&nbsp;Killian McManus,&nbsp;David Bates,&nbsp;John Showalter,&nbsp;Álvaro Pascual-Leone","doi":"10.1002/trc2.70088","DOIUrl":"https://doi.org/10.1002/trc2.70088","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;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.&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 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 &lt;i&gt;U&lt;/i&gt; test to compare the confidence ratings between participants with and without a self-reported diagnosis of neurodegenerative disease.&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 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, &lt;i&gt;U&lt;/i&gt; = 8908, &lt;i&gt;p&lt;/i&gt; &lt; .01).&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;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.&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 ","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}