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

{"title":"Perspective: Minimal clinically important difference (MCID) and Alzheimer's disease clinical trials","authors":"Jeffrey Cummings","doi":"10.1002/trc2.70059","DOIUrl":"https://doi.org/10.1002/trc2.70059","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The minimum clinically important difference (MCID) is a measure of the minimal clinically relevant change. The MCID represents the smallest difference in score on the measure or domain of interest which patients or clinicians perceive as beneficial or as meaningful decline. The MCID is not an alternative clinical trial outcome; it does not apply to group measures and is used as a means of determining whether an individual patient has reached a threshold of change. MCIDs have been derived for symptomatic treatments and for disease targeted therapies. MCIDs have been derived for nearly all clinical trial instruments used in AD therapeutic research. Application of the MCID to patients on disease-targeted therapies requires awareness of the expected increasing treatment-no treatment difference exhibited by these agents. The MCID complements other strategies for assessing the meaningfulness of interventions including effect size, number needed to treat, responder analyses, time saved, quality of life, and quality-adjusted life years. MCID is not a required measure for regulatory approval of a therapeutic since it is applicable to individual patients and not to group outcomes or mean differences used to determine treatment benefit in clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>MCID is a key measure of within-person change in cognition, function, or behavior when it is applied to metrics of Alzheimer's disease progression.</li>\u0000 \u0000 <li>In Alzheimer's disease, MCID or minimum within person change (MWPC) can function as useful means of determining if a patient has progressed to thresholds of detectable change.</li>\u0000 \u0000 <li>In Alzheimer's disease, MCID/MWPC can be used to determine the number or percent of individuals who have progressed to detectable levels of within-person change, with differences anticipated in active treatment and placebo groups.</li>\u0000 \u0000 <li>MCID/MWPC are not measures that are appropriately applied to group outcomes of 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 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581455","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":"Broad repetitive transcranial magnetic stimulation (rTMS) of the precuneus in Alzheimer's disease: A rationale and study design","authors":"Michael K. Leuchter,&nbsp;Hanadi A. Oughli,&nbsp;Kelly A. Durbin,&nbsp;Nicholas J. Jackson,&nbsp;David Elashoff,&nbsp;Timothy S. Chang,&nbsp;Juliana Corlier,&nbsp;Doan Ngo,&nbsp;Cole Matthews,&nbsp;Darice Wong,&nbsp;Brent L. Fogel,&nbsp;Gal Bitan,&nbsp;Andrew F. Leuchter,&nbsp;Keith Vossel,&nbsp;Nanthia Suthana","doi":"10.1002/trc2.70043","DOIUrl":"https://doi.org/10.1002/trc2.70043","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;Brain network dysfunction, particularly within the default mode network (DMN), is an increasingly apparent contributor to the clinical progression of Alzheimer's disease (AD). Repetitive transcranial magnetic stimulation (rTMS) can target key DMN hubs, maintain signaling function, and delay or improve clinical outcomes in AD. Here, we present the rationale and design of a study using off-the-shelf equipment and the latest clinical evidence to expand on prior rTMS work and reduce participant burden in the process.&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 will conduct a two-stage trial of large-coil rTMS targeting the precuneus (a key hub in the DMN affected by AD) in 54 participants with mild to moderate Alzheimer's Clinical Syndrome focused primarily on determining tolerability and feasibility and secondarily focused on determining short-term efficacy for memory. The first stage will involve 5 to 10 participants receiving open-label active treatment to refine the protocol. The following second stage will consist of a 1:1 randomized, double-blind, sham-controlled clinical trial to study feasibility and tolerability while exploring target engagement and short-term efficacy for memory. Participants will undergo 16 total rTMS brain stimulation sessions over the course of 5 weeks. A full course of open-label active treatment will be offered as an extension to the sham group after unblinding. Outcomes will focus on completion rates and adverse events to demonstrate feasibility and tolerability. Further exploratory outcomes will include neuropsychological assessments, electroencephalography, neuroimaging, and blood biomarkers to demonstrate the feasibility of collection and explore preliminary changes in these measures.&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 anticipate this treatment is feasible and tolerable and may show evidence of target engagement and clinical improvement.&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;Should we achieve expected positive outcomes in feasibility and tolerability, this will justify future work focusing on clear demonstrations of clinical efficacy and biomarker engagement, as well as enhancement of generalizability and scalability.&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;Induction-to-maintenance repetitive transcranial magnetic stimulation (rTMS) of the precuneus is a promising t","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581451","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":"Factors associated with adherence to tablet-based cognitive training: J-MINT study","authors":"Taiki Sugimoto,&nbsp;Kazuaki Uchida,&nbsp;Kenji Sato,&nbsp;Yoko Yokoyama,&nbsp;Ayaka Onoyama,&nbsp;Kosuke Fujita,&nbsp;Yujiro Kuroda,&nbsp;Satomu Wakayama,&nbsp;Hidenori Arai,&nbsp;Takashi Sakurai,&nbsp;J-MINT study group","doi":"10.1002/trc2.70062","DOIUrl":"https://doi.org/10.1002/trc2.70062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Cognitive training is a key component of multidomain interventions to prevent cognitive decline; however, low adherence remains a challenge. In this post hoc analysis of the Japan-Multimodal Intervention Trial for Prevention of Dementia (J-MINT), factors associated with cognitive training adherence in older adults with mild cognitive impairment were investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>J-MINT was an 18-month randomized controlled trial. The analyses included 191 participants (intervention group) who completed the trial. Adherence was assessed by calculating the number of days the participants engaged in tablet-based cognitive training for at least 30 min.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Vision difficulty and a larger friend network were negatively associated with adherence. Female sex, higher cognitive function, and satisfaction with training tasks and implementation goals were positively associated with adherence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The results imply that not only the participants’ characteristics but also the training task design and implementation goal setting (training duration and frequency) are associated with adherence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Clinical trial registration number</h3>\u0000 \u0000 <p>This trial was registered with the University hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN000038671).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Factors associated with adherence to cognitive training were evaluated.</li>\u0000 \u0000 <li>Vision difficulty was negatively associated with adherence.</li>\u0000 \u0000 <li>A larger network of friends was negatively associated with adherence.</li>\u0000 \u0000 <li>Female sex and higher cognitive function were positively associated with adherence.</li>\u0000 \u0000 <li>Satisfaction with training tasks and implementation goals was related to adherence.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581453","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":"Enhancing HRQoL assessment for economic evaluation in dementia populations","authors":"Hannah Hussain,&nbsp;Anju Keetharuth,&nbsp;Allan Wailoo,&nbsp;Donna Rowen","doi":"10.1002/trc2.70061","DOIUrl":"https://doi.org/10.1002/trc2.70061","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;This study aims to assess the feasibility, acceptability, and validity of EQ-5D instrument administration methods and proxy selection for evaluating health-related quality of life (HRQoL) in dementia populations. EQ-5D is a widely used measure of HRQoL and is recommended by the National Institute for Health and Care Excellence for cost-effectiveness analyses of health interventions.&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;Individual-level data from three trials were analyzed separately to evaluate missing data rates, inter-rater agreement, responsiveness, and predictors of EQ-5D (EQ-5D-3L and EQ-5D-5L) dimensions and index values. The study used psychometric analyses, correlations, and multivariate linear regression models to evaluate EQ-5D dimension reports. Reports from both people with dementia (PwD) and proxies were compared to assess reliability across different settings and proxy types.&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;Proxy-reported EQ-5D achieved higher completion rates compared to reports from PwD, with proxies showing greater responsiveness to changes in symptom scores over time. Face-to-face instrument administration for informal proxies was favored over postal methods, and proxy selection was found to be crucial, with informal proxies recommended for community-dwelling PwD and staff proxies for institutionalized populations. Inter-rater agreement was strongest for the “mobility” dimension, with differences in reporting by dimension. Novel guidelines on integrating EQ-5D data reported by PwD and proxies are proposed. Combining self- and proxy-reported data to generate an integrated utility score potentially reflects a more holistic perspective and may enhance the accuracy of HRQoL assessment, compared to relying solely on one respondent's reports.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The importance of careful administration and proxy selection for HRQoL data collection and application in dementia trials and studies is highlighted. These findings have implications for informing economic evaluations of dementia interventions, emphasizing the potential need for tailoring approaches to HRQoL assessment based on the residential status of the PwD.&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 EQ-5D is a widely used measure in dementia trials, but challenges like missing data and discrepancies ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581454","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":"Blood-based biomarker prescreening with different testing combinations and cutoffs: A simulation study examining efficacy and cost-effectiveness in Alzheimer's disease prevention studies","authors":"Kenichiro Sato,&nbsp;Yoshiki Niimi,&nbsp;Ryoko Ihara,&nbsp;Atsushi Iwata,&nbsp;Kazushi Suzuki,&nbsp;Takeshi Iwatsubo","doi":"10.1002/trc2.70065","DOIUrl":"https://doi.org/10.1002/trc2.70065","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;Blood-based biomarkers (BBBMs), including plasma amyloid beta (Aβ) or phosphorylated tau (p-tau), combined with apolipoprotein E (&lt;i&gt;APOE&lt;/i&gt;) testing, are anticipated to serve as prescreening tools before amyloid positron emission tomography (PET) for recruiting participants for Alzheimer's disease (AD) prevention studies. The predictive efficacy and cost-effectiveness of prescreening may vary with different testing combinations, sequences, and cutoff levels.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We conducted a simulation study utilizing data from our ongoing Japanese Trial-Ready Cohort (J-TRC) onsite study (&lt;i&gt;n&lt;/i&gt; = 202) recruited online. We included cognitively unimpaired individuals who had undergone amyloid PET, &lt;i&gt;APOE&lt;/i&gt; genotyping, and evaluation of BBBMs (i.e., plasma Aβ42/Aβ40 ratio, plasma p-tau217, and plasma p-tau217/Aβ42 ratio). We examined 14 different prescreening models incorporating &lt;i&gt;APOE&lt;/i&gt; genotype and/or BBBMs with varied combinations and cutoff levels. Models were evaluated for predictive performance (sensitivity, specificity, and positive predictive value [PPV]) and cost-effectiveness (cost per identified amyloid-positive case) across varied testing costs and the prevalence of amyloid positivity.&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;Applying BBBM prescreening significantly decreased sensitivity and increased specificity and PPV compared to the no-prescreening scenario. Although no single model was superior in all performance metrics, a trade-off between sensitivity and specificity was observed. Generalized linear models (GLMs) simultaneously incorporating plasma Aβ42/Aβ40 ratio and p-tau217 showed a balanced efficacy (the best level of improvement in number needed to screen (NNS) but modest worsening in sensitivity) and the best level of cost-effectiveness compared to other models, although there were substantial overlaps in their 95% confidence intervals (CIs). The minimum-required PET/BBBM cost ratio to achieve improved cost-effectiveness by employing the prescreening process was negatively associated with the background prevalence of amyloid positivity.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The choice of prescreening strategy in AD prevention studies/trials should be tailored to specific trial requirements, considering the relative importance of sensitivity versus cost-effectiveness, local testing cost environments, and background population characteristics.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581452","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":"Impact of study partner replacement in a mild cognitive impairment clinical trial","authors":"Lucy A. Dolmadjian,&nbsp;Mary Ryan Baumann,&nbsp;Joshua D. Grill,&nbsp;Daniel L. Gillen","doi":"10.1002/trc2.70063","DOIUrl":"https://doi.org/10.1002/trc2.70063","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; BACKGROUND&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In Alzheimer's disease (AD) clinical trials, including trials enrolling patients with mild cognitive impairment (MCI), participants must enroll with a study partner (SP). SPs ensure compliance and are a source of study data, including assessments of the participant's cognition and function. Consistency in SP reporting is essential to trial data integrity.&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 quantified SP replacement and its impact on bias and variance of SP-reported AD Cooperative Study Activities of Daily Living for MCI (ADCS-ADL-MCI) in the ADCS Vitamin E/Donepezil MCI Trial. We used logistic regression to estimate the association between SP type (spouse or non-spouse) and the odds of experiencing SP change. We used generalized estimating equations to longitudinally model the differences in consecutively recorded ADCS-ADL-MCI scores as a function of whether SP change occurred. We used a similar model to quantify end-of-study change from baseline in ADCS-ADL-MCI scores.&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 768 participants, 40 (5%) experienced at least one SP change. We estimated that the odds of experiencing a SP change were 65% lower for spousal dyads when compared to non-spousal dyads (odds ratio [OR] = 0.35; 95% confidence interval [CI]: [0.18–0.67]). Compared to those with a consistent SP, participants who experienced a SP change had, on average, a consecutive visit absolute score difference that was 1.60 points greater in magnitude (95% CI: [0.62–2.57]), suggesting greater volatility. ADCS-ADL-MCI scores were neither systematically higher nor lower when SP change occurred, on average (-0.23; 95% CI: [-1.60, 1.14]), suggesting minimal bias. The estimated difference in variance for end-of-study change from baseline ADCS-ADL-MCI was observed to be higher for those with SP change compared to those without, but the difference was not statistically significant (1.29; 95% CI: [0.47–1.17]).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; CONCLUSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;SP replacement occurred for a meaningful number of participants but did not result in systematic bias on a functional outcome in this trial, but it did increase variability.&lt;/p&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;Among participants in a mild cognitive impairment trial, approximately 5% experienced at least one study partner replacement.&lt;/li&gt;\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497262","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":"Predictive value and weight of factors associated with cognitive performance in Hispanics/Latinos enrolled in the Health and Aging Brain Study: Health Disparities","authors":"Raul Vintimilla,&nbsp;Darian Johnson,&nbsp;Douglas Taylor,&nbsp;James Hall,&nbsp;Fan Zhang,&nbsp;Sid O'Bryant,&nbsp;for the HABS-HD Study Team","doi":"10.1002/trc2.70060","DOIUrl":"https://doi.org/10.1002/trc2.70060","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;In this analysis of cognitively unimpaired (CU) Hispanic participants from the Health and Aging Brain Study: Health Disparities (HABS-HD), we aimed to identify the main predictor factors for cognitive performance and their relative importance (weight).&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 HABS-HD is a community-based longitudinal cohort study. Data from 952 CU Hispanics, enrolled from 2017 to February 2024, were analyzed. Random forest, an assembly learning method based on decision trees, was used to cross-sectionally forecast the predictive value of 42 risk factors (4 demographic variables, 4 socioeconomic variables, 6 psychosocial variables, 17 health variables, and 11 plasma and magnetic resonance imaging biomarkers) together, and the weighting of each factor for different cognitive domains (global cognition, memory, language, executive function, attention, and processing speed).&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;Participants included in the analyses had a mean age of 61.3 years (9.14), 69.4% were female, and had a mean of 10.52 (4.61) years of education. Income, glucose levels, plasma amyloid beta (Aβ)42, total tau, and neurofilament light chain were in the top 10 predictors in six cognitive domains. Age, education years, Penn State Worry Questionnaire, body mass index, and C-reactive protein were the main predictors in four cognitive domains, while plasma Aβ40 was in the top 10 list for five cognitive domains.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Results support the notion that cognitive performance depends on interactions among social, economic, biological, and functional factors. The effects of factors together, and the weight of each factor in various cognitive domains may be different in Hispanics. More studies comparing different ethnic groups are necessary to help in the development of tailored interventions to prevent cognitive decline.&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;Numerous factors have been associated with cognitive decline and dementia.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Research on these factors has relied on a meta-analysis of their individual association with cognition, consolidating data from different non-Hispanic White populations.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Hispanics are the largest minority group in the United States","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497237","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 treatments: Why we think they are worth it","authors":"Suzanne E. Schindler,&nbsp;Erik S. Musiek,&nbsp;John C. Morris","doi":"10.1002/trc2.70055","DOIUrl":"https://doi.org/10.1002/trc2.70055","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Years of experience watching our patients progressively decline and die from complications of Alzheimer's disease (AD) has strongly motivated us to provide newly approved anti-amyloid treatments to appropriate patients. Following detailed and personalized discussions of the potential risks and benefits of these treatments with patients and their families, almost 300 patients at our clinic have chosen to receive lecanemab infusions. We have found the frequency and severity of complications, including amyloid-related imaging abnormalities (ARIA), to be manageable and as expected based on clinical trials. While the longer-term benefits of these treatments are not yet clear, our patients and their families are accepting of even a modest slowing of disease progression. We have experienced the complexities, burdens, costs, and major logistical challenges associated with the treatment of AD with anti-amyloid treatments. However, we also understand that for some of our current patients with early symptomatic AD, anti-amyloid treatments are their best option for fighting this devastating disease, and we find it worthwhile to provide these treatments to our patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Many of our former patients have died from complications of AD.</li>\u0000 \u0000 <li>Our clinic now has nearly 300 patients receiving anti-amyloid treatments.</li>\u0000 \u0000 <li>We have found the complications of anti-amyloid treatments to be manageable.</li>\u0000 \u0000 <li>Despite the challenges, we find anti-amyloid treatments worthwhile.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475710","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":"FDA approval of Miplyffa and Aqneursa: A dual breakthrough for the treatment of Neimann–Pick disease type C","authors":"Mahnoor Jan,&nbsp;Hafiza Mutahra Akbar,&nbsp;Maria Ashfaque,&nbsp;Muskan Latif Khan,&nbsp;Muhammad Talha,&nbsp;Md Ariful Haque","doi":"10.1002/trc2.70029","DOIUrl":"https://doi.org/10.1002/trc2.70029","url":null,"abstract":"&lt;p&gt;In September 2024, the U.S. Food and Drug Administration (FDA) approved two innovative therapies for Niemann–Pick disease type C (NPC). The first drug, Miplyffa (arimoclomol), received approval on September 20, 2024, for treating NPC in adults and children aged 2 years and older.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Within a week, on September 24, 2024, Aqneursa (N-acetyl-L-leucine [NALL]) was also authorized to address neurological symptoms associated with NPC in both adult and pediatric patients weighing at least 15 kg.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; These approvals represent a groundbreaking advancement in the management of NPC, offering new hope for NPC patients as they are the first drugs to be approved by the FDA.&lt;/p&gt;&lt;p&gt;With approximately 1 in 120,000 live births reported worldwide, NPC is a rare autosomal recessive lysosomal storage disease that results from a mutation in genes of NPC1 or NPC2 proteins. Approximately 95% is due to the NPC1 mutation, and only 5% of pathogenic variants occur in NPC2 proteins. These proteins transport cholesterol from lysosomes and regulate lipid content within membranes. Mutation disrupts normal transport, accumulating cholesterol in various tissues, particularly the liver, spleen, and brain. Its prevalence varies by region and population.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Clinical manifestations of NPC are typically age-dependent. In the early infantile period, patients often exhibit delays in developmental motor milestones along with cognitive impairments. In the juvenile phase, individuals may experience gait problems and difficulties in school. In the adult form, psychiatric disturbances are commonly observed. Further neurological signs can include dysarthria, dysphagia, cerebral ataxia, dementia, and seizures. Visceral issues may involve hepatomegaly, splenomegaly, and cholestatic jaundice. Ocular abnormalities are also prevalent, with vertical supranuclear ophthalmoplegia (VSO) being the most common.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; In a study of NPC-diagnosed cases, 76% of patients presented with cerebral ataxia, 75% with VSO, 63% with dysarthria, 54% with splenomegaly, and 45% with psychiatric disorders. Despite the variable age of onset, it is essential to note that infantile onset of the disease, particularly with neurological impairment, is associated with a comparatively worse disease progression than juvenile or adult-onset.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;There is currently no cure for this disease. However, supportive treatment strategies include both pharmacological and non-pharmacological interventions. The only approved drug for NPC in Europe is miglustat (Zavesca), which inhibits glucosylceramide synthase, thereby reducing lipid accumulation.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; The drug has yet to be approved by the FDA and only slows down the progression of neurological symptoms. Non-pharmacological approaches, such as speech therapy, physical therapy, and nutritional support, are also important for improving the quality of l","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475711","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":"Person-centered care at population scale: The Swedish registry for behavioral and psychological symptoms of dementia","authors":"Linus Jönsson,&nbsp;Moa Wibom,&nbsp;Elisabet Londos,&nbsp;Katarina Nägga","doi":"10.1002/trc2.70057","DOIUrl":"https://doi.org/10.1002/trc2.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Behavioral and psychological symptoms of dementia (BPSD) are a common driver of suffering and high care needs. We describe the Swedish BPSD registry, founded in 2010 to develop an evidence base for quality improvement in the care of patients with BPSD. Further, we illustrate the potential of the registry by evaluating how individual BPSD affects mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The registry provides a framework for documenting the occurrence of BPSD, formulating individual care plans, and following up outcomes. Symptoms are recorded by the nursing home version of the neuropsychiatric inventory (NPI), and data are entered by trained staff, mainly at institutional care facilities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Enrollment in the registry totaled 114,869 patients with dementia and a mean age of 84 years. Patients were followed until death (median overall survival 2.2 years) or loss to follow-up (median time under observation 4.2 years in patients remaining alive). Common symptoms included agitation/aggression, aberrant motor behavior, and irritability. Mortality increased with NPI severity and use of neuroleptics but decreased in patients receiving cholinesterase inhibitors or memantine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The scale, completeness, and duration of the registry, together with the possibility of linking to other data sources, offer great potential for data-driven research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The Swedish BPSD Registry, founded in 2010, has followed over 114,000 patients collecting data on symptoms, care plans, interventions and outcomes.</li>\u0000 \u0000 <li>The registry provides a framework for providing and evaluating person-centered care for patients with BPSD, and represents an unparalleled data source for research into BPSD and its management.</li>\u0000 \u0000 <li>Mortality increased in patients with more severe BPSD symptoms and for those treated with neuroleptics, but decreased in patients receiving cholinesterase inhibitors or mematine.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475319","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}