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

{"title":"White matter microstructure mediates the association between cardiorespiratory fitness and cognitive performance in older adults","authors":"Emma M. Tinney, Aaron E. L. Warren, Amanda O'Brien, Hannah Odom, Meishan Ai, Bradley P. Sutton, Shivangi Jain, Chaeryon Kang, Haiqing Huang, Lu Wan, Lauren E. Oberlin, George Grove, John M. Jakicic, Audrey M. Collins, Kelsey R. Sewell, Jeffrey M. Burns, Eric D. Vidoni, Edward McAuley, Arthur F. Kramer, Kirk I. Erickson, Charles H. Hillman","doi":"10.1002/trc2.70125","DOIUrl":"https://doi.org/10.1002/trc2.70125","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Age-related cognitive decline occurs, in part, due to diminishing white matter integrity. Higher cardiorespiratory fitness (CRF) is associated with better cognitive performance, but the neurobiological mechanisms underlying this association remain uncertain. Previous magnetic resonance imaging (MRI) studies have suggested that CRF-related changes in white matter microstructure might prevent or slow age-related cognitive decline, but have been limited by small sample sizes and methodological limitations. Specifically, most prior studies used tensor-based diffusion-weighted MRI metrics, which are insensitive to complex white matter architectures, including crossing fibers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Here, we leveraged a novel analysis framework capable of resolving individual fiber populations at the within-voxel level—fixel-based analysis (FBA)—to analyze three metrics of white matter organization from diffusion-weighted MRI scans: fiber density (FD), fiber cross-section (FC), and their combined measure (FDC). Using a cross-sectional sample of 636 cognitively unimpaired older adults aged 65 to 80 years (mean age = 69.8 years; 71% female), we hypothesized that FBA metrics would be associated with CRF and that this variation in FBA metrics would mediate associations between CRF and cognitive performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In whole-brain analyses, higher CRF was associated with greater FD, FC, and FDC. Furthermore, these FBA-derived metrics statistically mediated the relationship between CRF and cognitive performance in the domains of visuospatial abilities, processing speed, working memory, and executive function/attentional control, but not episodic memory.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings highlight the potential for CRF in the preservation of multiple aspects of cognition as a function of white matter micro- and macro-structural properties. Our results provide novel insights into the neurobiological mechanisms of fitness-related cognitive resilience.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Higher cardiorespiratory fitness (CRF) is linked to better white matter integrity in older adults.</li>\u0000 \u0000 <li>Fixel-based analysis reveals CRF associations with fiber density and cross-section.</li>\u0000 \u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695909","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":"First-in-human positron emission tomography study of intranasal insulin in aging and MCI","authors":"Kiran K. Solingapuram Sai, Jennifer M. Erichsen, Krishna K. Gollapelli, Ivan Krizan, Mack Miller, Naresh Damuka, Thomas C. Register, Courtney Sutphen, Suzanne Craft","doi":"10.1002/trc2.70123","DOIUrl":"https://doi.org/10.1002/trc2.70123","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Intranasal insulin (INI) is being explored to treat Alzheimer's disease and other conditions. The method of intranasal delivery has been shown to affect outcomes, requiring validation prior to clinical investigation. We conducted a first-in-human positron emission tomography (PET) study using a novel radiotracer, [<sup>68</sup>Ga]Ga-NOTA-insulin, administered intranasally with a specialized device (Aptar Cartridge Pump System) to evaluate the kinetics of insulin uptake and distribution in the brain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>[<sup>68</sup>Ga]Ga-NOTA-insulin was intranasally administered (≈ 0.037 ± 0.001 GBq) to adults who were cognitively normal (CN, <i>n</i> = 7) or had mild cognitive impairment (MCI, <i>n</i> = 9). A dynamic 40 minute brain PET scan, followed by a 15 minute whole-body PET/computed tomography scan was acquired. Physiologic parameters were measured at baseline, during, and post-scan. Brain uptake and time-activity curves were determined for fused PET/magnetic resonance imaging images.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Radiochemistry was optimized for producing [<sup>68</sup>Ga]Ga-NOTA-insulin with high radiochemical purity (> 99%) and molar activity (95 GBq/µmol). No safety issues were identified. PMOD analyses showed whole-brain average standard uptake value (SUV;g/mL) ≈ 0.68 ± 0.01; radioactivity in the brain and whole body were undetectable by 40 and 60 minutes post radiotracer administration respectively. Elevated (<i>p</i> < 0.01) SUVs averaged over the 40 minute period after INI administration were observed for 11 regions: olfactory cortex, hippocampus, parahippocampus, amygdala, superior and middle temporal pole, insula, caudate, putamen, thalamus, and anterior cingulum. Time-activity curves showed different uptake patterns for MCI and CN groups. Baseline pulse pressure, plasma insulin, and phosphorylated tau217 correlated with uptake for subgroups based on cognitive status and sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>[<sup>68</sup>Ga]Ga-NOTA-insulin is a safe and effective PET radiotracer for validating intranasal delivery of insulin to the brain in humans and revealed significant insulin uptake in multiple brain regions. Future studies should incorporate such validation before initiating clinical trials of intranasally administered agents. Further investigation of mechanisms underlying differences in INI uptake among clinical subgroups is also needed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681219","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":"Comprehensive intervention combining group and personalized language therapy in primary progressive aphasia: Quantitative and qualitative findings","authors":"Tijana Simic, Laura Laird, Rudra Patel, Monica Lavoie, Maria Martinez, Paula Gosse, Alexandra Santos, David Tang-Wai, Regina Jokel, Carmela Tartaglia, Elizabeth Rochon","doi":"10.1002/trc2.70132","DOIUrl":"https://doi.org/10.1002/trc2.70132","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Increasingly, studies are demonstrating language and communication improvement after behavioral interventions for primary progressive aphasia (PPA), and the caregiver perspective has been highlighted as critically important to determining treatment success in this population. This is an exploratory study investigating a comprehensive, person-centered intervention promoting everyday communication, functional independence, and quality of life for people with PPA (PwPPA) and their caregivers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Four intervention programs were run separately in 6 to 8 week blocks with a total of 14 dyads (PwPPA and caregiver) enrolled. Group sessions lasted 2 hours and included communication strategy training, PPA education from multidisciplinary experts, speech therapy for PwPPA, and a support group for caregivers (blocks 1 and 2). Personalized language exercises were assigned for home practice, using apps or paper-and-pencil tasks. Quantitative and qualitative outcomes were measured before and after each treatment block and included: the Revised Western Aphasia Battery (WAB-R) Aphasia Quotient (AQ) and subtest scores, content information units (CIUs) on the WAB-R picture description task, and qualitative content analysis of semi-structured interviews, gathered from both PwPPA and caregivers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>No statistically significant changes were noted in mean WAB-AQ score pre- to post-intervention. Mean CIUs produced on the WAB-R picture description task pre- to post-intervention increased and approached significance (<i>β</i> = 2.7; confidence interval: −0.45, 5.86, <i>p</i> = 0.09). Qualitative findings from PwPPA and caregivers were very positive, and underscored the sense of community, improved language, communication, and well-being, and access to multidisciplinary expertise and resources afforded by the program.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Further investigation into the most appropriate assessment tools and intervention approaches for PPA is warranted and has the potential to make a significant positive impact on PwPPA and their families.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We combined quantitative and qualitative measures of efficacy in treating primary progressive aphasia.</li>\u0000 \u0000 <li>Language skil","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681029","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":"Patterns and predictors of cholinesterase inhibitor use in dementia with Lewy bodies","authors":"Rachel J. Heo, Ahmed Negida, Kathryn A. Wyman-Chick, James R. Bateman, Federico Rodriguez-Porcel, Brian D. Berman, Nitai Mukhopadhyay, Matthew J. Barrett","doi":"10.1002/trc2.70136","DOIUrl":"https://doi.org/10.1002/trc2.70136","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Current evidence supports the use of cholinesterase inhibitors (ChEIs) as the first-line symptomatic treatment for improving cognition in dementia with Lewy bodies (DLB). Little is known about current prescribing patterns of ChEIs in DLB. This study aimed to identify the patterns and predictors of ChEI prescribing in patients with DLB in the United States.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using the TriNetX database, we identified 20,643 US patients ages 45 to 90 who were diagnosed with DLB between 2004 and 2024. We only included those with more than one documented diagnosis. Prescription data and patterns for donepezil, rivastigmine, galantamine, and memantine were analyzed. We used multivariate logistic regression models to estimate the odds of ChEI prescription based on demographic factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We found that 51.9% of DLB patients were ever prescribed a ChEI, and those who were prescribed a ChEI had a greater diagnosis interval. Patients who were prescribed ChEIs were more likely to be Hispanic (odds ratio [OR] 1.36, 95% confidence interval [CI]: 1.15, 1.59) and reside in the Midwest (OR 1.93, 95% CI: 1.76, 2.13), while Black patients were less likely to be prescribed ChEIs (OR 0.80, 95% CI: 0.71, 0.91). Of patients prescribed ChEIs, the median time between the first and last prescription was 13.4 months (interquartile range: 1.1, 32.9), and donepezil was the most commonly prescribed (76.9%) followed by rivastigmine (35.6%) and galantamine (3.9%). Over the 20-year study period, there was a gradual increase in the rate of prescribing of ChEIs, and the prescribing frequency of individual ChEIs remained relatively stable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>Despite evidence supporting their tolerability and efficacy, ChEIs are under-prescribed in DLB patients within the United States, and there are differences in prescribing based on race, ethnicity, and region. There is a need to understand the reasons for under-prescribing ChEIs in DLB, so interventions focused on increasing use can be developed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Despite proven tolerability and efficacy, cholinesterase inhibitors (ChEIs) are under-prescribed in dementia with Lewy bodies (DLB).</li>\u0000 \u0000 <li>Race, ethnicity, and region significantly a","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive decline across five cognitive batteries: Sample size implications for clinical trials","authors":"Andrea R. Zammit, Ana W. Capuano, Lisa L. Barnes, Julie A. Schneider, Reisa A. Sperling, David A. Bennett, Francine Grodstein","doi":"10.1002/trc2.70137","DOIUrl":"https://doi.org/10.1002/trc2.70137","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We evaluated the statistical power for a theoretical randomized trial of anti-amyloid treatment in preclinical Alzheimer's Disease across five cognitive composites in preclinical Alzheimer's Disease across five cognitive composites: Alzheimer's Prevention Initiative Preclinical Composite Cognitive Test (APCC); Preclinical Alzheimer's Composite with Semantic Processing (PACC5); Preclinical Alzheimer's Cognitive Composite (PACC); and global and episodic memory composites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We utilized annual cognitive assessments from 517 decedents (78.2 ± 4.7years; 72% female) with <i>post mortem</i> pathologic Alzheimer's disease (AD) to represent amyloid positivity. We calculated sample sizes to detect 30% reduction in 5-year slopes of cognitive decline for equal size treatment versus placebo groups across composites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Estimated sample sizes for APCC (<i>n</i> = 1633, 95% confidence interval [CI] 1400–1823), PACC (<i>n</i> = 1822, 95% CI 1612–2122), and episodic memory (<i>n</i> = 3141 95%CI 2563–3732) were larger than for PACC5 (<i>n</i> = 1424, 95% CI 1249–1575). Sample size estimates were similar between PACC5 and the global composite (<i>n</i> = 1267, 95%CI 1336–1407).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Small changes in composites, such as addition of semantic fluency in PACC5, could be considered as part of approaches to improve statistical power.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> HIGHLIGHTS</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We evaluated statistical power of a theoretical 5-year randomized trial testing anti-amyloid treatments in early Alzheimer's across five cognitive composite endpoints.</li>\u0000 \u0000 <li>We leveraged annual cognitive assessment in Rush Alzheimer's Disease Center cohorts and used <i>post mortem</i> pathologic AD to represent amyloid positivity.</li>\u0000 \u0000 <li>Preclinical Alzheimer's Composite with Semantic Processing (PACC5) required significantly lower sample size to achieve power for a 30% reduction in cognitive slope than Alzheimer's Disease Cooperative Study-Preclinical Alzheimer's Cognitive Composite (PACC).</li>\u0000 \u0000 <li>PACC5 had better statistical power than Alzheimer's Prevention Initiative Preclinical Composite Cognitive Test (APCC) and a","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635586","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":"Cardiorespiratory fitness modifies the relationship between arterial stiffness and cerebral blood flow independent of physical activity","authors":"Brianne M. Breidenbach, Ira Driscoll, Matthew P. Glittenberg, Adam J. Paulsen, Sara Fernandes-Taylor, Tarun Naren, Grant S. Roberts, Talia L. Brach, Mackenzie M. Jarchow, Leah E. Symanski, Anna Y. Gaul, Sarah R. Lose, Leonardo A. Rivera-Rivera, Sterling C. Johnson, Sanjay Asthana, Bradley T. Christian, Dane B. Cook, Oliver Wieben, Ozioma C. Okonkwo","doi":"10.1002/trc2.70130","DOIUrl":"https://doi.org/10.1002/trc2.70130","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Central arterial stiffness and cerebral blood flow (CBF) are inversely related. Poor cardiorespiratory fitness (CRF) and low physical activity (PA) are related to both higher arterial stiffness and lower CBF. The present study examined (i) whether CRF or PA moderate the relationship between arterial stiffness and CBF, and (ii) whether the intensity or the type of PA needs to be considered.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Participants (<i>N</i> = 78, Mean<sub>AGE</sub> = 64.2±6.14, 72% female) from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center were categorized into low, average, and high fitness groups based on maximal graded exercise treadmill test performance. PA was assessed using the CHAMPS (Community Health Activities Model Program for Seniors) questionnaire. Based on hours/week, participants were classified as meeting the recommended 2.5 h of moderate intensity PA per week (PA Rec Met). Weekly hours of moderate and low intensity PA were calculated as activities of > 3 or < 3 metabolic equivalents, respectively. Activity type was categorized as exercise-, sports/leisure- and work-related. Arterial stiffness was measured as aortic pulse wave velocity (aoPWV) by 2D phase contrast magnetic resonance imaging (MRI). CBF was assessed by 4D flow MRI in the internal carotid arteries (ICAs), cavernous ICAs, middle cerebral arteries (MCAs), and via two composite measures of total and global flow.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The association between aoPWV and CBF differed by fitness levels, with a negative relationship in the low fitness group and positive relationships in the average and high fitness groups (all <i>P</i>s<0.05). Significant moderating effects on the relationships between aoPWV and CBF were also observed for PA Rec Met (all <i>P</i>s<0.05), moderate intensity (<i>p </i>= 0.05), and exercise-related (all <i>p’</i>s < 0.02) PA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Average or high fitness, meeting the PA guidelines, and more specifically, moderate intensity and exercise-related PA seem to attenuate the negative relationship between aoPWV on CBF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Higher cardiorespiratory fitness (CRF) reduces the negative impact of aortic pulse wave velocity (aoPWV) on cerebral blood ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624315","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":"A common outcome set for trials in dementia with Lewy bodies (DLB COS)","authors":"Joseph P. M. Kane,&nbsp;Rachel L. Fitzpatrick,&nbsp;Sara Betzhold,&nbsp;Gillian Daly,&nbsp;Emily Kalfas,&nbsp;Irina Kinchin,&nbsp;Dag Aarsland,&nbsp;Ken Greaney,&nbsp;Emilia Grycuk,&nbsp;Ann-Kristin Folkerts,&nbsp;Elke Kalbe,&nbsp;Federico Rodriguez-Porcel,&nbsp;Ian J. Saldanha,&nbsp;Valerie Smith,&nbsp;John-Paul Taylor,&nbsp;Rachel Thompson,&nbsp;Kathryn Wyman-Chick,&nbsp;Iracema Leroi,&nbsp;and The DLB COS Delphi Group","doi":"10.1002/trc2.70134","DOIUrl":"https://doi.org/10.1002/trc2.70134","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Methodological heterogeneity in dementia with Lewy bodies (DLB) trials contributes to publication bias and makes evidence synthesis and meta-analysis challenging. We aimed to develop a core outcome set for DLB (DLB COS) trials to improve consistency and comparability in DLB research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We conducted a systematic review to identify outcomes and administered a two-stage Delphi survey to a diverse panel of lay and professional stakeholders. We asked respondents which outcomes should be prioritized and included in DLB COS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Forty-nine outcomes were presented to survey respondents. Consensus was reached regarding eight outcomes for the final DLB COS: delusions/paranoia; fluctuations in cognition, attention, and arousal; functioning; global cognition; hallucinations; quality of life; motor parkinsonism; and rapid eye movement sleep behavior disorder.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>If adopted, DLB COS can enhance the comparability of research findings and facilitate standardization and harmonization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>A systematic review revealed heterogeneity in dementia with Lewy bodies (DLB) study outcomes.</li>\u0000 \u0000 <li>Our study produced a DLB Core Outcome Set (DLB COS) comprising eight outcomes.</li>\u0000 \u0000 <li>DLB COS sets the minimum reporting standards for future trials.</li>\u0000 \u0000 <li>DLB-specific rating scales incorporating these outcomes are needed.</li>\u0000 \u0000 <li>Addressing this gap is a strategic priority in DLB research.</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":4.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606447","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":"Correction to “The HOPE4MCI study: AGB101 treatment slows progression of entorhinal cortex atrophy in APOE ε4 non-carriers with mild cognitive impairment due to Alzheimer's disease”","authors":"","doi":"10.1002/trc2.70131","DOIUrl":"https://doi.org/10.1002/trc2.70131","url":null,"abstract":"<p>Bakker A, Rani N, Moh3 R, Gallagher M. The HOPE4MCI study: AGB101 treatment slows progression of entorhinal cortex atrophy in <i>APOE</i> ε4 non-carriers with mild cognitive impairment due to Alzheimer's disease. <i>Alzheimers Dement</i>. 2024;10(4):e70004. doi: 10.1002/trc2.70004.</p><p>In the acknowledgement section the sentence “The authors would also like to thank Ken Payie at KGP-Biotech for the production and manufacture of the extended-release medication, Kevin Arauz at Worldwide Clinical Trials for project management, and Carrie L. Speck at Johns Hopkins University for project coordination” inadvertently left out two people that should be recognized. The sentence should read “<i>The authors would also like to thank Marilyn Albert at Johns Hopkins University for scientific guidance, Kevin Arauz at Worldwide Clinical Trials for project management, Ken Payie at KGP-Biotech for the production and manufacture of the extended-release medication, Sharon Rosenzweig-Lipson at AgeneBio for program development, and Carrie L. Speck at Johns Hopkins University for project coordination</i>.”</p><p>We apologize for this oversight and thank you for your assistance in this matter.</p><p>Arnold Bakker</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589653","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":"Mind your nose: A randomized controlled trial of olfactory-based memory training for older people with subjective cognitive decline","authors":"Isabelle J. M. Burke,&nbsp;Courtney Chesser,&nbsp;Christopher P. K. Brown,&nbsp;Rachel Watkins,&nbsp;Peter Butterworth,&nbsp;Jonas K. Olofsson,&nbsp;Kate Laver,&nbsp;Benjamin M. Hampstead,&nbsp;Alex Bahar-Fuchs","doi":"10.1002/trc2.70120","DOIUrl":"https://doi.org/10.1002/trc2.70120","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;Olfactory-based cognitive training may be of benefit to individuals at risk of dementia given the strong association between olfactory impairment and cognitive decline. The Mind Your Nose (MYN) trial compared an olfactory-based memory training protocol (OMT) to a visually-based memory training protocol (VMT) among older adults with subjective cognitive decline.&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;Participants (&lt;i&gt;N&lt;/i&gt; = 53; 17 males; M&lt;sub&gt;age &lt;/sub&gt;= 72.77, standard deviation [SD] = 6.12) were randomly assigned in a 2:1 ratio to daily OMT (&lt;i&gt;n&lt;/i&gt; = 36) or VMT (&lt;i&gt;n&lt;/i&gt; = 17) intervention for 20 days. Outcomes were evaluated at baseline (T0), post-intervention (T1), and 1-month follow-up (T2) and included standardized measures of global olfaction (Sniffin’ Sticks) and cognition (National Institutes of Health Toolbox), as well as performance on the olfactory memory (OM) and the visual memory (VM) tasks, and measures of mood and meta-cognition.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A significant interaction was found between treatment allocation, time, and modality of memory task at T1(β = −37.50, &lt;i&gt;p&lt;/i&gt; = 0.008) and T2(β = −28.75, &lt;i&gt;p&lt;/i&gt; = 0.041). Post-hoc comparisons revealed improvement in trained tasks; OMT led to improvement on the OM task (T1; &lt;i&gt;g&lt;/i&gt; = 0.71, &lt;i&gt;p&lt;/i&gt; = 0.036; T2; &lt;i&gt;g&lt;/i&gt; = 0.72, &lt;i&gt;p&lt;/i&gt; = 0.035), and VMT led to improvement on the VM task (T1; &lt;i&gt;g&lt;/i&gt; = 1.22, &lt;i&gt;p&lt;/i&gt; = 0.011; T2; &lt;i&gt;g&lt;/i&gt; = 1.29, &lt;i&gt;p&lt;/i&gt; = 0.006). Improvement on the untrained memory task only occurred in OMT (VM task, T1; g = 0.63, &lt;i&gt;p&lt;/i&gt; = 0.071; T2; &lt;i&gt;g&lt;/i&gt; = 0.74, &lt;i&gt;p&lt;/i&gt; = 0.033). No interaction between treatment allocation and time was observed post intervention or at follow-up for global olfactory ability (T1; β = 0.27, &lt;i&gt;p&lt;/i&gt; = 0.871; T2; β = −1.27, &lt;i&gt;p&lt;/i&gt; = 0.296).&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;Consistent with previous research, transfer gains from the OMT condition to an untrained VM task suggest that olfaction may contribute to a-modal representations of memory. We argue that memory-based olfactory training offers a new frontier for cognitive interventions among those at risk of dementia.&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;Relatively few cognitive training programs engage the olfactory sense.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Olfactory memory trainin","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581913","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":"Response to: Refining the clinical interpretation of activity variability in cognitive impairment: The need for phenotypic specificity","authors":"Patrick T. Donahue,&nbsp;Jennifer A. Schrack,&nbsp;Johannes Thrul,&nbsp;Michelle C. Carlson","doi":"10.1002/trc2.70128","DOIUrl":"https://doi.org/10.1002/trc2.70128","url":null,"abstract":"&lt;p&gt;Dear Guo et al.,&lt;/p&gt;&lt;p&gt;We thank Guo et al.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; for their interest in our article&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; and for providing innovative thoughts regarding clinical translation of our activity variability metric.&lt;/p&gt;&lt;p&gt;We would first like to emphasize that we positioned our work as an exploratory analysis of a conceptually novel metric developed using available accelerometry data. It is fit for application in future longitudinal and clinical studies with accelerometry data, which can replicate our findings and establish clinically meaningful changes relevant to activity variability and cognition. Our cross-sectional study suggests that low activity variability is strongly associated with cognitive impairment, yet we acknowledge that this metric requires further validation before implementation as a digital biomarker of cognitive decline and impairment. We intend to extend this work to other studies and encourage other researchers and clinicians to pursue validation studies, which were beyond the scope of our analysis.&lt;/p&gt;&lt;p&gt;We agree with Guo et al.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; that cognitive impairment is heterogeneous and that it would be useful to distinguish subtypes of dementia, such as vascular versus Alzheimer's disease pathologies. The data we used have strengths and limitations, as noted in our article. As Guo et al. mention, and we discussed in our article, the National Health and Aging Trends Study (NHATS) dementia classification criteria are &lt;i&gt;not&lt;/i&gt; equivalent to a dementia diagnosis, nor do they distinguish subtypes of cognitive decline and impairment.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; As Guo et al. compellingly state, it is important to further extend the conceptual link between activity variability and cognitive risk to clinical neurological outcomes, not limited to dementia (e.g., traumatic brain injury). Guo et al.’s proposal to link activity variability to specific brain regions via neuroimaging and associated cognitive domains via neuropsychological testing presents exciting additional mechanistic areas of research, which would greatly complement our findings. We agree that identifying underlying brain regions and cognitive domains that may be specifically related to activity variability would enhance this metric's clinical utility for greater sensitivity in detection of cognitive and functional impairment. In addition, if activity variability can be linked to specific brain regions, it may serve as a potential intermediate outcome for cognitive interventions.&lt;/p&gt;&lt;p&gt;Guo et al. commented that, because activity variability and gait speed were correlated, we cannot disentangle “the cognitive versus biomechanical determinants of variability”. Importantly, our study was not intended to examine the cognitive versus biological determinants of activity variability. Although activity variability and gait speed were correlated, activity variability remained strongly associated with cognitive impairment even after controlling f","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514970","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}