Alzheimer's & Dementia最新文献

{"title":"Neuroimaging of vacuolar tauopathy: Response to letter","authors":"Ryohei Watanabe,&nbsp;John D. Papatriantafyllou,&nbsp;Kengo Maeda,&nbsp;Ilya M. Nasrallah,&nbsp;Edward B. Lee","doi":"10.1002/alz.70817","DOIUrl":"10.1002/alz.70817","url":null,"abstract":"<p>Dear Editor,</p><p>We thank Kobayashi and colleagues for their thoughtful letter and for sharing their valuable longitudinal radiologic–pathologic observations in a case of vacuolar tauopathy (VT) due to valosin-containing protein (<i>VCP</i>) p.Asp395Gly.<span>¹</span> Their case shows ribbon-like cortical hyperintensity on diffusion-weighted imaging (DWI) with later emergence of fluid-attenuated inversion recovery (FLAIR) changes—an evolution they note parallels patterns described in Creutzfeldt–Jakob disease (CJD)—thereby providing helpful time course context. Indeed, one of the cases we described (Case 5) underwent a brain biopsy, in part to rule out prion disease.<span>²</span></p><p>In our series of cases, VT was associated with occipital cortical diffusion abnormalities, and this signal correlated with the presence of neocortical microvacuolization across three autopsy-confirmed cases.<span>²</span></p><p>Interestingly, Kobayashi and colleagues highlighted the variability in the timing of DWI and FLAIR changes.<span>¹</span> In our series, DWI changes were often detected early, including at the initial presentation, whereas in their case, DWI changes appeared 3 years after the initial visit, with FLAIR changes occurring later.</p><p>We note that there is significant technical variability across all of the neuroradiologic assessments for these VT cases where more standardized, longitudinal imaging would be helpful. We appreciate the contribution by Kobayashi et al.; their time series strengthens the association of cortical ribboning as a characteristic imaging signature of VT.</p><p>E.B.L. received consulting fees from Eli Lilly, unrelated to this study. I.M.N. served on a scientific advisory board for Eisai, unrelated to this study. All other authors declare no conflicts of interest. Author disclosures are available in the Supporting Information.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306125","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":"Addressing language challenges in bilingual neuropsychological assessments at the South Texas Alzheimer's Disease Research Center (ADRC)","authors":"Stephanie Santiago-Mejias,&nbsp;Gabrielle Hromas,&nbsp;Ashley LaRoche,&nbsp;David A. Gonzalez,&nbsp;Robin C. Hilsabeck,&nbsp;Katya Rascovsky,&nbsp;Silvia Mejia Arango,&nbsp;Amy Werry-McFarlin,&nbsp;Claudia L. Satizabal,&nbsp;Hector Trevino,&nbsp;Monica Goss,&nbsp;Jennifer Del Bosque,&nbsp;Amaya Seidl,&nbsp;Roberto Garcia,&nbsp;Marialy Salinas Valdez,&nbsp;Angel Velarde,&nbsp;Jessica Zapata,&nbsp;Samantha Gates,&nbsp;Patricia Hernandez,&nbsp;Juan Toranzo,&nbsp;Marucela Uscamayta Ayvar,&nbsp;Denisse Garcia Cisneros,&nbsp;Vanessa M. Young,&nbsp;Sudha Seshadri,&nbsp;Anna Campbell Sullivan","doi":"10.1002/alz.70800","DOIUrl":"10.1002/alz.70800","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Neuropsychological assessment of bilingual (English/Spanish) individuals presents challenges that can impact test validity. Language proficiency influences cognitive performance, yet clear guidelines for determining the appropriate test language are lacking. We describe our experiences at the South Texas Alzheimer's Disease Research Center (STAC) in addressing these challenges within the context of National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) assessments and broader Alzheimer's Disease Research Center (ADRC) protocols. We outline steps toward a structured language assessment approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We implemented a process to assess language proficiency, integrating self-reported and objective measures, including the language dominance index (LDI). Case examples illustrate the impact of language on cognitive testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Challenges included discrepancies between self-reported and objective language proficiency, language switching during assessments, and resistance to testing in the dominant language.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Language assessment improves test validity and research consistency. Future efforts should refine bilingual assessment methods and establish standardized protocols.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Systematic test language selection may improve accuracy in bilingual assessments.</li>\u0000 \u0000 <li>Discrepancies in reported versus objective language proficiency challenge bilingual assessments.</li>\u0000 \u0000 <li>Language evaluation guidelines are needed to improve test validity and data consistency.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70800","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305944","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":"Creutzfeldt–Jakob disease-like imaging in valosin-containing protein D395G mutation","authors":"Ryota Kobayashi,&nbsp;Masafumi Kanoto,&nbsp;Shinobu Kawakatsu,&nbsp;Akihito Suzuki","doi":"10.1002/alz.70816","DOIUrl":"10.1002/alz.70816","url":null,"abstract":"&lt;p&gt;Dear Editor:&lt;/p&gt;&lt;p&gt;We read the recent study by Watanabe et al.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; on vacuolar tauopathy associated with a &lt;i&gt;D395G&lt;/i&gt; mutation in the valosin-containing protein (VCP), published in this journal, with great interest. Based on five cases with the VCP &lt;i&gt;D395G&lt;/i&gt; mutation, the authors reported that a ribbon-like hyperintensity in the occipital cortex on diffusion-weighted magnetic resonance imaging (DWI) may be a characteristic neuroradiological finding associated with this mutation.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Their analysis of three autopsy cases revealed that DWI hyperintensity typically corresponded to vacuolar changes in brain tissue.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;We previously reported the clinical course and pathological findings of a Japanese individual with the VCP &lt;i&gt;D395G&lt;/i&gt; mutation.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; Motivated by the findings of Watanabe et al.,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; we retrospectively reviewed the longitudinal changes in fluid-attenuated inversion recovery (FLAIR) imaging and DWI in our case. The patient, who presented with typical behavioral variant frontotemporal dementia symptoms, showed no signal abnormalities in the occipital cortex on either FLAIR imaging or DWI at the initial visit (Figure 1A). However, a magnetic resonance imaging (MRI) scan conducted 3 years after the initial visit showed a ribbon-like hyperintensity in the occipital cortex on DWI, with no apparent changes on FLAIR imaging (Figure 1B). A subsequent MRI scan conducted 10 years after the initial visit revealed slight hyperintensity in the occipital cortex on FLAIR imaging, in addition to a persistent ribbon-like hyperintensity on DWI (Figure 1C). The areas of hyperintensity on FLAIR imaging and DWI roughly corresponded to regions with vacuolar changes in brain tissue (Figure 1D,E).&lt;/p&gt;&lt;p&gt;In Creutzfeldt–Jakob disease (CJD), hyperintensity on FLAIR imaging and DWI are characteristic imaging features,&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; with DWI demonstrating higher diagnostic sensitivity.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; In early-stage CJD, vacuolar change is the predominant neuropathological feature and is thought to underlie the high sensitivity of DWI.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; As the disease progresses, reactive astrogliosis becomes more prominent and may contribute to hyperintensity on FLAIR imaging.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; In our case, the MRI obtained after 3 years demonstrated DWI hyperintensity only, whereas the scan after 10 years showed hyperintensity on both DWI and FLAIR imaging. Histological examination revealed vacuolar changes that correlated with the DWI hyperintensity, as well as mild neuronal loss and reactive gliosis (Figure 1D-G). These findings suggest that in VCP &lt;i&gt;D395G&lt;/i&gt;-associated vacuolar tauopathy, severe vacuolar change in the occipital cortex may initially present as DWI hyperintensity, followed later by FLAIR imaging hyperintensity as reactive astrogliosis develops. This temporal imaging evolution parallels the","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70816","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306124","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":"White matter microstructure is differentially impacted by cerebral amyloid angiopathy, neurofibrillary tangles, and neuritic plaque co-pathology","authors":"Alexandra Santos,&nbsp;Francisco C. Almeida,&nbsp;Kathryn Gauthreaux,&nbsp;Charles N. Mock,&nbsp;Walter A. Kukull,&nbsp;John F. Crary,&nbsp;Tiago Gil Oliveira","doi":"10.1002/alz.70637","DOIUrl":"10.1002/alz.70637","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>White matter (WM) is affected by and serves as a pathway to neurofibrillary tangle (NFT) propagation in Alzheimer's disease (AD). Cerebral amyloid angiopathy (CAA) associates with neuritic plaques (NPs) to exacerbate NFT accumulation. We aim to study how these co-pathologies affect WM integrity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We performed a cross-sectional study of <i>ante mortem</i> diffusion tensor imaging (DTI) data according to participants’ <i>post mortem</i> NFT, NP, and CAA neuropathology, from the National Alzheimer's Coordinating Center dataset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We found asymmetric DTI changes in several WM regions between Braak NFT stages II and IV and V/VI, and across CAA pathological burden, with increased mean, radial, and axial diffusivities. CAA-NFT co-pathology effects were observed mainly in the splenium of the corpus callosum. DTI metrics were associated with cognitive function and hippocampal volumes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our results suggest that WM integrity is differentially impacted by AD neuropathology, with CAA and NFTs influencing each other's effects on WM microstructure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Diffusion tensor imaging (DTI) changes were observed in several white matter (WM) regions between advanced Braak stages and across cerebral amyloid angiopathy (CAA).</li>\u0000 \u0000 <li>CAA demonstrated a greater WM impact on the right hemisphere, while neurofibrillary tangles (NFTs) had greater impact on the left.</li>\u0000 \u0000 <li>CAA–NFT concurrent effects were mainly noticed in the splenium of the corpus callosum.</li>\u0000 \u0000 <li>WM DTI metrics were associated with cognition and hippocampal volumes.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70637","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282840","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":"Cross-country variance in facial emotion recognition in presymptomatic and symptomatic behavioral variant frontotemporal dementia: Insights from the GENFI and ReDLat consortia","authors":"Liset de Boer,&nbsp;Lize C. Jiskoot,&nbsp;Harro Seelaar,&nbsp;John C. van Swieten,&nbsp;Agustin Ibanez,&nbsp;Marcelo Maito,&nbsp;Sol Fittipaldi,&nbsp;Julie F. H. De Houwer,&nbsp;Tine Swartenbroekx,&nbsp;Pam A. Boesjes,&nbsp;Rhian S. Convery,&nbsp;Eve Ferry-Bolder,&nbsp;Phoebe Foster,&nbsp;Arabella Bouzigues,&nbsp;Lucy Chisman-Russell,&nbsp;Esther van den Berg,&nbsp;Janne Papma,&nbsp;Sanne Franzen,&nbsp;Renelle Bourdage,&nbsp;James B. Rowe,&nbsp;Barbara Borroni,&nbsp;Daniela Galimberti,&nbsp;Pietro Tiraboschi,&nbsp;Mario Masellis,&nbsp;Elizabeth Finger,&nbsp;Robert Laforce,&nbsp;Caroline Graff,&nbsp;Alexander Gerhard,&nbsp;Raquel Sanchez-Valle,&nbsp;Alexandre Mendonça,&nbsp;Fermin Moreno,&nbsp;Matthis Synofzik,&nbsp;Rik Vandenberghe,&nbsp;Simon Ducharme,&nbsp;Isabelle Le Ber,&nbsp;Johannes Levin,&nbsp;Thibaud Lebouvier,&nbsp;Benedetta Nacmias,&nbsp;Markus Otto,&nbsp;Christopher R. Butler,&nbsp;Isabel Santana,&nbsp;Maxime Bertoux,&nbsp;M. Carmela Tartaglia,&nbsp;Jonathan D. Rohrer,&nbsp;Jackie M. Poos,&nbsp;the GENFI Consortium","doi":"10.1002/alz.70741","DOIUrl":"10.1002/alz.70741","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We investigated international differences in facial emotion recognition (FER) across stages of frontotemporal dementia (FTD). Previous studies may have missed early decline by combining data and masking variations in FER across countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>An FER test was administered to 159 individuals with behavioral variant FTD, 521 presymptomatic pathogenic variant carriers, and 583 controls from 16 countries of residence. Linear mixed models assessed age, sex, education, and country effects on FER. Voxel-based morphometry examined neural correlates across countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> REULTS</h3>\u0000 \u0000 <p>Country accounted for 18%–18.3% of FER variance in presymptomatic carriers and controls and 9.9% in individuals with behavioral variant of FTD (bvFTD). Cross-country differences interacted with the effects of sex, age, and education. Neural correlates involving the frontal lobe and basal ganglia were identified in individuals with bvFTD, but no cross-country differences were found.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These results underscore the need for culturally sensitive FER tools in research and clinical practice, especially as global multinational clinical trials emerge.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Performance on a test for facial emotion recognition (FER) varies between countries.</li>\u0000 \u0000 <li>The percentage of variance is lower in the behavioral variant of frontotemporal dementia (bvFTD) compared to presymptomatic pathogenic variant carriers and healthy controls.</li>\u0000 \u0000 <li>Cross-country differences interacted with the effects of sex, age, and education.</li>\u0000 \u0000 <li>There were no differences in brain correlates of FER across countries.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285430","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":"Cortical thickness subtypes in cognitively unimpaired individuals: Differential network and transcriptomic vulnerability to cortical thinning","authors":"Luigi Lorenzini,&nbsp;Mario Tranfa,&nbsp;Leonard Pieperhoff,&nbsp;Federico Masserini,&nbsp;Mara ten Kate,&nbsp;Lyduine E. Collij,&nbsp;Giuseppe Pontillo,&nbsp;Emma S. Luckett,&nbsp;Alle Meije Wink,&nbsp;Henk JMM Mutsaerts,&nbsp;Tiago Gil Oliveira,&nbsp;Daniele Altomare,&nbsp;Mercè Boada,&nbsp;Anouk den Braber,&nbsp;Cindy Birck,&nbsp;Christopher Buckley,&nbsp;Gill Farrar,&nbsp;Wiesje van der Flier,&nbsp;Giovanni B. Frisoni,&nbsp;Rossella Gismondi,&nbsp;Juan Domingo Gispert,&nbsp;Bernard J. Hanseeuw,&nbsp;Frank Jessen,&nbsp;Marta Marquié,&nbsp;Anja Mett,&nbsp;Craig Ritchie,&nbsp;Gemma Salvadó,&nbsp;Michael Schöll,&nbsp;Mahnaz Shekari,&nbsp;Andrew W. Stephens,&nbsp;Betty M. Tijms,&nbsp;David Vállez García,&nbsp;Rik Vandenberghe,&nbsp;Pieter Jelle Visser,&nbsp;Luca Roccatagliata,&nbsp;Neil P. Oxtoby,&nbsp;Matteo Pardini,&nbsp;Frederik Barkhof","doi":"10.1002/alz.70762","DOIUrl":"10.1002/alz.70762","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The emergence, stability, and contributing factors of Alzheimer's disease (AD) gray matter subtypes remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We analyzed data from 1323 individuals without a diagnosis of dementia (CDR &lt; 1) with T1w-MRI and amyloid-PET, including 622 with longitudinal data (3.66 ± 1.78 years). Cortical thickness subtypes were identified using a non-negative matrix factorization (NMF) clustering algorithm. We examined clinical and demographic differences, subtype stability, and longitudinal thinning patterns using brain network models and imaging-transcriptomic analysis. Replication was performed with an alternative clustering approach and a validation cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Two stable subtypes emerged: limbic-predominant and hippocampal-sparing. Limbic-predominant participants were older, had higher amyloid burden, and faster memory decline, while hippocampal-sparing individuals showed greater attention and executive function decline. Distinct thinning patterns were linked to specific network properties and gene expression profiles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These MRI-based subtypes reflect underlying pathophysiological mechanisms and may aid in prognostication and clinical trial stratification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Two gray matter thickness subtypes can already be identified in preclinical stages, exhibiting distinct clinical characteristics and progression patterns.</li>\u0000 \u0000 <li>Individual subtype assignment remains stable over time.</li>\u0000 \u0000 <li>Longitudinal cortical thinning patterns follow distinct network- and transcriptomic-based mechanisms within each subtype.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70762","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282744","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":"Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers","authors":"D. Luke Fischer,&nbsp;Lea T. Grinberg,&nbsp;Jared T. Ahrendsen,&nbsp;Thomas G. Beach,&nbsp;Kevin F. Bieniek,&nbsp;Rudolph J. Castellani,&nbsp;Rati Chkheidze,&nbsp;Inma Cobos,&nbsp;Mark Cohen,&nbsp;John F. Crary,&nbsp;Dennis W. Dickson,&nbsp;Brittany N. Dugger,&nbsp;Sara R. Dunlop,&nbsp;Kurt Farrell,&nbsp;Bernardino Ghetti,&nbsp;Mohammad Haeri,&nbsp;William Harrison,&nbsp;Elizabeth Head,&nbsp;Annie Hiniker,&nbsp;Eric J. Huang,&nbsp;Anita Huttner,&nbsp;Pouya Jamshidi,&nbsp;Alifiya Kapasi,&nbsp;C. Dirk Keene,&nbsp;Julia Kofler,&nbsp;Caitlin S. Latimer,&nbsp;Ann C. McKee,&nbsp;Karin Mente,&nbsp;Michael B. Miller,&nbsp;Thomas J. Montine,&nbsp;Meaghan Morris,&nbsp;Melissa E. Murray,&nbsp;Peter T. Nelson,&nbsp;Kathy L. Newell,&nbsp;Richard J. Perrin,&nbsp;Biswarathan Ramani,&nbsp;R. Ross Reichard,&nbsp;Subhojit Roy,&nbsp;Johannes C. M. Schlachetzki,&nbsp;William W. Seeley,&nbsp;Geidy E. Serrano,&nbsp;Salvatore Spina,&nbsp;Andrew F. Teich,&nbsp;Shih-Hsiu J. Wang,&nbsp;Thomas Wisniewski,&nbsp;Edward B. Lee","doi":"10.1002/alz.70734","DOIUrl":"10.1002/alz.70734","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Our understanding of Alzheimer's disease (AD) and related dementias (ADRD) has grown exponentially, thanks to significant investments by the National Institute on Aging (NIA). This article celebrates the 40th anniversary of the NIA's Alzheimer's Disease Research Centers, highlighting the pivotal role of neuropathology as the bedrock for neurodegeneration research. Neuropathology has championed the key principles of proteinopathy, selective vulnerability, and stereotypic spread. Furthermore, neuropathologic studies advanced our understanding of ADRD prevalence, heterogeneity, clinical–pathological correlations, and genetic underpinnings, spurring biomarker development for target engagement and disease monitoring. Disease-modifying therapies for AD were inspired and informed by neuropathology. The neuropathology community is poised to refine diagnostics, leveraging digital pathology and integrating genetics and pathomics to enhance subtyping for novel precision medicine approaches. Despite some common misconceptions and logistical challenges, neuropathology continues to be a critical component of the ADRD research infrastructure, serving as a key bridge between allied basic and clinical sciences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We celebrate 40 years of NIA-funded ADRCs and their contributions through neuropathology studies that have significantly advanced our understanding and treatment of ADRD.</li>\u0000 \u0000 <li>Neuropathology uncovers principles of neurodegenerative disease: proteinopathy, selective vulnerability, and stereotypic spread, informing diagnostics and therapies.</li>\u0000 \u0000 <li>Development of AD biomarkers with reference to neuropathology enhances accuracy in diagnosis and monitoring, paving the way for targeted disease-modifying therapies.</li>\u0000 \u0000 <li>Integration of digital pathology, genetics, and novel tools in neurodegeneration research promises advanced precision medicine approaches and refined diagnostics.</li>\u0000 \u0000 <li>Misconceptions and logistical challenges to neuropathological research are addressed to improve understanding and collaboration.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70734","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282792","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":"The association of human apolipoprotein ε4 with dementia, cognition, imaging, and plasma biomarkers of neurodegeneration in a sample of older adults in the Democratic Republic of the Congo","authors":"Jean Ikanga,&nbsp;Saranya Sundaram Patel,&nbsp;Megan Schwinne,&nbsp;Caterina Alessandra Obenauf,&nbsp;Emmanuel Epenge,&nbsp;Guy Gikelekele,&nbsp;Nathan Tshengele,&nbsp;Immaculee Kavugho,&nbsp;Samuel Mampunza,&nbsp;Lelo Mananga,&nbsp;Charlotte E. Teunissen,&nbsp;Julio C. Rojas,&nbsp;Brandon Chan,&nbsp;Argentina Lario Lago,&nbsp;Adam L. Boxer,&nbsp;Andreas Jeromin,&nbsp;Emile Omba,&nbsp;Alden L. Gross,&nbsp;Alvaro Alonso","doi":"10.1002/alz.70735","DOIUrl":"10.1002/alz.70735","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study examined the association between the apolipoprotein E (<i>APOE</i>) ε4 allele and cognitive performance, neuroimaging, and plasma biomarkers in Congolese older adults in the Democratic Republic of the Congo (DRC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Eighty-four participants (39 healthy controls [HCs], 45 with suspected dementia), aged 73.0 years on average, were assessed using the African Neuropsychology Battery, magnetic resonance imaging, and blood-based biomarkers. Regression models adjusted for age, sex, and education evaluated <i>APOE</i>’s impact.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p><i>APOE</i> ε4 was more prevalent in dementia cases than in HCs. Overall, <i>APOE</i> ε4 status significantly affected naming and memory scores, mesial temporal and entorhinal cortex atrophy scores, and glial fibrillary acidic protein concentration levels. In HCs, it showed no significant impact on cognitive or neuroimaging tests, except for neurofilament light chain concentration levels. Among dementia participants, <i>APOE</i> ε4 status influenced only naming and memory scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p><i>APOE</i> ε4 carriers in this DRC cohort showed greater cognitive decline and neurodegeneration, highlighting its significant impact in African populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Apolipoprotein E (<i>APOE</i>) ε4 was more frequent in dementia cases than in healthy controls in a Democratic Republic of the Congo cohort.</li>\u0000 \u0000 <li><i>APOE</i> ε4 carriers showed greater cognitive decline, especially in memory and visuospatial skills.</li>\u0000 \u0000 <li>Neuroimaging findings revealed increased hippocampal atrophy and cortical thinning in carriers.</li>\u0000 \u0000 <li>Plasma biomarkers in dementia showed higher amyloid beta 40, phosphorylated tau181, neurofilament light chain, and tumor necrosis factor alpha levels.</li>\u0000 \u0000 <li>Findings underscore <i>APOE</i> ε4's impact on neurodegeneration in African populations.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70735","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282846","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":"Independent effects of white matter lesion volume and APOE ɛ4 on ARIA-H in A4 Study","authors":"Zahra Shirzadi,&nbsp;Aaron P. Schultz,&nbsp;Nazila Loghmani,&nbsp;Hyun-Sik Yang,&nbsp;Jeremy Ford,&nbsp;Roy Yaari,&nbsp;Michael Properzi,&nbsp;Wai-Ying W. Yau,&nbsp;Lei Liu,&nbsp;Michael S. Rafii,&nbsp;Michael C. Donohue,&nbsp;Adam M. Brickman,&nbsp;Clifford R. Jack Jr,&nbsp;Steven M. Greenberg,&nbsp;Paul Aisen,&nbsp;Reisa A. Sperling,&nbsp;Jasmeer P. Chhatwal,&nbsp;the A4 Study Team","doi":"10.1002/alz.70751","DOIUrl":"10.1002/alz.70751","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Increased white matter hyperintensity (WMH) volume is a common but non-specific finding in AD. This study investigates the effect of baseline WMH volume and <i>APO</i><i>E</i> ε4 on magnetic resonance imaging (MRI)-visible hemorrhagic lesion emergence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We included A4 participants with 0/1 hemorrhagic lesion at baseline and &gt;1 post-baseline MRI. We examined age, sex, amyloid, WMH, <i>APOE</i>ε4, and cardiovascular risk as predictors of whether people would accrue ≥2 hemorrhagic lesions by their last MRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Among 1097 individuals with 0/1 baseline lesion, 120 had at least two hemorrhagic lesions on their last MRI. Elevated baseline WMH (odds ratio [OR] = 2.3, <i>p</i> = 0.002) and <i>APOE</i> ɛ4/ɛ4 (OR = 4.8, <i>p</i> &lt; 0.001) independently predicted membership to this group. Both hetero- and homozygous <i>APOE</i> ɛ4 carriers with low WMH volume had a low risk of accumulating hemorrhagic lesions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These results support the independent consideration of WMH and <i>APOE</i> ɛ4 in the natural history of hemorrhagic lesion accumulation and suggest that individuals with low WMH volume have a low short-term risk, irrespective of <i>APOE</i> genotype.</p>\u0000 \u0000 <p><b>Trial Registration</b>: NCT02008357</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Elevated baseline white matter lesion volume is related to the risk of ARIA-H emergence.</li>\u0000 \u0000 <li>The effects of white matter lesion volume and <i>APOE</i> ɛ4 on ARIA-H are independent.</li>\u0000 \u0000 <li><i>APOE</i> ɛ4 carriers with low white matter lesion volume had a low risk of ARIA-H emergence.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285420","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":"A randomized trial of two online platforms for dementia family caregivers: GamePlan4Care and Resources4Care","authors":"Alan B. Stevens,&nbsp;Jinmyoung Cho,&nbsp;Thomas Birchfield,&nbsp;Jordan Reese,&nbsp;Gang Han,&nbsp;Jennifer L. Thorud,&nbsp;Marcia G. Ory","doi":"10.1002/alz.70690","DOIUrl":"10.1002/alz.70690","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Digital technologies can increase the accessibility of evidence-based caregiver programs.&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;A 6-month, phase I, exploratory, randomized-controlled trial of two dementia caregiver support platforms, GamePlan4Care (GP4C) and Resources4Care (R4C), each enrolling 120 community-based family caregivers. Outcome measures included burden, positive aspects of caregiving, social support, and depression.&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;Caregivers showed significant follow-up improvements in burden (GP4C: effect size [ES] = 0.50, &lt;i&gt;p&lt;/i&gt; &lt; 0.001; R4C: ES = 0.47, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), positive aspects of caregiving (GP4C: ES = 0.26, &lt;i&gt;p&lt;/i&gt; = 0.022; R4C: ES = 0.23, &lt;i&gt;p&lt;/i&gt; = 0.030), social support (GP4C: ES = 0.21, &lt;i&gt;p&lt;/i&gt; = 0.035), and distress (GP4C: ES = 0.30, &lt;i&gt;p&lt;/i&gt; = 0.010). Caregivers engaged more in GP4C (GP4C: mean 5.5 h, SD = 0.61; R4C: mean 1.9 h, SD = 0.20) and set more goals for the safety domain (mean 8.9 goals, SD = 7.60).&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;GP4C was not superior to R4C; however, both platforms demonstrated improved outcomes. Findings highlight a health system's successful development and implementation of online dementia caregiver platforms. Improving digital technology for caregivers requires studies with larger populations and longitudinal outcomes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; TRIAL REGISTRATION NUMBER&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;ClinicalTrials.gov Identifier: NCT04540198&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;Online platforms can be useful in the goal of supporting family caregivers with educational and skills-training material to reduce the negative consequences of caregiving and to improve positive feelings of caregiving.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Rules-based conditional logic was successfully integrated into a Web-based platform to tailor evidence-based strategies to an individual's unique caregiving context and needs.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Health systems are in an ideal position to adopt online technologies that provide education, skills training, and support for family caregivers of persons living with dementia.&lt;/li&gt;\u0000 &lt;/ul&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70690","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282745","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}