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Perspective: Minimal clinically important difference (MCID) and Alzheimer's disease clinical trials
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-10 DOI: 10.1002/trc2.70059
Jeffrey Cummings

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.

Highlights

  • 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.
  • 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.
  • 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.
  • MCID/MWPC are not measures that are appropriately applied to group outcomes of clinical trials.
最小临床相关性差异(MCID)是对最小临床相关性变化的衡量。MCID 代表患者或临床医生认为有益或有意义下降的相关指标或领域得分的最小差异。MCID 并非一种可供选择的临床试验结果;它不适用于群体测量,而是用来确定单个患者是否达到了变化阈值。对症治疗和疾病靶向治疗都有 MCID。AD治疗研究中使用的几乎所有临床试验工具都已得出MCID。要将 MCID 应用于接受疾病靶向治疗的患者,就必须认识到这些药物所表现出的治疗-无治疗差异预期会越来越大。MCID是对其他评估干预措施意义的策略的补充,包括效应大小、治疗所需人数、应答者分析、节省的时间、生活质量和质量调整生命年。MCID 并非监管部门批准治疗方法的必要指标,因为它适用于单个患者,而不适用于临床试验中用于确定治疗效果的群体结果或平均差异。 亮点 MCID 是衡量人体内认知、功能或行为变化的关键指标,适用于衡量阿尔茨海默病的进展。 在阿尔茨海默病中,MCID 或最小人内变化(MWPC)可作为一种有用的方法,用于确定患者的病情是否已发展到可检测到变化的阈值。 在阿尔茨海默病中,MCID/MWPC 可用来确定已发展到可检测到的人体内变化水平的人数或百分比,预计积极治疗组和安慰剂组之间存在差异。 MCID/MWPC 并非适用于临床试验分组结果的测量指标。
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引用次数: 0
Broad repetitive transcranial magnetic stimulation (rTMS) of the precuneus in Alzheimer's disease: A rationale and study design
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-10 DOI: 10.1002/trc2.70043
Michael K. Leuchter, Hanadi A. Oughli, Kelly A. Durbin, Nicholas J. Jackson, David Elashoff, Timothy S. Chang, Juliana Corlier, Doan Ngo, Cole Matthews, Darice Wong, Brent L. Fogel, Gal Bitan, Andrew F. Leuchter, Keith Vossel, Nanthia Suthana
<div> <section> <h3> INTRODUCTION</h3> <p>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.</p> </section> <section> <h3> METHODS</h3> <p>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.</p> </section> <section> <h3> RESULTS</h3> <p>We anticipate this treatment is feasible and tolerable and may show evidence of target engagement and clinical improvement.</p> </section> <section> <h3> DISCUSSION</h3> <p>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.</p> </section> <section> <h3> Highlights</h3> <div> <ul> <li>Induction-to-maintenance repetitive transcranial magnetic stimulation (rTMS) of the precuneus is a promising t
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引用次数: 0
Factors associated with adherence to tablet-based cognitive training: J-MINT study
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-10 DOI: 10.1002/trc2.70062
Taiki Sugimoto, Kazuaki Uchida, Kenji Sato, Yoko Yokoyama, Ayaka Onoyama, Kosuke Fujita, Yujiro Kuroda, Satomu Wakayama, Hidenori Arai, Takashi Sakurai, J-MINT study group

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

DISCUSSION

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.

Clinical trial registration number

This trial was registered with the University hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN000038671).

Highlights

  • Factors associated with adherence to cognitive training were evaluated.
  • Vision difficulty was negatively associated with adherence.
  • A larger network of friends was negatively associated with adherence.
  • Female sex and higher cognitive function were positively associated with adherence.
  • Satisfaction with training tasks and implementation goals was related to adherence.
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引用次数: 0
Enhancing HRQoL assessment for economic evaluation in dementia populations
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-10 DOI: 10.1002/trc2.70061
Hannah Hussain, Anju Keetharuth, Allan Wailoo, Donna Rowen
<div> <section> <h3> INTRODUCTION</h3> <p>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.</p> </section> <section> <h3> METHODS</h3> <p>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.</p> </section> <section> <h3> RESULTS</h3> <p>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.</p> </section> <section> <h3> DISCUSSION</h3> <p>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.</p> </section> <section> <h3> Highlights</h3> <div> <ul> <li>The EQ-5D is a widely used measure in dementia trials, but challenges like missing data and discrepancies
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引用次数: 0
Blood-based biomarker prescreening with different testing combinations and cutoffs: A simulation study examining efficacy and cost-effectiveness in Alzheimer's disease prevention studies
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-10 DOI: 10.1002/trc2.70065
Kenichiro Sato, Yoshiki Niimi, Ryoko Ihara, Atsushi Iwata, Kazushi Suzuki, Takeshi Iwatsubo
<div> <section> <h3> INTRODUCTION</h3> <p>Blood-based biomarkers (BBBMs), including plasma amyloid beta (Aβ) or phosphorylated tau (p-tau), combined with apolipoprotein E (<i>APOE</i>) 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.</p> </section> <section> <h3> METHODS</h3> <p>We conducted a simulation study utilizing data from our ongoing Japanese Trial-Ready Cohort (J-TRC) onsite study (<i>n</i> = 202) recruited online. We included cognitively unimpaired individuals who had undergone amyloid PET, <i>APOE</i> 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 <i>APOE</i> 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.</p> </section> <section> <h3> RESULTS</h3> <p>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.</p> </section> <section> <h3> DISCUSSION</h3> <p>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.</p> </section> <section>
{"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}
引用次数: 0
Impact of study partner replacement in a mild cognitive impairment clinical trial
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-27 DOI: 10.1002/trc2.70063
Lucy A. Dolmadjian, Mary Ryan Baumann, Joshua D. Grill, Daniel L. Gillen
<div> <section> <h3> BACKGROUND</h3> <p>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.</p> </section> <section> <h3> METHODS</h3> <p>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.</p> </section> <section> <h3> RESULTS</h3> <p>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]).</p> </section> <section> <h3> CONCLUSION</h3> <p>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.</p> <section> <h3> Highlights</h3> <div> <ul> <li>Among participants in a mild cognitive impairment trial, approximately 5% experienced at least one study partner replacement.</li>
{"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}
引用次数: 0
Predictive value and weight of factors associated with cognitive performance in Hispanics/Latinos enrolled in the Health and Aging Brain Study: Health Disparities
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-27 DOI: 10.1002/trc2.70060
Raul Vintimilla, Darian Johnson, Douglas Taylor, James Hall, Fan Zhang, Sid O'Bryant, for the HABS-HD Study Team
<div> <section> <h3> INTRODUCTION</h3> <p>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).</p> </section> <section> <h3> METHODS</h3> <p>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).</p> </section> <section> <h3> RESULTS</h3> <p>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.</p> </section> <section> <h3> DISCUSSION</h3> <p>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.</p> </section> <section> <h3> Highlights</h3> <div> <ul> <li>Numerous factors have been associated with cognitive decline and dementia.</li> <li>Research on these factors has relied on a meta-analysis of their individual association with cognition, consolidating data from different non-Hispanic White populations.</li> <li>Hispanics are the largest minority group in the United States
引言 在对 "健康与老龄化脑研究"(HABS-HD)中认知能力未受损(CU)的西班牙裔参与者进行的分析中,我们旨在确定认知能力的主要预测因素及其相对重要性(权重):Health Disparities (HABS-HD))的西班牙裔参与者进行分析,旨在确定认知表现的主要预测因素及其相对重要性(权重)。 方法 HABS-HD 是一项基于社区的纵向队列研究。研究分析了从 2017 年到 2024 年 2 月注册的 952 名中美洲大学西班牙裔学生的数据。随机森林是一种基于决策树的集合学习方法,用于横截面预测 42 个风险因素(4 个人口统计学变量、4 个社会经济变量、6 个社会心理变量、17 个健康变量以及 11 个血浆和磁共振成像生物标志物)的预测价值,以及每个因素在不同认知领域(整体认知、记忆、语言、执行功能、注意力和处理速度)的权重。 结果 分析对象的平均年龄为 61.3 岁(9.14),69.4% 为女性,平均受教育年限为 10.52 年(4.61)。收入、血糖水平、血浆淀粉样 beta (Aβ)42、总 tau 和神经丝轻链在六个认知领域的预测指标中名列前 10 位。年龄、受教育年限、宾夕法尼亚州忧虑问卷、体重指数和 C 反应蛋白是四个认知领域的主要预测因子,而血浆淀粉样β40 在五个认知领域的预测因子中位列前 10。 讨论 结果支持认知能力取决于社会、经济、生物和功能因素之间相互作用的观点。在西班牙裔中,各种因素的共同影响以及每个因素在不同认知领域中的权重可能有所不同。有必要对不同种族群体进行更多的比较研究,以帮助制定有针对性的干预措施,预防认知能力下降。 要点 许多因素都与认知能力下降和痴呆症有关。 对这些因素的研究依赖于对其与认知能力的个体关联性进行荟萃分析,并整合来自不同非西班牙裔白人群体的数据。 西班牙裔是美国最大的少数民族群体,只有少数研究分析了这些因素的整体影响,以及它们在不同认知领域的个体相对影响。 我们发现,西班牙裔的认知能力可能是社会、经济、生物和功能因素相互作用的结果。
{"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}
引用次数: 0
Anti-amyloid treatments: Why we think they are worth it
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-24 DOI: 10.1002/trc2.70055
Suzanne E. Schindler, Erik S. Musiek, John C. Morris

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.

Highlights

  • Many of our former patients have died from complications of AD.
  • Our clinic now has nearly 300 patients receiving anti-amyloid treatments.
  • We have found the complications of anti-amyloid treatments to be manageable.
  • Despite the challenges, we find anti-amyloid treatments worthwhile.
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引用次数: 0
FDA approval of Miplyffa and Aqneursa: A dual breakthrough for the treatment of Neimann–Pick disease type C
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-24 DOI: 10.1002/trc2.70029
Mahnoor Jan, Hafiza Mutahra Akbar, Maria Ashfaque, Muskan Latif Khan, Muhammad Talha, Md Ariful Haque
<p>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.<span><sup>1</sup></span> 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.<span><sup>2</sup></span> 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.</p><p>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.<span><sup>3</sup></span></p><p>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.<span><sup>3</sup></span> 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.<span><sup>4</sup></span></p><p>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.<span><sup>5</sup></span> 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
2024 年 9 月,美国食品和药物管理局(FDA)批准了两种治疗 C 型尼曼-皮克病(NPC)的创新疗法。第一种药物 Miplyffa(arimoclomol)于 2024 年 9 月 20 日获得批准,用于治疗成人和 2 岁及以上儿童的 NPC。1 一周之内,Aqneursa(N-乙酰-L-亮氨酸 [NALL])也于 2024 年 9 月 24 日获得批准,用于治疗成人和体重至少 15 公斤的儿童患者 NPC 相关的神经症状。据报道,全球每 12 万活产婴儿中约有 1 例患有鼻咽癌,鼻咽癌是一种罕见的常染色体隐性溶酶体储积症,由 NPC1 或 NPC2 蛋白基因突变引起。大约 95% 是由于 NPC1 基因突变,只有 5% 的致病变异发生在 NPC2 蛋白中。这些蛋白从溶酶体中转运胆固醇,并调节膜内的脂质含量。变异会破坏正常转运,使胆固醇在不同组织中积聚,尤其是肝脏、脾脏和大脑。其发病率因地区和人群而异3。鼻咽癌的临床表现通常与年龄有关。在婴儿早期,患者通常表现出运动发育里程碑延迟和认知障碍。在少年期,患者可能会出现步态问题和上学困难。在成人期,通常会出现精神障碍。其他神经系统症状包括构音障碍、吞咽困难、大脑共济失调、痴呆和癫痫发作。内脏问题可能包括肝脏肿大、脾脏肿大和胆汁淤积性黄疸。3 在一项对确诊为鼻咽癌病例的研究中,76% 的患者表现为大脑共济失调,75% 表现为 VSO,63% 表现为构音障碍,54% 表现为脾肿大,45% 表现为精神障碍。尽管发病年龄不一,但必须注意的是,与幼年或成年发病相比,婴儿发病,尤其是伴有神经功能损害时,疾病进展相对较慢。不过,支持性治疗策略包括药物和非药物干预。欧洲唯一获准治疗鼻咽癌的药物是米格鲁司他(Zavesca),它能抑制葡萄糖醛酸合成酶,从而减少脂质堆积。言语治疗、物理治疗和营养支持等非药物疗法对于改善鼻咽癌患者的生活质量也很重要。8 此外,组蛋白去乙酰化酶抑制剂 Vorinostat 能有效防止脂质在溶酶体中的积聚。Arimoclomol 可增强热休克蛋白 (HSP) 的活性,从而改善溶酶体功能和细胞稳态。HSPs 在处理 NPC1 蛋白、溶酶体膜稳定性和保护细胞免于死亡方面发挥着重要作用。9 另一方面,NALL 是 N-acetyl-DL-leucine 的 L-对映体,口服后可被遍布全身(包括大脑)的单羧酸盐转运体吸收。它通过纠正代谢功能障碍,改善线粒体和溶酶体功能,从而提高三磷酸腺苷(ATP)能量的产生。能量代谢的正常化可减少未酯化胆固醇和鞘脂的积累。此外,它似乎还能减轻各种动物模型的神经炎症,这表明它具有潜在的神经保护作用10。Arimoclomol(随机、双盲、安慰剂对照、2/3 期试验)纳入了 50 名年龄在 2-18 岁、经基因证实有鼻咽癌突变的患者,根据他们使用米格鲁司他的情况进行分组。然后,患者按 2:1 的比例随机接受阿瑞莫司洛尔或安慰剂治疗,每天三次,为期 12 个月。在12个月后的主要终点方面,与安慰剂组相比,阿瑞莫司洛尔的五域NPCCSS评分有显著变化,表明阿瑞莫司洛尔的治疗效果显著,每年疾病进展相对减少65%。该药的安全性与胃肠道不良反应一致,主要是呕吐。不过,阿瑞莫司洛尔组比安慰剂组更容易发生上呼吸道感染和体重下降。
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引用次数: 0
Person-centered care at population scale: The Swedish registry for behavioral and psychological symptoms of dementia
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-24 DOI: 10.1002/trc2.70057
Linus Jönsson, Moa Wibom, Elisabet Londos, Katarina Nägga

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

DISCUSSION

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.

Highlights

  • The Swedish BPSD Registry, founded in 2010, has followed over 114,000 patients collecting data on symptoms, care plans, interventions and outcomes.
  • 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.
  • Mortality increased in patients with more severe BPSD symptoms and for those treated with neuroleptics, but decreased in patients receiving cholinesterase inhibitors or mematine.
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引用次数: 0
期刊
Alzheimer''s and Dementia: Translational Research and Clinical Interventions
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