Alzheimer's & Dementia最新文献

{"title":"The prevalence of apathy in Lewy body dementia: A systematic review and meta-analysis","authors":"Jenny Jia Yu,&nbsp;Kai Sin Chin,&nbsp;Paula M. Loveland,&nbsp;Leonid Churilov,&nbsp;Samantha M. Loi,&nbsp;Nawaf Yassi,&nbsp;Rosie Watson","doi":"10.1002/alz.70425","DOIUrl":"https://doi.org/10.1002/alz.70425","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Apathy is an important syndrome in Lewy body dementia (LBD), although reported prevalences vary. We aimed to estimate the prevalence of apathy in LBD through systematic review and meta-analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Five databases were searched for articles reporting the prevalence of apathy in LBD (dementia with Lewy bodies [DLB] and Parkinson's disease dementia [PDD]) and prodromal/mild cognitive impairment (MCI) LBD. Linear mixed model random effect meta-analysis was performed to determine the prevalence of apathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Of 7846 articles identified, 49 met inclusion criteria. The average pooled prevalence of apathy was 57% (95% confidence interval [CI] 52%–63%, <i>I</i>² = 85.6%) in DLB, 56% (95% CI 43%–70%, <i>I</i>² = 97.6%) in PDD, 46% (95% CI 32%–61%, <i>I</i>² = 90.6%) in Lewy body-MCI, and 38% (95% CI 25%–50%, <i>I</i>² = 88.1%) in Parkinson's disease-MCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Apathy affects more than half of individuals with LBD. The high prevalence in prodromal DLB supports the notion that apathy may assist in more timely and accurate diagnosis of DLB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Reported apathy prevalence in Lewy body dementia (LBD) varies widely in the existing literature.</li>\u0000 \u0000 <li>The pooled prevalence of apathy was &gt; 50% in LBD and &gt; 40% in prodromal disease stages.</li>\u0000 \u0000 <li>Apathy may have utility in earlier, more accurate diagnosis of dementia with Lewy bodies.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550837","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":"Small-diffusible aggregates, plaques, tangles, and dynamic equilibria: Untangling Alzheimer's disease","authors":"Emre Fertan,&nbsp;Georg Meisl,&nbsp;David Klenerman","doi":"10.1002/alz.70462","DOIUrl":"https://doi.org/10.1002/alz.70462","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Beta-amyloid plaques and hyperphosphorylated tau tangles are the neuropathological hallmarks of Alzheimer's disease; however, their relevance in the pathophysiology is not fully understood. It has been suggested that these larger and insoluble aggregates may not be the most toxic forms of beta-amyloid and tau in Alzheimer's disease, and the disease progression may actually be promoted by the small-diffusible aggregates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS AND RESULTS</h3>\u0000 \u0000 <p>We combine the recent findings from our group and other key research to put forward the hypotheses that the formation of the small-diffusible aggregates of beta-amyloid and tau and their larger insoluble counterparts is not a linear process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>While the small-diffusible aggregate formation of beta-amyloid and tau is a passive process, regulated by thermodynamic equilibria, the formation of large-insoluble aggregates is an active process, regulated by microglia and neurons, which to an extent is a protective mechanism against the toxicity of the smaller aggregates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Plaques and tangles may be made by active processes in Alzheimer's disease.</li>\u0000 \u0000 <li>The small-soluble aggregates may be the more toxic species in Alzheimer's disease.</li>\u0000 \u0000 <li>Pathology may be caused by the imbalance of production and clearance of aggregates.</li>\u0000 \u0000 <li>Plaques and tangle formation may be attempts to restore the homeostatic equilibrium.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551202","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":"Impact of Alzheimer's disease on sleep in adults with Down syndrome","authors":"Sandra Giménez,&nbsp;Lídia Vaqué-Alcázar,&nbsp;Nuole Zhu,&nbsp;Bessy Benejam,&nbsp;Javier Arranz,&nbsp;Lucia Maure-Blesa,&nbsp;Laura Videla,&nbsp;Maria Carmona-Iragui,&nbsp;Isabel Barroeta,&nbsp;Anne-Sophie Rebillat,&nbsp;Íñigo Rodríguez-Baz,&nbsp;Alexandre Bejanin,&nbsp;José Enrique Arriola-Infante,&nbsp;Ana Bueno,&nbsp;Susana Fernandez,&nbsp;Laia Ribas,&nbsp;Sara E. Zsadanyi,&nbsp;Alejandra O. Morcillo-Nieto,&nbsp;Daniel Alcolea,&nbsp;Christos Panagiotis Lisgaras,&nbsp;Esther Blessing,&nbsp;Ricardo S. Osorio,&nbsp;Alberto Lleó,&nbsp;Juan Fortea","doi":"10.1002/alz.70400","DOIUrl":"https://doi.org/10.1002/alz.70400","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Down syndrome (DS) is a genetic form of Alzheimer's disease (AD), with a high prevalence of sleep disorders, but data in adults with DS and dementia are lacking. We aim to assess sleep in adults with DS across the AD continuum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We studied 78 healthy controls and 229 adults with DS (154 asymptomatic, 25 with prodromal AD, and 75 with AD) with subjective sleep measures and objective nocturnal polysomnography.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Adults with DS presented worse sleep quality and higher prevalence of unnoticed obstructive sleep apnea (OSA) than controls. Sleep disruption and OSA severity increased across the AD continuum. Age-related decreases in slow-wave sleep and rapid eye movement sleep were more pronounced in the DS group. Subjective sleep measures did not capture sleep disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSIONS</h3>\u0000 \u0000 <p>In DS, AD is linked to worse sleep disturbances and altered architecture. However, longitudinal studies are needed to clarify directionality and disease progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Down syndrome (DS) is associated with increased slow-wave sleep (SWS) and reduced rapid eye movement (REM) sleep.</li>\u0000 \u0000 <li>Obstructive sleep apnea prevalence increases along the Alzheimer's disease continuum in DS.</li>\u0000 \u0000 <li>Age-related decreases in SWS and REM sleep are accelerated in DS.</li>\u0000 \u0000 <li>Subjective sleep measures do not detect sleep disturbances in adults with DS.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537125","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":"Gut microbiome compositional and functional features associate with Alzheimer's disease pathology","authors":"Jea Woo Kang,&nbsp;Lora A. Khatib,&nbsp;Margo B. Heston,&nbsp;Amanda H. Dilmore,&nbsp;Jennifer S. Labus,&nbsp;Yuetiva Deming,&nbsp;Leyla Schimmel,&nbsp;Colette Blach,&nbsp;Daniel McDonald,&nbsp;Antonio Gonzalez,&nbsp;MacKenzie Bryant,&nbsp;Tyler K. Ulland,&nbsp;Sterling C. Johnson,&nbsp;Sanjay Asthana,&nbsp;Cynthia M. Carlsson,&nbsp;Nathaniel A. Chin,&nbsp;Kaj Blennow,&nbsp;Henrik Zetterberg,&nbsp;Federico E. Rey,&nbsp;Alzheimer Gut Microbiome Project Consortium,&nbsp;Rima Kaddurah-Daouk,&nbsp;Rob Knight,&nbsp;Barbara B. Bendlin","doi":"10.1002/alz.70417","DOIUrl":"https://doi.org/10.1002/alz.70417","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>The gut microbiome is a potentially modifiable risk factor for Alzheimer's disease (AD); however, understanding of its composition and function regarding AD pathology is limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Shallow-shotgun metagenomics was used to analyze the fecal microbiome of participants in the Wisconsin Microbiome in Alzheimer's Risk Study, leveraging clinical data and cerebrospinal fluid (CSF) biomarkers. Differential abundance and ordinary least squares regression analyses were performed to find differentially abundant gut microbiome features and their associations with CSF biomarkers of AD and related pathologies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Gut microbiome composition and function differed between individuals with and without AD dementia. The compositional difference was replicated in an independent cohort. Differentially abundant gut microbiome features were associated with CSF biomarkers of AD and related pathologies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings enhance our understanding of alterations in gut microbial composition and function in AD, and suggest that gut microbes and their pathways are linked to AD pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Gut microbiome composition and function differ between people with Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals.</li>\u0000 \u0000 <li>Co-occurring gut microbes show differential abundance across AD-related groups (AD vs CU, amyloid status+ vs amyloid status−, and apolipoprotein E (<i>APOE</i>) ε4 status+ vs <i>APOE</i> ε4 status−).</li>\u0000 \u0000 <li>Gut microbiome composition also differs between people with AD dementia and CU individuals in a larger validation cohort.</li>\u0000 \u0000 <li>Differentially abundant gut microbiome composition and function between AD and CU groups are correlated with cerebrospinal fluid biomarkers for AD and related pathologies.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70417","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537126","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":"Genetically determined Alzheimer's disease research advances: The Down Syndrome & Autosomal Dominant Alzheimer's Disease 2024 Conference","authors":"Neus Falgàs,&nbsp;Lucia Maure-Blesa,&nbsp;Beau Ances,&nbsp;Lisi Flores-Aguilar,&nbsp;Sigan Hartley,&nbsp;Jason Hassenstab,&nbsp;M Florencia Iulita,&nbsp;Matthew Janicki,&nbsp;Katherine Koenig,&nbsp;Patrick Lao,&nbsp;Johannes Levin,&nbsp;Eric McDade,&nbsp;Laurent Meijer,&nbsp;Michael S. Rafii,&nbsp;Heather M. Snyder,&nbsp;Raquel Sánchez-Valle,&nbsp;Juan Fortea,&nbsp;DSAD-ADAD conference group,&nbsp;Jose Arriola Infante,&nbsp;Mirea Balasa,&nbsp;Isabel Barroeta,&nbsp;Nicolas Barthelemy R,&nbsp;Alexandre Bejanin,&nbsp;Bessy Benejam,&nbsp;Beatriz Bosch,&nbsp;Angela Bradshaw,&nbsp;Maria Carmona-Iragui,&nbsp;Ann Cohen,&nbsp;Aina Comas Albertí,&nbsp;Lajos Csincsik,&nbsp;A. Claudio Cuello,&nbsp;Laura del Hoyo Soriano,&nbsp;Janna Dijkstra,&nbsp;Natalie Edwards,&nbsp;Sandra Giménez,&nbsp;Fernando Gonzalez-Ortiz,&nbsp;Brian Gordon,&nbsp;Sara Gutiérrez Fernández,&nbsp;Benjamin Handen,&nbsp;Charlotte Jacob,&nbsp;Erik Johnson,&nbsp;Charlotte Johansson,&nbsp;Albert Lladó,&nbsp;Alberto Lleó,&nbsp;Samuel Morabito,&nbsp;Alejandra. O. Morcillo-Nieto,&nbsp;Laia Montoliu-Gaya,&nbsp;Michael Okafor,&nbsp;Agnes Pérez-Millan,&nbsp;Marie Claude Potier,&nbsp;John Ringman,&nbsp;Íñigo Rodríguez-Baz,&nbsp;Eric Rubenstein,&nbsp;Natalie S. Ryan,&nbsp;André Strydom,&nbsp;Lidia Vaqué-Alcázar,&nbsp;Lisa Vermunt,&nbsp;Laura Videla Toro,&nbsp;Shahid Zaman","doi":"10.1002/alz.70309","DOIUrl":"https://doi.org/10.1002/alz.70309","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;The Down syndrome-associated Alzheimer's disease (DSAD) autosomal dominant Alzheimer's disease (ADAD) 2024 Conference in Barcelona, convened under an Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) grant through the Down syndrome and Alzheimer's disease (AD) Professional Interest Area (PIA), brought together global researchers to foster collaboration and knowledge exchange between the fields of DSAD and ADAD.&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;This article provides a synthesis review of the conference proceedings, summarizing key discussions on biomarkers, natural history models, clinical trials, and ethical considerations in anti-amyloid therapies.&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 211 attendees from 16 countries joined the meeting. Global researchers presented on disease mechanisms, therapeutic developments, and patient care strategies. Discussions focused on challenges and opportunities unique to DSAD and ADAD. Experts emphasized the urgent need for tailored clinical trials for ADAD and DSAD and debated the safety and efficacy of anti-amyloid treatments. Ethical considerations highlighted equitable access to therapies and the crucial role of patient and caregiver involvement.&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 conference highlighted the importance of inclusive research and collaboration across the genetic forms of AD.&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;Biomarker research and natural history models developed in Down syndrome-associated Alzheimer's disease (DSAD) and autosomal dominant Alzheimer's disease (ADAD) enable the prediction of disease progression not only for DSAD and ADAD, but also for sporadic Alzheimer's disease (AD).&lt;/li&gt;\u0000 \u0000 &lt;li&gt;-Collaboration and knowledge exchange among researchers across these genetic forms of AD will accelerate our understanding of the pathophysiology and advance preventive trials in DSAD and ADAD.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;-Tailored clinical trials for DSAD are urgently needed to address specific safety and efficacy concerns.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;-Inclusive research practices are crucial for advancing treatments and understanding of DSAD and ADAD.&lt;/li&gt;\u0000 &lt;/ul&gt;\u0000 ","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537073","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":"Mitochondrial DNA affects tau phosphorylation in aging and Alzheimer's disease","authors":"Riley E. Kemna,&nbsp;Paul J. Kueck,&nbsp;Robyn Honea,&nbsp;Zachary Clark,&nbsp;Michaella Rekowski,&nbsp;Ian Weidling,&nbsp;Hana Mayfield,&nbsp;Casey S. John,&nbsp;Jeffrey Burns,&nbsp;Heather M. Wilkins,&nbsp;Russell Swerdlow,&nbsp;Jill K. Morris","doi":"10.1002/alz.70390","DOIUrl":"https://doi.org/10.1002/alz.70390","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Impaired mitochondrial function is seen in Alzheimer's disease (AD), but its role is unclear. Mitochondrial DNA (mtDNA) supports bioenergetic metabolism, but it is uncertain how it might influence AD neuropathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We used cytoplasmic hybrid (cybrid) cell lines made from SH-SY5Y cells expressing mtDNA from cognitively healthy (CH), mild cognitive impairment (MCI), or AD individuals to investigate the impact of mtDNA-determined mitochondrial function on amyloid, tau, and neurodegeneration (ATN) markers. Cybrid measurements were correlated with cognition and brain morphometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Relative to cybrids expressing mtDNA from CH individuals, MCI and AD cybrids contained more phosphorylated tau-217 (p-tau217), p-tau181, and total tau. Cybrid p-tau217 correlated with plasma p-tau217 from the mtDNA donor (<i>β</i> = 0.605, <i>p</i> &lt; 0.001). We observed negative relationships between cybrid p-tau217 and cognition and brain morphometry. MCI and AD cybrid proteomes showed mitochondrial dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>mtDNA-determined mitochondrial function affects cell physiology in AD-relevant ways. Our study suggests that mtDNA affects ATN status and clinical state.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Mitochondrial DNA (mtDNA)–determined mitochondrial function drives Alzheimer's disease (AD) hallmarks.</li>\u0000 \u0000 <li>Cytoplasmic hybrid outcomes associate with mtDNA-donor clinical measures.</li>\u0000 \u0000 <li>Proteomic analyses indicate mitochondrial dysfunction in AD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525003","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":"Locus coeruleus integrity correlates with plasma soluble Axl levels in Alzheimer's disease patients","authors":"Alessandro Galgani,&nbsp;Arnaud Mary,&nbsp;Francesco Lombardo,&nbsp;Nicola Martini,&nbsp;Marco Scotto,&nbsp;Gloria Tognoni,&nbsp;Gabriele Siciliano,&nbsp;Roberto Ceravolo,&nbsp;Filippo S. Giorgi,&nbsp;Michael T. Heneka","doi":"10.1002/alz.70434","DOIUrl":"https://doi.org/10.1002/alz.70434","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Locus coeruleus (LC) is one of the earliest structures altered in Alzheimer's disease (AD). Inflammation is also now considered critical in AD pathology, early stage included. However, no association between LC degeneration and the peripheral inflammation has been reported yet.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A cohort of 102 patients was studied for which both magnetic resonance imaging (MRI) scans and blood samples were available. LC integrity was assessed by MRI, and plasma soluble TAMs (Tyro3, Axl, and MerTK) receptor levels were measured by enzyme-linked immunosorbent assay (ELISA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We found that plasma levels of the soluble TAMs receptor Axl were correlated with LC rostral degeneration in the whole cohort (<i>p</i> = 0.007), as well as in the AD+ group (<i>p</i> = 0.017), but not in the AD– group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These results uncover a new relationship between peripheric markers of inflammation and central early AD neurodegeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>In Alzheimer's disease, no link between locus coeruleus degeneration and microglial activation was reported.</li>\u0000 \u0000 <li>Plasma Axl, Tyro3, and MerTK levels and locus coeruleus integrity were assessed in Alzheimer's disease patients.</li>\u0000 \u0000 <li>Locus coeruleus integrity positively correlates with plasma AXL, linked to microglia activation.</li>\u0000 \u0000 <li>Axl–noradrenergic signaling interplay deserves further larger longitudinal studies.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70434","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525004","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":"Differential dementia detection from multimodal brain images in a real-world dataset","authors":"Matthew Leming,&nbsp;Hyungsoon Im","doi":"10.1002/alz.70362","DOIUrl":"https://doi.org/10.1002/alz.70362","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Artificial intelligence (AI) models have been applied to differential dementia detection tasks in brain images from curated, high-quality benchmark databases, but not real-world data in hospitals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We describe a deep learning model specially trained for disease detection in heterogeneous clinical images from electronic health records without focusing on confounding factors. It encodes up to 14 multimodal images, alongside age and demographics, and outputs the likelihood of vascular dementia, Alzheimer's, Lewy body dementia, Pick's disease, mild cognitive impairment, and unspecified dementia. We use data from Massachusetts General Hospital (183,018 images from 11,015 patients) for training and external data (125,493 images from 6,662 patients) for testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Performance ranged between 0.82 and 0.94 area under the curve (AUC) on data from 1003 sites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Analysis shows that the model focused on subcortical brain structures as the basis for its decisions. By detecting biomarkers in real-world data, the presented techniques will help with clinical translation of disease detection AI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Our artificial intelligence (AI) model can detect neurodegenerative disorders in brain imaging electronic health record (EHR) data.</li>\u0000 \u0000 <li>It encodes up to 14 brain images and text information from a single patient's EHR.</li>\u0000 \u0000 <li>Attention maps show that the model focuses on subcortical brain structures.</li>\u0000 \u0000 <li>Performance ranged from 0.82 to 0.94 area under the curve (AUC) on data from 1003 external sites.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70362","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525001","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 criteria for frontotemporal dementia with right anterior temporal lobe predominance","authors":"Na-Yeon Jung,&nbsp;SeungWook Kim,&nbsp;Joon-Kyung Seong,&nbsp;Duk L. Na,&nbsp;Sang Won Seo,&nbsp;Jihwan Yun,&nbsp;Eun Hye Lee,&nbsp;Daeun Shin,&nbsp;Heeyoung Kang,&nbsp;Sung Hoon Kang,&nbsp;Kyung Won Park,&nbsp;Geon Ha Kim,&nbsp;Jee Hyang Jeong,&nbsp;Hee Jin Kim,&nbsp;Sun Min Lee,&nbsp;Hyemin Jang,&nbsp;So Young Moon,&nbsp;Eun-Joo Kim,&nbsp;and the Longitudinal Study of Early Onset Dementia and Family Members (LEAF) Investigators","doi":"10.1002/alz.70443","DOIUrl":"https://doi.org/10.1002/alz.70443","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Frontotemporal dementia (FTD) with right anterior temporal lobe (rATL) predominance lacks universally agreed-upon diagnostic criteria. This study validated the Amsterdam diagnostic tree (ADT) for right temporal variant FTD (rtvFTD) and the diagnostic criteria for semantic behavioral variant FTD (sbvFTD), examining clinical, behavioral, and imaging differences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The study included 138 patients with behavioral variant FTD and 87 with semantic variant primary progressive aphasia who had 3D T1-weighted magnetic resonance imaging scans. The participants were grouped into rtvFTD and sbvFTD by respective imaging criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We identified 42 rtvFTD and 20 sbvFTD patients. ADT showed 81% sensitivity and 29% specificity, whereas sbvFTD criteria had 45% sensitivity and 55% specificity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The unfavorable validation of both diagnostic criteria in Korean FTD patients may result from socio-cultural differences, the lack of standardized tools for assessing abnormal behaviors, and the retrospective nature of the study. The perspectives on rATL also differed between the two studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Frontotemporal dementia (FTD) with right anterior temporal lobe (rATL) predominance is a controversial FTD syndrome, also referred to as right temporal variant FTD (rtvFTD), or right predominant semantic variant primary progressive aphasia.</li>\u0000 \u0000 <li>Two clinical criteria for rATL have been proposed: One is the Amsterdam diagnostic tree for rtvFTD and the other is for semantic behavioral variant FTD (sbvFTD).</li>\u0000 \u0000 <li>Our validation study suggested the need for standardized tools and highlighted theoretical distinctions between rtvFTD and sbvFTD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524999","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":"ARTS is associated with vascular risk factors, MCI, dementia, and stroke","authors":"Debra A. Fleischman,&nbsp;Konstantinos Arfanakis,&nbsp;Sue E. Leurgans,&nbsp;Arnold M. Evia,&nbsp;Melissa Lamar,&nbsp;Alifiya Kapasi,&nbsp;S. Duke Han,&nbsp;Victoria N. Poole,&nbsp;Maude Wagner,&nbsp;David A. Bennett,&nbsp;Lisa L. Barnes","doi":"10.1002/alz.70430","DOIUrl":"https://doi.org/10.1002/alz.70430","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>ARTS, an in vivo marker of cerebral arteriolosclerosis, may identify older individuals at risk of mild cognitive impairment (MCI), dementia, and stroke due to cerebral small vessel disease, but deeper characterization in a large, diverse sample is needed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Associations between ARTS and incident MCI, dementia, and stroke, and with several common vascular risk factors, were examined in 1226 older adults without dementia and within White (<i>n</i> = 707), Black (<i>n</i> = 400), and Latino (<i>n</i> = 110) subgroups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Higher ARTS score was associated (all <i>p</i>s &lt; 0.01) with incident MCI (hazard ratio [HR] = 1.29), dementia (HR = 1.33), and stroke (HR = 1.52) and with diastolic/systolic blood pressure, self-reported hypertension, claudication, congestive heart failure, smoking, and glomerular filtration rate in the combined sample. Results varied across racial and ethnic groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>ARTS has utility as an in vivo marker of cerebral arteriolosclerosis and risk of MCI, dementia, and stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>ARTS score, an in vivo marker of cerebral arteriolosclerosis, was associated with incident mild cognitive impairment (MCI), dementia, and stroke in a diverse sample.</li>\u0000 \u0000 <li>ARTS score was associated with incident dementia in the non-Latino (NL) White and NL Black subgroups separately.</li>\u0000 \u0000 <li>ARTS score was associated with incident MCI in the NL Black subgroup.</li>\u0000 \u0000 <li>Common vascular risk factors were associated with ARTS score, consistent with ex vivo studies.</li>\u0000 \u0000 <li>ARTS has utility as a marker for the risk of MCI, dementia, and stroke.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70430","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520153","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}