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

{"title":"Livestream, group movement program for people living with cognitive impairment and care partners: A randomized clinical trial","authors":"Deborah E. Barnes, Fei Jiang, Cynthia Benjamin, Jennifer A. Lee, Rebecca L. Sudore, Wolf E. Mehling, Margaret A. Chesney, Linda L. Chao, Francesca M. Nicosia","doi":"10.1002/trc2.12467","DOIUrl":"https://doi.org/10.1002/trc2.12467","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>There are few widely-available, evidence-based options to support quality of life (QOL) for people living with Alzheimer's disease and related dementias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We performed a randomized, controlled trial with a Waitlist control group to determine whether an online, livestream, mind-body, group movement program (Moving Together, 1 hour, 2 days/week, 12 weeks) improves QOL in people with cognitive impairment (PWCI) or care partners (CPs) and explore mechanisms of action. The primary outcome for both participants was self-reported QOL. Secondary outcomes and potential mediators included mobility, isolation, well-being, cognitive function, and sleep in PWCI and burden, positive emotions, caregiver self-efficacy, stress management, and sleep in CPs. Blinded assessors collected outcome data at baseline, 12, and 24 weeks. We assessed adverse events including falls through monthly check-in surveys and collected qualitative data through evaluation surveys. Intention-to-treat analyses used linear mixed models to compare mean change over time between groups and calculated standardized effect sizes (ESs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Ninety-seven dyads enrolled (PWCI: age 76 ± 11 years, 43% female, 80% non-Hispanic White; CPs: age 66 ± 12 years, 78% female, 71% non-Hispanic White); 15% withdrew before 12 weeks and 22% before 24 weeks. PWCI self-reported significantly better QOL from baseline to 12 weeks in the Moving Together group compared to the Waitlist group (ES = 0.474, <i>p</i> = 0.048) and CPs self-reported improved ability to manage stress (ES = 0.484, <i>p</i> = 0.021). Improvements in participant self-reported QOL were mediated by improvements in their self-reported well-being and CP-reported ability to manage stress. Results were similar when the Waitlist group participated in the program (QOL ES = 0.663, <i>p</i> = 0.006; stress management ES = 0.742, <i>p</i> = 0.002) and were supported by qualitative data. Exploratory analyses suggested possible fall reduction in PWCI. There were no study-related serious adverse events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Online programs such as Moving Together offer a scalable strategy for supporting high QOL for PWCI and helping CPs manage stress.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> TRIAL REGISTRATION</h3>\u0000 \u0000 <p>ClinicalTrials.gov NCT04621448</p>\u0000 </section>\u0000 \u0000 <section>\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140818956","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":"Induction of tauopathy in a mouse model of amyloidosis using intravenous administration of adeno-associated virus vectors expressing human P301L tau","authors":"Dylan J. Finneran,&nbsp;Taylor Desjarlais,&nbsp;Alayna Henry,&nbsp;Brianna M. Jackman,&nbsp;Marcia N. Gordon,&nbsp;David Morgan","doi":"10.1002/trc2.12470","DOIUrl":"https://doi.org/10.1002/trc2.12470","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is a progressive neurodegenerative disease in which extracellular aggregates of the amyloid beta (Aβ) peptide precede widespread intracellular inclusions of the microtubule-associated protein tau. The autosomal dominant form of AD requires mutations that increase production or aggregation of the Aβ peptide. This has led to the hypothesis that amyloid deposition initiates downstream responses that lead to the hyperphosphorylation and aggregation of tau.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Here we use a novel approach, somatic gene transfer via intravenous adeno-associated virus (AAV), to further explore the effects of pre-existing amyloid deposits on tauopathy. APP+PS1 mice, which develop amyloid deposits at 3 to 6 months of age, and non-transgenic littermates were injected at 8 months of age intravenously with AAV-PHP.eB encoding P301L human tau. Tissue was collected at 13 months and tauopathy was assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Total human tau expression was observed to be relatively uniform throughout the brain, reflecting the vascular route of AAV administration. Phospho-tau deposition was not equal across brain regions and significantly increased in APP+PS1 mice compared to non-transgenic controls. Interestingly, the rank order of phospho-tau deposition of affected brain regions in both genotypes paralleled the rank order of amyloid plaque deposits in APP+PS1 mice. We also observed significantly increased <i>MAPT</i> RNA expression in APP+PS1 mice compared to non-transgenic despite equal AAV transduction efficiency between groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This model has advantages over prior approaches with widespread uniform human tau expression throughout the brain and the ability to specify the stage of amyloidosis when the tau pathology is initiated. These data add further support to the amyloid cascade hypothesis and suggest RNA metabolism as a potential mechanism for amyloid-induced tauopathy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12470","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814250","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":"Alzheimer's disease drug development pipeline: 2024","authors":"Jeffrey Cummings,&nbsp;Yadi Zhou,&nbsp;Garam Lee,&nbsp;Kate Zhong,&nbsp;Jorge Fonseca,&nbsp;Feixiong Cheng","doi":"10.1002/trc2.12465","DOIUrl":"https://doi.org/10.1002/trc2.12465","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>New therapies to prevent or delay the onset of symptoms, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We interrogated clinicaltrials.gov including all clinical trials assessing pharmaceutical therapies for AD active in on January 1, 2024. We used the Common Alzheimer's Disease Research Ontology (CADRO) to classify the targets of therapies in the pipeline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>There are 164 trials assessing 127 drugs across the 2024 AD pipeline. There were 48 trials in Phase 3 testing 32 drugs, 90 trials in Phase 2 assessing 81 drugs, and 26 trials in Phase 1 testing 25 agents. Of the 164 trials, 34% (<i>N</i> = 56) assess disease-modifying biological agents, 41% (<i>N</i> = 68) test disease-modifying small molecule drugs, 10% (<i>N</i> = 17) evaluate cognitive enhancing agents, and 14% (<i>N</i> = 23) test drugs for the treatment of neuropsychiatric symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Compared to the 2023 pipeline, there are fewer trials (164 vs. 187), fewer drugs (127 vs. 141), fewer new chemical entities (88 vs. 101), and a similar number of repurposed agents (39 vs. 40).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>In the 2024 Alzheimer's disease drug development pipeline, there are 164 clinical trials assessing 127 drugs.</li>\u0000 \u0000 <li>The 2024 Alzheimer's disease drug development pipeline has contracted compared to the 2023 Alzheimer pipeline with fewer trials, fewer drugs, and fewer new chemical entities.</li>\u0000 \u0000 <li>Drugs in the Alzheimer's disease drug development pipeline target a wide array of targets; the most common processes targeted include neurotransmitter receptors, inflammation, amyloid, and synaptic plasticity.</li>\u0000 \u0000 <li>The total development time for a potential Alzheimer's disease therapy to progress from nonclinical studies to FDA review is approximately 13 years.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12465","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639585","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":"Genetic and multi-omic risk assessment of Alzheimer's disease implicates core associated biological domains","authors":"Gregory A. Cary,&nbsp;Jesse C. Wiley,&nbsp;Jake Gockley,&nbsp;Stephen Keegan,&nbsp;Sai Sruthi Amirtha Ganesh,&nbsp;Laura Heath,&nbsp;Robert R. Butler III,&nbsp;Lara M. Mangravite,&nbsp;Benjamin A. Logsdon,&nbsp;Frank M. Longo,&nbsp;Allan Levey,&nbsp;Anna K. Greenwood,&nbsp;Gregory W. Carter","doi":"10.1002/trc2.12461","DOIUrl":"https://doi.org/10.1002/trc2.12461","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is the predominant dementia globally, with heterogeneous presentation and penetrance of clinical symptoms, variable presence of mixed pathologies, potential disease subtypes, and numerous associated endophenotypes. Beyond the difficulty of designing treatments that address the core pathological characteristics of the disease, therapeutic development is challenged by the uncertainty of which endophenotypic areas and specific targets implicated by those endophenotypes to prioritize for further translational research. However, publicly funded consortia driving large-scale open science efforts have produced multiple omic analyses that address both disease risk relevance and biological process involvement of genes across the genome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Here we report the development of an informatic pipeline that draws from genetic association studies, predicted variant impact, and linkage with dementia associated phenotypes to create a genetic risk score. This is paired with a multi-omic risk score utilizing extensive sets of both transcriptomic and proteomic studies to identify system-level changes in expression associated with AD. These two elements combined constitute our target risk score that ranks AD risk genome-wide. The ranked genes are organized into endophenotypic space through the development of 19 biological domains associated with AD in the described genetics and genomics studies and accompanying literature. The biological domains are constructed from exhaustive Gene Ontology (GO) term compilations, allowing automated assignment of genes into objectively defined disease-associated biology. This rank-and-organize approach, performed genome-wide, allows the characterization of aggregations of AD risk across biological domains.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The top AD-risk-associated biological domains are Synapse, Immune Response, Lipid Metabolism, Mitochondrial Metabolism, Structural Stabilization, and Proteostasis, with slightly lower levels of risk enrichment present within the other 13 biological domains.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This provides an objective methodology to localize risk within specific biological endophenotypes and drill down into the most significantly associated sets of GO terms and annotated genes for potential therapeutic targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632003","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":"Awareness and cognitive rehabilitation in Alzheimer's disease and frontotemporal dementia","authors":"Eric Salmon,&nbsp;Françoise Lekeu,&nbsp;Anne Quittre,&nbsp;Vinciane Godichard,&nbsp;Catherine Olivier,&nbsp;Vinciane Wojtasik,&nbsp;Christine Bastin","doi":"10.1002/trc2.12469","DOIUrl":"https://doi.org/10.1002/trc2.12469","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Awareness influences the evolution of neurodegenerative dementias. We gathered participants’ and caregivers assessments of dependence in daily activities and we studied how each score would be related to next year participant autonomy, independently of other explicative variables.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHOD</h3>\u0000 \u0000 <p>We retrospectively analyzed data from mildly demented participants with a clinical diagnosis of Alzheimer's disease (AD, <i>n</i> = 186) and frontotemporal dementia (FTD, <i>n</i> = 29) and their relatives. A research tool was used to assess participant dependence in 98 daily activities and associated caregiver burden. A discrepancy score between the patient's and relative's judgment was calculated to evaluate awareness of dependence in activities at baseline. This dependence scores, as well as sex, age, education, and 1 year difference in Mini-Mental State Examination were taken as possible explicative variables for dependence in activities adapted by therapists during a 1-year cognitive rehabilitation program.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Patients with FTD showed less awareness for daily dependence (discrepancy 20.9% vs. 11.8% in AD). Both groups benefited from cognitive rehabilitation (25% decrease in dependence) and subjective burden of relatives was decreased in both groups. In the AD group, there was a significant positive relationship between both caregiver (<i>P</i> &lt; 0.001) and participant's (<i>P</i> &lt; 0.02) evaluation of dependence in daily activities at inclusion and dependence of participants in adapted activities after 1 year.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Awareness of impairment in daily activities is a clinical symptom that is more important at inclusion in FTD than in AD. However, in participants with AD who, as a group, significantly benefit from a cognitive rehabilitation program, not only caregiver's but also participant's assessment of dependence at baseline is correlated to subsequent, next year greater dependence in daily activities adapted by the therapists. Although discrepant, both caregiver and participant evaluations appear to be important variables to understand the evolution and the benefit of care in participants at early stages of dementia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559638","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":"Sex differences in Alzheimer's disease blood biomarkers in a Caribbean population of African ancestry: The Tobago Health Study","authors":"Caterina Rosano,&nbsp;Thomas K. Karikari,&nbsp;Ryan Cvejkus,&nbsp;Bruna Bellaver,&nbsp;Pamela C. L. Ferreira,&nbsp;Joseph Zmuda,&nbsp;Victor Wheeler,&nbsp;Tharick A. Pascoal,&nbsp;Iva Miljkovic","doi":"10.1002/trc2.12460","DOIUrl":"https://doi.org/10.1002/trc2.12460","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is increasing in the Caribbean, especially for persons of African ancestry (PAA) and women. However, studies have mostly utilized surveys without AD biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In the Tobago Health Study (<i>n</i> = 309; 109 women, mean age 70.3 ± 6.6), we assessed sex differences and risk factors for serum levels of phosphorylated tau-181 (p-tau181), amyloid-beta (Aβ)42/40 ratio, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Blood samples were from 2010 to 2013 for men and from 2019 to 2023 for women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Women were more obese, hypertensive, and sedentary but reported less smoking and alcohol use than men (age-adjusted <i>p</i> &lt; 0.04). Compared to men, women had worse levels of AD biomarkers, with higher p-tau181 and lower Aβ42/40, independent of covariates (<i>p</i> &lt; 0.001). In sex-stratified analyses, higher p-tau181 was associated with older age in women and with hypertension in men. GFAP and NfL did not differ by sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Women had worse AD biomarkers than men, unexplained by age, cardiometabolic diseases, or lifestyle. Studying risk factors for AD in PAA is warranted, especially for women earlier in life.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140546654","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":"The AUstralian multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention study (AU-ARROW): A study protocol for a single-blind, multi-site, randomized controlled trial","authors":"Samantha L. Gardener,&nbsp;Stephanie J. Fuller,&nbsp;Sharon L. Naismith,&nbsp;Laura Baker,&nbsp;Miia Kivipelto,&nbsp;Victor L. Villemagne,&nbsp;Stuart M. Grieve,&nbsp;Paul Yates,&nbsp;Stephanie R. Rainey-Smith,&nbsp;Juliana Chen,&nbsp;Belinda Thompson,&nbsp;Nicola J. Armstrong,&nbsp;Malika G. Fernando,&nbsp;Carolina Blagojevic Castro,&nbsp;Silochna Meghwar,&nbsp;Rema Raman,&nbsp;Andrew Gleason,&nbsp;Catriona Ireland,&nbsp;Roger Clarnette,&nbsp;Kaarin J. Anstey,&nbsp;Kevin Taddei,&nbsp;Manohar Garg,&nbsp;Hamid R. Sohrabi,&nbsp;Ralph N. Martins","doi":"10.1002/trc2.12466","DOIUrl":"https://doi.org/10.1002/trc2.12466","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World-Wide FINGERS (WW-FINGERS). As part of WW-FINGERS, the Australian AU-ARROW study mirrors aspects of FINGER, as well as US-POINTER.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHOD</h3>\u0000 \u0000 <p>AU-ARROW is a randomized, single-blind, multisite, 2-year clinical trial (<i>n</i> = 600; aged 55–79). The multimodal lifestyle intervention group will engage in aerobic exercise, resistance training and stretching, dietary advice to encourage MIND diet adherence, BrainHQ cognitive training, and medical monitoring and health education. The Health Education and Coaching group will receive occasional health education sessions. The primary outcome measure is the change in a global composite cognitive score. Extra value will emanate from blood biomarker analysis, positron emission tomography (PET) imaging, brain magnetic resonance imaging (MRI), and retinal biomarker tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The finalized AU-ARROW protocol is expected to allow development of an evidence-based innovative treatment plan to reduce cognitive decline and dementia risk, and effective transfer of research outcomes into Australian health policy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Study protocol for a single-blind, randomized controlled trial, the AU-ARROW Study.</li>\u0000 \u0000 <li>The AU-ARROW Study is a member of the World-Wide FINGERS (WW-FINGERS) initiative.</li>\u0000 \u0000 <li>AU-ARROW's primary outcome measure is change in a global composite cognitive score.</li>\u0000 \u0000 <li>Extra significance from amyloid PET imaging, brain MRI, and retinal biomarker tests.</li>\u0000 \u0000 <li>Leading to development of an innovative treatment plan to reduce cognitive decline.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12466","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140537565","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 “Masking the transmembrane region of the amyloid β precursor protein as a safe means to lower amyloid β production”","authors":"","doi":"10.1002/trc2.12468","DOIUrl":"https://doi.org/10.1002/trc2.12468","url":null,"abstract":"<p>Khan, A, Killick, R, Wirth, D, et al. Masking the transmembrane region of the amyloid β precursor protein as a safe means to lower amyloid β production. <i>Alzheimer's Dement</i>. 2023; 9:e12428. https://doi.org/10.1002/trc2.12428</p><p>The figure images are placed in the wrong order in the paper: The image for Figure 1 should be for Figure 2, the image for Figure 2 should be for Figure 3, and the image for Figure 3 should be for Figure 1. The correct order of the figures with matching legends are below:</p><p>We apologize for this error.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140537566","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 value of Alzheimer's disease biomarker testing","authors":"Khushbu J. Patel,&nbsp;David Yang,&nbsp;John R. Best,&nbsp;Colleen Chambers,&nbsp;Philip E. Lee,&nbsp;Alexandre Henri-Bhargava,&nbsp;Clark R. Funnell,&nbsp;Dean J. Foti,&nbsp;Jacqueline A. Pettersen,&nbsp;Howard H. Feldman,&nbsp;Haakon B. Nygaard,&nbsp;Ging-Yuek R. Hsiung,&nbsp;Mari L. DeMarco","doi":"10.1002/trc2.12464","DOIUrl":"https://doi.org/10.1002/trc2.12464","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>In the Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia (IMPACT-AD BC) study, we aimed to understand how Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing—used in medical care—impacted medical decision-making (medical utility), personal decision-making (personal utility), and health system economics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The study was designed as an observational, longitudinal cohort study. A total of 149 patients were enrolled between February 2019 and July 2021. Patients referred to memory clinics were approached to participate if their dementia specialist ordered AD CSF biomarker testing as part of their routine medical care, and the clinical scenario met the appropriate use criteria for lumbar puncture and AD CSF biomarker testing. For the medical utility pillar, detailed clinical management plans were collected via physician questionnaires pre- and post-biomarker disclosure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Patients with completed management questionnaires (<i>n</i> = 142) had a median age of 64 (interquartile range: 59–69) years, 48% were female, and 60% had CSF biomarker profiles on the AD continuum. Clinical management changed in 89.4% of cases. AD biomarker testing was associated with decreased need for other diagnostic procedures, including brain imaging (–52.0%) and detailed neuropsychological assessments (–63.2%), increased referrals and counseling (57.0%), and guided AD-related drug prescriptions (+88.4% and –50.0% in biomarker-positive and -negative cases, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>AD biomarker testing was associated with significant and positive changes in clinical management, including decreased health care resource use, therapy optimization, and increased patient and family member counseling. While certain changes in management were linked to the AD biomarker profile (e.g., referral to clinical trials), the majority of changes were independent of baseline clinical presentation and level of cognitive impairment, demonstrating a broad value for AD biomarker testing in individuals meeting the appropriate use criteria for testing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140537470","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":"Personal value of Alzheimer's disease biomarker testing and result disclosure from the patient and care partner perspective","authors":"Khushbu J. Patel,&nbsp;David Yang,&nbsp;Howard H. Feldman,&nbsp;Ging-Yuek R. Hsiung,&nbsp;Haakon B. Nygaard,&nbsp;John R. Best,&nbsp;Emily Dwosh,&nbsp;Julie M. Robillard,&nbsp;Mari L. DeMarco","doi":"10.1002/trc2.12463","DOIUrl":"https://doi.org/10.1002/trc2.12463","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We described patients’ and care partners’ experiences with Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing and result disclosure in routine care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>IMPACT-AD BC is an observational study of clinic patients who underwent AD CSF biomarker testing as part of their routine medical care (<i>n</i> = 142). In the personal utility arm of the study, semi-structured phone interviews were conducted with a subset of patients (<i>n</i> = 34), and separately with their care partners (<i>n</i> = 31). Post-disclosure interviews were conducted ∼1 month and ∼6 months after biomarker result disclosure and investigated the patients’ decision-making process around testing, impact of receiving results, wellness and lifestyle changes, and future planning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>A majority of patients (90%) rated their decision to undergo testing as “easy.” Post-disclosure, the majority (82%) reported overall positive feelings from having greater certainty and the ability to plan ahead, and results spurred them to adopt/continue healthy behaviors such as exercise (84%) and cognitive activities (54%). Care partners expressed relief from having more diagnostic certainty, increased appreciation of future caregiving responsibilities, and a desire to connect with support resources.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Perspectives of persons with lived experience in dementia provide new insight into the value of biomarker testing and should be included as part of evidence-guided considerations for pre-test counseling and result disclosure. Moreover, study findings identify an interval when patients and care partners are highly receptive to positive lifestyle and medical interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"10 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12463","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140537469","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}