Alzheimer's & Dementia最新文献

{"title":"Alzheimer's disease and related disorders in patients with bipolar disorders and other mental disorders: Actual neurodegenerative processes or phenocopies?","authors":"Emmanuel Cognat,&nbsp;Emeline Marlinge,&nbsp;Capucine Blaise,&nbsp;Claire Paquet","doi":"10.1002/alz.70110","DOIUrl":"https://doi.org/10.1002/alz.70110","url":null,"abstract":"<p>Dear Editor,</p><p>We read with great interest the study by Liu et al.<span>¹</span>, which leverages a robust methodological framework in a large sample of nearly 500,000 participants to investigate the association between chronic psychiatric disorders and the risk of late-life neurocognitive diseases.</p><p>The study highlights an increased risk of neurocognitive disorders in patients with mood disorders and especially bipolar disorder (BD), with particular emphasis on Alzheimer's disease (AD). This conclusion is supported by the use of Mendelian randomization, which suggests a causal link between BD and AD. However, the study also uncovers an elevated risk for other types of dementia, including vascular dementia (VD) and frontotemporal dementia (FTD), with hazard ratios exceeding those for AD (AD 2.37 [1.43–3.94], VD 3.82 [2.16–6.75], FTD 5.80 [1.86–18.13]).<span>¹</span> This broader finding is important, as it points to the possibility of multiple underlying mechanisms contributing to late cognitive impairment in BD.</p><p>These observations lead us to commend Liu et al. for their important contribution while also highlighting the complexity of interpreting their findings. The increased risk of neurocognitive disorders in BD, as demonstrated by their study, may include AD but also other dementias, each with distinct pathophysiological underpinnings. This aligns with prior research suggesting an elevated risk of other neurodegenerative conditions, such as Parkinson's disease, among patients with BD.<span>⁸</span></p><p>To advance in the field, it will be essential to determine whether patients with BD and cognitive decline exhibit the characteristic pathological hallmarks of these neurodegenerative diseases or whether the observed associations reflect phenocopies. Such an effort requires the integration of biomarkers and neuropathological data into future studies, as well as the establishment of dedicated cohorts to explore these questions.</p><p>Altogether, these findings resonate with the historical concept of “vesanic dementia” a term that encapsulates the complex interplay between psychiatric disorders and late-life cognitive decline.<span>⁹</span> This also underscores the importance of distinguishing late-life cognitive impairment in patients with BD from the cognitive impairments observed in younger patients, which likely arise from different mechanisms.</p><p>The authors declare no conflicts of interest. Author disclosures are available in the Supporting Information.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers of blood–brain barrier and neurovascular unit integrity in human cognitive impairment and dementia","authors":"Scott R. French,&nbsp;Briana P. Meyer,&nbsp;Juan C. Arias,&nbsp;Swati Rane Levendovzsky,&nbsp;Craig C. Weinkauf","doi":"10.1002/alz.70104","DOIUrl":"https://doi.org/10.1002/alz.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Blood–brain barrier (BBB) dysfunction is recognized as an early step in the development of Alzheimer's disease and related dementias (ADRD). Biomarkers are needed to monitor BBB integrity over time, better understand the role of the BBB in neurodegeneration, potentially help define long-term ADRD risk, and monitor effects of therapeutics. In this review, we discuss the current biomarkers used to detect human BBB dysfunction in the context of cognitive decline and dementia. We also discuss promising candidate fluid biomarkers to detect BBB dysfunction in blood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>BBB permeability occurs during normal aging and is further exacerbated in ADRD.</li>\u0000 \u0000 <li>In this review, we discuss in vivo imaging and CSF biomarkers of BBB dysfunction currently used in the setting of aging and ADRD in humans.</li>\u0000 \u0000 <li>We also review promising candidate blood-based biomarkers that may represent BBB dysfunction.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of the CAMCOG-DS-II, a neuropsychological test battery for Alzheimer's disease in people with Down syndrome: A Horizon 21 European Down syndrome Consortium study","authors":"Phoebe Ivain,&nbsp;Asaad Baksh,&nbsp;Fedal Saini,&nbsp;Mina Idris,&nbsp;Miren Tamayo-Elizalde,&nbsp;Jasmine Wells,&nbsp;Bessy Benejam,&nbsp;Sandra Virginia Loosli,&nbsp;Katja Sandkühler,&nbsp;Elisabeth Wlasich,&nbsp;Olivia Wagemann,&nbsp;Johannes Levin,&nbsp;Diane Martet,&nbsp;Silvia Sacco,&nbsp;Ségolène Falquero,&nbsp;Manon Clert,&nbsp;Anne-Sophie Rebillat,&nbsp;Wan Ming Khoo,&nbsp;Madelaine Amelia Smith,&nbsp;Jessica Beresford-Webb,&nbsp;Shahid Zaman,&nbsp;María Carmona-Iragui,&nbsp;Laura Videla,&nbsp;Juan Fortea,&nbsp;Ellen Melbye Langballe,&nbsp;Ingrid Tøndel Medbøen,&nbsp;Frode Kibsgaard Larsen,&nbsp;Eleni Baldimtsi,&nbsp;Raphaella Paradisi,&nbsp;Panagiotis Ntailakis,&nbsp;Magdalini Tsolaki,&nbsp;Georgia Papantoniou,&nbsp;Eimear McGlinchey,&nbsp;Mary McCarron,&nbsp;Seán Kennelly,&nbsp;André Strydom","doi":"10.1002/alz.70071","DOIUrl":"https://doi.org/10.1002/alz.70071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The Cambridge Cognitive Examination modified for use in people with Down syndrome (CAMCOG-DS) is a sensitive cognitive test for Alzheimer's disease (AD)–related decline in people with DS, but needs updates for sensitivity, cultural adaptability, and additional memory/executive function items. This study aimed to develop and validate the CAMCOG-DS-II.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In this multi-language, multi-site study, the psychometric properties of the CAMCOG-DS-II were evaluated against previously validated measures in 223 participants (mean age: 40.18 years) with DS across seven countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The CAMCOG-DS-II had a high completion rate, minimal floor/ceiling effects (compared to the modified Cued Recall Test, the CANTAB Paired Associates Learning, and the Purdue Pegboard), strong validity and reliability, and performance was unaffected by language across sites. It differentiated between those with/without AD and distinguished clinically rated cognitively stable and prodromal individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>The CAMCOG-DS-II is a sensitive measure of cognitive performance in people with DS at risk of AD. Its cross-language and site reliability support its potential use in AD–DS clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Developed and validated the Cambridge Cognitive Examination modified for use in people with Down syndrome (CAMCOG-DS-II) for Alzheimer's disease in Down syndrome.</li>\u0000 \u0000 <li>CAMCOG-DS-II shows increased sensitivity to Alzheimer's disease–related decline in Down syndrome.</li>\u0000 \u0000 <li>Improved applicability across an international and culturally diverse population.</li>\u0000 \u0000 <li>Differentiates Alzheimer's disease status: cognitively stable, prodromal, and clinical.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updates and future perspectives on neuropsychiatric symptoms in Alzheimer's disease","authors":"Myuri Ruthirakuhan,&nbsp;Dylan X. Guan,&nbsp;Moyra Mortby,&nbsp;Jennifer Gatchel,&nbsp;Ganesh M. Babulal","doi":"10.1002/alz.70079","DOIUrl":"https://doi.org/10.1002/alz.70079","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Neuropsychiatric symptoms (NPS) are common throughout the Alzheimer's disease (AD) continuum and profoundly affect patients, caregivers, and health-care systems. This review synthesizes key research presented in the 2022 and 2023 Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment Neuropsychiatric Syndromes–Professional Interest Area (NPS-PIA) Year-In-Reviews, emphasizing six critical areas: (1) diversity and disparities, (2) diagnostic frameworks, (3) neurobiology of NPS, (4) NPS as a disease marker, (5) the impact of COVID-19, and (6) interventions. NPS accelerates AD progression, increases functional decline, diminishes quality of life, and heightens caregiver burden and institutionalization rates. Current treatments primarily rely on psychotropics, which offer limited efficacy and raise safety concerns. This review aims to inform clinicians and researchers about recent NPS advancements while identifying gaps for future studies to improve outcomes for individuals with AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Research in Alzheimer's disease–related neuropsychiatric symptoms has rapidly increased, indicating heightened interest.</li>\u0000 \u0000 <li>Key areas include: diversity, diagnostics, markers, COVID-19 impact, and treatments.</li>\u0000 \u0000 <li>A road map for future studies, based on the key areas of research, is provided.</li>\u0000 \u0000 <li>This road map includes considerations to improve study applicability and validity.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel blood-based proteomic signatures across multiple neurodegenerative diseases","authors":"Robert Durcan,&nbsp;Amanda Heslegrave,&nbsp;Peter Swann,&nbsp;Julia Goddard,&nbsp;Leonidas Chouliaras,&nbsp;Alexander G. Murley,&nbsp;George Savulich,&nbsp;W. Richard Bevan-Jones,&nbsp;Owen Swann,&nbsp;Nicholas J. Ashton,&nbsp;Kaj Blennow,&nbsp;William McEwan,&nbsp;Henrik Zetterberg,&nbsp;James B. Rowe,&nbsp;John T. O'Brien,&nbsp;Maura Malpetti","doi":"10.1002/alz.70116","DOIUrl":"https://doi.org/10.1002/alz.70116","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;Blood-based biomarkers have the potential to support early and accurate diagnoses of neurodegenerative diseases, which are sensitive to molecular pathology and are predictive of outcome. We evaluated a novel multiplex proteomic method in people with diverse neurodegenerative diseases.&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;Serum from people with Alzheimer's disease (&lt;i&gt;N&lt;/i&gt; = 36), Lewy body dementia (&lt;i&gt;N&lt;/i&gt; = 34), frontotemporal dementia (&lt;i&gt;N&lt;/i&gt; = 36), and progressive supranuclear palsy (&lt;i&gt;N&lt;/i&gt; = 36) and age-matched controls (&lt;i&gt;N&lt;/i&gt; = 30) was analyzed with the nucleic acid linked immuno-sandwich assay (NULISA) central nervous system panel (≈ 120 analytes) and inflammation panel (250 analytes). Biomarkers were compared across groups and included as predictors of survival.&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 NULISA panels demonstrated high sensitivity and reliability for detecting multiple biomarkers across neurodegenerative disorders. There were condition-specific proteomic biomarkers, while neurofilament light chain, corticotropin-releasing hormone, CD276, and a data-driven inflammation pattern were significant transdiagnostic outcome predictors.&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 sensitive NULISA multiplex approach supports differential diagnosis and target identification, with prognostically informative dementia-related biomarkers.&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 tested the novel technology nucleic acid linked immuno-sandwich assay (NULISA) in people with diverse neurodegenerative diseases, which demonstrated high sensitivity and reliability for detecting multiple biomarkers in serum samples.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We compared the NULISA central nervous system serum results to single molecule array (Simoa) plasma assays for phosphorylated tau (p-tau)217, p-tau231, neurofilament light chain (NfL), and glial fibrillary acidic protein, finding strong correlations.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Increased levels of serum NfL were identified across all patient groups and most elevated in the frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP) cohorts, while p-tau epitopes were the most significant markers in patients with Alzheimer's disease (AD) and Lewy body dementia.&lt;/li&gt;\u0000 \u0000 ","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations among sleep quality, sleep duration, and Alzheimer's disease biomarkers: A systematic review and meta-analysis","authors":"Chun-Lin Chen,&nbsp;Miao-Yu Zhang,&nbsp;Zhi-Lin Wang,&nbsp;Jia-Hui Deng,&nbsp;Yan-Ping Bao,&nbsp;Jie Shi,&nbsp;Lin Lu,&nbsp;Le Shi","doi":"10.1002/alz.70096","DOIUrl":"https://doi.org/10.1002/alz.70096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Although sleep disturbances are widely recognized as risk factors for cognitive decline and Alzheimer's disease (AD), their influence on AD biomarkers remains unclear. This study aimed to clarify whether sleep quality or sleep duration affect amyloid beta (Aβ) and tau levels in plasma, cerebrospinal fluid (CSF), and positron emission tomography (PET) in non-demented populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>PubMed, Web of Science, and Embase were systematically searched up to February 2025.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In total, 30 studies were included comprising 14,997 subjects. Individuals with poor sleep quality exhibited greater PET Aβ burden and higher Aβ42 levels in plasma than those with good sleep quality. Shorter sleep duration was associated with higher Aβ burden on PET. However, no association between either sleep quality or sleep duration and tau levels was found.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Sleep may be a modifiable marker of early AD management by modulating Aβ levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>lPoor sleep quality and shorter sleep duration were significantly associated with higher amyloid beta (Aβ) burden detected by positron emission tomography (PET) in non-demented populations. Poor sleep quality was also associated with elevated Aβ42 levels in plasma.</li>\u0000 \u0000 <li>lNo significant associations were found between sleep quality or sleep duration and tau levels in plasma, cerebrospinal fluid, or PET.</li>\u0000 \u0000 <li>lInterventions targeting sleep could serve as a viable and low-cost prevention strategy for early management of Alzheimer's disease.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Communication Bridge-2 for primary progressive aphasia: A randomized controlled trial of communication intervention","authors":"Emily Rogalski,&nbsp;Matthew Bona,&nbsp;Marissa Esparza,&nbsp;Ollie Fegter,&nbsp;Rhiana Schafer,&nbsp;Aimee Mooney,&nbsp;Melanie Fried-Oken,&nbsp;Alfred Rademaker,&nbsp;Angela Roberts","doi":"10.1002/alz.70088","DOIUrl":"https://doi.org/10.1002/alz.70088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Primary progressive aphasia (PPA), a language-based neurodegenerative dementia, negatively impacts communication and quality of life. Previous non-pharmacologic interventions show promise but lack efficacy trials. Here, outcomes are provided from Communication Bridge-2 (CB2), a speech-language randomized controlled trial (RCT) for PPA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>CB2 is the first Phase 2, Stage II, parallel-group RCT delivered via video chat with global enrollment. Ninety-five dyads were randomized into one of two speech-language intervention arms. Primary outcomes included communication confidence and participation measures. Marginal linear models assessed efficacy across ≈12 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Ninety-five dyads were randomized from four countries. Experimental arm superiority in communication-participation measurement of goal attainment was demonstrated (66.7% vs 49.1%, respectively, <i>p </i>= 0.006), and corroborated by post-study interviews.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Outcomes demonstrate the feasibility and initial efficacy of a person-centered telemedicine intervention for maximizing communication participation for mild-to-moderate PPA, providing a pathway for developing and implementing clinically meaningful interventions for Alzheimer's disease and related dementias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Primary progressive aphasia (PPA) negatively impacts communication participation.</li>\u0000 \u0000 <li>Communication Bridge-2 (CB2) is a telemedicine-delivered randomized controlled trial (RCT).</li>\u0000 \u0000 <li>Global recruitment of 95 PPA participant dyads into an RCT with low dropout.</li>\u0000 \u0000 <li>First international superiority trial for PPA using video chat shows efficacy.</li>\u0000 \u0000 <li>The study provides a model for rigorous non-pharmacologic trials for Alzheimer's disease/Alzheimer's disease and related dementias (AD/ADRD).</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting of phosphorylated tau at threonine 181 by a Qβ virus-like particle vaccine is safe, highly immunogenic, and reduces disease severity in mice and rhesus macaques","authors":"Nicole M. Maphis,&nbsp;Jonathan Hulse,&nbsp;Julianne Peabody,&nbsp;Somayeh Dadras,&nbsp;Madelin J Whelpley,&nbsp;Manas Kandath,&nbsp;Colin Wilson,&nbsp;Sasha Hobson,&nbsp;Jeff Thompson,&nbsp;Suttinee Poolsup,&nbsp;Danielle Beckman,&nbsp;Sean P Ott,&nbsp;Jennifer W. Watanabe,&nbsp;Jodie L. Usachenko,&nbsp;Koen K Van Rompay,&nbsp;John Morrison,&nbsp;Reed Selwyn,&nbsp;Gary Rosenberg,&nbsp;Janice Knoefel,&nbsp;Bryce Chackerian,&nbsp;Kiran Bhaskar","doi":"10.1002/alz.70101","DOIUrl":"https://doi.org/10.1002/alz.70101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Pathological accumulation of tau (pTau) contributes to various tauopathies, including Alzheimer's disease (AD), and correlates with cognitive decline. A rapid surge in tau-targeted approaches via anti-sense oligonucleotides, active/passive immunotherapies suggests that targeting p-Tau is a viable strategy against tauopathies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHOD</h3>\u0000 \u0000 <p>We describe a multi-species validation of our previously described Qß virus-like particle (VLP)–based vaccine technology targeting phosphorylated tau on threonine 181 (pT181-Qß).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Two vaccine doses of pT181-Qß, without any adjuvants, elicited robust antibody responses in two different mouse models of tauopathy (PS19 and hTau) and rhesus macaques. In mouse models, vaccination reduced AT180+ hyperphosphorylated, Sarkosyl insoluble, Gallyas silver positive tau, inflammasomes/neuroinflammation, and improved recognition memory and motor function without inducing adverse T-cell activation. Anti-pT181 antibodies are reactive to pTau in human AD brains, engage pT181+ tau in human brain lysates, and are central nervous system bioavailable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our results suggest the translational utility of pT181-Qß against tauopathies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Icosahedral display of phosphorylated tau at threonine 181 (pT181) Qß virus-like particle surface (“pT181-Qß” vaccine) induces a robust immune response in mice and in non-human primates (NHPs)</li>\u0000 \u0000 <li>pT181-Qß vaccination reduces pathological tau (pTau) and brain atrophy, and improves memory and motor function in PS19 and hTau mice.</li>\u0000 \u0000 <li>pT181-Qß vaccination–induced immunoglobulin Gs (IgGs) are safe, Th2 skewed (anti-inflammatory), specific to pTau in human AD brain, and efficiently engage pT181 in NHPs and human brain lysate.</li>\u0000 \u0000 <li>pT181⁺ tau in human plasma correlates with the neurofilament light in subjects with mild cognitive impairment (MCI)—suggesting the presence of pT181-Qß vaccine target in the early disease state.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinician type and care setting for treatment of Medicare beneficiaries with dementia","authors":"Donovan T. Maust,&nbsp;Rachel C. Davis,&nbsp;Ulrike Muench,&nbsp;Steven C. Marcus,&nbsp;Joanne Spetz","doi":"10.1002/alz.70102","DOIUrl":"https://doi.org/10.1002/alz.70102","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Coordinating care for people living with dementia (PLWD) requires understanding which clinicians deliver care and the settings of that care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We used the Medicare Carrier file to characterize the settings in which clinicians deliver care to PLWD, clinician types providing care, and whether clinicians record a dementia diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>A total of 1,934,318 PLWD received care from 783,225 unique clinicians in 2019; PLWD saw a median of eight clinicians (interquartile range 5, 14). The most common settings were office (74.8% of PLWD), emergency room (63.9%), inpatient hospital (52.1%), and skilled nursing facility (37.1%). In addition, 87.0% of PLWD received care from a primary care physician, 62.9% from a nurse practitioner, and 33.1% from a physician assistant. Of the clinicians providing care, 2.4% are psychiatrists, 1.7% are neurologists, and 0.5% are geriatric subspecialists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Care for PLWD must be coordinated across multiple clinicians and settings, recognizing that few PLWD receive psychiatry, neurology, or geriatric subspecialty care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>In 2019 the median Medicare beneficiary living with dementia saw eight different clinicians.</li>\u0000 \u0000 <li>Care of beneficiaries living with dementia is distributed across settings, with large percentages seen in each of the office, emergency room, inpatient hospital, and skilled nursing settings.</li>\u0000 \u0000 <li>Primary care physicians and nurse practitioners are the clinician types seen by the largest percentage of beneficiaries living with dementia.</li>\u0000 \u0000 <li>Geriatric subspecialist physicians account for less than 1% of the clinicians that provide care to beneficiaries living with dementia.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commonly prescribed multi-medication therapies exert sex-specific effects on Alzheimer's disease pathology and metabolomic profiles in AppNL-G-F mice: Implications for personalized therapeutics in aging","authors":"Francesca Eroli,&nbsp;Kristina Johnell,&nbsp;Zeynep Acararicin,&nbsp;Christina Tsagkogianni,&nbsp;Stefania Zerial,&nbsp;Saverio Lancia,&nbsp;Maria Latorre-Leal,&nbsp;Vilma Alanko,&nbsp;Sarah N. Hilmer,&nbsp;Anna Matton,&nbsp;Jonas W. Wastesson,&nbsp;Angel Cedazo-Minguez,&nbsp;Silvia Maioli","doi":"10.1002/alz.70081","DOIUrl":"https://doi.org/10.1002/alz.70081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Polypharmacy is common among older adults and people with dementia. Multi-medication therapy poses risks of harm but also targets comorbidities and risk factors associated with dementia, offering therapeutic potential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We evaluated the effects of two polypharmacy regimens and monotherapies on male and female <i>App^NL-G-F</i> knock-in mice. We assessed functional, emotional, and cognitive outcomes;amyloid pathology; and serum metabolomics profiles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>A combination of metoprolol, simvastatin, aspirin, paracetamol, and citalopram improved memory, reduced amyloid burden and neuroinflammation, and modulated AD-associated metabolomic signatures in male mice, with negligible effects in female mice. Substituting two cardiovascular drugs impacted emotional domains but worsened memory, predominantly in female mice. In males, monotherapies could not explain the combination effects, suggesting drug synergy, whereas in female mice, certain monotherapy effects were lost when combined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study uncovers the sex-specific effects of polypharmacy in an AD model, identifying mechanisms and biomarkers that can guide gender-specific use of medicines in dementia prevention and management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Two polypharmacy combinations show sex-specific effects on AD pathology and serum metabolomic profiles.</li>\u0000 \u0000 <li>Metoprolol+simvastatin+aspirin+paracetamol+citalopram improves memory and amyloid pathology in male mice.</li>\u0000 \u0000 <li>Replacing metoprolol and simvastatin with enalapril and atorvastatin eliminates benefits in male mice and impairs memory in female mice.</li>\u0000 \u0000 <li>Selected monotherapies produce sex-specific effects but only partially explain the outcomes of the combinations.</li>\u0000 \u0000 <li>Metabolomic pathways in serum indicate possible mechanisms and biomarkers for evaluating the effectiveness and safety of personalized therapies in aging and dementia.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}