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

{"title":"Associations between neuronavigated rTMS-mediated functional connectome plasticity and neurotransmitter receptors in Alzheimer's disease","authors":"Weina Yao,&nbsp;Tingyu Lv,&nbsp;Wenao Zheng,&nbsp;Yukai Liu,&nbsp;Xian Shi,&nbsp;Yuan Zhang,&nbsp;Yulei Song,&nbsp;Yamei Bai,&nbsp;Feng Bai","doi":"10.1002/trc2.70294","DOIUrl":"https://doi.org/10.1002/trc2.70294","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Cognitive improvement is mediated by repetitive transcranial magnetic stimulation (rTMS) in Alzheimer's disease (AD), and connectome gradient analysis has important potential to explore more comprehensive information for treatment efficacy. However, it remains unclear whether and how rTMS mediates connectome gradient reconstruction and its spatial neurotransmitter associations in subjects on the AD spectrum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A total of 84 subjects on the AD spectrum underwent 4 weeks of conventional neuronavigated rTMS targeting the left angular gyrus (20 Hz, 20 sessions over 4 weeks, 20 minutes per session), including 60 subjects with true stimulation and 24 with sham stimulation. This study identified functional connectome gradients and investigated their neuroplasticity between pre- and post-rTMS intervention. A support vector regression model was subsequently used to explore the cognitive prediction value of baseline measures. Finally, connectome‒neurotransmitter association analysis was used to investigate neurotransmitter profiles related to rTMS therapeutic efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>These findings showed that rTMS treatment mainly mediated the decreased gradient values in the somatomotor regions and such baseline values of these regions showed preliminary predictive value for memory improvement after treatment (<i>R</i>²: 0.40–0.63, mean absolute error: 1.54–3.19, root mean square error: 1.98–3.94, <i>p</i> = 0.0002). Moreover, connectome–neurotransmitter association analysis suggested spatial associations between these gradient changes and normative metabotropic glutamate receptor 5 (mGluR5) and 5-hydroxytryptamine receptor 2A (5HT2a) receptor distributions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>rTMS mediates plasticity in high-order metric levels in the brain and is linked to the spatial distributions of specific neurotransmitter receptors in subjects on the AD spectrum.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70294","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467433","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":"Short-term psychological impacts of Alzheimer's disease risk disclosure based on blood-biomarker results","authors":"Bhargavi Ramamurthy,&nbsp;Adena Cho,&nbsp;Maryam Abdolmaleki,&nbsp;Nathan Fayez,&nbsp;Dominic Roby,&nbsp;Karen B, Maynard,&nbsp;Angela L. Jefferson,&nbsp;Corey Bolton","doi":"10.1002/trc2.70295","DOIUrl":"https://doi.org/10.1002/trc2.70295","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Blood-based biomarkers (BBMs) of Alzheimer's disease (AD) provide important information about risk for dementia, but little is known about the psychological impact of sharing BBM results to participants with mild cognitive impairment (MCI). Most AD risk disclosure studies have been conducted in cognitively unimpaired individuals and have not used BBMs. This pilot randomized trial tests the hypothesis that disclosing AD risk based on BBMs is not associated with increased psychological harm compared to standard disclosure methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Participants (<i>n</i> = 27, 73 ± 11 years) with MCI were enrolled and randomized to the intervention (<i>n</i> = 16) or control (<i>n</i> = 11) arm. Participants received a risk estimate based on their age, sex, and equivalent Mini-Mental State Examination score for both groups, with plasma phosphorylated tau 181 results included for the intervention group. Participants completed questionnaires assessing depression, anxiety, and hopelessness prior to disclosure and 2 weeks later. A repeated measures multivariate analysis of variance (MANOVA) was used to determine changes in psychological responses over the follow-up period with a time x group interaction term assessing group differences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Participants in the intervention and control group were similar across baseline demographic and clinical factors (<i>P</i> values ≥ 0.23). Repeated measures MANOVA showed a significant reduction in psychological symptoms from baseline to 2-week follow-up (<i>P</i> = 0.006) in the combined sample. Follow-up univariate models showed the reduction was driven by a significant reduction in anxiety (mean ± standard deviation; baseline = 13.3 ± 7.7; follow-up = 9.8 ± 9.9; <i>P</i> = 0.02). Time x group interaction was non-significant (<i>P</i> = 0.31) indicating similar psychological responses across groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>In this pilot study of participants with MCI, psychological response to learning risk of progression to dementia did not differ between those who received a risk estimate based on a BBM versus standard clinical information. Two weeks after disclosure, there was an overall decline in anxiety. These preliminary findings suggest that AD risk disclosure using BBMs is not associated with psychological distress.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467546","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":"Agentic neurotechnology: A multi-agent AI framework for next-generation dementia care","authors":"Kevin Mekulu,&nbsp;Faisal Aqlan,&nbsp;Hui Yang","doi":"10.1002/trc2.70299","DOIUrl":"https://doi.org/10.1002/trc2.70299","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Dementia care is reaching a technological turning point as rapid advances in artificial intelligence (AI), digital biomarkers, and sensor-based monitoring continue to outpace current clinical practice. Yet most tools remain episodic and disconnected from the everyday environments where cognitive change unfolds. Early cognitive drift often goes unnoticed, the mild cognitive impairment (MCI) window remains a major diagnostic gap, and care teams lack continuous, actionable insights. In this perspective, we introduce Agentic Neurotechnology, an integrated framework that combines adaptive multi-agent AI systems with longitudinal cognitive modeling to support proactive and individualized dementia care. We define a five-layer agentic stack consisting of (1) sensing and digital biomarker agents, (2) interpretation and reasoning agents, (3) longitudinal cognitive trajectory models, (4) care navigation agents, and (5) population-level forecasting agents. We further outline the Cognitive Continuum Loop, a closed-cycle process in which detection, interpretation, reasoning, monitoring, intervention, and adaptation occur continuously across the care environment. This framework highlights three actionable windows for cognitive intervention: the Preclinical Risk Detection window, the MCI Detection window, and the Functional Instability Response window. Each stage presents unique opportunities for agentic AI systems that operate continuously rather than through isolated assessments. We conclude by presenting a translational pathway for deploying agentic neurotechnologies across assisted living, primary care, telehealth, and home-based settings. The goal is to enable earlier detection, greater clinical efficiency, and more personalized cognitive support. Agentic Neurotechnology reframes AI not as a passive screening tool but as an active partner in continuous cognitive care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467432","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":"Six-month real-world amyloid PET outcomes after lecanemab: Greater amyloid reduction at the MCI stage than in dementia","authors":"Geon Ha Kim,&nbsp;Hai-Jeon Yoon,&nbsp;Eun Hee Kim,&nbsp;Ji-Young Kim,&nbsp;Jiyoung Yeom,&nbsp;Seo Young Kang,&nbsp;Boeun Lee,&nbsp;Jee Hyang Jeong","doi":"10.1002/trc2.70300","DOIUrl":"https://doi.org/10.1002/trc2.70300","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Evidence from routine clinical practice regarding stage-dependent responses to lecanemab remains limited. We examined early amyloid positron emission tomography (PET) and clinical trajectories according to disease stage in a real-world cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Among 89 patients who received lecanemab, 50 individuals with baseline amyloid positivity and follow-up amyloid PET were included in the primary amyloid PET efficacy analysis. Amyloid burden was quantified using the Centiloid scale. Longitudinal Centiloid trajectories were analyzed using linear mixed-effects models including disease stage, time from baseline amyloid PET, and the disease stage × time interaction, with adjustment for cumulative dose exposure, age, sex, and apolipoprotein E (<i>APOE</i>) ε4 carrier status. Cognitive and functional outcomes were assessed using mixed-effects models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Amyloid burden decreased substantially during follow-up. After adjustment for cumulative dose exposure, age, sex, and <i>APOE</i> ε4 carrier status, the disease stage × time interaction was significant (β = +1.62 Centiloid/month; 95% confidence interval, 0.80 to 2.43; <i>p</i> &lt; 0.001), indicating a faster rate of Centiloid reduction in patients with mild cognitive impairment (MCI) than in those with dementia (estimated −2.34 vs. −0.72 Centiloid/month). Conversion to amyloid-negative status (full treatment-related amyloid clearance) occurred in 9 of 50 patients (18.0%) and was more frequent at the MCI stage (<i>p</i> = 0.022). Patients treated at the MCI stage also showed more favorable short-term cognitive and functional trajectories than those treated at the dementia stage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>In real-world clinical practice, lecanemab treatment was associated with substantial amyloid reduction, with faster amyloid clearance observed at the MCI stage. These findings support the potential value of earlier intervention with anti-amyloid therapy, although longer follow-up and controlled comparisons are needed to determine whether early biomarker changes translate into sustained clinical benefit.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70300","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467431","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":"Response to “Reanalyzing the impact of cognitive training over 20 years in the ACTIVE study: Losing the forest in the trees”","authors":"Alden L. Gross,&nbsp;George W. Rebok,&nbsp;Marilyn S. Albert","doi":"10.1002/trc2.70290","DOIUrl":"10.1002/trc2.70290","url":null,"abstract":"&lt;p&gt;We are grateful for the Letter to the Editor by Dr. Dickens and the opportunity to discuss our findings further. The Letter suggests that six hazard ratios in Table 2 of Coe et al.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; ought to be corrected for multiple comparisons, but paradoxically that 12 hazard ratios in Table 3 do not need such correction. Regardless of that logical inconsistency, multiplicity correction (e.g., a Bonferroni–Dunn correction) has to do with controlling the family-wise error rate across a family of inferences that are considered jointly. Our perspective is that the definition of that family of inferences is conceptual, not purely statistical.&lt;/p&gt;&lt;p&gt;In our case, the conclusion supported by the Coe et al.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; paper is not generally that “any cognitive training reduces risk of dementia.” It is instead that training specifically in speed of processing appears to confer a benefit. In this sense, we do not believe a correction multiple testing is necessary. Our analyses of the effects of each independent training group on the risk of dementia were pre-specified as distinct primary hypotheses. That is, each training group corresponds to a distinct scientific question with its own inference. Clinical trials often do not Bonferroni-adjust across arms if each is a pre-specified primary comparison.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Such correction is somewhat more common in exploratory trials or trials with multiple doses of the same treatment,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; neither of which is true of the ACTIVE trial.&lt;/p&gt;&lt;p&gt;In the Letter, Dr. Dickens switches frameworks to aggregate evidence when looking at patterns in Table 3. In other words, instead of treating each hazard ratio individually, he changes the estimand from the generic question of whether any training reduces risk of dementia, to “is there a consistent direction across all 12 hazard ratios?” In this way, the he uses multiplicity control to weaken the result, and then abandons multiplicity control when it strengthens an alternative result.&lt;/p&gt;&lt;p&gt;As noted in our Discussion, the finding in Coe et al. of an effect specifically in the training group that received speed of processing training is not without precedent.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Setting aside for a moment the logical inconsistency in the Letter to consider the implications of the sign test, which suggests a common underlying training effect concentrated at younger ages, such a conclusion is difficult to interpret in this context. The memory training intervention, the speed training intervention, and the reasoning training intervention each targeted different cognitive abilities. What policies or specific interventions might we promote based on the conclusion that any generic cognitive training seems to reduce the risk of dementia? To draw a parallel, should we pool together everyone who has ever taken any medication for dementia—including memantine, donepezil, and donanemab—to see whether medications help reduce risk","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13364747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148450331","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":"Anti-amyloid nanobody-Fc fusion protein drives potent amyloid clearance through microglial recruitment","authors":"Zonghui Ding,&nbsp;Katelin A. Gibson,&nbsp;David G. Nascari,&nbsp;Lauren E. Tallant,&nbsp;Samantha M. Bouchal,&nbsp;Dennis W. Dickson,&nbsp;John D. Fryer","doi":"10.1002/trc2.70269","DOIUrl":"10.1002/trc2.70269","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Anti-amyloid beta (Aβ) monoclonal antibodies are effective at lowering amyloid in Alzheimer's disease (AD). However, whether Fc-mediated effector function is absolutely required for efficacy is not completely understood. This is important for optimizing therapeutic efficacy and mitigating side effects such as amyloid-related imaging abnormalities (ARIA). Antibodies lacking Fc effector function, like single-domain antibodies (nanobodies), offer a unique tool to dissect these mechanisms, as their small size facilitates blood–brain barrier (BBB) penetration and allows Fc-mediated functions to be studied independently.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We immunized a llama with Aβ aggregates and constructed a phage display library to screen for aggregate-specific nanobodies. Lead candidates were characterized by epitope mapping and binding affinity to amyloid plaques in both murine and human AD brain tissues. We further assessed their BBB permeability and evaluated their efficacy in clearing pre-existing plaques in amyloid precursor protein (APP)/presenilin 1 (PS1) mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We identified two lead nanobodies, 3A11 and 2D10, that bind distinct epitopes and specifically bind Aβ plaques in murine and human AD brain tissues. Following systemic administration, the monovalent, unmodified (Fc-less) 2D10 nanobody, but not 3A11, successfully crossed the BBB and engaged amyloid plaques in APP/PS1 mice. However, despite robust target engagement, the Fc-less 2D10 failed to recruit microglia or reduce plaque burden. In contrast, an engineered 2D10-Fc fusion antibody potently cleared amyloid plaques, achieving a reduction in pathology comparable to aducanumab treatment. This efficacy was directly correlated with Fc-mediated microglial recruitment and activation, demonstrating that the Fc domain is essential for phagocytic plaque removal.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our findings demonstrate that Fc effector function is indispensable for microglial-mediated amyloid clearance in vivo. By clarifying this fundamental mechanism, this study provides a framework for the rational design of next-generation immunotherapies. Furthermore, 2D10-Fc represents a promising therapeutic candidate, combining the high-affinity targeting of nanobodies with the effector power necessary for robust plaque clearance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13357696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148438883","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":"Heterogeneous responses to memantine in Alzheimer's disease: A precision medicine approach using iPSC models","authors":"Cristina Zivko,&nbsp;Ram Sagar,&nbsp;Waqar Ahmed,&nbsp;Ariadni Xydia,&nbsp;Federica Farinelli,&nbsp;Isaac Ostlund,&nbsp;Debamitra Das,&nbsp;Brady J. Maher,&nbsp;Constantine G. Lyketsos,&nbsp;Vasiliki Mahairaki","doi":"10.1002/trc2.70271","DOIUrl":"10.1002/trc2.70271","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive and functional decline. Memantine, a commonly prescribed N-methyl-D-aspartate receptor antagonist, appears to slightly delay symptom progression in moderate or advanced stages of AD. Clinical response is highly variable across patients with some benefiting but others not. Induced pluripotent stem cell (iPSC)–derived neurons can provide a donor-dependent model to predict the therapeutic efficacy of memantine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We generated iPSC-derived cortical neurons from 19 individuals (12 AD and 7 cognitively unimpaired [CU]). Assays for calcium influx and oxidative stress were developed and optimized for neurons. Memantine was tested under different treatment conditions. Neurons were exposed to glutamate/glycine to induce calcium influx and menadione to generate oxidative stress. Memantine treatment was applied either acutely (1 hour) or as a 24-hour pre-treatment to evaluate its neuroprotective effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Peripheral blood mononuclear cell–derived iPSCs were successfully differentiated into functional neurons, exhibiting comparable electrophysiological properties between AD and CU lines. Calcium influx assays revealed a heterogeneous response among AD and CU neurons, with AD neurons generally displaying higher baseline fluorescence. Memantine treatment for 24 hours significantly reduced calcium influx, with a −9.85% average reduction and a range of −0.39% to −39%. Similarly, reactive oxygen species assays showed menadione-induced oxidative stress was attenuated by 24-hour memantine pre-treatment for a mean −26.05% reduction and a range of −4.23% to −72.21%. The observed variability indicates differential susceptibility to excitotoxicity reduction and or oxidative stress mitigation across lines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This exploratory study establishes a robust in vitro platform to test memantine efficacy using iPSC-derived neurons to model calcium dysregulation and oxidative stress in AD. The observed variability in response highlights the importance of personalized approaches in AD treatment, emphasizing the potential for iPSC-based platforms in precision medicine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13357697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148438885","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 Indiana University Brain Health Program to deliver amyloid-targeted therapy to Alzheimer's disease patients","authors":"Jared R. Brosch,&nbsp;Sophia Wang,&nbsp;Liana G. Apostolova,&nbsp;Atul Agarwal,&nbsp;Jason W. Allen,&nbsp;Laurie Gutmann,&nbsp;Meredith Tobar,&nbsp;Linda Gonzalez,&nbsp;Dontraelle Johnson,&nbsp;Lindsay Treadway,&nbsp;Julie Connolly,&nbsp;Angela Tang,&nbsp;Ethan Lettich,&nbsp;Sam Davies,&nbsp;Nancy Kuhn,&nbsp;Dustin B. Hammers,&nbsp;David Clark,&nbsp;Martin Farlow,&nbsp;Deanna R. Willis,&nbsp;Nicole Fowler,&nbsp;Donna M. Wilcock","doi":"10.1002/trc2.70291","DOIUrl":"10.1002/trc2.70291","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The Indiana University Brain Health Program was developed to support safe implementation of amyloid-targeting therapies (ATTs) for early Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We established Neurology Brain Health Navigators (neuroBHNs) to extend our Brain Health Navigator model into specialty care. NeuroBHNs pre-screen patients for ATT eligibility, coordinate biomarker and imaging evaluation, provide structured education, and guide treatment initiation and monitoring. The program includes a dedicated social worker and insurance pre-authorization specialist to streamline infusion access. Blood pressure is monitored at each visit, and infusions are deferred if readings exceed 140/90 mmHg.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Through December 16, 2025, 243 patients initiated lecanemab therapy. Apolipoprotein E (APOE) ε4 homozygotes were not excluded; 74% of treated patients carried at least one Apoε4 allele. The ARIA rate was 13.2%, and 40% of patients experienced infusion-related reactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSIONS</h3>\u0000 \u0000 <p>A navigator-centered model can efficiently deliver ATT while supporting structured education, screening, and safety monitoring, potentially contributing to favorable safety outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13344895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148413794","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":"Real-time digital assessment of sleep–cognition dynamics in dementia care dyads","authors":"Yeonsu Song,&nbsp;Carter Peterson-Meyer,&nbsp;Laura M. Campbell,&nbsp;Mary-Lynn Brecht,&nbsp;Brent T. Mausbach,&nbsp;Jennifer L. Martin,&nbsp;Raeanne C. Moore","doi":"10.1002/trc2.70279","DOIUrl":"10.1002/trc2.70279","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Sleep disturbance is common in persons living with dementia (PLWD) and may contribute to day-to-day variability in cognitive functioning, with implications for daily activities and caregiving. However, traditional cognitive assessments may not capture these short-term fluctuations. Ecological momentary cognitive testing (EMCT) enables repeated, real-world assessment of cognitive performance. This study examined day-to-day associations between sleep and cognitive performance in PLWD–caregiver dyads.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Baseline data from PLWD–caregiver dyads enrolled in a behavioral sleep trial were analyzed. PLWD completed smartphone-based EMCT tasks assessing processing speed and response inhibition three times daily for 7 days, along with the Mini-Mental State Examination (MMSE). Caregivers reported daily sleep outcomes for themselves and PLWD. Pearson correlations and mixed-effects models adjusted for PLWD age, gender, education, and phone type.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>EMCT performance correlated significantly with MMSE scores (<i>r =</i> 0.51–0.58, all <i>p</i> &lt; 0.01). Higher EMCT scores were associated with shorter time in bed and greater percentage of good sleep in both PLWD and caregivers. Mixed-effects models revealed significant sleep-by-session interactions: the association between PLWD sleep and processing speed was stronger in the evening than the morning, while longer caregiver time in bed was more strongly associated with PLWD cognitive performance in the morning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>EMCT captured within-person, time-varying associations between dyad sleep and cognitive performance in PLWD, highlighting its utility for identifying daily fluctuations relevant to functioning and caregiving. These findings support digital, dyadic approaches to monitoring sleep and cognitive function in dementia care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13344890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148413769","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":"Identifying populations with faster cognitive decline using blood-based biomarkers","authors":"James Russell Pike,&nbsp;Yongmei Liu,&nbsp;Theresa Chisolm,&nbsp;Jennifer Deal,&nbsp;Jingzhong Ding,&nbsp;Rebecca F. Gottesman,&nbsp;Alison Huang,&nbsp;Timothy M. Hughes,&nbsp;Kurt Lohman,&nbsp;Mason McCray,&nbsp;Thomas H. Mosley,&nbsp;Anh Tram Nguyen,&nbsp;Priya Palta,&nbsp;Nicholas Reed,&nbsp;Kevin J. Sullivan,&nbsp;Bharat Thyagarajan,&nbsp;Keenan A. Walker,&nbsp;Josef Coresh","doi":"10.1002/trc2.70289","DOIUrl":"10.1002/trc2.70289","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Identifying individuals who undergo cognitive decline is vital to the success of prevention trials that aim to slow cognitive decline. Yet, the benefits of using blood-based biomarkers of neurodegeneration, as well as amyloid and tau, to enrich population-based prevention trials have not been quantified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The association of thresholds of Quanterix single molecule array (SiMoA) assays with subsequent change in cognition was estimated in the Atherosclerosis Risk in Communities cohort (<i>N</i> = 1826) using linear mixed effects models, validated in the Multi-Ethnic Study of Atherosclerosis cohort (<i>N</i> = 383), and extended to Alamar Nucleic acid Linked Immuno-Sandwich Assay (NULISA) assays in the Aging and Cognitive Health Evaluation in Elders cohort (<i>N</i> = 552).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Elevated plasma biomarker levels identified dementia-free older adults with faster cognitive decline. By selecting participants with Quanterix SiMoA measurements of neurofilament light &gt; 30.65 pg/mL, the sample size needed to detect a 33% reduction in cognitive decline in a clinical trial decreased by 57%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Clinical trials can use plasma biomarkers as a screening tool to increase statistical power.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13344891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148413838","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}