Alzheimer's & Dementia最新文献

{"title":"An AI-first framework for multimodal data in Alzheimer's disease and related dementias","authors":"Varuna H. Jasodanand,&nbsp;Matteo Bellitti,&nbsp;Vijaya B. Kolachalama","doi":"10.1002/alz.70719","DOIUrl":"10.1002/alz.70719","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Advancing the understanding and management of Alzheimer's disease and related dementias requires integrating and analyzing diverse data modalities. Traditional diagnostic tools, like neuroimaging, provide valuable insights but are limited by accessibility and infrastructure demands. Meanwhile, emerging modalities, including wearable sensors and speech analysis, enable less invasive and more continuous data collection but introduce challenges related to standardization and privacy. The coexistence of these heterogeneous data streams complicates multimodal integration across cohorts, populations, and clinical settings. Current analytical approaches typically require modality-specific preprocessing pipelines and harmonization methods that were not designed to accommodate modern AI-based capabilities, such as multimodal fusion. In this perspective, we propose an “AI-first” strategy for multimodal data integration that aligns data structuring, harmonization, and modeling within a unified set of guiding principles to optimize modern AI development, while remaining flexible enough to support classical analytical approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Understanding and managing ADRD requires integrating biological, cognitive, and behavioral data across multiple modalities.</li>\u0000 \u0000 <li>Incorporating multiple modalities requires new standards for harmonization and interoperability.</li>\u0000 \u0000 <li>Current data platforms are not necessarily built to support multimodal fusion or generalizable AI models across diverse ADRD populations.</li>\u0000 \u0000 <li>Modern AI models are capable of learning from messy, multimodal, and incomplete data but require infrastructure designed for this purpose.</li>\u0000 \u0000 <li>We propose rethinking ADRD data systems to prioritize AI compatibility, enabling scalable tools for early diagnosis and longitudinal care.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70719","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111359","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":"Combining Lumipulse p-tau217 and Aβ42/40 as confirmatory tests for Aβ positivity prior to disease-modifying therapy","authors":"James D. Doecke,&nbsp;Ahmed Chenna,&nbsp;Mintzu Lo,&nbsp;Youssouf Badal,&nbsp;Brandon Yee,&nbsp;Robert Martone,&nbsp;Christos Petropoulos,&nbsp;Christopher J. Fowler,&nbsp;Simon Laws,&nbsp;Stephanie R. Rainey-Smith,&nbsp;Ralph N. Martins,&nbsp;Christopher C. Rowe,&nbsp;Colin L. Masters,&nbsp;John Winslow","doi":"10.1002/alz.70707","DOIUrl":"10.1002/alz.70707","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>For a blood-based biomarker to be considered a confirmatory test for the detection of abnormal amyloid beta (Aβ) levels, the sensitivity and specificity must be equivalent to that of current cerebrospinal fluid tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In the current study we assessed the ability of phosphorylated tau (p-tau)217 and Aβ42/40 from the Lumipulse G p-tau217 and β-amyloid ratio (1-42/1-40) tests, individually and combined, to predict Aβ positron emission tomography status in two sub-cohorts from the Australian Imaging, Biomarkers, and Lifestyle Study of Ageing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Testing an Alzheimer's disease continuum cohort, the area under the curve (AUC), sensitivity, specificity, and accuracy for the p-tau217/Aβ42 ratio reached 0.961, 93%, 92%, and 93%, respectively. Validation in an intention-to-treat cohort demonstrated similar AUC (0.959), with increased sensitivity (99%), decreased specificity (87%), and increased accuracy (95%). Dual cut-offs generating balanced 95% sensitivity/specificity result in 93% accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Combinations of plasma p-tau217 and Aβ42 demonstrate recommended performance, confirming the presence of Aβ positivity prior to selection for disease-modifying therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The phosphorylated tau (p-tau)217/amyloid beta (Aβ)42 ratio had high performance to detect Aβ positron emission tomography (PET) status, with &gt; 90% sensitivity, specificity, and accuracy.</li>\u0000 \u0000 <li>p-tau217/Aβ42 ratio dual cut-offs set at 95% sensitivity and specificity found 10% to 15% of participants in the intermediate zone.</li>\u0000 \u0000 <li>Cut-offs derived for the intention-to-treat cohort meet confirmatory assay criteria for a disease-modifying therapy and can be used in clinical settings.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70707","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110695","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":"Caregivers' perspectives on lecanemab use for Alzheimer's disease: A national survey in China","authors":"Shuai Liu,&nbsp;Shiyu Fan,&nbsp;Jinghuan Gan,&nbsp;Wang Liao,&nbsp;Qin Chen,&nbsp;Xia Li,&nbsp;Jiewen Zhang,&nbsp;Xiaochun Chen,&nbsp;Yong Ji","doi":"10.1002/alz.70680","DOIUrl":"10.1002/alz.70680","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Caregivers' decisions significantly influence Alzheimer's disease progression, yet research on the benefits of disease-modifying therapy (DMT) from their perspective is limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This cross-sectional survey included 345 informal caregivers of lecanemab-treated patients. We collected online questionnaires from 37 tertiary hospitals across 31 provinces/autonomous regions/municipalities in China (2024/06/24 ∼ 2024/12/24).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Approximately 94.5% of the caregivers opined that the burden of care did not intensify (including remaining constant or being alleviated) subsequent to the administration of lecanemab, among which 25.8% of the caregivers stated that the burden of care was mitigated. Those caregivers with a higher annual family income (≥¥400,000, <i>p </i>&lt; 0.01) and filial caregivers exhibited greater confidence in the therapeutic efficacy of lecanemab.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Most caregivers hold a positive attitude toward lecanemab, particularly filial caregivers. The application of lecanemab may alleviate the care burden on caregivers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We conducted the first China national survey on Alzheimer's disease (AD) caregiver decision-making and lecanemab experience, collecting 345 questionnaires.</li>\u0000 \u0000 <li>The majority of caregivers in China hold a favorable attitude toward lecanemab.</li>\u0000 \u0000 <li>Higher education, younger age, and filial relationships are associated with reduced caregiver burden.</li>\u0000 \u0000 <li>Higher income is linked to increased caregiver confidence and better lecanemab adherence.</li>\u0000 \u0000 <li>There is a low adoption rate of blood-based AD biomarkers in caregiver decisions.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70680","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110696","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":"Free water predicts dementia with Lewy bodies in isolated REM sleep behavior disorder","authors":"Celine Haddad,&nbsp;Véronique Daneault,&nbsp;Violette Ayral,&nbsp;Marie Filiatrault,&nbsp;Alexandre Pastor-Bernier,&nbsp;Christina Tremblay,&nbsp;Arnaud Boré,&nbsp;Maxime Descoteaux,&nbsp;Andrew Vo,&nbsp;Jean-François Gagnon,&nbsp;Ronald B. Postuma,&nbsp;Petr Dusek,&nbsp;Stanislav Marecek,&nbsp;Zsoka Varga,&nbsp;Johannes Klein,&nbsp;Michele T. Hu,&nbsp;Stéphane Lehéricy,&nbsp;Isabelle Arnulf,&nbsp;Marie Vidailhet,&nbsp;Jean-Christophe Corvol,&nbsp;ICEBERG Study Group,&nbsp;Shady Rahayel","doi":"10.1002/alz.70570","DOIUrl":"10.1002/alz.70570","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Most individuals with isolated rapid eye movement sleep behavior disorder (iRBD) develop dementia with Lewy bodies (DLB) or Parkinson's disease (PD). Brain biomarkers predicting specific phenoconversion trajectories are lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In this multicenter diffusion magnetic resonance imaging study (261 iRBD, 177 controls), free water (FW) was measured in the nucleus basalis of Meynert (NBM) and posterior substantia nigra (SN). Among 230 iRBD patients with follow-up, 64 converted (16 DLB, 38 PD). Time-to-event analyses were performed to assess differential phenoconversion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Phenoconverters had higher FW in the NBM and posterior SN. Only FW in the NBM predicted conversion to DLB over PD. NBM volume predicted DLB conversion, but only FW remained significant when both were modeled. FW in the NBM correlated with lower MoCA scores in iRBD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>FW in the NBM is a sensitive biomarker of cognitive decline and DLB progression in iRBD, outperforming volume and supporting its use in early stratification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>FW in the NBM specifically identifies conversion to DLB.</li>\u0000 \u0000 <li>Increased FW in the NBM is associated with lower global cognition in iRBD.</li>\u0000 \u0000 <li>FW in the SN in iRBD does not relate more to DLB than PD.</li>\u0000 \u0000 <li>FW in the NBM is a biomarker of differential phenoconversion in iRBD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70570","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084283","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":"Mild kidney dysfunction affects the predictive accuracy of blood-based biomarkers for neuropsychological and neuroimaging outcomes over a 9 year follow-up period","authors":"Corey J. Bolton,&nbsp;Panpan Zhang,&nbsp;Devika Nair,&nbsp;Dandan Liu,&nbsp;L. Taylor Davis,&nbsp;Kimberly R. Pechman,&nbsp;Niranjana Shashikumar,&nbsp;Sydney Wilhoite,&nbsp;Dominic Roby,&nbsp;Carlie Beeson,&nbsp;Haley Komorowski,&nbsp;Katherine A. Gifford,&nbsp;Timothy J. Hohman,&nbsp;Kaj Blennow,&nbsp;Henrik Zetterberg,&nbsp;Angela L. Jefferson","doi":"10.1002/alz.70651","DOIUrl":"10.1002/alz.70651","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The impact of chronic kidney disease (CKD) on Alzheimer's disease (AD) plasma biomarkers is poorly understood. We tested whether kidney function decline affects the predictive accuracy of plasma biomarkers on neuropsychological or neuroimaging outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Three hundred thirty-three non-demented older adults were included. Linear regressions related plasma glial fibrillary acidic protein, neurofilament light chain (NfL), amyloid beta 42, and phosphorylated tau₂₃₁, with a blood-based biomarker x estimated glomerular filtration rate (eGFR) interaction term, to cross-sectional and longitudinal (mean follow-up time = 6.4 ± 2.8 years) neuropsychological and neuroimaging outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Plasma NfL interacted with eGFR on the longitudinal trajectory of nearly all neuropsychological outcomes (<i>p</i> values &lt; 0.02) and several neuroimaging outcomes (<i>p</i> values &lt; 0.02). Associations were stronger in individuals with no CKD/stage 1 and stage 2 CKD, while associations were weaker or not significant in individuals with stage 3 CKD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Among older adults free of severe CKD, the ability of plasma NfL to predict key AD-related biomarker outcomes was moderated by renal function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Reduced kidney function was associated with increased blood biomarker levels.</li>\u0000 \u0000 <li>The predictive accuracy of neurofilament light chain was reduced in participants with kidney dysfunction.</li>\u0000 \u0000 <li>Even mild kidney dysfunction can affect blood biomarkers of Alzheimer's disease.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084284","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":"Periventricular diffusivity reflects APOE ε4–modulated amyloid accumulation and cognitive impairment in the Alzheimer's disease continuum","authors":"Chang-Le Chen,&nbsp;Sang Joon Son,&nbsp;Noah Schweitzer,&nbsp;Hecheng Jin,&nbsp;Jinghang Li,&nbsp;Linghai Wang,&nbsp;Shaolin Yang,&nbsp;Chang Hyung Hong,&nbsp;Hyun Woong Roh,&nbsp;Bumhee Park,&nbsp;Jin Wook Choi,&nbsp;Young-Sil An,&nbsp;Sang Woon Seo,&nbsp;Yong Hyuk Cho,&nbsp;Sunhwa Hong,&nbsp;You Jin Nam,&nbsp;Davneet S. Minhas,&nbsp;Charles M. Laymon,&nbsp;George D. Stetten,&nbsp;Dana L. Tudorascu,&nbsp;Howard J. Aizenstein,&nbsp;Minjie Wu,&nbsp;Mayo Clinic Study of Aging","doi":"10.1002/alz.70659","DOIUrl":"10.1002/alz.70659","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Altered glymphatic-related fluid dynamics are increasingly recognized as a feature of Alzheimer's disease (AD). We generalized an established diffusion imaging framework to quantify periventricular diffusivity (PVeD), hypothesizing that fast diffusion signals in the periventricular region can reflect amyloid beta (Aβ) deposition across the AD continuum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Participants from two multi-site cohorts (<i>n</i> = 440 and 414), comprising cognitively unimpaired individuals, those with mild cognitive impairment, and patients with AD, were included. We tested and validated the association of PVeD with Aβ burden and core AD characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Lower PVeD was extensively associated with greater Aβ burden, neurodegeneration, cognitive impairment, and clinical severity in the clinical cohort. Importantly, the relationship between PVeD and Aβ burden was significantly modulated by apolipoprotein E (<i>APOE</i>) ε4 status; <i>APOE</i> ε4 carriers exhibited a replicable stronger negative association. Baseline PVeD also predicted longitudinal cognitive decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings suggest that periventricular diffusion signals reflect <i>APOE</i> ε4–modulated Aβ burden and cognitive decline in AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>An automated method for quantifying periventricular diffusivity (PVeD) is developed.</li>\u0000 \u0000 <li>Lower PVeD is associated with higher amyloid load only in a mild cognitive impairment–dominant cohort.</li>\u0000 \u0000 <li>Higher amyloid burden may mediate the link between lower PVeD and poorer cognitive outcomes in the clinical cohort.</li>\u0000 \u0000 <li>Apolipoprotein E ε4 carriers show a reproducibly stronger inverse PVeD—amyloid association than non-carriers.</li>\u0000 \u0000 <li>Baseline PVeD can predict longitudinal Mini-Mental State Examination decline in two independent cohorts.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079276","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":"Study of brain perfusion in adults with Down syndrome along the Alzheimer's disease continuum","authors":"Maria Franquesa-Mullerat,&nbsp;Alejandra O. Morcillo-Nieto,&nbsp;José Enrique Arriola-Infante,&nbsp;Sara E. Zsadanyi,&nbsp;Lídia Vaqué-Alcázar,&nbsp;Mateus Rozalem-Aranha,&nbsp;Javier Arranz,&nbsp;Íñigo Rodríguez-Baz,&nbsp;Lucia Maure-Blesa,&nbsp;Laura Videla,&nbsp;Isabel Barroeta,&nbsp;Laura Del Hoyo Soriano,&nbsp;Bessy Benejam,&nbsp;Susana Fernández,&nbsp;Aida Sanjuan Hernandez,&nbsp;Sandra Giménez,&nbsp;Daniel Alcolea,&nbsp;Olivia Belbin,&nbsp;Alberto Lleó,&nbsp;María Carmona-Iragui,&nbsp;Juan Fortea,&nbsp;Alexandre Bejanin","doi":"10.1002/alz.70581","DOIUrl":"10.1002/alz.70581","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We assessed pseudo-continuous arterial spin labeling (pCASL) sensitivity to detect changes in cerebral blood flow (CBF) in adults with Down syndrome (DS) along the Alzheimer's disease (AD) continuum and explored the similarity with sporadic AD (sAD) hypoperfusion profile.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Fifty-one euploid cognitively unimpaired individuals, 54 adults with DS (34.54% symptomatic for AD), and 25 sAD patients underwent 3T magnetic resonance imaging. pCASL images were preprocessed using ASLprep. Analyses explored, globally and regionally, the effects of demographic variables, clinical stages, and AD biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Age and sex differently impacted CBF in euploids versus the DS population. Asymptomatic DS showed temporo-parietal hypoperfusion, extending into frontal areas in symptomatic cases. This pattern closely resembled sAD's pattern and correlated with AD biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Adults with DS present CBF changes before symptom onset, primarily affecting posterior regions as in sAD. pCASL is a sensitive imaging modality that captures early AD-related functional abnormalities in DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Perfusion is negatively affected by age and correlates with Alzheimer's disease (AD) biomarkers in Down syndrome (DS).</li>\u0000 \u0000 <li>Hypoperfusion in DS was observed even before the onset of the AD clinical symptoms.</li>\u0000 \u0000 <li>The pattern of hypoperfusion in the DS population resembles the one observed in the sporadic AD population.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70581","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083919","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":"Objective physical activity and Alzheimer's disease burden in the population-based Rotterdam Study","authors":"Phuong Thuy Nguyen Ho,&nbsp;Meike W. Vernooij,&nbsp;Trudy Voortman,&nbsp;María Rodriguez-Ayllon,&nbsp;Julia Neitzel","doi":"10.1002/alz.70655","DOIUrl":"10.1002/alz.70655","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Physical activity is linked to lower dementia risk, but its connection to Alzheimer's disease (AD) pathology remains uncertain. This study examined the relationship between objectively measured physical activity and early AD biomarkers in cognitively unimpaired adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Accelerometer-measured physical activity and plasma AD biomarkers (beta-amyloid [Aβ]42/Aβ40, p-tau217) were assessed in 242 participants (age = 63.37 [54–79] years) of the population-based Rotterdam Study. Cortical Aβ was assessed via ¹⁸F-florbetaben positron emission tomography (PET) 7 years later. Robust regression assessed the relationship between physical activity, plasma AD biomarkers, and Aβ PET burden, while compositional analysis examined how the time-use composition relates to AD outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Physical activity was not associated with plasma Aβ42/Aβ40, p-tau217, or brain Aβ burden 7 years later. Reallocating awake sedentary time to physical activity showed no association with AD biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>No relationship was identified between physical activity and AD biomarkers, suggesting physical activity might affect dementia risk through other pathways or in an earlier life phase.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Physical activity was not associated with plasma beta-amyloid (Aβ)42/Aβ40 nor p-tau217.</li>\u0000 \u0000 <li>No association was observed between physical activity and brain Aβ 7 years later.</li>\u0000 \u0000 <li>Age, sex, and apolipoprotein E ε4 carriership did not moderate these relationships.</li>\u0000 \u0000 <li>Reallocating 30 minutes of sedentary time to physical activity resulted in no change in Alzheimer's disease (AD) biomarkers.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079085","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":"Protective mechanisms against Alzheimer's disease in APOE3-Christchurch homozygous astrocytes","authors":"Xinran Tian,&nbsp;Erica Keane Rivera,&nbsp;Inyoung Hwang,&nbsp;Arina A. Nikitina,&nbsp;Jennifer A. Smith,&nbsp;Youngsuh J. Cho,&nbsp;Julia Sala-Jarque,&nbsp;Austin DuBose,&nbsp;Clare Andriola,&nbsp;Toby Gollan-Myers,&nbsp;Kenneth S. Kosik","doi":"10.1002/alz.70589","DOIUrl":"10.1002/alz.70589","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Alzheimer's disease (AD) is characterized by tau pathology, leading to neurodegeneration. Astrocytes regulate central nervous system homeostasis and influence AD progression. The APOE3-Christchurch (APOE3-Ch) variant is linked to AD resilience, but its protective mechanisms remain unclear.&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;Human induced pluripotent stem cell–derived astrocytes (APOE3-Ch and wild type) were used to assess tau uptake, clearance, lipid metabolism, and transcriptomic adaptations. Fluorescently labeled 2N4R-P301L tau oligomers were tracked, and pathway-specific inhibitors dissected tau clearance mechanisms. Lipidomic and transcriptomic analyses were performed to identify genotype-specific adaptations.&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;APOE3-Ch astrocytes exhibited enhanced tau uptake via heparan sulfate proteoglycan- and lipoprotein receptor-related protein 1-mediated pathways and superior clearance through lysosomal and proteasomal degradation. They exported less tau, limiting propagation. Transcriptomic analyses revealed upregulation of genes involved in cell projection assembly and endocytosis. Lipidomic profiling showed reduced ceramides and gamma-linolenic acid, linked to decreased neuroinflammation and ferroptosis.&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;APOE3-Ch astrocytes promote tau clearance and metabolic adaptations, providing insights into genetic resilience in AD and potential therapeutic targets.&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;APOE3-Christchurch (APOE3-Ch) astrocytes exhibit significantly increased tau internalization compared to wild-type astrocytes, facilitated by upregulated heparan sulfate proteoglycan and low-density lipoprotein receptor-related protein 1 pathways.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;APOE3-Ch astrocytes demonstrate more efficient tau degradation via both lysosomal and proteasomal pathways, while exporting significantly less tau, potentially reducing tau propagation in the central nervous system.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;APOE3-Ch astrocytes show upregulation of genes involved in cell projection assembly and endocytosis, suggesting structural and functional modifications that enhance tau processing.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Lipidomic profiling reveals reduced ceramide lev","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079325","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":"Stroke–heart syndrome and risk of incident dementia among patients with first-ever ischemic stroke: A territory-wide population-based cohort study","authors":"Christopher T. W. Tsang,&nbsp;Sylvia E. Choi,&nbsp;Tommaso Bucci,&nbsp;Alfred C. W. Lau,&nbsp;Qing-Wen Ren,&nbsp;Jia-Yi Huang,&nbsp;Mei-Zhen Wu,&nbsp;Wen-Li Gu,&nbsp;Ran Guo,&nbsp;Jing-Nan Zhang,&nbsp;Yuen-Ching Ng,&nbsp;Benjamin J. R. Buckley,&nbsp;Jan F. Scheitz,&nbsp;Yap-Hang Chan,&nbsp;Kui-Kai Lau,&nbsp;Hung-Fat Tse,&nbsp;Azmil H. Abdul-Rahim,&nbsp;Gregory Y. H. Lip,&nbsp;Kai-Hang Yiu","doi":"10.1002/alz.70716","DOIUrl":"10.1002/alz.70716","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The risk of dementia in patients with ischemic stroke and early cardiovascular complications (i.e., stroke–heart syndrome [SHS]) remains underexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Patients with first-ever ischemic stroke in Hong Kong between 2005 and 2020 were included. Multivariable Fine–Gray competing risk analysis was performed after 1:1 propensity score matching to evaluate the association between SHS and the risk of dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Of the 130,605 included patients with ischemic stroke, 12,696 (9.7%) patients developed SHS. Patients with SHS had a 19% increased risk of dementia compared to those without SHS at 1 year post-stroke, driven mainly by vascular dementia. This increased risk gradually declined and became non-significant after 3 years post-stroke. Appropriate antithrombotic therapy and comorbidities optimization were associated with a 32% reduced dementia risk in patients with SHS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>SHS is associated with an increased risk of incident dementia. Appropriate antithrombotic therapy and comorbidities optimization post-stroke may reduce this heightened risk of cognitive impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Association between stroke–heart syndrome (SHS) and dementia was evaluated in a population-based cohort.</li>\u0000 \u0000 <li>Development of SHS associated with a 19% increased 1 year risk of dementia.</li>\u0000 \u0000 <li>The increased risk of dementia gradually declined with each year of follow-up.</li>\u0000 \u0000 <li>Integrated post-stroke management may reduce this heightened risk of cognitive impairment.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079267","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}