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

{"title":"Vestibular-related dizziness duration and cognitive deficits in older adults","authors":"Xiaobao Ma, Jiali Shen, Wei Wang, Lu Wang, Yulian Jin, Maoli Duan, Qing Zhang, Jun Yang, Jianyong Chen","doi":"10.1002/trc2.70153","DOIUrl":"https://doi.org/10.1002/trc2.70153","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> OBJECTIVE</h3>\u0000 \u0000 <p>The objective of this study is to investigate the relationship between symptom duration of vestibular-related dizziness/vertigo and cognitive function in elderly patients, and to establish clinical guidance for assessing and intervening in vestibular-related cognitive impairments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This study included 100 elderly patients with vestibular dysfunction presenting dizziness, vertigo, or balance disorders, categorized into short-duration (<i>n</i> = 64) and long-duration (<i>n</i> = 36) groups based on symptom duration. A control group of 21 healthy elderly individuals was included. Cognitive assessments comprised P300 event-related potentials (latency/amplitude) and Montreal Cognitive Assessment (MoCA) with domain-specific analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Significant between-group differences in P300 latency were observed (control vs short-duration vs long-duration: <i>p</i> < 0.001), whereas amplitude showed no difference (<i>p</i> = 0.817). MoCA total scores differed significantly across groups (<i>p</i> = 0.001), although abnormality rates were comparable (<i>p</i> = 0.093). Domain analysis revealed significant differences in visuospatial (<i>p</i> < 0.001) and abstract abilities (<i>p</i> = 0.005). Symptom duration correlated with: MoCA total (<i>R</i><sup>2</sup> = 0.113), visuospatial ability (<i>R</i><sup>2</sup> = 0.181), attention (<i>R</i><sup>2</sup> = 0.068), and orientation (<i>R</i><sup>2</sup> = 0.157). P300 latency correlated with: MoCA total (<i>R</i><sup>2</sup> = 0.141), visuospatial ability (<i>R</i><sup>2</sup> = 0.090), delayed recall (<i>R</i><sup>2</sup> = 0.112), and orientation (<i>R</i><sup>2</sup> = 0.082).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>Prolonged vestibular-related dizziness/vertigo in elderly patients is associated with cognitive deficits, particularly in visuospatial and executive functions. P300 latency demonstrates greater sensitivity than both P300 amplitude and MoCA screening, suggesting that combined electrophysiological and neuropsychological assessment enhances early detection of vestibular-related cognitive impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Long-duration vestibular-related dizziness or balance disorders are associated with a higher risk of cognitive impairment in el","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057753","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":"Low intrinsic capacity is associated with a blunted exercise-induced cognitive enhancement in physically active middle-aged and older adults","authors":"Brandon A. Yates, Ariela R. Orkaby, Jakob L. Vingren, Lawrence E. Armstrong","doi":"10.1002/trc2.70141","DOIUrl":"https://doi.org/10.1002/trc2.70141","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The World Health Organization supports intrinsic capacity (IC) as a framework for assessing and monitoring an older person's cognitive health. Low IC is associated with higher dementia risk. Regular exercise participation improves cognitive health, reduces dementia risk, and may increase IC. However, the long-term chronic brain benefits of regular exercise training are dependent upon the effectiveness of single exercise bouts to augment cognition. Yet, how IC influences the magnitude of improvement following a single exercise bout has not been elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A convenience sampling of 40 physically active adults (55 ± 6 years; mean ± SD) with a body mass index ≥ 24.9 kg/m<sup>2</sup> (range: 24.9 to 36.3) were included in this study. IC domains were operationally defined as follows: <i>cognitive</i> (Mini Cog and Trail Making Test Parts A and B [TMT A+B] performance), <i>vitality</i> (body composition and exercise performance), and <i>locomotor function</i> (habitual gait speed). Participants were stratified by <i>locomotor function</i> into a slow group (≤1.0 m/s; LOW-IC) and a normal group (>1.0 m/s; NORM-IC). Immediately prior to and following the exercise session (161-km cycling event) participants completed the executive function task (TMT A+B). An analysis of covariance, controlling for baseline TMT A+B performance, was used to detect a significant improvement in TMT A+B (<i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Participants had similar <i>cognitive abilities</i> and <i>vitality</i>, but groups significantly differed by <i>locomotor function</i>. A significant interaction (<i>p</i> = 0.004) was revealed where improvement for NORM-IC (−13 s [−18 to −8]; <i>p</i> < 0.001; partial <i>η<sup>2</sup></i> = 0.47; adjusted mean [95% confidence interval]) was greater than for LOW-IC (−3 s [−9 to 2]; <i>p</i> = 0.25; partial <i>η<sup>2</sup></i> = 0.04) following the exercise session.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Low IC is associated with a blunted acute exercise-induced cognitive enhancement in mid to late adulthood. Future research is justified to determine the physiological mechanisms underpinning this novel finding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Adults with overweight/obesity show cognitive gains after endurance exercise.</l","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037568","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":"Implications of practice effects for the design of Alzheimer clinical trials","authors":"Jasmin A. Duehring, Diane M. Jacobs, Michael L. Thomas, Hiroko H. Dodge, Howard H. Feldman, Steven D. Edland","doi":"10.1002/trc2.70154","DOIUrl":"https://doi.org/10.1002/trc2.70154","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Practice effects (PEs) are a well-known potential confound in natural history studies of longitudinal cognitive decline in aging and early-stage Alzheimer's disease. The implication of PEs on Alzheimer's disease clinical trials is less well understood, although we have previously speculated that a “run-in” period of repeated cognitive assessments prior to randomization may improve the efficiency of clinical trials [Jacobs et al. <i>Alzheimer's & Dementia</i> 2017;3(4):531-535]. We have also described how the performance of composite outcome measures depends on parameters that may be influenced by PEs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>To investigate this, we used the cognitive battery within the National Alzheimer's Coordinating Center (NACC) Uniform Data Set to characterize the potential impact of PEs on clinical trial design and outcome measures. The analysis restricted to <i>N</i> = 1094 amnestic mild cognitively impaired participants with 3 years of follow-up data. Linear mixed effects models estimate the magnitude of PEs observed in aMCI participants. Power calculations informed by the pattern of progression in the NACC sample were used to describe the net impact of PEs on trials with and without a run-in phase. Weighting parameters of optimal composite measures constructed from the NACC battery were also compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>PEs were large, often exceeding the magnitude of annual rate of change observed in later assessments. Annualized rate of change, and therefore target treatment effect sufficient to achieve a specified percentage reduction in rate of decline, was larger after run-in. Sample size projections for the run-in design were a fraction of those required for trials without run-in. Weighting parameters that optimize composite outcome performance were also different for the two designs, underscoring the importance of considering design in the construction of composite outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Clinical trials randomizing after a run-in period measure treatment efficacy relative to decline unbiased by PEs, and require smaller sample size.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>In the National Alzheimer's Coordinating Center (NACC), amnestic mild cognitive impairment (aMCI) cohort practice effects often exceed annualized rate of c","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022056","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":"Sex differences in treatment effects of lecanemab and donanemab: A Bayesian reanalysis of CLARITY-AD and TRAILBLAZER-ALZ2","authors":"Stefan J. Teipel,&nbsp;Yi Tang,&nbsp;Ara Khachaturian","doi":"10.1002/trc2.70155","DOIUrl":"https://doi.org/10.1002/trc2.70155","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study investigated evidence for or against a difference in treatment effect between women and men for lecanemab and donanemab.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Data were derived from supplementary analyses of the regulatory studies CLARITY-AD (lecanemab) and TRAILBLAZER-ALZ2 (donanemab). Bayes factor functions were used to analyze treatment effects on Clinical Dementia Rating Sum of Boxes (CDR-SB) scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We found moderate evidence of a lower treatment effect in women than in men for lecanemab (maximum Bayes factor = 5.97), suggesting that the presence of an effect was almost six times more likely than the absence of an effect. For donanemab, there was evidence against a treatment effect difference between women and men. There was evidence of a treatment effect difference between lecanemab and donanemab (maximum Bayes factor = 8.47) in women, but not in men.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>A better understanding of sex differences in treatment efficacy and their causes is urgently needed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Lecanemab was six times more likely to be ineffective than effective in women.</li>\u0000 \u0000 <li>There was no evidence of a difference between the sexes in the effect of donanemab.</li>\u0000 \u0000 <li>Lecanemab and donenamb differed in treatment efficacy in women but not in men.</li>\u0000 \u0000 <li>Future trials should include sufficient power for sex related interaction effects.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998890","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":"Donanemab immunogenicity in participants with early symptomatic Alzheimer's disease","authors":"Garrett R. Mullins,&nbsp;Paul Ardayfio,&nbsp;Ivelina Gueorguieva,&nbsp;Greg Anglin,&nbsp;Jason Bailey,&nbsp;Laiyi Chua,&nbsp;Jennifer A. Zimmer,&nbsp;Cynthia D. Evans,&nbsp;Emel Serap Monkul Nery,&nbsp;Hong Wang,&nbsp;Rashna Khanna,&nbsp;Dawn A. Brooks,&nbsp;John R. Sims","doi":"10.1002/trc2.70149","DOIUrl":"https://doi.org/10.1002/trc2.70149","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;Donanemab is an immunoglobulin G1 antibody that targets an N-terminal truncated form of amyloid beta present in mature plaques. Treatment-emergent (TE) anti-drug antibodies (ADAs) were quantified in donanemab-treated participants from two pivotal clinical trials, and effects of TE ADAs on donanemab pharmacokinetics, efficacy, and safety were assessed.&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;Data were pooled from the phase 2 TRAILBLAZER-ALZ (NCT03367403) and phase 3 TRAILBLAZER-ALZ 2 trials (NCT04437511). Eligible participants were randomized 1:1 to donanemab (700 mg for the first three doses, 1400 mg thereafter) or placebo intravenously every 4 weeks up to 72 weeks. TE ADA-evaluable participants had a non-missing baseline ADA result and ≥ 1 non-missing post-baseline ADA result. TE ADA incidence and effect of titer on pharmacokinetics, amyloid plaque reduction, clinical efficacy (measured by change from baseline of integrated Alzheimer's Disease Rating Scale [iADRS] score and Clinical Dementia Rating Scale Sum of Boxes [CDR-SB]), and safety were assessed.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Of 922 TE ADA-evaluable donanemab-treated participants, 56 (6.1%) had ADAs detected at baseline, and 812 (88.1%) were TE ADA positive. Donanemab clearance increased linearly with logarithm of ADA titer; however, titer did not affect maximum donanemab concentration. Amyloid plaque level was significantly reduced with donanemab versus placebo, irrespective of titer (&lt;i&gt;P&lt;/i&gt; &lt; 0.001 for all). No association was found between ADA presence or titer and donanemab efficacy by iADRS or CDR-SB. Eighty-four of 984 (8.5%) donanemab-treated participants and 4 of 999 (0.4%) placebo-treated participants reported infusion-related reactions (IRRs). All donanemab-treated participants reporting immediate IRRs developed ADAs at some point during the study; however, 90.5% of TE ADA-positive participants did not experience IRRs.&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;Most participants were TE ADA positive. TE ADAs increased donanemab clearance but did not have clinically meaningful impact on plaque reduction or efficacy. While all participants reporting IRRs developed ADAs at some point during the study, the majority of participants with ADAs did not experience IRRs.&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;In pivotal trials, most do","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927321","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":"Long-term value of lecanemab to individuals and families","authors":"Bryan Tysinger,&nbsp;Yifan Wei,&nbsp;Hanke Heun-Johnson,&nbsp;Julie M. Zissimopoulos","doi":"10.1002/trc2.70151","DOIUrl":"https://doi.org/10.1002/trc2.70151","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;An assessment of the value of lecanemab for patients living with Alzheimer's disease (AD) and their care partners provides them and their health-care providers important information for deciding treatment initiation.&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 data from a nationally representative sample of middle aged and older Americans combined with data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) on AD progression and data on lecanemab treatment effects from Clarity AD clinical trials. We use dynamic microsimulation modeling to quantify the long-term health and economic value of lecanemab for persons living with AD and their care partners.&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;We quantified five measures of value: quality of life of the persons living with AD and their care partners, medical costs, caregiving costs, and earnings, and estimated that lecanemab had a value of $21,398 relative to no treatment after 4 years and $37,943 after 10 years. Extending the treatment to 48 months resulted in a value of $42,821 relative to no treatment after 4 years and $95,311 after 10 years. Forty-eight months of a similar next-generation therapy but with 50% efficacy in slowing cognitive and functional decline resulted in a value of $82,116 relative to no treatment after 4 years and $189,691 after 10 years.&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;Over time, lecanemab treatment reduced medical costs, hours of care required from care partners, and improved quality of life. There is much value to be gained with next-generation treatments that have a larger impact on slowing decline. Considering a wider range of outcomes in future assessments will provide a more complete understanding of value to support decision making about treatment initiation and about reimbursement for payers.&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;There is significant value of lecanemab for persons with mild cognitive impairment or mild dementia.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Over time, lecanemab reduces medical costs, caregiver hours, and improves the quality of life of persons living with Alzheimer's disease (AD) and their care partners.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;A next-generation treatment for AD with similar features to lecanemab but higher efficacy, more than doubles the","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915028","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":"Characterizing clinician communication with patients about lecanemab: A qualitative study of clinicians across seven academic medical centers","authors":"Anna L. Parks,&nbsp;Ayush Thacker,&nbsp;Daniel Dohan,&nbsp;Liliana A. Ramirez Gomez,&nbsp;Seth A. Gale,&nbsp;Kim G. Johnson,&nbsp;Christine S. Ritchie,&nbsp;Sachin J. Shah,&nbsp;Joanna Paladino","doi":"10.1002/trc2.70150","DOIUrl":"https://doi.org/10.1002/trc2.70150","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;Anti-amyloid monoclonal antibodies (mAbs) slow cognitive decline in Alzheimer's disease but may cause amyloid-related imaging abnormalities (ARIA), which can rarely be disabling or fatal. This qualitative study investigates how clinicians communicate the benefits and risks of mAbs to patients and caregivers.&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;Semi-structured interviews with clinicians who prescribe mAbs at seven academic medical centers. Hybrid inductive-deductive thematic analysis by interdisciplinary researchers.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In 27 clinician interviews (women [&lt;i&gt;n&lt;/i&gt; = 17], White individuals [&lt;i&gt;n&lt;/i&gt; = 19], neurologists [&lt;i&gt;n&lt;/i&gt; = 17]), three themes emerged. First, clinicians varied in techniques used and concepts emphasized, including using analogies, discussing statistics, and emphasizing versus de-emphasizing risks. Second, patient contextual factors (e.g., comorbidities), hopes, and fears shaped communication. Third, clinician communication varied by training, personal style, and ambivalence. While clinicians honor patients’ choices to pursue treatment, many do not “recommend” it (but may recommend against it).&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;Preliminary insights about how clinicians communicate tradeoffs can guide future shared decision-making interventions for mAbs.&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 qualitative study among 27 clinicians across seven academic medical centers examined how clinicians communicate with people with Alzheimer's disease about risks and benefits of anti-amyloid therapy, which can influence treatment decisions.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Clinicians varied in what techniques they employed and how they portrayed risks and benefits, and whether they incorporated patients’ values.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;They cited comorbidities, eligibility criteria fit, and degree of social support or family involvement in decisions as factors used in framing discussions, while fewer used patients’ goals to guide discussion.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The professional training, individual practice style, and personal sense of ambivalence of clinicians shaped conversations.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;These findings can guide future interve","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897726","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":"Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP): A global effort to identify genetic factors in Alzheimer's disease","authors":"Rufus Akinyemi,&nbsp;Olabode Omotoso,&nbsp;Lwere Kamada,&nbsp;David Ndetei,&nbsp;Michael Cuccaro,&nbsp;Albert Akpalu,&nbsp;Larry D. Adams,&nbsp;Stephen F. Sarfo,&nbsp;Alfred K. Njamnshi,&nbsp;Patrice Whitehead,&nbsp;Njideka Okubadejo,&nbsp;Mena Pedro Ramon,&nbsp;Albertino Damasceno,&nbsp;Scott Williams,&nbsp;Biniyam Ayele,&nbsp;Yared Zenebe,&nbsp;Thierry Adokounou,&nbsp;Jean Ikanga,&nbsp;Judith Boshe,&nbsp;Joshua Akinyemi,&nbsp;Olufisayo Elugbadebo,&nbsp;Reginald Obiako,&nbsp;Kolawole Wahab,&nbsp;Emmanuel Iwuozo,&nbsp;Kazeem Akinwande,&nbsp;Stella-Marie Paddick,&nbsp;Mayowa Ogunronbi,&nbsp;Christine Musyimi,&nbsp;Anyamele Ibuchim,&nbsp;Gabriel Ogunde,&nbsp;Motunrayo Coker,&nbsp;Olaleye Adeniji,&nbsp;Eniola Cadmus,&nbsp;Oladotun Olalusi,&nbsp;Timothy Ciesielski,&nbsp;Paul Nwani,&nbsp;Susan Halloran Blanton,&nbsp;Paul Olowoyo,&nbsp;Oluwadamilola Ojo,&nbsp;Rasaq Durodoye,&nbsp;Godwin Osaigbovo,&nbsp;Noeline Nakasujja,&nbsp;Mlaki Damas Andrea,&nbsp;Akinsola Ojagbemi,&nbsp;Godwin Ogbole,&nbsp;Temitope Farombi,&nbsp;Adefolakemi T. Ogundele,&nbsp;Azizi Seixas,&nbsp;Lawrence Adebusoye,&nbsp;Michelle Nichols,&nbsp;Ernest O. Nwazor,&nbsp;Nosakhare Osemwegie,&nbsp;Maeleen Guerchet,&nbsp;Farid Rajabli,&nbsp;Olufemi Olowookere,&nbsp;Jacob L. McCauley,&nbsp;Oyedunni Arulogun,&nbsp;Sudha Seshadri,&nbsp;Mayowa Owolabi,&nbsp;Guiseppe Tosto,&nbsp;Goldie Byrd,&nbsp;Richard Walker,&nbsp;Christiane Reitz,&nbsp;William Bush,&nbsp;Olusegun Baiyewu,&nbsp;Anthony J. Griswold,&nbsp;Brian W. Kunkle,&nbsp;Jonathan Haines,&nbsp;Rajesh N. Kalaria,&nbsp;Jeffery M. Vance,&nbsp;Adesola Ogunniyi,&nbsp;Margaret Pericak-Vance","doi":"10.1002/trc2.70148","DOIUrl":"https://doi.org/10.1002/trc2.70148","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) remains a major neurocognitive disorder of global health significance. Globalizing ancestral diversity in AD genetics is essential to identify causal variants, improve diagnosis, and enable equitable therapeutic interventions across populations. The Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP) initiative addresses this by including African ancestry and Hispanic/Latinx (HL) ancestry populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>READD-ADSP, a case–control study, aims to recruit, evaluate, and retain 13,000 participants: 5000 Indigenous Africans, 4000 African Americans, and 4000 Hispanic/Latinix individuals. In Africa, recruitment involves nine sub-Saharan African countries under the African Dementia Consortium, and with protocols ensuring standardized data collection, phenotype harmonization, culturally informed diagnostic algorithms, and robust community engagement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Study pparticipants are recruited, ascertained and retained. Blood samples and fractions (DNA, plasma, RNA) are biobanked for genomic, epigenomic, proteomic, and transcriptomic analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study will advance precision ADRD medicine and establish a model for working with diverse global cohorts of brain disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP) addresses critical gaps in Alzheimer's Disease and Related Dementias (ADRD) research by including underrepresented groups.</li>\u0000 \u0000 <li>The study recruits 13,000 participants of African, African American, and Hispanic/Latinx ancestries.</li>\u0000 \u0000 <li>Standardized protocols enable rigorous phenotyping and harmonization across diverse populations.</li>\u0000 \u0000 <li>Findings will inform precision medicine and reduce health disparities in ADRD outcomes.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894096","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":"Cognitive effects of dopaminergic treatment in Alzheimer's disease: Systematic review and meta-analysis","authors":"Cristina Bonet Olivares,&nbsp;Michael C. B. David,&nbsp;Marta Estrada Obeso,&nbsp;Martina Del Giovane,&nbsp;Suzanne Reeves,&nbsp;Paresh A. Malhotra","doi":"10.1002/trc2.70142","DOIUrl":"https://doi.org/10.1002/trc2.70142","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;Despite advances in disease-modifying drugs, better treatments for symptomatic Alzheimer's disease (AD) are needed, with dopaminergic neurotransmission representing a potential target. The objective of this systematic review and meta-analysis was to evaluate the efficacy of drugs with predominantly dopaminergic action in improving cognitive symptoms in AD.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The MEDLINE, Embase, and ClinicalTrials.gov databases were searched from 1980 to January 2023. We used random effect models to generate pooled effect estimates&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;We included 19 prospective randomized controlled AD trials (1408 total participants), of which 7 were of “good” quality, 8 “fair,” and 4 “poor.” All were included in the analysis. The overall pooled effect was small but showed a significant positive effect of dopaminergic drugs compared to placebo (standardized mean difference [SMD]: 0.33, 95% confidence interval [CI]: 0.08 to 0.59, &lt;i&gt;P&lt;/i&gt; = 0.01; &lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 79%). Significance remained after removing outliers to account for heterogeneity. When exploring subgroups (divided by mechanism of action), 5 trials of dopamine reuptake inhibitors did not show a significant effect on cognition, whereas 12 monoamine oxidase B (MAO-B) inhibitor trials showed a moderately significant positive effect (SMD: 0.52, 95% CI: 0.13 to 0.90, &lt;i&gt;P&lt;/i&gt; = 0.01; &lt;i&gt;I&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 84%).&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 show evidence of the benefit of dopaminergic medications, specifically MAO-B inhibitors, on cognitive symptoms in AD. Several studies included here also used drugs with both noradrenergic and dopaminergic action, highlighting a potential dual stimulation that could lead to better clinical efficacy. Trials targeting well-defined patient populations, ideally supported by biomarker evidence of dopaminergic dysfunction, are needed to compare noradrenergic and dopaminergic agents—both separately and in combination—on cognitive function to maximize treatment effects. Particularly, further research should explore the impact of MAO-B drugs on specific aspects of cognitive function to better understand their mechanism given the upregulation of MAO-B expression in AD.&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 conducted a meta-analysis investigating the efficacy ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869883","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":"ACE trial design: Equol targeting estrogen receptor-β in vascular and cognitive aging","authors":"Akira Sekikawa,&nbsp;Whitney Wharton,&nbsp;Cristina Murray-Krezan,&nbsp;Minjie Wu,&nbsp;Yuefang Chang,&nbsp;Beth E. Snitz,&nbsp;Mindy Coccari,&nbsp;Shaolin Yang,&nbsp;Monica L. Love,&nbsp;Deborah Cusick,&nbsp;Rongrong Wang,&nbsp;Mengyi Li,&nbsp;Chloe Park,&nbsp;Jiatong Li,&nbsp;Theodore M. DeConne,&nbsp;Carrie Smith,&nbsp;Danielle D. Verble,&nbsp;Michelle Quallich Lancet,&nbsp;Tatiana Foroud,&nbsp;Tae Kim,&nbsp;Neelesh K. Nadkarni,&nbsp;Joseph M. Mettenburg,&nbsp;Ezequiel Zamora,&nbsp;Oscar L. Lopez,&nbsp;Timothy M. Hughes","doi":"10.1002/trc2.70144","DOIUrl":"https://doi.org/10.1002/trc2.70144","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;Equol, a gut microbiome-derived metabolite of soy isoflavone daidzein, functions as a selective estrogen receptor beta (ERβ) agonist. In preclinical studies, it has demonstrated vascular protective and antioxidant effects, with emerging evidence suggesting potential neuroprotective properties. However, its role in preventing vascular aging and cognitive decline in humans remains unexplored. The Arterial Stiffness, Cognition, and Equol (ACE) trial investigates whether daily equol supplementation can slow the progression of arterial stiffness, brain white matter lesions, and cognitive decline in older adults without 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;ACE is a multicenter, randomized, double-blind, placebo-controlled clinical trial conducted at the University of Pittsburgh, Wake Forest University, and Emory University. Community-dwelling adults aged 65 to 85 years without dementia were enrolled and randomized 1:1 to receive either 10 mg/day of equol or placebo for 24 months. The primary outcome is arterial stiffness assessed by carotid-femoral pulse wave velocity. Secondary outcomes include white matter lesions detected on the brain magnetic resonance imaging and cognitive function as assessed by the Preclinical Alzheimer Cognitive Composite. Power calculations were based on a planned sample size of 400 participants, accounting for an anticipated 20% attrition rate.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A total of 1783 individuals were pre-screened, and 764 underwent in-person eligibility assessment. Of these, 369 participants were randomized into two groups: Arm A (&lt;i&gt;n&lt;/i&gt; = 185) and Arm B (&lt;i&gt;n&lt;/i&gt; = 184). The randomized sample self-reported as 52% women and 22% Black/African American participants. Baseline demographic and clinical characteristics were well balanced between the two arms, indicating successful randomization.&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;ACE successfully enrolled a racially diverse population of older adults and achieved near-target recruitment. ACE is the first large-scale trial to evaluate whether equol, a selective ERβ agonist, can impact vascular and cognitive aging, paving the way for precision nutrition strategies in dementia prevention.&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 detail the first randomized controlled trial of equol, an estrogen receptor bet","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869288","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}