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

{"title":"FDA approval of Miplyffa and Aqneursa: A dual breakthrough for the treatment of Neimann–Pick disease type C","authors":"Mahnoor Jan, Hafiza Mutahra Akbar, Maria Ashfaque, Muskan Latif Khan, Muhammad Talha, Md Ariful Haque","doi":"10.1002/trc2.70029","DOIUrl":"https://doi.org/10.1002/trc2.70029","url":null,"abstract":"<p>In September 2024, the U.S. Food and Drug Administration (FDA) approved two innovative therapies for Niemann–Pick disease type C (NPC). The first drug, Miplyffa (arimoclomol), received approval on September 20, 2024, for treating NPC in adults and children aged 2 years and older.<span><sup>1</sup></span> Within a week, on September 24, 2024, Aqneursa (N-acetyl-L-leucine [NALL]) was also authorized to address neurological symptoms associated with NPC in both adult and pediatric patients weighing at least 15 kg.<span><sup>2</sup></span> These approvals represent a groundbreaking advancement in the management of NPC, offering new hope for NPC patients as they are the first drugs to be approved by the FDA.</p><p>With approximately 1 in 120,000 live births reported worldwide, NPC is a rare autosomal recessive lysosomal storage disease that results from a mutation in genes of NPC1 or NPC2 proteins. Approximately 95% is due to the NPC1 mutation, and only 5% of pathogenic variants occur in NPC2 proteins. These proteins transport cholesterol from lysosomes and regulate lipid content within membranes. Mutation disrupts normal transport, accumulating cholesterol in various tissues, particularly the liver, spleen, and brain. Its prevalence varies by region and population.<span><sup>3</sup></span></p><p>Clinical manifestations of NPC are typically age-dependent. In the early infantile period, patients often exhibit delays in developmental motor milestones along with cognitive impairments. In the juvenile phase, individuals may experience gait problems and difficulties in school. In the adult form, psychiatric disturbances are commonly observed. Further neurological signs can include dysarthria, dysphagia, cerebral ataxia, dementia, and seizures. Visceral issues may involve hepatomegaly, splenomegaly, and cholestatic jaundice. Ocular abnormalities are also prevalent, with vertical supranuclear ophthalmoplegia (VSO) being the most common.<span><sup>3</sup></span> In a study of NPC-diagnosed cases, 76% of patients presented with cerebral ataxia, 75% with VSO, 63% with dysarthria, 54% with splenomegaly, and 45% with psychiatric disorders. Despite the variable age of onset, it is essential to note that infantile onset of the disease, particularly with neurological impairment, is associated with a comparatively worse disease progression than juvenile or adult-onset.<span><sup>4</sup></span></p><p>There is currently no cure for this disease. However, supportive treatment strategies include both pharmacological and non-pharmacological interventions. The only approved drug for NPC in Europe is miglustat (Zavesca), which inhibits glucosylceramide synthase, thereby reducing lipid accumulation.<span><sup>5</sup></span> The drug has yet to be approved by the FDA and only slows down the progression of neurological symptoms. Non-pharmacological approaches, such as speech therapy, physical therapy, and nutritional support, are also important for improving the quality of l","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475711","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":"Person-centered care at population scale: The Swedish registry for behavioral and psychological symptoms of dementia","authors":"Linus Jönsson,&nbsp;Moa Wibom,&nbsp;Elisabet Londos,&nbsp;Katarina Nägga","doi":"10.1002/trc2.70057","DOIUrl":"https://doi.org/10.1002/trc2.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Behavioral and psychological symptoms of dementia (BPSD) are a common driver of suffering and high care needs. We describe the Swedish BPSD registry, founded in 2010 to develop an evidence base for quality improvement in the care of patients with BPSD. Further, we illustrate the potential of the registry by evaluating how individual BPSD affects mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The registry provides a framework for documenting the occurrence of BPSD, formulating individual care plans, and following up outcomes. Symptoms are recorded by the nursing home version of the neuropsychiatric inventory (NPI), and data are entered by trained staff, mainly at institutional care facilities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Enrollment in the registry totaled 114,869 patients with dementia and a mean age of 84 years. Patients were followed until death (median overall survival 2.2 years) or loss to follow-up (median time under observation 4.2 years in patients remaining alive). Common symptoms included agitation/aggression, aberrant motor behavior, and irritability. Mortality increased with NPI severity and use of neuroleptics but decreased in patients receiving cholinesterase inhibitors or memantine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The scale, completeness, and duration of the registry, together with the possibility of linking to other data sources, offer great potential for data-driven research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The Swedish BPSD Registry, founded in 2010, has followed over 114,000 patients collecting data on symptoms, care plans, interventions and outcomes.</li>\u0000 \u0000 <li>The registry provides a framework for providing and evaluating person-centered care for patients with BPSD, and represents an unparalleled data source for research into BPSD and its management.</li>\u0000 \u0000 <li>Mortality increased in patients with more severe BPSD symptoms and for those treated with neuroleptics, but decreased in patients receiving cholinesterase inhibitors or mematine.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475319","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":"Exercise intensity matters: A review on evaluating the effects of aerobic exercise intensity on muscle-derived neuroprotective myokines","authors":"Navabeh Zare,&nbsp;David J. Bishop,&nbsp;Itamar Levinger,&nbsp;Mark A. Febbraio,&nbsp;James R. Broatch","doi":"10.1002/trc2.70056","DOIUrl":"https://doi.org/10.1002/trc2.70056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Exercise as a medical intervention is effective to help prevent and manage many chronic and complex diseases, including dementia. There is evidence to suggest that regular aerobic exercise protects against age-related brain atrophy and reduces the risk of cognitive decline. The mechanisms by which exercise infers a neuroprotective effect remain to be established but may be related to a maintenance of brain volume and neuronal survival, improved cerebrovascular density and function, and/or increased synaptic plasticity. In addition, there is growing evidence to suggest the beneficial effects of exercise on brain health and cognitive function are, at least in part, mediated by factors released by skeletal muscle during contraction. The fact that the brain responds to exercise suggests that muscle-derived peripheral factors, or “myokines,” may play a key role in muscle–brain crosstalk and exercise neuroprotection. However, the most effective “dose” of aerobic exercise to promote beneficial changes in these myokine pathways is currently unknown. Specifically, most of the evidence to date is from studies that have used moderate-intensity exercise, and research investigating the merit of high-intensity exercise is scarce. Considering the well-established role of high-intensity interval training in protecting against numerous medical conditions, more research is needed to identify the most effective “dose” of exercise to improve the beneficial effects of these myokines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li><b>Neuroprotection through exercise</b>: Regular aerobic exercise mitigates age-related brain atrophy and cognitive decline via multiple mechanisms, including brain volume maintenance, improved cerebrovascular function, and synaptic plasticity.</li>\u0000 \u0000 <li><b>Myokines as mediators</b>: Muscle-derived factors (myokines) play a crucial role in muscle–brain crosstalk, significantly contributing to the neuroprotective effects of exercise.</li>\u0000 \u0000 <li><b>Intensity matters</b>: The review underscores the necessity to define and study exercise intensity, revealing high-intensity exercise may be as effective, if not more, in promoting neuroprotective myokine levels compared to moderate-intensity exercise.</li>\u0000 \u0000 <li><b>Future research directions</b>: This review emphasizes the need for well-controlled studies to explore the optimal exercise dose for enhancing myokine pathways and their implications for neurodegenerative disease prevention.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446733","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":"Meaningful to whom? Minimal clinically important differences and the priorities of individuals living with dementia for everyday function","authors":"Andrea Gilmore-Bykovskyi,&nbsp;Kayla Dillon,&nbsp;Beth Fields,&nbsp;Clark Benson,&nbsp;Dorothy Farrar Edwards","doi":"10.1002/trc2.70052","DOIUrl":"https://doi.org/10.1002/trc2.70052","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) have a significant impact on an individual's functional cognitive abilities, highlighting the need to prioritize measures of function in evaluating minimally clinically important difference (MCID) thresholds in AD/ADRD research. Input directly from individuals living with AD/ADRD on measures of function are lacking in MCID discussions, including what it means to live with AD/ADRD and what type and degree of improvements are most meaningful across the disease continuum. Most measures for assessing function in AD/ADRD trials are largely focused on basic and instrumental activities of daily living (BADL, IADL), which lack aspects of everyday function that matter most to individuals living with AD/ADRD. Expanding outcome evaluation to other dimensions of everyday function and diversifying measurement approaches is essential for optimizing inclusion of personally meaningful aspects of everyday function prioritized by individuals living with AD/ADRD and improving detection of potentially more sensitive changes in functioning. This perspective outlines four directions to expand and integrate what matters most to individuals living with AD/ADRD into trial outcome evaluation, including (1) consideration of how what matters most to individuals living with AD/ADRD may change across the disease continuum from mild to advanced dementia, (2) identification and evaluation of goals around strengths-based domains such as social participation rather than solely emphasizing deficits and losses, (3) utilization of goal-attainment scaling to more specifically match individually-specific functional goals, and (4) strengthening the inclusion and use of self-report and performance-based measures of function and triangulating these measures with informant-report measures.&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;Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) have a significant impact on an individual’ functional cognitive abilities, of which changes in these abilities are measured through detection of minimally clinically important difference (MCID) thresholds to determine the effectiveness of AD/ADRD clinical trials.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Widely used measures for assessing MCID thresholds in AD/ADRD trials focus on basic and instrumental activities of daily living, presenting opportunities to expand measurement of MCID to account for other dimensions of everyday function that are prioritized by individuals living with AD/ADRD.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;To expand outcome evaluation and improve integration of aspects of functioning that matter most to peop","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446730","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 outcomes in Alzheimer's disease and Alzheimer's disease related dementias trials","authors":"Luke E. Stoeckel,&nbsp;Elena M. Fazio,&nbsp;Kristina K. Hardy,&nbsp;Nicole Kidwiler,&nbsp;Kristina A. McLinden,&nbsp;Benfeard Williams","doi":"10.1002/trc2.70058","DOIUrl":"https://doi.org/10.1002/trc2.70058","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>On March 12–14, 2024, the National Institute on Aging (NIA) together with the National Institute of Neurological Disorders and Stroke (NINDS) led a workshop exploring clinically meaningful changes in the context of Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) clinical trials (https://www.nia.nih.gov/research/dbsr/workshops/clinically-meaningful-outcomes-ad-adrd-trials). The goals were to identify research gaps, opportunities, and tools to advance patient-centered, equitable assessment of clinically meaningful change focused on biomarker status, cognition, and everyday function. The workshop fostered robust, multidisciplinary discussion between lived experience experts, advocates, researchers, clinicians, funders, payers, and regulators. The workshop addressed the criteria used to assess whether an intervention has had a clinically meaningful impact, including consideration of both benefit and harm. Here, we report on (1) criteria to consider for development, testing, and selection of clinically meaningful outcomes in AD/ADRD clinical trials; (2) methods to validate and customize clinically meaningful outcomes that are fit-for-purpose; and (3) practices that will ensure that clinically meaningful outcomes are applicable to diverse populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li><b>Patient-Centered Outcomes</b>: Inclusive AD/ADRD clinical trials incorporate assessments that reflect what matters most to those impacted by these diseases, including patient- and caregiver-reported outcome measures.</li>\u0000 \u0000 <li><b>Culturally Relevant Assessments</b>: There is a need for culturally sensitive and equitable assessments to better serve diverse populations in AD/ADRD research.</li>\u0000 \u0000 <li><b>Framework for Clinically Meaningful Change</b>: We present a framework for defining and evaluating clinically meaningful outcomes in AD/ADRD trials, tailored to diverse stages of disease progression.</li>\u0000 \u0000 <li><b>Interdisciplinary Approach</b>: We draw on insights from a multidisciplinary workshop, fostering collaboration among researchers, clinicians, and lived experience experts to advance the field.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446734","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":"Two new positive psychosocial measures for persons living with dementia","authors":"Sheila L. Molony,&nbsp;Sam Fazio,&nbsp;Kimberly Van Haitsma,&nbsp;Richard Feinn,&nbsp;Joseph Montminy,&nbsp;Maureen Rulison,&nbsp;Ricci Sanchez,&nbsp;Sheryl Zimmerman","doi":"10.1002/trc2.70024","DOIUrl":"https://doi.org/10.1002/trc2.70024","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;Differences in adaptive strategies used by individuals and families living with dementia have the potential to impact day-to-day well-being. The Living Well Inventory for Dementia (LWI-D) is a new measure to capture these strategies and to illuminate new options to support families living with dementia. The Quality of Day Scale (QODS) is a new measure to capture global well-being in persons based on a shorter temporal frame than traditional quality of life measures. This article summarizes the initial evaluation of the LWI-D and the QODS for face validity, content validity, and user acceptability.&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;Initial acceptability and feasibility testing were conducted with a sample of 17 community-dwelling individuals with early-stage dementia (Montreal Cognitive Assessment [MoCA] scores of 12–30).&lt;/p&gt;\u0000 \u0000 &lt;p&gt;After revision and optimization of the two measures, a second pilot test was conducted with a sample of 30 dyads (persons living with dementia and family caregivers) in nursing home, assisted living, and community settings.&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;Data from both pilot studies are reported including item analysis and quantitative and qualitative results. Outcomes related to convergent validity between the LWI-D and the QODS with measures of positive affect-balance, quality of life, and well-being are presented. Within-dyad differences in ratings on both measures are discussed.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The LWI-D and the QODS are developing measures that warrant further testing and may enhance the ability to (1) identify strengths in living well with dementia, and (2) identify and test new interventions to bolster care and support.&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;This article describes the process used to develop and test two new measures for research and clinical practice related to positive psychosocial approaches to dementia.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The measures were developed with a team that included persons living with Alzheimer's disease as co-researchers in the process.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;A novel method of human-centered design was used to cultivate deep empathy, generate options, and conduct small, iterative tests of prototype measures.&lt;/li&gt;\u0000","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447063","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":"Sick sinus syndrome and high-degree atrioventricular block in dementia with Lewy bodies and other dementia subtypes: A study of ≈ 73,000 patients with dementia","authors":"Isak Heyman,&nbsp;Mattias Haglund,&nbsp;Maria Eriksdotter,&nbsp;Elisabet Londos","doi":"10.1002/trc2.70053","DOIUrl":"https://doi.org/10.1002/trc2.70053","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Lewy body pathology is commonly found in cardiac nervous tissue, including the cardiac conduction system. This study aimed to investigate the occurrence of sick sinus syndrome (SSS) and high-degree atrioventricular block in dementia with Lewy bodies (DLB) compared to Alzheimer's disease (AD) and other dementia subtypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We included 73,619 individuals diagnosed with dementia from the Swedish Dementia Registry. Data pertaining to incident pacemaker implantation was obtained from the Swedish Pacemaker Registry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>SSS was more common in the DLB compared to the AD cohort (2.2% vs. 1.5%, <i>P</i> = 0.008). In adjusted models, SSS was associated with DLB compared to AD (odds ratio, 1.49; 95% confidence interval: 1.11–2.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>We showed that incident pacemaker implantation secondary to SSS was more common in patients with DLB compared to those with AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> HIGHLIGHTS</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Incident pacemaker implantation secondary to sick sinus syndrome (SSS; but not high-degree atrioventricular block [HAVB]) was more common in dementia with Lewy bodies (DLB) versus Alzheimer's disease (AD).</li>\u0000 \u0000 <li>In adjusted models, SSS (but not HAVB) was positively associated with DLB compared to AD.</li>\u0000 \u0000 <li>Pacemaker data of various dementia disorders are presented.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446731","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 Dementia Literacy Assessment (DeLA): A novel measure of Alzheimer's disease and related disorders health literacy in diverse populations","authors":"James E. Galvin,&nbsp;Deborah M. Germain,&nbsp;Claudia P. Moore,&nbsp;Jennifer A. Jeanty,&nbsp;Vaatausili Tofaeono,&nbsp;Lisa K. Wiese","doi":"10.1002/trc2.70054","DOIUrl":"https://doi.org/10.1002/trc2.70054","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;Low health literacy about Alzheimer's disease and related disorders (ADRD) may limit help-seeking, early detection, and enrollment in clinical trials, particularly in minoritized communities. We created the Dementia Literacy Assessment (DeLA) to improve ADRD health literacy.&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 DeLA, a storytelling method that included culturally adaptable vignettes embedded with important factoids about ADRD, was administered to 213 participants from urban and rural regions of Palm Beach and Broward County in Florida and 193 participants in American Samoa.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The DeLA increased dementia health literacy and performed well across different participant characteristics (age, sex, education, geographic locale, race, ethnicity, and cognitive performance). Gains in ADRD health literacy were associated with older age, more education, better socioeconomic status, greater resilience, and better cognitive performance.&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;Increasing ADRD health literacy could increase health-seeking behaviors in diverse populations for treatment, enrich recruitment into clinical trials, and may help reduce disparities in health outcomes.&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;Low health literacy about Alzheimer's disease and related disorders (ADRD) may limit help-seeking, early detection, and enrollment in clinical trials, particularly in minoritized communities.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The Dementia Literacy Assessment (DeLA), a storytelling method that included culturally adaptable vignettes embedded with important factoids about ADRD, was administered to 406 participants from urban and rural regions of Palm Beach and Broward County in Florida and American Samoa (11.8% White, 39.8% Black or African American, and 48.4% Pacific Islander [predominantly Samoan] individuals).&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The DeLA increased dementia health literacy and performed well across different participant characteristics (age, sex, education, geographic locale, race, and cognitive performance).&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Gains in ADRD health literacy were associated with older age, more education, better socioeconomic status, greater resilience, and better cognitive performan","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446732","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":"Characterization of plasma AT(N) biomarkers among a racial and ethnically diverse community-based cohort: an HABS-HD study","authors":"Melissa E. Petersen,&nbsp;Fan Zhang,&nbsp;James Hall,&nbsp;Courtney Brock,&nbsp;Robert A. Rissman,&nbsp;Tori Como,&nbsp;David Julovich,&nbsp;Mark Mapstone,&nbsp;Beau M. Ances,&nbsp;Karin Meeker,&nbsp;Raymond Palmer,&nbsp;Robert Barber,&nbsp;David Mason,&nbsp;Leigh Johnson,&nbsp;Kristine Yaffe,&nbsp;Arthur W. Toga,&nbsp;Annie Cohen,&nbsp;Sid E. O'Bryant,&nbsp;for the HABS-HD Study Team","doi":"10.1002/trc2.70045","DOIUrl":"https://doi.org/10.1002/trc2.70045","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;Alzheimer's disease (AD) biomarkers of Amyloid(A), Tau(T), and Neurodegeneration(N) have been increasingly studied to fill the gap in our understanding of racial and ethnic differences. This study aimed to examine the relationship between plasma AT(N) biomarkers and (1) AT(N) neuroimaging biomarkers, (2) demographics, (3) medical comorbidities, and (4) cognitive diagnosis.&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;Data were analyzed from &lt;i&gt;n&lt;/i&gt; = 764 non-Hispanic Black (NHB), &lt;i&gt;n&lt;/i&gt; = 1230 Hispanic, and &lt;i&gt;n&lt;/i&gt; = 1232 non-Hispanic White (NHW) participants. Plasma AT(N) biomarkers were derived using single molecule array (SIMOA) technology on an HD-X imager and included amyloid beta (Aβ)42/40, total tau, ptau181, and neurofilament light chain (NfL). Clinical reads of positron emission tomography (PET) amyloid and tau positivity were used to examine the link between AT(N) plasma and neuroimaging biomarkers. Generalized linear models were conducted to examine the relationship between plasma AT(N) biomarkers and select demographic, diagnostic, and medical comorbidities (hypertension, diabetes, dyslipidemia, chronic kidney disease).&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;Differences in the AT(N) biomarkers were found across racial/ethnic groups. Plasma Aβ42/40 was found to be associated with PET amyloid positivity only among NHW participants, while plasma NfL was found to correlate with Meta-ROI among NHB and Hispanic participants. Ptau181 was associated with PET amyloid positivity among NHB and NHW participants and well as PET tau positivity among the latter group and Hispanic participants. Diabetes was related to increased plasma AT(N) biomarkers among NHB and Hispanic participants. CKD was associated with increased AT(N) biomarkers for all race/ethnic groups with the exception of Aβ42/40. While Aβ42/40, total tau, ptau181, and NfL were found to be related to a dementia diagnosis among NHW participants, only ptau181 and NfL were found to be related to this same diagnostic category among NHB and Hispanic participants.&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;Our findings indicate differential relationships between comorbidities (demographic, medical, diagnostic) across NHB, Hispanic, and NHW participants. This work expands our knowledge regarding the associations of plasma biomarkers to AD pathology in diverse populations.&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 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447064","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":"Assessing the clinical meaningfulness of slowing CDR-SB progression with disease-modifying therapies for Alzheimer's disease","authors":"Sarah M. Hartz,&nbsp;Suzanne E. Schindler,&nbsp;Marissa L. Streitz,&nbsp;Krista L. Moulder,&nbsp;Jessica Mozersky,&nbsp;Guoqiao Wang,&nbsp;Chengjie Xiong,&nbsp;John C. Morris","doi":"10.1002/trc2.70033","DOIUrl":"https://doi.org/10.1002/trc2.70033","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;For many patients and caregivers, a major goal of disease-modifying treatments (DMTs) for Alzheimer's disease (AD) dementia is to extend independence in instrumental and basic activities of daily living (IADLs and BADLs). The goal of this study was to estimate the effect of treatments on the time remaining independent in IADLs and BADLs.&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 at the Knight Alzheimer Disease Research Center (Knight ADRC) who met eligibility criteria for recent DMT trials were studied: age ≥60 years at baseline, clinical diagnosis of very mild or mild AD dementia (global Clinical Dementia Rating [CDR] score 0.5 or 1), biomarker confirmation of amyloid pathology, and at least one follow-up CDR assessment within 5 years. For IADLs, a subset of the Functional Assessment Questionnaire (FAQ) was examined that rated the degree of independence in the following: paying bills, driving, remembering medications and appointments, and preparing meals. For BADLs, the Personal Care domain of the CDR was used. Mixed-effects logistic and ordinal regression models were used to examine the relationship between CDR Sum of Boxes (CDR-SB) and the individual functional outcomes and their components. The change in CDR-SB over time was estimated with linear mixed-effects models.&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 total of 282 participants were followed for an average of 2.9 years (standard deviation [SD] 1.3 years). For 50% of individuals, loss of independence in IADLs occurred at CDR-SB &gt;4.5 and in BADLs at CDR-SB &gt;11.5. For individuals with a baseline CDR-SB = 2, treatment with lecanemab would extend independence in IADLs for 10 months (95% confidence interval [CI] 4–18 months) and treatment with donanemab in the low/medium tau group would extend independence in IADLs by 13 months (95% CI 6–24 months).&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;Independence in ADLs can be related to CDR-SB and used to demonstrate the effect of AD treatments in extending the time of independent function, a meaningful outcome for patients and their families.&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;We estimated time to loss of independence for people with AD dementia&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Estimating time to loss of independence can help with clinical decision-making&lt;/li&gt;\u0000 ","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397190","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}