Alzheimer's & Dementia最新文献

{"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}

{"title":"Impact of kidney function on biomarkers of neurodegeneration, white matter hyperintensities, and cognition in older adults","authors":"Anisa Dhana,&nbsp;Charles S. DeCarli,&nbsp;Klodian Dhana,&nbsp;Pankaja Desai,&nbsp;Kristin Krueger,&nbsp;Kyle Dennis,&nbsp;Ted K. S. Ng,&nbsp;Denis Evans,&nbsp;Kumar B. Rajan","doi":"10.1002/alz.70397","DOIUrl":"10.1002/alz.70397","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>We evaluated the association between kidney function, neurodegenerative biomarkers (i.e., neurofilament light chain [NfL], total tau [t-tau], and glial fibrillary acidic protein [GFAP]), white matter hyperintensities, and global cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The study consisted of 1207 participants living on the south side of Chicago, Illinois, enrolled in the Chicago Health and Aging Project, a population-based cohort since 1993. Kidney function was assessed using the estimated glomerular filtration rate (eGFRcr), calculated according to the 2021 Chronic Kidney Disease Epidemiology (CKD-EPI) based on age, sex, and serum creatinine levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In a multivariable-adjusted model, lower levels of eGFRcr were associated with higher levels of biomarkers of neurodegeneration. Specifically, for a 1-SD decrease of eGFRcr, there was a 22% increase in NfL levels in serum. eGFRcr levels were not associated with white matter hyperintensities or global cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Kidney function may be considered when interpreting NfL, GFAP, and t-tau levels for risk stratification in research and clinical applications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Kidney function is associated with higher neurfilament light chain (NfL), total tau (t-tau), and glial fibrillary acidic protein (GFAP) serum concentrations, while there was no association with white matter hyperintensities or global cognition.</li>\u0000 \u0000 <li>Individuals with severely impaired kidney function had 146.7% higher serum concentrations of NfL when compared to people with normal kidney function.</li>\u0000 \u0000 <li>This study suggests assessing kidney function in older adults when interpreting NfL, GFAP, and t-tau levels in the serum for risk stratification.</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.70397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282795","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 cerebral small vessel disease on cognitive outcomes in early age at onset MCI and dementia: Findings from the DIASPORA study","authors":"Jonathan Naftali,&nbsp;Amir Glik,&nbsp;Ruth Eliahou,&nbsp;Gil D Rabninovici,&nbsp;Howar J Rosen,&nbsp;Fanny Elahi,&nbsp;Felix Benninger,&nbsp;Ilan Goldberg,&nbsp;Eitan Auriel,&nbsp;Ophir Keret","doi":"10.1002/alz.70773","DOIUrl":"10.1002/alz.70773","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>This study assessed the impact of cerebral small vessel disease (CSVD) on cognition in individuals with early-onset (EO; &lt;65 years) and late-onset (LO; ≥65 years) cognitive complaints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Participants underwent prospective evaluations including cognitive testing, hyperphosphorylated tau-217 (p-tau217) and neurofilament-light-chain (NfL), and magnetic resonance imaging (MRI). Each CSVD marker was modeled for interaction with group age on results on cognitive outcomes: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory Questionnaire (NPI-Q), and Clinical Dementia Rating (CDR) scale plus National Alzheimer's Coordinating Center–Frontotemporal Lobar Degeneration module (NACC-FTLD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Altogether, 168 patients (91 EO) were included. white matter hyperintensity (WMH) volume was associated with worse CDR+NACC-FTLD in EO (<i>β </i>= 17.8, <i>p </i>= 0.013), remaining significant after adjusting for p-tau217 and NfL, but not gray matter atrophy. Lacunes were associated with worse CDR plus NACC-FTLD in EO (<i>β </i>= 4.3, <i>p </i>= 0.011), with age-dependent associations with MoCA, MMSE, CDR + NACC-FTLD, and NPI-Q (<i>p</i> &lt; 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>CSVD markers, although less prevalent in EO, had greater clinical impact. These findings highlight an increased vulnerability to vascular pathology in EO patients and the importance of early detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Cerebral small vessel disease (CSVD) markers were more impactful in early-onset than late-onset dementia.</li>\u0000 \u0000 <li>White matter hyperintensity (WMH) volume predicted functional decline in early onset, independent of neurodegeneration.</li>\u0000 \u0000 <li>Lacunes showed age-dependent effects on multiple cognitive outcomes.</li>\u0000 \u0000 <li>Findings support early detection of CSVD in younger individuals with dementia.</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/PMC12519510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285470","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":"Cerebrospinal fluid proteomic associations of APOE genotypes reveal distinct protective and risk mechanisms for Alzheimer's disease","authors":"Eleonora M. Vromen,&nbsp;Senne B. Lageman,&nbsp;Johan Gobom,&nbsp;Rik van der Kant,&nbsp;Valerija Dobricic,&nbsp;Lars Bertram,&nbsp;Johannes Streffer,&nbsp;Simon Lovestone,&nbsp;Stephanie J. B. Vos,&nbsp;Mikel Tainta,&nbsp;Yvonne Freund-Levi,&nbsp;Lutz Frölich,&nbsp;Julius Popp,&nbsp;Gwendoline Peyratout,&nbsp;Magda Tsolaki,&nbsp;Frans Verhey,&nbsp;Rik Vandenberghe,&nbsp;Jolien Schaeverbeke,&nbsp;Kaj Blennow,&nbsp;Sven J. van der Lee,&nbsp;Philip Scheltens,&nbsp;Yolande A. L. Pijnenburg,&nbsp;Wiesje M. van der Flier,&nbsp;Charlotte E. Teunissen,&nbsp;Henrik Zetterberg,&nbsp;Pieter Jelle Visser,&nbsp;Betty Tijms","doi":"10.1002/alz.70738","DOIUrl":"10.1002/alz.70738","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>The apolipoprotein E (<i>APOE</i>) gene includes the strongest protective (ε2) and risk (ε4) variants for sporadic Alzheimer's disease (AD), but underlying mechanisms remain unclear. We studied <i>APOE</i> genotype effects on the cerebrospinal fluid (CSF) proteome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using untargeted tandem mass tag mass spectrometry, we analyzed CSF from 227 cognitively normal (CN) controls (A–T–), 165 CN A+, and 177 individuals with mild cognitive impairment (MCI A+) from two large cohorts. We compared protein levels across <i>APOE</i> genotypes using linear regression and characterized biological pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Five hundred forty-nine of 978 proteins (56%) differed between ε2/ε3 (<i>n</i> = 32 individuals) or ε4 carriers (<i>n</i> = 181 individuals) and ε3/ε3 controls. ε2/ε3 controls showed the most differences, with higher levels of 280 proteins enriched for neuronal plasticity. ε4 carrier controls showed increased proteins linked to blood–brain barrier dysfunction, and A+ ε4 carriers were related to glucose metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Combining two cohorts enabled analysis of the rare <i>APOE</i> ε2 genotype, suggesting protective effects may occur through improved neuronal plasticity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Apolipoprotein E (<i>APOE</i>) genotypes show distinct cerebrospinal fluid proteomic mechanisms in early Alzheimer's disease (AD).</li>\u0000 \u0000 <li>Combining cohorts enabled analysis of rare <i>APOE</i> ε2–associated protection in AD.</li>\u0000 \u0000 <li>The rare ε2 genotype may confer protection through improved neuronal plasticity.</li>\u0000 \u0000 <li><i>APOE</i> ε4 carriers show increased blood–brain barrier dysfunction and glucose metabolism.</li>\u0000 \u0000 <li>These findings offer new insights into genotype-specific mechanisms in early AD.</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.70738","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282747","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}