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

{"title":"Estimating preclinical amyloid positivity: A case study transporting ADNI to ARIC.","authors":"Emma K Stapp, Elizabeth Rose Mayeda, Elizabeth A Stuart, Rebecca F Gottesman, Scott C Zimmerman, Dean F Wong, Thomas H Mosley, Michael E Griswold, M Maria Glymour, Melinda C Power","doi":"10.1002/trc2.70158","DOIUrl":"https://doi.org/10.1002/trc2.70158","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease and related dementias researchers have benefited from deeply phenotyped clinical samples; however, there is a critical need for estimates that generalize to diverse, representative populations. Use of a statistical approach from causal inference, \"transport,\" may allow generalization of findings from clinical samples to other target populations. Here we explore the feasibility and validity of extending results from a clinical sample, the Alzheimer's Disease Neuroimaging Initiative (ADNI), to a community-based target sample, the Atherosclerosis Risk in Communities Study Positron Emission Tomography Amyloid Imaging Study (ARIC-PET) using transport estimation and a standard approach, direct standardization, which itself can be considered a simple transport.</p><p><strong>Methods: </strong>Eligible ARIC-PET (<i>n</i> = 343) and ADNI (<i>n</i> = 821) participants were White or Black, with normal cognition or mild cognitive impairment (MCI; 26.5% ARIC-PET, 56.4% ADNI). Estimates of amyloid positivity prevalence were derived from transporting from ADNI to ARIC-PET or standardizing ADNI to ARIC-ET using only sociodemographic characteristics and apolipoprotein E (<i>APOE</i>) ε4 status. Resulting estimates were compared to observed prevalences in ARIC-PET, overall and by age, sex, race, education, <i>APOE</i> ε4 status, and cognitive status.</p><p><strong>Results: </strong>Approximately half of transported prevalences were closer to observed ARIC-PET prevalences than the crude ADNI prevalences, including in all five subgroups in which crude prevalences differed substantially across cohorts. However, for many subgroups, transported prevalences were substantially further from observed ARIC-PET prevalences than crude ADNI prevalences. Standardization produced more variable estimates, which were not systematically closer to observed ARIC-PET prevalence than the crude ADNI prevalence estimates. Restriction to more homogenous samples did not improve performance of either method.</p><p><strong>Discussion: </strong>Although transport performed better than direct standardization in this example, available data appear insufficient to generalize findings from convenience samples to less selected samples with high confidence using either method. Recruitment of diverse, representative samples will likely be needed to derive population-level statistics given limitations of legacy samples.</p><p><strong>Highlights: </strong>Prior prevalence estimates of amyloid positivity are variable.Transport may improve generalization from samples to target populations.We standardized and transported estimates to a target with known prevalence.Neither worked reliably; transport performed better than standardization.Clinical convenience samples are inadequate to derive population-level statistics.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 4","pages":"e70158"},"PeriodicalIF":6.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12520865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310077","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":"Chronic cerebral hypoperfusion-induced myelin loss in normal-appearing white matter correlates with cognitive decline: insights from moyamoya disease.","authors":"Xinfeng Yu, Duo Xu, Yannan Yu, Junwen Hu, Lin Wang, Biao Jiang, Minming Zhang","doi":"10.1002/trc2.70164","DOIUrl":"10.1002/trc2.70164","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic cerebral hypoperfusion (CCH)-induced white matter hyperintensities (WMHs) are a well-established risk factor for cognitive impairment and dementia. While animal and <i>post mortem</i> studies suggest that myelin loss in normal-appearing white matter (NAWM) precedes WMHs, in vivo evidence in human brain remains limited. We aimed to investigate the associations between myelin changes in NAWM, CCH, and cognitive function in patients with moyamoya disease (MMD, a human model of CCH).</p><p><strong>Methods: </strong>We included 58 patients with MMD and 36 healthy controls, and all participants underwent 3.0T magnetic resonance imaging (MRI) with T1-weighted, T2-weighted, and arterial spin labeling (ASL) sequences. Myelin was assessed by the T1-weighted/T2-weighted ratio (rT1/T2), and cerebral blood flow (CBF) in each arterial region was measured by ASL. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA).</p><p><strong>Results: </strong>Patients exhibited decreased rT1/T2 at lower percentiles (P5 and P10) and increased rT1/T2 at higher percentiles (P75, P90, and P95) in NAWM (false discovery rate [FDR]-corrected <i>p</i> < 0.005), along with reduced CBF in the region of anterior circulation (FDR-corrected <i>p</i> < 0.05). Voxel-based analysis of NAWM showed region-specific decreases and increases in rT1/T2 in MMD. The percentile ranges (P90-P10 and P95-P5) of rT1/T2 showed high accuracy in differentiating patients from controls (accuracy: 88% to 90%). Multivariate analysis further revealed that in patients, both P5 and P10 of rT1/T2 were significantly associated with reduced CBF in the anterior circulation region (standardized <i>β</i> = 0.318, <i>p</i> = 0.016 and standardized <i>β</i> = 0.267, <i>p</i> = 0.043), and P5 of rT1/T2 significantly correlated with MMSE and MoCA (standardized <i>β</i> = 0.332, <i>p</i> = 0.004 and standardized <i>β</i> = 0.260, <i>p</i> = 0.011).</p><p><strong>Discussion: </strong>Our study provides in vivo evidence that CCH induces both myelin loss and potential plastic adaptations in NAWM, with severe myelin loss being associated with cognitive decline.</p><p><strong>Highlights: </strong>MMD features CCH and cognitive decline.Decreased rT1/T2 (myelin loss) in NAWM was detected in MMD.The lower percentage of rT1/T2 correlated with CCH.The lowest percentage of rT1/T2 correlated with cognitive decline.The rT1/T2 showed high accuracy in differentiating patients from controls.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 4","pages":"e70164"},"PeriodicalIF":6.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12516246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294218","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":"Potential of low-field MRI for increasing participation of Filipino Americans and underrepresented populations in Alzheimer's and dementia research.","authors":"Mikkael Lamoca, Sandra Rothenberg, Roman Czornobil, Eugenie Mamuyac, Karl Korfmacher, Iris Asllani, Jessica de Leon","doi":"10.1002/trc2.70168","DOIUrl":"10.1002/trc2.70168","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Lack of racial and ethnic minority representation in Alzheimer's disease and related dementias (ADRD) research studies leads to inaccurate trial results and health outcomes disparities. This study examines barriers to ADRD research participation in under-studied Filipino American participants and explores the potential of low-field magnetic resonance imaging (LF-MRI) to mitigate these barriers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We utilized GIS mapping to analyze demographic differences across geographic distances from Alzheimer's Disease Research Centers (ADRCs) in the United States. The number of visits in racial and ethnic minority populations was examined using regression analysis of participant data from the National Alzheimer's Coordinating Center (NACC). Surveys and interviews were conducted with researchers and participants from the University of California, San Francisco Memory and Aging Center to identify barriers and explore LF-MRI's potential to increase Filipino American participation. We conclude with recommendations for LF-MRI implementation in ADRD research.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Location-based analysis demonstrates that LF-MRI may help diversify ADRD research participation by offering portable, cheap imaging modalities in satellite locations. Moreover, many racial and ethnic minority populations, particularly Asians, are underrepresented and less likely to have multiple ADRC visits compared to non-Hispanic and White individuals. Interviews and surveys identified participation barriers, including navigation, scheduling, fear of MRI, health-related stigma, and discomfort with conventional MRI procedures. It also suggested that LF-MRI may offer increased portability, reduced costs, improved physical comfort, and less anxiety. Additionally, researchers identified barriers to implementation, including lack of efficacy and reliability data for advanced imaging requirements, and logistical, privacy, and staff bandwidth concerns.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;These findings contribute to improved understanding of clinical research participation barriers among racial and ethnic minority populations. LF-MRI implementation was explored as a potential way to mitigate these barriers. Future research should address scientific and infrastructural limitations and explore ways to leverage the benefits of LF-MRI in advancing diversity in ADRD research.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Highlights: &lt;/strong&gt;Racial and ethnic minorities in Alzheimer's disease and related dementias (ADRD) research are underrepresented, including Asians.Expanding ADRD research access for Asian and minority groups needs broader outreach.Many minority populations are located beyond the typical travel distance from Alzheimer's Disease Research Centers (ADRCs).low-field magnetic resonance imaging (LF-MRI) may address comfort, cost, accessibility, and geographical barriers.LF-MRI implementation may lead to an increase in research participation.&lt;/p","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 4","pages":"e70168"},"PeriodicalIF":6.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12518030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304375","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":"Digital efforts in Spanish for enrolling Latino adults in the Brain Health Registry","authors":"Miriam T. Ashford,&nbsp;Anna Aaronson,&nbsp;Chengshi Jin,&nbsp;Monica R. Camacho,&nbsp;Joseph Eichenbaum,&nbsp;Aaron Ulbricht,&nbsp;Roxanne Alaniz,&nbsp;Jennefer Sorce,&nbsp;Sandhya Kannan,&nbsp;Lourdes Guerrero,&nbsp;David X. Marquez,&nbsp;Derek Flenniken,&nbsp;Juliet Fockler,&nbsp;Diana Truran,&nbsp;R. Scott Mackin,&nbsp;Monica Rivera Mindt,&nbsp;Alejandra Morlett Paredes,&nbsp;Hector M. González,&nbsp;Michael W. Weiner,&nbsp;Rachel L. Nosheny","doi":"10.1002/trc2.70096","DOIUrl":"https://doi.org/10.1002/trc2.70096","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;Previous culturally informed digital inclusion efforts in English effectively enrolled Latino adults into the Brain Health Registry (BHR), an online Alzheimer's disease (AD)–related registry. Because these efforts were in English only, we did not successfully reach individuals from the U.S. Latino community whose language preference is Spanish. The English-language effort had limited success enrolling Latino participants from diverse sociodemographic backgrounds (e.g., gender, education, nativity). Therefore, we tested the hypothesis that Spanish-language efforts would increase the sociodemographic diversity of enrolled Latino participants.&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 BHR is an online registry that collects longitudinal cognitive and health data. We worked in partnership with a Latino Community Science Partnership Board to develop Spanish-language, culturally informed digital inclusion efforts, including a Spanish translation of BHR, Facebook advertisements, and culturally informed recruitment websites. Here, we (1) report on the Spanish-language digital advertisement results, (2) compare the characteristics of participants enrolled through Spanish (July 2021 through June 2022) versus English (September 2020 to June 2022) advertisements, and (3) compare the characteristics of those using the BHR assessment portal in Spanish versus in English.&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;Culturally informed Spanish-language advertisements enrolled 1059 participants, including 986 who identify as Latino. Compared to participants enrolled through culturally informed English-language efforts (&lt;i&gt;N&lt;/i&gt; = 6985), participants enrolled via Spanish-language efforts were significantly older, had less education, and had a higher percentage of male participants and those born outside the United States. Compared to participants who opted to use the BHR website in English (&lt;i&gt;N&lt;/i&gt; = 37,199), those who opted to use the website in Spanish (&lt;i&gt;n&lt;/i&gt; = 1088), were significantly younger, reported fewer years of education, and more frequently self-identified as male and Latino. However, these efforts failed to increase BHR task completion.&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;Culturally informed digital efforts in Spanish are effective at increasing sociodemographic diversity of a Latino, digital research cohort. Similar efforts can be adapted to other studies and settings to improve the generalizability of AD research.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 4","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145272310","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":"Neurovascular de-coupling underlies dual-task cost across cognitive abilities","authors":"Laura K. Fitzgibbon-Collins,&nbsp;Sarah Best,&nbsp;Mamiko Noguchi,&nbsp;Corey Guest,&nbsp;Michael Borrie,&nbsp;J. Kevin Shoemaker,&nbsp;Jaspreet Bhangu","doi":"10.1002/trc2.70156","DOIUrl":"https://doi.org/10.1002/trc2.70156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We tested the hypothesis that increased middle cerebral artery velocity (MCA velocity) during complex motor (overground walking) and cognitive tasks (e.g., dual task) is associated with cognitive performance in older adults with varying levels of cognitive ability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Fifty-six participants (19 females, 75 ± 7 years old) completed a seated single task that assessed working memory performance; a walking single task, assessing overground walking gait speed; and a dual task, combining both. Continuous MCA velocity was collected, and participants completed a Montreal Cognitive Assessment (MoCA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Higher MCA velocity was associated with faster gait speed, better working memory performance, and greater MoCA scores (all <i>p</i> &lt; 0.05). Participants with lower MoCA scores had lower MCA velocity (<i>p</i> = 0.052), slower gait speed (<i>p</i> = 0.035), and lower working memory performance (<i>p</i> = 0.016) than people with higher MoCA scores. The hyperemic response of MCA velocity from single task walking to the dual task with increased cognitive load significantly contributed to MoCA scores (<i>p</i> = 0.017).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The functional response of cerebral blood flow with these tests suggests vascular properties may be considered a biomarker indicative of subclinical cognitive function during walking tasks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Mobile devices simultaneously assessed neurovascular coupling and dual-task cost.</li>\u0000 \u0000 <li>Middle cerebral artery velocity (MCA velocity) is negatively associated with dual-task cost.</li>\u0000 \u0000 <li>MCA velocity is associated with gait speed, working memory, and Montreal Cognitive Assessment scores.</li>\u0000 \u0000 <li>MCA velocity decreased from controls to mild cognitive impairment to dementia.</li>\u0000 \u0000 <li>Novel methodological approach to utilize MCA velocity during overground walking, single-tasks, and dual-tasks.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","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/trc2.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237279","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":"Mitochondrial blood-based biomarker is related to cardiorespiratory fitness and aging in a sex-dependent manner","authors":"Riley E. Kemna,&nbsp;Amanda Szabo-Reed,&nbsp;Hana D. Mayfield,&nbsp;Paul J. Kueck,&nbsp;Jenae Pennington,&nbsp;Casey S. John,&nbsp;Brittany M. Hauger,&nbsp;Heather M. Wilkins,&nbsp;Eric D. Vidoni,&nbsp;Jill K. Morris","doi":"10.1002/trc2.70163","DOIUrl":"https://doi.org/10.1002/trc2.70163","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;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.&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 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).&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;As expected, males had higher lean mass and VO&lt;sub&gt;2peak&lt;/sub&gt; than females (&lt;i&gt;p&lt;/i&gt; = 0.01), but groups did not differ in body mass index (&lt;i&gt;p&lt;/i&gt; = 0.51). Males had a higher MFI compared to females (&lt;i&gt;p&lt;/i&gt; = 0.01). Within each sex, we observed unique metabolic relationships. In males, there was an age-associated decline in MFI (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.382, &lt;i&gt;p&lt;/i&gt; = 0.01). In females, our systemic measure of mitochondrial superoxides had a negative relationship with lean mass (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.648, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and oxygen uptake efficiency slope (OUES) (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.271, &lt;i&gt;p&lt;/i&gt; = 0.04).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We 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.&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;Mitochondrial blood-biomarker shows sex-","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/trc2.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recruitment and 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}

{"title":"Simulation of Alzheimer's diagnostic flows with blood biomarker test options in Japan","authors":"Ataru Igarashi,&nbsp;Noriyuki Kimura,&nbsp;Takuya Ataka,&nbsp;Temmei Ito,&nbsp;Kotaro Sasaki,&nbsp;Chizuru Kobayashi,&nbsp;Mayaka Tani,&nbsp;Yukinori Sakata,&nbsp;Mie Azuma,&nbsp;Ayano Chida,&nbsp;Tomomi Takeshima,&nbsp;Kosuke Iwasaki,&nbsp;Etsuro Matsubara","doi":"10.1002/trc2.70157","DOIUrl":"https://doi.org/10.1002/trc2.70157","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study projected the diagnostic testing landscape for lecanemab treatment in Japan under different workflows.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>A dynamic simulation models Alzheimer's diagnostic workflows in Japan.</li>\u0000 \u0000 <li>Blood biomarker (BBM) tests reduce diagnostic wait times for Alzheimer's in Japan.</li>\u0000 \u0000 <li>Implementing BBM tests improves access to Alzheimer's diagnostics.</li>\u0000 \u0000 <li>Study quantifies demand for diagnostic testing based on costs and accessibility.</li>\u0000 \u0000 <li>Testing costs impact the number of treatment-eligible Alzheimer's patients.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","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/trc2.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237268","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":"Clinical factors predicting the rate of cognitive decline in a US memory clinic: An electronic health record study","authors":"Yuchan Wang,&nbsp;Qian Liu,&nbsp;Wenyong Li","doi":"10.1002/trc2.70166","DOIUrl":"https://doi.org/10.1002/trc2.70166","url":null,"abstract":"&lt;p&gt;To the Editor,&lt;/p&gt;&lt;p&gt;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 &lt;i&gt;Translational Research &amp; Clinical Interventions&lt;/i&gt;.&lt;sup&gt;1&lt;/sup&gt; 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.&lt;/p&gt;&lt;p&gt;First, this study reveals that hypertension is not associated with a decline in cognitive scores, but some studies contradict this conclusion.&lt;span&gt;&lt;sup&gt;2-4&lt;/sup&gt;&lt;/span&gt; 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 study&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; 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.&lt;/p&gt;&lt;p&gt;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.&lt;/p&gt;&lt;p&gt;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 studies&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt; to account for the causal effects of these medications, so as to further clarify the risk factors for cognitive decline.&lt;/p&gt;&lt;p&gt;Yuchan Wang: manuscript writing, final approval. Qian Liu: revision for academic advice in the field of neurology. Wenyong Li: critical revision for important intelle","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/trc2.70166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237267","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":"Clinically meaningful changes in cognitive and functional outcomes in a population-based study of cognitive aging","authors":"Jeremiah A. Aakre,&nbsp;Anna M. Castillo,&nbsp;Jonathan Graff-Radford,&nbsp;Prashanthi Vemuri,&nbsp;Mary M. Machulda,&nbsp;Clifford R. Jack Jr,&nbsp;David S. Knopman,&nbsp;Ronald C. Petersen,&nbsp;Maria Vassilaki","doi":"10.1002/trc2.70160","DOIUrl":"10.1002/trc2.70160","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>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).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study provides within-patient estimates of clinically meaningful change early in disease progression in a community-based sample.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We studied incident mild cognitive impairment (MCI) participants from a population-based study.</li>\u0000 \u0000 <li>Within-patient change thresholds were estimated for clinical outcome assessments (COAs) used in clinical trials for Alzheimer's disease and related dementia (ADRD).</li>\u0000 \u0000 <li>These estimates may be used to plan and evaluate clinical trials involving disease-modifying therapies (DMTs).</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129360","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}