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

{"title":"Alzheimer's disease drug development pipeline: 2025","authors":"Jeffrey L. Cummings,&nbsp;Yadi Zhou,&nbsp;Garam Lee,&nbsp;Kate Zhong,&nbsp;Jorge Fonseca,&nbsp;Amanda M. Leisgang-Osse,&nbsp;Feixiong Cheng","doi":"10.1002/trc2.70098","DOIUrl":"https://doi.org/10.1002/trc2.70098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Clinical trials for Alzheimer's disease (AD) must be registered on clinicaltrials.gov. The registry presents a variety of types of information related to the planned clinical trial. We assess clinicaltrials.gov to document and compare aspects of drug development across the AD pipeline. Currently, there are 138 drugs being assessed in 182 clinical trials in the AD pipeline. Biological disease-targeted therapies (DTTs) comprise 30% of the pipeline; small molecule DTTs account for 43% of the pipeline; drugs addressing cognitive enhancement account for 14% of the pipeline; and drugs aiming to ameliorate neuropsychiatric symptoms in participants with AD contribute 11% of the pipeline. Biomarkers are among the primary outcomes of 27% of active trials. Repurposed agents represent 33% of the pipeline agents. The pipeline has more trials and more drugs compared to the 2024 pipeline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The 2025 Alzheimer's disease drug development pipeline hosts 182 trials and 138 novel drugs.</li>\u0000 \u0000 <li>The 2025 Alzheimer's disease drug development pipeline is diverse, with agents that address 15 basic disease processes.</li>\u0000 \u0000 <li>The 2025 Alzheimer's disease drug development pipeline has more trials and more drugs than the 2024 pipeline.</li>\u0000 \u0000 <li>Biomarkers play an important role in current trials to determine trial eligibility and as outcomes of trials.</li>\u0000 \u0000 <li>Repurposed agents comprise approximately one-third of the agents and trials in the 2025 Alzheimer's disease drug development pipeline.</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":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197228","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":"Digital biomarkers: Redefining clinical outcomes and the concept of meaningful change","authors":"Maria Florencia Iulita,&nbsp;Emmanuel Streel,&nbsp;John Harrison","doi":"10.1002/trc2.70114","DOIUrl":"https://doi.org/10.1002/trc2.70114","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;MCID (minimal clinically important difference) is a patient-centered concept used in clinical research that represents the smallest change that someone living with Alzheimer's disease would identify as important. There are several challenges associated with the universal application of this construct. Alzheimer's disease progresses differently for each individual, complicating the establishment of a universal standard that accounts for individual-level issues. Alzheimer's disease is also a gradual and evolving disorder, and what is perceived as clinically meaningful can vary significantly at early and late disease stages. People living with Alzheimer's disease and caregivers may have differing perspectives on the benefits of treatment outcomes, making it more challenging to establish an appropriate MCID. Moreover, Alzheimer's trials rely on a variety of tests to evaluate cognitive and functional impairments. However, these tests often lack sensitivity to early-stage changes and are affected by variability in rater rankings. Digital biomarkers and advanced health technologies have emerged as a hot topic in modern medicine. They offer a promising approach for detecting real-time, objective clinical differences and improving patient outcomes by enabling continuous monitoring, individualized assessments, and leveraging artificial intelligence learning for complex analytical predictions. However, while these advancements hold great potential, they also raise important considerations around standardization, accuracy, and integration into current clinical frameworks. As new technologies are introduced alongside evolving regulatory frameworks, the primary focus must remain on outcomes that truly matter to people living with Alzheimer's disease and their caregivers, ensuring that the principle of clinical meaningfulness is not lost.&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;Minimal clinically important difference (MCID) represents the smallest change in a patient's condition that would be considered meaningful, but defining this for Alzheimer's disease is challenging due to its heterogeneity.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The perception of what is clinically meaningful may differ at the individual level, at different disease stages within the same individual, and between patient and caregiver.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Traditional tests used as endpoints in Alzheimer's trials lack the sensitivity to detect subtle changes and are limited by range restrictions, making them less effective for accurately capturing treatment efficacy.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Digital biomarkers and artificial intelligence (AI)-driven heal","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197051","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":"Therapeutic time window of disease-modifying therapy for early Alzheimer's disease","authors":"Saki Nakashima,&nbsp;Kenichiro Sato,&nbsp;Yoshiki Niimi,&nbsp;Ryoko Ihara,&nbsp;Kazushi Suzuki,&nbsp;Atsushi Iwata,&nbsp;Tatsushi Toda,&nbsp;Takeshi Iwatsubo,&nbsp;for Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/trc2.70102","DOIUrl":"https://doi.org/10.1002/trc2.70102","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;Recently approved disease-modifying therapies (DMT) for early Alzheimer's disease (AD), including lecanemab and donanemab, require patients to meet specific eligibility criteria for treatment. These criteria define a limited “therapeutic time window,” after which patients become ineligible as the disease advances. Understanding factors influencing this window may help clinicians optimize patient management and reduce lost treatment opportunities.&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 analyzed longitudinal data from two observational cohorts, the National Alzheimer's Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). At each visit, individuals were deemed eligible if they were amyloid-positive and had a Mini-Mental State Examination (MMSE) score of 22–30 (lecanemab) or 20–30 (donanemab), plus a Clinical Dementia Rating-Global Score (CDR-GS) of 0.5 or 1. We then applied survival analyses and Cox proportional hazards models to estimate time-to-ineligibility based on baseline cognitive 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;Across both datasets, higher baseline CDR-GS and MMSE were associated with a lower risk of becoming ineligible (pooled hazard ratio of 1.601 for CDR-GS of 1 vs. 0.5, and pooled hazard ratio of 0.660 per 1-point increase in MMSE score above the lower limit of eligibility). The estimated 75% survival time for patients with baseline CDR-GS 0.5 was over 12 months, suggesting only 25% would become ineligible within 12 months. For those with CDR-GS 1, the estimated 50% survival time was approximately 12 months, depending on the data, indicating that half might become ineligible within 1 year.&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;We quantitatively outlined the duration of the therapeutic time window for early AD patients who qualify for lecanemab or donanemab, which is significantly influenced by baseline CDR-GS and MMSE scores. These findings will support more proactive patient management, ensuring timely evaluations and prioritization of patients at higher risk of ineligibility, particularly where DMT access is limited.&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;We examined the “therapeutic time window” eligibility for disease-modifying therapy.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Longitudinal data from National Alzheimer's Coordi","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171898","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":"APOE ε4-independent pathways predominate in the association between retinal nerve fiber layer thinning and 12-year incident dementia","authors":"Yuzhuo Wang,&nbsp;Xiaoxi Ma,&nbsp;Haoze Cen,&nbsp;Jie Wang,&nbsp;Jie Wu,&nbsp;Ding Ding,&nbsp;Yiqin Xiao,&nbsp;Qianhua Zhao","doi":"10.1002/trc2.70104","DOIUrl":"https://doi.org/10.1002/trc2.70104","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;Emerging evidence links retinal nerve fiber layer (RNFL) thinning to cognitive impairment, while the apolipoprotein E (&lt;i&gt;APOE&lt;/i&gt;) ε4 allele, the key genetic dementia risk factor, is also found to be associated with RNFL thickness. This study investigated the longitudinal association between RNFL thinning and 12-year dementia risk, evaluated the role of &lt;i&gt;APOE&lt;/i&gt; ε4 in this relationship, and clarified the independent value of retinal imaging as a predictive biomarker for 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;This study included 35,433 participants from the UK Biobank. Generalized linear models and Jonckheere-Terpstra tests assessed the association between &lt;i&gt;APOE&lt;/i&gt; ε4 allele dosage and macular RNFL (mRNFL) thickness. Cox models evaluated the association between mRNFL thickness and incident dementia. To address potential confounding by &lt;i&gt;APOE&lt;/i&gt; ε4, inverse probability weighting was applied. Mediation analysis quantified the contribution of &lt;i&gt;APOE&lt;/i&gt; pathways to the mRNFL-dementia association.&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;Among 35,433 participants, 392 (1.11%) developed dementia over a median follow-up of 12.49 years (interquartile range: 12.39 to 12.64). &lt;i&gt;APOE&lt;/i&gt; ε4 carriers exhibited a dose-dependent reduction in mRNFL thickness (β = −0.14, 95% confidence interval [CI]: −0.23 to −0.05, &lt;i&gt;p&lt;/i&gt; = 0.002). After adjusting for age, sex, vascular risk factors, and &lt;i&gt;APOE&lt;/i&gt; ε4 carrier status, the lowest mRNFL quintile group had a 64% higher dementia risk compared to the highest quintile (hazard ratio [HR] = 1.64, 95% CI: 1.17 to 2.30, &lt;i&gt;p&lt;/i&gt; = 0.004). Each 5-µm reduction in mRNFL thickness corresponded to a 15% increased risk (HR = 1.15, 95% CI: 1.02 to 1.30, &lt;i&gt;p&lt;/i&gt; = 0.02), which remained significant after inverse probability weighting. Mediation analysis revealed that &lt;i&gt;APOE&lt;/i&gt; pathways accounted for 7.6% (95% CI: 2.6% to 28.6%, &lt;i&gt;p&lt;/i&gt; = 0.01) of the mRNFL-dementia association.&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 findings resolve a controversy by showing that while &lt;i&gt;APOE&lt;/i&gt; ε4 accelerates mRNFL degeneration, retinal imaging captures dementia-related neuropathology through pathways distinct from direct &lt;i&gt;APOE&lt;/i&gt; effects, solidifying its potential as an etiologically informative biomarker.&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 association between","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171912","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":"Physical activity may mitigate sleep-related cognitive deficits in older adults: Findings from the IGNITE study","authors":"Kelsey R. Sewell,&nbsp;Audrey M. Collins,&nbsp;Lauren E. Oberlin,&nbsp;Miranda G. Chappel-Farley,&nbsp;Haiqing Huang,&nbsp;George Grove,&nbsp;John M. Jakicic,&nbsp;Arthur F. Kramer,&nbsp;Edward McAuley,&nbsp;Jeffrey M. Burns,&nbsp;Charles H. Hillman,&nbsp;Eric D. Vidoni,&nbsp;Anna L. Marsland,&nbsp;Chaeryon Kang,&nbsp;Lu Wan,&nbsp;Kristine A. Wilckens,&nbsp;Kirk I. Erickson","doi":"10.1002/trc2.70110","DOIUrl":"https://doi.org/10.1002/trc2.70110","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;Poor sleep is commonly associated with poorer cognition in older adults. Unfortunately, effective sleep improvement therapies for older adults are limited in their accessibility and have shown only subtle effects on cognition. Physical activity, however, is associated with better cognition in older adults and may compensate for cognitive deficits related to poor sleep. This study examined whether greater engagement in physical activity moderates the association between sleep and cognitive function in older adults.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODOLOGY&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We utilized baseline data from the Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE) study. Cognitively unimpaired older adults (&lt;i&gt;n&lt;/i&gt; = 589, mean age ± SD: 69.8 ± 3.7, 70% female) underwent a comprehensive cognitive assessment. Sleep was measured via the Pittsburgh Sleep Quality Index (PSQI), and both sleep and physical activity were measured using 24-h actigraphy for 7 days.&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;Moderate-to-vigorous physical activity (MVPA) accumulated in at least 10-min bouts moderated the association between self-reported sleep efficiency and episodic memory, processing speed, executive function (EF)/attentional control, and working memory (β&lt;sub&gt;[range]&lt;/sub&gt; = −0.10 to −0.17, all &lt;i&gt;p &lt;/i&gt;&lt; 0.05). In addition, light-intensity physical activity moderated the association of actigraphy-measured wake after sleep onset (WASO) with EF/attentional control and processing speed (β&lt;sub&gt;s&lt;/sub&gt; = 0.10, all &lt;i&gt;p&lt;/i&gt; &lt; 0.05). The direction of these results was such that lower sleep efficiency and greater WASO was associated with poorer cognitive performance, but this association was attenuated by engaging in greater amounts of physical activity.&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 results support the hypothesis that physical activity may mitigate the association between poor sleep and cognitive deficits in older adulthood. We highlight the need for further longitudinal studies and randomized clinical trials of exercise to further examine these associations. These results suggest that even small amounts of MVPA or light intensity physical activity mitigate the association between poor sleep and cognitive deficits in older adulthood.&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;Moderate-to-vigoro","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171911","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":"What is older adults’ understanding of Alzheimer's disease research registries? Findings from 20 focus group studies","authors":"Litty Samuel,&nbsp;Katelynn Kuijpers,&nbsp;Erin K. Maloney,&nbsp;Jessica B. Langbaum,&nbsp;Amy Bleakley","doi":"10.1002/trc2.70111","DOIUrl":"https://doi.org/10.1002/trc2.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Research registries address the challenges associated with enrollment of individuals in research studies by matching members to current studies and trials in need of participants. However, recruitment into research registries can be challenging as many lack awareness regarding research registries and need to be educated on their existence, purpose, and significance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The present study uses data from 20 online focus groups conducted in English with Black (<i>n</i> = 89), White (<i>n</i> = 83), and Hispanic (<i>n</i> = 44) older adults to investigate their understanding of research registries. Participants were recruited through paid advertisements, and the focus groups were conducted between September 2022 and 2023 with a sample of 188 adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>There was a general lack of awareness about Alzheimer's disease (AD) research registries. Participants expressed unfamiliarity with the concept of AD research registries, confusion about eligibility criteria and their purpose, and often conflated them with individual clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Research registries can play a crucial role in identifying and referring potential participants to AD prevention studies. Given the lack of understanding about registries, interventions such as messaging with familiar language can help to address lack of awareness and increase enrollment into AD research registries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>A better understanding of older adults’ perceptions about research registries.</li>\u0000 \u0000 <li>More relatable and easy-to-comprehend messaging is needed to raise awareness of research registries.</li>\u0000 \u0000 <li>Targeted messaging strategies are needed to recruit participants directly into Alzheimer's disease (AD) clinical trials.</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":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148289","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 the impact of amyloid beta targeted therapies on biomarkers and clinical endpoints in Alzheimer's disease","authors":"Ronald C. Petersen,&nbsp;Ana Graf,&nbsp;Alexandra S. Atkins,&nbsp;Miroslaw Brys,&nbsp;Jennifer Murphy,&nbsp;David S. Miller,&nbsp;Larisa Reyderman,&nbsp;Eric Siemers,&nbsp;Janice Smith,&nbsp;Maria C. Carrillo,&nbsp;Christopher J. Weber","doi":"10.1002/trc2.70069","DOIUrl":"https://doi.org/10.1002/trc2.70069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The Alzheimer's disease (AD) scientific field continues to make significant advances in early detection and treatments, which importantly rest on advances in our fundamental understanding of AD pathobiology and its contribution to cognitive decline. Clinical readouts of monoclonal antibodies against various forms of the amyloid beta (Aβ) protein indicate that the impact of these treatments may extend beyond reduction in amyloid plaques. The Alzheimer's Association Research Roundtable meeting held on May 17 and 18, 2022, reviewed our understanding to date of the impact of treatments targeting various species of Aβ; its impact on other related pathophysiology including tau; and ultimately, its effects on neurodegeneration and clinical decline, driven by the latest available data. Participants discussed the current evidence for a causal relationship among amyloid accumulation, tau alteration, and cognitive decline; the effect of anti-amyloid therapies on clinical and biomarker endpoints; and how we can accelerate the pathway to therapeutic approval and what should guide us for the near future.</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 convened leaders from industry and academia, as well as patients, clinicians, and government and regulatory agency scientists to discuss the topic “Current Understanding of AD Pathophysiology &amp; Impact of Amyloid-beta Targeted Treatments on Biomarkers and Clinical Endpoints.”</li>\u0000 \u0000 <li>The totality of scientific evidence (clinical trials, animal data, modeling, and observational studies) on the relationship between amyloid beta (Aβ), amyloid, tau, and cognitive impairment is helping our understanding of the downstream effects and overall importance of lowering amyloid plaque load.</li>\u0000 \u0000 <li>Based on data from multiple phase 2 and 3 clinical trials of anti-amyloid monoclonal antibodies, there is strong evidence to support that a sufficiently large reduction in amyloid plaque load to near-normal levels is associated with positive changes in tau biomarkers and clinical endpoints.</li>\u0000 \u0000 <li>Reduction of Aβ plaque, measured easily by plasma amyloid biomarkers, is reasonably likely to predict benefit in clinical outcome 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":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A psychometric study of the Flourishing Scale for people living with dementia","authors":"Chris Clarke,&nbsp;Kalpita Baird,&nbsp;Esme Moniz-Cook,&nbsp;Gail Mountain,&nbsp;Emma Wolverson,&nbsp;Ellen Lee,&nbsp;Catherine Hewitt","doi":"10.1002/trc2.70097","DOIUrl":"https://doi.org/10.1002/trc2.70097","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;There are few validated strengths-based outcome measures for evaluations of psychosocial interventions in dementia and measurement of the concept of flourishing has not been directly explored. This study therefore examined the psychometric properties of the Flourishing Scale (FS)—an eight-item generic self-report measure of social-psychological well-being—and how it might be adapted for people with dementia.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHOD&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A secondary data analysis of baseline data from the &lt;i&gt;Journeying Through Dementia&lt;/i&gt; study, a randomized controlled trial of a self-management intervention for older adults with dementia living in the community in the United Kingdom (&lt;i&gt;n&lt;/i&gt; = 480). Confirmatory Factor Analysis (CFA), Item Response Theory (IRT) analyses, and convergent/discriminatory analyses were undertaken.&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;Moderate negative skew in total FS scores was noted and adjusted for. A good level of internal consistency reliability was evident (alpha = 0.83). Both CFA and IRT analyses verified the unidimensionality of the scale and there was evidence of item discrimination. Measurement precision appeared greater for lower to moderate levels of well-being, with some item-level variation. Total FS scores were significantly associated with quality of life, self-efficacy, and mood, supporting convergent validity. FS total scores were not associated with cognitive ability or time since diagnosis in this sample but were associated with living alone / with others.&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 offer new avenues for strengths-based research and practice of psychosocial interventions for people with dementia in relation to the measurement social-psychological well-being. The FS shows promise as a valid and reliable self-report instrument for people with early-stage dementia but further validation research is needed to confirm optimum item content and responsiveness. The measurement of well-being of people living with moderate to severe cognitive impairments requires further research.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Previous work suggests that well-being in dementia could align with the concept of flourishing—optimized social-psychological well-being—but valid and reliable measurement of flourishing in dementia has not yet been directly e","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126036","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":"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}