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Mitochondrial blood-based biomarker is related to cardiorespiratory fitness and aging in a sex-dependent manner 线粒体血液生物标志物与心肺健康和衰老以性别依赖的方式相关
IF 6.8 Q1 CLINICAL NEUROLOGY
Alzheimer''s and Dementia: Translational Research and Clinical Interventions
Pub Date : 2025-10-07 DOI: 10.1002/trc2.70163
Riley E. Kemna, Amanda Szabo-Reed, Hana D. Mayfield, Paul J. Kueck, Jenae Pennington, Casey S. John, Brittany M. Hauger, Heather M. Wilkins, Eric D. Vidoni, Jill K. Morris
<div> <section> <h3> INTRODUCTION</h3> <p>A sedentary lifestyle increases the risk for Alzheimer's disease (AD), whereas exercise has been shown to benefit brain health. Physiological factors, such as female sex, are linked to lower cardiorespiratory fitness and can increase the risk of AD, which might impact exercise benefits to the brain. Exploring cellular mechanisms underlying fitness in older adults is essential to understanding exercise and AD risk and how sex might impact this interaction.</p> </section> <section> <h3> METHODS</h3> <p>We collected blood from 34 cognitively healthy older adults (age 65+, 18 male, 16 female) enrolled in the COMbined Exercise Trial (COMET; NCT04848038). Subjects underwent a blood draw and clinical assessments for cardiorespiratory fitness and body composition. Blood was collected in ACD tubes, and lymphocytes were isolated. Fluorescent stains used were MitoTracker, Annexin V, MitoSOX, TMRE (tetramethylrhodamine ethyl ester), and Hoechst, analyzed by flow cytometry, and used to calculate a composite mitochondrial function index (MFI).</p> </section> <section> <h3> RESULTS</h3> <p>As expected, males had higher lean mass and VO<sub>2peak</sub> than females (<i>p</i> = 0.01), but groups did not differ in body mass index (<i>p</i> = 0.51). Males had a higher MFI compared to females (<i>p</i> = 0.01). Within each sex, we observed unique metabolic relationships. In males, there was an age-associated decline in MFI (<i>R</i><sup>2</sup> = 0.382, <i>p</i> = 0.01). In females, our systemic measure of mitochondrial superoxides had a negative relationship with lean mass (<i>R</i><sup>2</sup> = 0.648, <i>p</i> < 0.01) and oxygen uptake efficiency slope (OUES) (<i>R</i><sup>2</sup> = 0.271, <i>p</i> = 0.04).</p> </section> <section> <h3> DISCUSSION</h3> <p>We combined an MFI with measures related to fitness in a cognitively healthy older adult population. We explored physiological factors that impact cardiorespiratory fitness, such as sex. We observed relationships between mitochondrial superoxides and OUES and lean mass in females, whereas males had higher MFI overall. Sex-dependent differences in mitochondrial function and superoxide might be an underlying factor of variable cardiorespiratory fitness between sexes and could help explain differences in AD risk.</p> </section> <section> <h3> Highlights</h3> <div> <ul> <li>Mitochondrial blood-biomarker shows sex-
久坐不动的生活方式会增加患阿尔茨海默病（AD）的风险，而运动已被证明有益于大脑健康。生理因素，如女性，与较低的心肺健康有关，并可能增加患阿尔茨海默病的风险，这可能会影响锻炼对大脑的好处。探索老年人健康的细胞机制对于理解运动和AD风险以及性别如何影响这种相互作用至关重要。方法：我们收集了34名参加联合运动试验（COMET; NCT04848038）的认知健康老年人（65岁以上，18名男性，16名女性）的血液。受试者接受了抽血和心肺健康和身体成分的临床评估。ACD管采血，分离淋巴细胞。使用的荧光染色剂为MitoTracker、Annexin V、MitoSOX、TMRE（四甲基罗丹明乙酯）和Hoechst，流式细胞术分析，并用于计算复合线粒体功能指数（MFI）。结果男性的瘦体重和vo2峰值均高于女性（p = 0.01），而体重指数各组间差异无统计学意义（p = 0.51）。男性的MFI高于女性（p = 0.01）。在每个性别中，我们观察到独特的代谢关系。在男性中，MFI与年龄相关（R2 = 0.382, p = 0.01）。在女性中，我们的线粒体超氧化物的全身测量与瘦质量（R2 = 0.648, p < 0.01）和氧吸收效率斜率（OUES）呈负相关（R2 = 0.271, p = 0.04）。我们将MFI与认知健康的老年人群的健康相关测量相结合。我们探索了影响心肺健康的生理因素，如性别。我们观察到线粒体超氧化物与女性OUES和瘦质量之间的关系，而男性总体上具有更高的MFI。线粒体功能和超氧化物的性别依赖性差异可能是两性之间心肺适应性变化的潜在因素，并有助于解释AD风险的差异。线粒体血液生物标志物在衰老过程中显示性别依赖关系。老年成年男性线粒体功能指数较高。男性线粒体功能指数随年龄增长而下降。线粒体活性氧（ROS）与女性的适应性呈负相关。线粒体ROS与女性瘦体重呈负相关。
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引用次数: 0
Recruitment and eligibility in a Phase 1 early Alzheimer's disease trial of Sabirnetug Sabirnetug在早期阿尔茨海默病1期临床试验中的招募和资格
IF 6.8 Q1 CLINICAL NEUROLOGY
Alzheimer''s and Dementia: Translational Research and Clinical Interventions
Pub Date : 2025-10-07 DOI: 10.1002/trc2.70161
Robyn Moxon, Todd Feaster, Gopalan Sethuraman, Alyssa Carroll, Siew Tin Gan, Vladimir Skljarevski, Karen Sundell, Janice Hitchcock, Eric Siemers
<div> <section> <h3> INTRODUCTION</h3> <p>Historically underrepresented racial and ethnic groups may face a higher risk and burden of dementia but continue to be underrepresented in Alzheimer's disease (AD) clinical research. Recent efforts have been insufficient to identify and address race-related disparities in recruitment and eligibility for AD clinical trials.</p> </section> <section> <h3> METHODS</h3> <p>INTERCEPT-AD was a Phase 1 randomized, placebo-controlled, double-blind, first-in-human study of sabirnetug (ACU193) in participants with early symptomatic AD (mild cognitive impairment [MCI] or mild dementia due to AD). Participants were referred through seven site-selected recruitment strategies across 17 study sites in the United States (June 2021–January 2023). Numbers of pre-screened (<i>n</i> = 1025), screened (<i>n</i> = 260), and eligible (<i>n</i> = 70) participants were compared by recruitment strategy. Recruitment strategy effectiveness (percentage of eligible participants among screened participants) and reasons for screening ineligibility were compared between non-Hispanic White participants and participants from other racial and ethnic groups (i.e., participants who self-identified as American Indian or Alaska Native, Asian, Black or African American, or Hispanic or Latino).</p> </section> <section> <h3> RESULTS</h3> <p>Local site databases were used at 13 of 17 sites (76%) and accounted for the most screened (<i>n</i> = 107, 41%) and eligible (<i>n</i> = 32, 46%) participants. Non-Hispanic White participants were recruited from all seven recruitment strategies, whereas participants of other racial and ethnic groups were recruited primarily from site databases. Significantly more participants of other racial and ethnic groups were ineligible for the study after screening, largely due to ineligible amyloid positron emission tomography (PET) scans (+13.9%).</p> </section> <section> <h3> DISCUSSION</h3> <p>Diverse recruitment tactics, customized to capabilities of study sites and patient populations, may be more successful in recruiting diverse populations than a one-size-fits-all approach. Although a diverse pool of potential participants was screened, a less diverse group was enrolled, largely due to race- and ethnicity-related disparities in screening eligibility rates. Further investigation is needed to assess equitable screening methods for AD clinical trials.</p> </section> <section> <h3> Highlights</h3> <div>
历史上代表性不足的种族和族裔群体可能面临更高的痴呆症风险和负担，但在阿尔茨海默病（AD）临床研究中仍然代表性不足。最近的努力还不足以确定和解决阿尔茨海默病临床试验招募和资格方面的种族差异。方法：INTERCEPT-AD是一项随机、安慰剂对照、双盲、首次在患者身上进行的1期研究，受试者为早期症状性AD（轻度认知障碍[MCI]或AD引起的轻度痴呆）患者，使用sabirnetug （ACU193）。参与者通过美国17个研究地点的7个地点选择的招募策略（2021年6月至2023年1月）被推荐。通过招募策略比较了预筛选（n = 1025）、筛选（n = 260）和合格（n = 70）参与者的数量。招募策略有效性（筛选参与者中合格参与者的百分比）和筛选不合格的原因在非西班牙裔白人参与者和来自其他种族和民族群体的参与者（即，自认为是美洲印第安人或阿拉斯加原住民的参与者，亚洲人，黑人或非裔美国人，或西班牙裔或拉丁裔）之间进行比较。结果：17个站点中的13个（76%）使用了本地站点数据库，其中筛选最多（n = 107, 41%）和符合条件（n = 32, 46%）的参与者。非西班牙裔白人参与者从所有七种招募策略中招募，而其他种族和族裔群体的参与者主要从网站数据库中招募。筛选后，其他种族和族裔群体的参与者明显不符合研究条件，主要是由于淀粉样蛋白正电子发射断层扫描（PET）扫描不合格（+13.9%）。多样化的招募策略，根据研究地点和患者群体的能力定制，可能比一刀切的方法更能成功地招募多样化的人群。虽然筛选了不同的潜在参与者，但由于筛选合格率的种族和民族差异，入选的群体较少。需要进一步的调查来评估公平的阿尔茨海默病临床试验筛选方法。网站数据库招募了筛选和登记最多的参与者。不同的参与者主要是从网站数据库中招募的。入组参与者的多样性低于筛选参与者。更多不符合条件的参与者来自不同的种族和族裔群体。没有一种方法被观察到是一种适合所有人的方法来招募和登记不同的参与者。
{"title":"Recruitment and eligibility in a Phase 1 early Alzheimer's disease trial of Sabirnetug","authors":"Robyn Moxon,&nbsp;Todd Feaster,&nbsp;Gopalan Sethuraman,&nbsp;Alyssa Carroll,&nbsp;Siew Tin Gan,&nbsp;Vladimir Skljarevski,&nbsp;Karen Sundell,&nbsp;Janice Hitchcock,&nbsp;Eric Siemers","doi":"10.1002/trc2.70161","DOIUrl":"https://doi.org/10.1002/trc2.70161","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;Historically underrepresented racial and ethnic groups may face a higher risk and burden of dementia but continue to be underrepresented in Alzheimer's disease (AD) clinical research. Recent efforts have been insufficient to identify and address race-related disparities in recruitment and eligibility for AD clinical trials.&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;INTERCEPT-AD was a Phase 1 randomized, placebo-controlled, double-blind, first-in-human study of sabirnetug (ACU193) in participants with early symptomatic AD (mild cognitive impairment [MCI] or mild dementia due to AD). Participants were referred through seven site-selected recruitment strategies across 17 study sites in the United States (June 2021–January 2023). Numbers of pre-screened (&lt;i&gt;n&lt;/i&gt; = 1025), screened (&lt;i&gt;n&lt;/i&gt; = 260), and eligible (&lt;i&gt;n&lt;/i&gt; = 70) participants were compared by recruitment strategy. Recruitment strategy effectiveness (percentage of eligible participants among screened participants) and reasons for screening ineligibility were compared between non-Hispanic White participants and participants from other racial and ethnic groups (i.e., participants who self-identified as American Indian or Alaska Native, Asian, Black or African American, or Hispanic or Latino).&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;Local site databases were used at 13 of 17 sites (76%) and accounted for the most screened (&lt;i&gt;n&lt;/i&gt; = 107, 41%) and eligible (&lt;i&gt;n&lt;/i&gt; = 32, 46%) participants. Non-Hispanic White participants were recruited from all seven recruitment strategies, whereas participants of other racial and ethnic groups were recruited primarily from site databases. Significantly more participants of other racial and ethnic groups were ineligible for the study after screening, largely due to ineligible amyloid positron emission tomography (PET) scans (+13.9%).&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;Diverse recruitment tactics, customized to capabilities of study sites and patient populations, may be more successful in recruiting diverse populations than a one-size-fits-all approach. Although a diverse pool of potential participants was screened, a less diverse group was enrolled, largely due to race- and ethnicity-related disparities in screening eligibility rates. Further investigation is needed to assess equitable screening methods for AD clinical trials.&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 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237147","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
Simulation of Alzheimer's diagnostic flows with blood biomarker test options in Japan 在日本用血液生物标志物测试选项模拟阿尔茨海默病的诊断流程
IF 6.8 Q1 CLINICAL NEUROLOGY
Alzheimer''s and Dementia: Translational Research and Clinical Interventions
Pub Date : 2025-10-07 DOI: 10.1002/trc2.70157
Ataru Igarashi, Noriyuki Kimura, Takuya Ataka, Temmei Ito, Kotaro Sasaki, Chizuru Kobayashi, Mayaka Tani, Yukinori Sakata, Mie Azuma, Ayano Chida, Tomomi Takeshima, Kosuke Iwasaki, Etsuro Matsubara

INTRODUCTION

This study projected the diagnostic testing landscape for lecanemab treatment in Japan under different workflows.

METHODS

A dynamic simulation estimated wait times and treatment-eligible patient numbers under four scenarios: current diagnostic workflow, blood biomarker (BBM) tests as triage tools, BBM tests for confirmatory diagnostics, and both combined. Willingness-to-pay (WTP) and intangible costs were assessed via an online survey to estimate testing demand.

RESULTS

The maximum mean wait time under the current workflow was projected at 6.4 months, decreasing with BBM integration. The number of treatment-eligible patients increased considerably with BBM-based confirmatory diagnostics. BBM triage testing reduced wait times but temporarily increased treatment-eligible patients.

DISCUSSION

Replacing positron emission tomography (PET) or cerebrospinal fluid with BBM-based diagnostics may increase treatment eligibility because of lower costs, driving higher demand for testing.

Highlights

  • A dynamic simulation models Alzheimer's diagnostic workflows in Japan.
  • Blood biomarker (BBM) tests reduce diagnostic wait times for Alzheimer's in Japan.
  • Implementing BBM tests improves access to Alzheimer's diagnostics.
  • Study quantifies demand for diagnostic testing based on costs and accessibility.
  • Testing costs impact the number of treatment-eligible Alzheimer's patients.
本研究预测了日本在不同工作流程下莱卡耐单抗治疗的诊断测试前景。方法动态模拟估计了四种情况下的等待时间和符合治疗条件的患者人数：当前诊断工作流程，血液生物标志物（BBM）检测作为分诊工具，BBM检测用于确诊诊断，以及两者结合。通过在线调查评估支付意愿（WTP）和无形成本，以估计测试需求。结果当前工作流程下的最长平均等待时间预计为6.4个月，随着BBM的整合而减少。通过基于bbm的确诊诊断，符合治疗条件的患者数量显著增加。BBM分诊测试减少了等待时间，但暂时增加了符合治疗条件的患者。用基于bbm的诊断取代正电子发射断层扫描（PET）或脑脊液可能会增加治疗资格，因为成本更低，从而推动更高的检测需求。一个动态模拟模型在日本的阿尔茨海默病诊断工作流程。在日本，血液生物标志物（BBM）测试减少了阿尔茨海默氏症的诊断等待时间。实施BBM测试改善了阿尔茨海默病诊断的可及性。研究量化了基于成本和可及性的诊断测试需求。检测费用影响了符合治疗条件的阿尔茨海默病患者的数量。
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引用次数: 0
Clinical factors predicting the rate of cognitive decline in a US memory clinic: An electronic health record study 预测美国记忆诊所认知衰退率的临床因素：一项电子健康记录研究
IF 6.8 Q1 CLINICAL NEUROLOGY
Alzheimer''s and Dementia: Translational Research and Clinical Interventions
Pub Date : 2025-10-07 DOI: 10.1002/trc2.70166
Yuchan Wang, Qian Liu, Wenyong Li

To the Editor,

We read the article entitled “Clinical factors predicting the rate of cognitive decline in a US memory clinic: An electronic health record study” that was published in 2025, by Roy Adams et al. in Translational Research & Clinical Interventions.1 This study used real-world clinical data to examine predictors of cognitive decline after an initial memory care visit. It reveals that more rapid deterioration in Mini-Mental State Examination (MMSE) scores was linked to older age, a diagnosis of dementia, and the use of cholinesterase inhibitors or memantine. A slower decline was associated with the patient's total number of prescriptions. Neither race nor ethnicity was associated with rate of decline, and nor was baseline mild cognitive impairment, other non-dementia cognitive impairment, diabetes, hypertension, obesity, depression, anxiety, chronic pain, fatigue, or hearing loss. The authors utilized real-world electronic health records as the data foundation, which best reflects patients’ conditions in actual clinical settings. However, we note that some issues need to be further elucidated.

First, this study reveals that hypertension is not associated with a decline in cognitive scores, but some studies contradict this conclusion.2-4 For example, a study by Ding L et al. showed that a longer hypertension duration was associated with worse memory test; in addition, the Framingham Offspring cohort study by McGrath et al. revealed that midlife hypertension is associated with increased risk of a late life dementia. We speculate that the reason this study1 concluded that there is no association between hypertension and cognitive decline may be due to its relatively short follow-up period (6 months) and minimal changes in blood pressure. However, this does not definitively rule out a relationship between hypertension and cognitive decline, and further research is warranted.

Second, the authors mentioned in the abstract that faster decline in MMSE scores was associated with cholinesterase inhibitor or memantine prescription. We believe that this expression may mislead readers into thinking that the cognitive decline was caused by increased medication use. However, as the authors clarified in the discussion, this is expected and reflects increased prescribing in sicker patients.

In summary, we believe that this study offers valuable empirical evidence for the investigation of cognitive decline. Building on these findings, the authors could consider extending the follow-up duration and incorporating insights from additional studies5, 6 to account for the causal effects of these medications, so as to further clarify the risk factors for cognitive decline.

Yuchan Wang: manuscript writing, final approval. Qian Liu: revision for academic advice in the field of neurology. Wenyong Li: critical revision for important intelle

致编辑，我们阅读了罗伊·亚当斯等人于2025年发表在《转化研究与临床干预》杂志上的题为“预测美国记忆诊所认知衰退速度的临床因素：一项电子健康记录研究”的文章。该研究使用真实世界的临床数据来检查首次记忆护理访问后认知衰退的预测因素。研究表明，最小精神状态检查（MMSE）评分的快速恶化与年龄、痴呆诊断以及胆碱酯酶抑制剂或美金刚的使用有关。较慢的下降与患者的处方总数有关。种族和民族与下降率无关，基线轻度认知障碍、其他非痴呆性认知障碍、糖尿病、高血压、肥胖、抑郁、焦虑、慢性疼痛、疲劳或听力损失也无关。作者利用真实世界的电子健康记录作为数据基础，最能反映患者在实际临床环境中的情况。然而，我们注意到一些问题需要进一步阐明。首先，本研究揭示高血压与认知评分下降无关，但一些研究与此结论相矛盾。2-4例如，Ding L等人的研究表明，高血压持续时间越长，记忆力测试越差；此外，McGrath等人的Framingham Offspring队列研究显示，中年高血压与晚年痴呆的风险增加有关。我们推测，本研究1得出高血压与认知能力下降无关联的原因可能是其随访时间相对较短（6个月），血压变化较小。然而，这并不能完全排除高血压和认知能力下降之间的关系，需要进一步的研究。其次，作者在摘要中提到，胆碱酯酶抑制剂或美金刚处方与MMSE评分下降更快有关。我们认为这种表达可能会误导读者，使他们认为认知能力下降是由药物使用增加引起的。然而，正如作者在讨论中澄清的那样，这是预期的，反映了病情较重的患者处方增加。总之，我们认为本研究为认知衰退的研究提供了有价值的经验证据。在这些发现的基础上，作者可以考虑延长随访时间，并结合其他研究的见解5,6来解释这些药物的因果效应，从而进一步阐明认知能力下降的风险因素。王玉婵：稿件撰写，最终审定。刘谦：神经病学领域学术建议修订。李文勇：对重要知识内容的批判性修改。作者声明无利益冲突。
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引用次数: 0
Clinically meaningful changes in cognitive and functional outcomes in a population-based study of cognitive aging 一项基于人群的认知衰老研究中认知和功能结果的临床意义变化
IF 6.8 Q1 CLINICAL NEUROLOGY
Alzheimer''s and Dementia: Translational Research and Clinical Interventions
Pub Date : 2025-09-24 DOI: 10.1002/trc2.70160
Jeremiah A. Aakre, Anna M. Castillo, Jonathan Graff-Radford, Prashanthi Vemuri, Mary M. Machulda, Clifford R. Jack Jr, David S. Knopman, Ronald C. Petersen, Maria Vassilaki

INTRODUCTION

Research is limited regarding meaningful change thresholds for individual patients on clinical outcome assessments (COAs) frequently used in clinical trials for Alzheimer's disease and related dementias (ADRD), particularly in population-based studies early in the disease course.

METHODS

There were 646 study participants in the population-based Mayo Clinic Study of Aging (MCSA), 54–99 years old (47% females), who developed the clinical syndromes of mild cognitive impairment (MCI) with complete data to establish clinically meaningful within-patient change thresholds in cognitive and functional COAs.

RESULTS

Using the diagnosis of incident MCI as the anchor, mean (95% confidence interval [CI]) annualized estimates of change were: Clinical Dementia Rating (CDR) scale Sum of Boxes (SB) 0.49 (0.43, 0.55), Mini-Mental State Examination (MMSE) −1.01 (−1.12, −0.91), and Functional Activities Questionnaire (FAQ) score 1.04 (0.82, 1.26).

DISCUSSION

This study provides within-patient estimates of clinically meaningful change early in disease progression in a community-based sample.

Highlights

  • We studied incident mild cognitive impairment (MCI) participants from a population-based study.
  • Within-patient change thresholds were estimated for clinical outcome assessments (COAs) used in clinical trials for Alzheimer's disease and related dementia (ADRD).
  • These estimates may be used to plan and evaluate clinical trials involving disease-modifying therapies (DMTs).
在阿尔茨海默病和相关痴呆（ADRD）临床试验中经常使用的临床结果评估（COAs）的个体患者有意义的变化阈值方面的研究有限，特别是在疾病病程早期的基于人群的研究中。方法在基于人群的梅奥临床衰老研究（MCSA）中，有646名研究参与者，年龄54-99岁（47%为女性），出现轻度认知障碍（MCI）的临床综合征，数据完整，以建立具有临床意义的患者内认知和功能coa变化阈值。结果：以MCI诊断为锚点，平均（95%置信区间[CI]）年化估计变化为：临床痴呆评分（CDR）量表盒和（SB） 0.49(0.43, 0.55)，简易精神状态检查(MMSE) - 1.01(- 1.12, - 0.91)，功能活动问卷（FAQ）评分1.04（0.82,1.26）。本研究在社区样本中提供了疾病进展早期临床有意义变化的患者内估计。我们研究了一项基于人群的研究中的轻度认知障碍（MCI）参与者。用于阿尔茨海默病和相关痴呆（ADRD）临床试验的临床结果评估（COAs）的患者内变化阈值进行了估计。这些估计可用于计划和评估涉及疾病改善疗法（dmt）的临床试验。
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引用次数: 0
Mental health counseling for caregivers is associated with a slower rate of health-care use in people with dementia 护理人员的心理健康咨询与痴呆症患者较低的医疗保健使用率有关
IF 6.8 Q1 CLINICAL NEUROLOGY
Alzheimer''s and Dementia: Translational Research and Clinical Interventions
Pub Date : 2025-09-24 DOI: 10.1002/trc2.70159
Mia Yang, Natasha Collier, Joseph Rigdon, Christina E. Hugenschmidt

BACKGROUND

Caregiver support interventions can reduce depression symptoms for caregivers of persons living with cognitive impairment and dementia (PwCI). However, few studies have assessed the effect of caregiver counseling support on the health-care use of the PwCI. The objective of this study was to assess if caregiver participation in mental health counseling can slow health-care use in PwCI.

METHODS

The analysis included all PwCI with cognitive impairment identified through the electronic health records as seen in either the Wake Forest Memory Counseling Program (MCP), providing mental health counseling, and/or the Kulynych Geriatric Consult Clinic (KGCC), providing memory assessment and care, between August 1, 2016, and February 28, 2020. Health-care use (emergency department [ED] use and hospitalization) pre- and post-index date were compared between PwCI who received only medical care (MC) and those who received both medical and mental health care (MC+MHC) using a mixed effects logistic regression model adjusted for age, sex, race, ethnicity, KGCC visit type, and primary diagnosis. Hypothesis testing was accomplished with two-sided Wald tests, and odds ratios (ORs) were used to characterize effect sizes.

RESULTS

Compared to the 1 year pre-index visit, PwCI who received medical care (MC) only experienced an increase in ED visits (OR 1.73, P < 0.0001) and hospitalizations (OR 1.42, P < 0.0001) in the 1 year post-index visit. In contrast, PwCI and caregivers who received medical + mental health care (MC+MHC) did not experience increases in ED visits (OR 1.13, P = 0.5104) or hospitalizations (OR 1.15, P = 0.4849). Compared to MC only, PwCI who received MC+MHC had significantly lower odds of post- versus pre-ED visits (OR 0.65, P = 0.0322) but not hospitalizations (OR 0.81, P = 0.3270).

CONCLUSION

Providing mental health counseling to caregivers in addition to medical care for the PwCI may reduce ED visits among PwCI.

Highlights

  • This study tests whether caregiver participation in mental health counseling can slow health-care use in the person living with dementia (PLWD).
  • PLWDs who received medical o
背景：照顾者支持干预可以减轻认知障碍和痴呆患者（PwCI）照顾者的抑郁症状。然而，很少有研究评估照顾者咨询支持对PwCI保健使用的影响。本研究的目的是评估看护者参与心理健康咨询是否可以减缓PwCI患者的医疗保健使用。方法分析包括2016年8月1日至2020年2月28日期间，通过提供心理健康咨询的Wake Forest记忆咨询项目（MCP）和/或提供记忆评估和护理的Kulynych老年咨询诊所（KGCC）的电子健康记录确定的所有认知障碍PwCI。采用混合效应logistic回归模型，对仅接受医疗护理（MC）和同时接受医疗和精神保健（MC+MHC）的PwCI患者的医疗保健使用（急诊科[ED]使用和住院）前后日期进行比较，该模型调整了年龄、性别、种族、民族、KGCC就诊类型和初步诊断。采用双侧Wald检验完成假设检验，并使用优势比（ORs）来表征效应大小。结果与指数访视前1年相比，接受医疗护理（MC）的PwCI在指数访视后1年的急诊科就诊次数（OR 1.73, P < 0.0001）和住院次数（OR 1.42, P < 0.0001）均有所增加。相比之下，接受医疗+精神卫生保健（MC+MHC）的PwCI和护理人员的ED就诊次数（OR 1.13, P = 0.5104）或住院次数（OR 1.15, P = 0.4849）均未增加。与仅接受MC治疗相比，接受MC+MHC治疗的PwCI患者在ed治疗后与ed治疗前就诊的几率显著降低（OR 0.65, P = 0.0322），但住院率没有显著降低（OR 0.81, P = 0.3270）。结论在护理护理的基础上，对护理人员进行心理健康咨询，可减少重症监护患者的急诊科就诊。本研究测试了照顾者参与心理健康咨询是否可以减缓痴呆症患者的医疗保健使用。与接受医疗和精神卫生保健的患者相比，只接受医疗保健的plwd患者急诊就诊次数增加。除了医疗护理外，向护理人员提供心理健康咨询可能会减少ptsd患者的急诊科就诊。
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引用次数: 0
Transcriptome profiling of cerebrospinal fluid in Alzheimer's disease reveals molecular dysregulations associated with disease 阿尔茨海默病脑脊液转录组分析揭示了与疾病相关的分子失调。
IF 6.8 Q1 CLINICAL NEUROLOGY
Alzheimer''s and Dementia: Translational Research and Clinical Interventions
Pub Date : 2025-09-16 DOI: 10.1002/trc2.70152
Rhys E. De Sota, Bojk A. Berghuis, Samantha J. Khoury, Jiali Zhuang, Robert A. Rissman, James B. Brewer, Stephen R. Quake, John J. Sninsky, Shusuke Toden
<div> <section> <h3> BACKGROUND</h3> <p>Despite the increasing prevalence of neurodegenerative diseases, the molecular characterization of brain pathologies remains challenging due to limited tissue access. Cerebrospinal fluid (CSF) contains a significant proportion of brain-derived molecular contents, and characterizing these molecules has served as a proxy for evaluating molecular dysregulation in the brain. Here we have characterized the CSF cell-free messenger RNA (cf-mRNA) transcriptome and identified genes and pathways altered in Alzheimer's disease (AD).</p> </section> <section> <h3> METHODS</h3> <p>We performed cf-mRNA sequencing on 52 human CSF samples and further compared their transcriptomic profiles to matched plasma samples. In addition, we also investigated the cf-mRNA profiles of CSF in individuals with AD as well as non-cognitively impaired (NCI) controls.</p> </section> <section> <h3> RESULTS</h3> <p>The molecular content of CSF cf-mRNA was distinct from that of plasma cf-mRNA, with a substantially higher number of brain-associated genes identified in CSF. A large set of dysregulated gene transcripts from CSF was detected in the AD subjects, and these gene transcripts were able to discriminate AD from NCI subjects. Notably, the gene transcripts were enriched in biological processes closely associated with AD, such as brain development and synaptic signaling. In addition, we discovered a subset of gene transcripts that exhibited a high correlation in matched CSF and plasma samples from AD subjects.</p> </section> <section> <h3> CONCLUSIONS</h3> <p>This study not only reveals the novel cf-mRNA content of CSF but also highlights the potential of CSF cf-mRNA profiling as a tool to garner pathophysiological insights into AD.</p> </section> <section> <h3> Highlights</h3> <div> <ul> <li>Cell-free messenger RNA (cf-mRNA) sequencing was performed on 52 human cerebrospinal fluid (CSF) samples.</li> <li>CSF exhibited a distinct transcriptional profile with a higher prevalence of brain-associated genes compared to plasma.</li> <li>Dysregulated genes in Alzheimer's disease (AD) CSF effectively distinguished AD from non-cognitively impaired controls.</li> <li>CSF cf-mRNA profiling holds potential as a tool for gaining pathophysiological insights into AD.</li>
背景：尽管神经退行性疾病越来越普遍，但由于组织通路有限，脑病理的分子表征仍然具有挑战性。脑脊液（CSF）含有相当大比例的脑源性分子内容，表征这些分子已成为评估脑分子失调的代理。在这里，我们描述了脑脊液无细胞信使RNA （cf-mRNA）转录组，并鉴定了阿尔茨海默病（AD）中改变的基因和途径。方法：我们对52份人脑脊液样本进行了cf-mRNA测序，并进一步将其转录组谱与匹配的血浆样本进行了比较。此外，我们还研究了AD患者以及非认知障碍（NCI）对照者脑脊液的cf-mRNA谱。结果：脑脊液cf-mRNA的分子含量与血浆cf-mRNA不同，脑脊液中鉴定的脑相关基因数量要多得多。在AD受试者中检测到大量来自脑脊液的失调基因转录本，这些基因转录本能够区分AD和NCI受试者。值得注意的是，这些基因转录本在与AD密切相关的生物学过程中富集，如大脑发育和突触信号传导。此外，我们发现了一个基因转录子子集，在匹配的脑脊液和AD受试者的血浆样本中表现出高度相关性。结论：本研究不仅揭示了脑脊液中新的cf-mRNA含量，而且强调了脑脊液cf-mRNA谱分析作为一种获得阿尔茨海默病病理生理学见解的工具的潜力。重点：对52例人脑脊液（CSF）样本进行了无细胞信使RNA （cf-mRNA）测序。脑脊液表现出明显的转录谱，与血浆相比，脑相关基因的患病率更高。阿尔茨海默病（AD）脑脊液中的失调基因可以有效地将AD与非认知受损的对照区分开来。CSF cf-mRNA谱分析具有作为一种获得AD病理生理学见解的工具的潜力。
{"title":"Transcriptome profiling of cerebrospinal fluid in Alzheimer's disease reveals molecular dysregulations associated with disease","authors":"Rhys E. De Sota,&nbsp;Bojk A. Berghuis,&nbsp;Samantha J. Khoury,&nbsp;Jiali Zhuang,&nbsp;Robert A. Rissman,&nbsp;James B. Brewer,&nbsp;Stephen R. Quake,&nbsp;John J. Sninsky,&nbsp;Shusuke Toden","doi":"10.1002/trc2.70152","DOIUrl":"10.1002/trc2.70152","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;Despite the increasing prevalence of neurodegenerative diseases, the molecular characterization of brain pathologies remains challenging due to limited tissue access. Cerebrospinal fluid (CSF) contains a significant proportion of brain-derived molecular contents, and characterizing these molecules has served as a proxy for evaluating molecular dysregulation in the brain. Here we have characterized the CSF cell-free messenger RNA (cf-mRNA) transcriptome and identified genes and pathways altered in Alzheimer's disease (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;We performed cf-mRNA sequencing on 52 human CSF samples and further compared their transcriptomic profiles to matched plasma samples. In addition, we also investigated the cf-mRNA profiles of CSF in individuals with AD as well as non-cognitively impaired (NCI) controls.&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;The molecular content of CSF cf-mRNA was distinct from that of plasma cf-mRNA, with a substantially higher number of brain-associated genes identified in CSF. A large set of dysregulated gene transcripts from CSF was detected in the AD subjects, and these gene transcripts were able to discriminate AD from NCI subjects. Notably, the gene transcripts were enriched in biological processes closely associated with AD, such as brain development and synaptic signaling. In addition, we discovered a subset of gene transcripts that exhibited a high correlation in matched CSF and plasma samples from AD subjects.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; CONCLUSIONS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study not only reveals the novel cf-mRNA content of CSF but also highlights the potential of CSF cf-mRNA profiling as a tool to garner pathophysiological insights into 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;Cell-free messenger RNA (cf-mRNA) sequencing was performed on 52 human cerebrospinal fluid (CSF) samples.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;CSF exhibited a distinct transcriptional profile with a higher prevalence of brain-associated genes compared to plasma.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Dysregulated genes in Alzheimer's disease (AD) CSF effectively distinguished AD from non-cognitively impaired controls.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;CSF cf-mRNA profiling holds potential as a tool for gaining pathophysiological insights into AD.&lt;/li&gt;","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12438960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082321","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
Vestibular-related dizziness duration and cognitive deficits in older adults 老年人前庭相关头晕持续时间与认知缺陷
IF 6.8 Q1 CLINICAL NEUROLOGY
Alzheimer''s and Dementia: Translational Research and Clinical Interventions
Pub Date : 2025-09-15 DOI: 10.1002/trc2.70153
Xiaobao Ma, Jiali Shen, Wei Wang, Lu Wang, Yulian Jin, Maoli Duan, Qing Zhang, Jun Yang, Jianyong Chen
<div> <section> <h3> OBJECTIVE</h3> <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> </section> <section> <h3> METHODS</h3> <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> </section> <section> <h3> RESULTS</h3> <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> </section> <section> <h3> CONCLUSION</h3> <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> </section> <section> <h3> Highlights</h3> <div> <ul> <li>Long-duration vestibular-related dizziness or balance disorders are associated with a higher risk of cognitive impairment in el
目的探讨老年患者前庭相关性头晕/眩晕症状持续时间与认知功能的关系，为评估和干预前庭相关性认知障碍提供临床指导。方法本研究纳入100例表现为头晕、眩晕或平衡障碍的老年前庭功能障碍患者，根据症状持续时间分为短期组（n = 64）和长期组（n = 36）。对照组为21名健康老年人。认知评估包括P300事件相关电位（潜伏期/振幅）和蒙特利尔认知评估（MoCA）以及特定领域分析。结果P300潜伏期组间差异显著（对照组、短时间潜伏期和长时间潜伏期：p <； 0.001），而振幅无差异（p = 0.817）。各组间MoCA总分差异显著（p = 0.001），但异常率具有可比性（p = 0.093）。领域分析显示，视觉空间（p < 0.001）和抽象能力（p = 0.005）存在显著差异。症状持续时间与MoCA总分（R2 = 0.113）、视觉空间能力（R2 = 0.181）、注意力（R2 = 0.068）、定向（R2 = 0.157）相关。P300潜伏期与MoCA总量（R2 = 0.141）、视觉空间能力（R2 = 0.090）、延迟回忆（R2 = 0.112）和定向（R2 = 0.082）相关。结论：老年患者前庭相关性头晕/眩晕伴认知功能障碍，尤其是视觉空间和执行功能障碍。P300潜伏期比P300振幅和MoCA筛查更敏感，表明电生理和神经心理学联合评估有助于前庭相关认知障碍的早期检测。在老年患者中，长期前庭相关的头晕或平衡障碍与认知障碍的高风险相关。在早期的评估工具中，P300潜伏期被证明比P300振幅和蒙特利尔认知评估（MoCA）问卷更敏感。使用P300潜伏期和MoCA的联合评估可以更有效地衡量眩晕如何影响这一人群的认知功能。
{"title":"Vestibular-related dizziness duration and cognitive deficits in older adults","authors":"Xiaobao Ma,&nbsp;Jiali Shen,&nbsp;Wei Wang,&nbsp;Lu Wang,&nbsp;Yulian Jin,&nbsp;Maoli Duan,&nbsp;Qing Zhang,&nbsp;Jun Yang,&nbsp;Jianyong Chen","doi":"10.1002/trc2.70153","DOIUrl":"10.1002/trc2.70153","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; OBJECTIVE&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;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.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study included 100 elderly patients with vestibular dysfunction presenting dizziness, vertigo, or balance disorders, categorized into short-duration (&lt;i&gt;n&lt;/i&gt; = 64) and long-duration (&lt;i&gt;n&lt;/i&gt; = 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.&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;Significant between-group differences in P300 latency were observed (control vs short-duration vs long-duration: &lt;i&gt;p&lt;/i&gt; &lt; 0.001), whereas amplitude showed no difference (&lt;i&gt;p&lt;/i&gt; = 0.817). MoCA total scores differed significantly across groups (&lt;i&gt;p&lt;/i&gt; = 0.001), although abnormality rates were comparable (&lt;i&gt;p&lt;/i&gt; = 0.093). Domain analysis revealed significant differences in visuospatial (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) and abstract abilities (&lt;i&gt;p&lt;/i&gt; = 0.005). Symptom duration correlated with: MoCA total (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.113), visuospatial ability (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.181), attention (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.068), and orientation (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.157). P300 latency correlated with: MoCA total (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.141), visuospatial ability (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.090), delayed recall (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.112), and orientation (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.082).&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;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.&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;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}
引用次数: 0
Low intrinsic capacity is associated with a blunted exercise-induced cognitive enhancement in physically active middle-aged and older adults 在身体活跃的中老年人中，低内在能力与运动引起的认知增强减弱有关
IF 6.8 Q1 CLINICAL NEUROLOGY
Alzheimer''s and Dementia: Translational Research and Clinical Interventions
Pub Date : 2025-09-11 DOI: 10.1002/trc2.70141
Brandon A. Yates, Ariela R. Orkaby, Jakob L. Vingren, Lawrence E. Armstrong
<div> <section> <h3> INTRODUCTION</h3> <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> </section> <section> <h3> METHODS</h3> <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> </section> <section> <h3> RESULTS</h3> <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> </section> <section> <h3> DISCUSSION</h3> <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> </section> <section> <h3> Highlights</h3> <div> <ul> <li>Adults with overweight/obesity show cognitive gains after endurance exercise.</l
世界卫生组织支持将内在能力（IC）作为评估和监测老年人认知健康的框架。低智商与较高的痴呆风险相关。定期运动可以改善认知健康，降低痴呆风险，并可能增加IC。然而，定期运动训练对大脑的长期慢性益处取决于单次运动增强认知的有效性。然而，IC如何影响单次锻炼后的改善幅度尚未阐明。方法选取40名身体质量指数≥24.9 kg/m2（范围：24.9 ~ 36.3）、身体活跃的成年人（55±6岁，平均±SD）为研究对象。IC域在操作上定义如下：认知（Mini Cog和Trail Making Test part A和B [TMT A+B]性能）、活力（身体组成和运动性能）和运动功能（习惯性步速）。根据运动功能将参与者分为慢速组（≤1.0 m/s; LOW-IC）和正常组（>1.0 m/s; NORM-IC）。在锻炼（161公里自行车项目）之前和之后，参与者完成了执行功能任务（TMT A+B）。在控制基线TMT A+B表现的情况下，采用协方差分析检测TMT A+B的显著改善（p < 0.05）。结果被试具有相似的认知能力和活力，但两组在运动功能上存在显著差异。在运动后，NORM-IC的改善（- 13 s[- 18至- 8]；p < 0.001；偏η2 = 0.47；调整后的平均值[95%置信区间]）大于LOW-IC (- 3 s[- 9至2]；p = 0.25；偏η2 = 0.04)，显示出显著的相互作用（p = 0.004）。在成年中后期，低IC与钝化的急性运动诱导的认知增强有关。未来的研究有理由确定支撑这一新发现的生理机制。超重/肥胖的成年人在耐力运动后表现出认知能力的提高。运动功能差限制了超重成年人从运动中获得的认知能力。IC比认知能力更能预测运动相关的认知收益。
{"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,&nbsp;Ariela R. Orkaby,&nbsp;Jakob L. Vingren,&nbsp;Lawrence E. Armstrong","doi":"10.1002/trc2.70141","DOIUrl":"10.1002/trc2.70141","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;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.&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;A convenience sampling of 40 physically active adults (55 ± 6 years; mean ± SD) with a body mass index ≥ 24.9 kg/m&lt;sup&gt;2&lt;/sup&gt; (range: 24.9 to 36.3) were included in this study. IC domains were operationally defined as follows: &lt;i&gt;cognitive&lt;/i&gt; (Mini Cog and Trail Making Test Parts A and B [TMT A+B] performance), &lt;i&gt;vitality&lt;/i&gt; (body composition and exercise performance), and &lt;i&gt;locomotor function&lt;/i&gt; (habitual gait speed). Participants were stratified by &lt;i&gt;locomotor function&lt;/i&gt; into a slow group (≤1.0 m/s; LOW-IC) and a normal group (&gt;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 (&lt;i&gt;p&lt;/i&gt; &lt; 0.05).&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 had similar &lt;i&gt;cognitive abilities&lt;/i&gt; and &lt;i&gt;vitality&lt;/i&gt;, but groups significantly differed by &lt;i&gt;locomotor function&lt;/i&gt;. A significant interaction (&lt;i&gt;p&lt;/i&gt; = 0.004) was revealed where improvement for NORM-IC (−13 s [−18 to −8]; &lt;i&gt;p&lt;/i&gt; &lt; 0.001; partial &lt;i&gt;η&lt;sup&gt;2&lt;/sup&gt;&lt;/i&gt; = 0.47; adjusted mean [95% confidence interval]) was greater than for LOW-IC (−3 s [−9 to 2]; &lt;i&gt;p&lt;/i&gt; = 0.25; partial &lt;i&gt;η&lt;sup&gt;2&lt;/sup&gt;&lt;/i&gt; = 0.04) following the exercise session.&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;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.&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;Adults with overweight/obesity show cognitive gains after endurance exercise.&lt;/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}
引用次数: 0
Implications of practice effects for the design of Alzheimer clinical trials 实践效应对阿尔茨海默病临床试验设计的影响
IF 6.8 Q1 CLINICAL NEUROLOGY
Alzheimer''s and Dementia: Translational Research and Clinical Interventions
Pub Date : 2025-09-09 DOI: 10.1002/trc2.70154
Jasmin A. Duehring, Diane M. Jacobs, Michael L. Thomas, Hiroko H. Dodge, Howard H. Feldman, Steven D. Edland
<div> <section> <h3> INTRODUCTION</h3> <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> </section> <section> <h3> METHODS</h3> <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> </section> <section> <h3> RESULTS</h3> <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> </section> <section> <h3> DISCUSSION</h3> <p>Clinical trials randomizing after a run-in period measure treatment efficacy relative to decline unbiased by PEs, and require smaller sample size.</p> </section> <section> <h3> Highlights</h3> <div> <ul> <li>In the National Alzheimer's Coordinating Center (NACC), amnestic mild cognitive impairment (aMCI) cohort practice effects often exceed annualized rate of c
在衰老和早期阿尔茨海默病的纵向认知能力下降的自然历史研究中，实践效应（PEs）是一个众所周知的潜在混淆。PEs对阿尔茨海默病临床试验的影响尚不清楚，尽管我们先前推测在随机化之前反复进行认知评估的“磨合期”可能会提高临床试验的效率[Jacobs等人]。阿尔茨海默病[j]； Dementia; 2017;3(4):531-535。我们还描述了复合结果测量的性能如何取决于可能受pe影响的参数。为了研究这一点，我们使用了国家阿尔茨海默病协调中心（NACC）统一数据集中的认知电池来表征PEs对临床试验设计和结果测量的潜在影响。该分析仅限于N = 1094名轻度认知障碍的健忘参与者，随访数据为3年。线性混合效应模型估计了在aMCI参与者中观察到的pe的大小。根据NACC样本进展模式的功率计算被用来描述pe对有或没有磨合阶段的试验的净影响。并对NACC电池构建的最优复合措施的权重参数进行了比较。结果pe很大，经常超过后来评估中观察到的年变化率。磨合后的年化变化率更大，因此目标处理效果足以实现特定百分比的下降率降低。磨合设计的样本量预测是无磨合试验所需样本量的一小部分。两种设计中优化复合结局表现的权重参数也不同，强调了在构建复合结局时考虑设计的重要性。在磨合期后随机分配的临床试验测量治疗效果相对于pe的无偏倚下降，并且需要较小的样本量。在国家阿尔茨海默病协调中心（NACC），健忘轻度认知障碍（aMCI）队列实践的效果往往超过年化变化率。磨合临床试验设计可以用来消除实践效果。磨合后的下降速度更快，且不受实践影响。磨合设计正确地针对最临床相关的结果信号。实践效果也影响了最优复合措施的权重。
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