Alzheimer's & Dementia最新文献

{"title":"Creating harmony at home via environmental cueing: A feasibility trial of a non-pharmacological intervention for rural caregivers of persons with dementia","authors":"Elizabeth K. Rhodus,&nbsp;Richard Kryscio,&nbsp;Gregory Jicha,&nbsp;Carolyn Baum,&nbsp;Laura Henley,&nbsp;Vickie Fairchild,&nbsp;Celeste Roberts,&nbsp;Allison Gibson","doi":"10.1002/alz.70405","DOIUrl":"10.1002/alz.70405","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Behavioral and psychiatric symptoms of dementia (BPSDs) and functional impairment have a major impact on quality of life for people living with dementia (PLWD). Development of caregiver-initiated interventions, including environmental assessment and modification, are priorities in the field.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>An open-label study of 40 caregivers of PLWD with BPSDs that underwent a 6-week telehealth person-environment intervention, <i>Harmony at HOME</i>, was conducted. Feasibility was assessed by improved caregiver mastery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Twenty-eight caregivers completed the intervention, which increased caregiver mastery and decreased stress and burden. There were statistically significant improvements in functional performance of the person living with dementia (<i>p</i> &lt; 0.005) and caregivers’ satisfaction with the person living with dementia's functional performance (<i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The intervention increased caregivers’ skills and knowledge in assessing and modifying the environment to address BPSDs. Although overall caregiver mastery was not changed significantly, additional clinical research assessing caregiver mastery in relation to specific caregiving tasks within the home environment is needed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CLINICAL TRIAL REGISTRATION</h3>\u0000 \u0000 <p>Clinicaltrials.gov NCT05202223</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Aging in place is difficult to achieve for individuals with dementia.</li>\u0000 \u0000 <li>A novel dyadic care intervention, Harmony at HOME, improved caregiver outcomes.</li>\u0000 \u0000 <li>Future care research should explore performance-based patient outcomes.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70405","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568436","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":"Plasma placental growth factor as a biomarker for subcortical ischemic vascular dementia and its cognitive correlation mediated by white matter hyperintensities","authors":"Ping Che,&nbsp;Siqi Wang,&nbsp;Xiaojiao Liu,&nbsp;Yunyao Lu,&nbsp;Zhuo Tian,&nbsp;Qixin Feng,&nbsp;Feifan Chen,&nbsp;Nan Zhang","doi":"10.1002/alz.70461","DOIUrl":"10.1002/alz.70461","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Placental growth factor (PlGF) was recently shown to be associated with cerebrovascular and neurodegenerative diseases. The changes of PlGF level in patients with subcortical ischemic vascular dementia (SIVD) and its associations with cognitive function remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Seventy patients with SIVD, 102 patients with symptomatic Alzheimer's disease, 40 patients with frontotemporal lobar degeneration, and 38 cognitively unimpaired controls (CUCs) were included. The plasma level of PlGF was measured via electrochemiluminescence immunoassay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The plasma PlGF level was significantly elevated in patients with SIVD compared with CUCs, and showed a high accuracy with an area under the curve of 0.893. Mediation analysis revealed that white matter hyperintensities (WMHs) volume mediated the effect of plasma PlGF levels on cognitive functions in a transdiagnostic cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The plasma PlGF is a potential biomarker for screening and diagnosing SIVD, and its correlation with cognitive function may be partly mediated by the WMHs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Plasma placental growth factor (PlGF) showed high diagnostic value for subcortical ischemic vascular dementia.</li>\u0000 \u0000 <li>Plasma PlGF showed significantly negative correlation with cognition.</li>\u0000 \u0000 <li>White matter hyperintensities mediated the relationship between plasma PlGF and cognition.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568432","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":"Community engagement, recruitment, and retention of minoritized participants in Alzheimer's disease and related dementia research: A systematic review of disparities","authors":"Araya Dimtsu Assfaw,&nbsp;Ganesh M. Babulal,&nbsp;Joyce Balls-Berry,&nbsp;Jessica Mozersky,&nbsp;Krista Moulder,&nbsp;John C. Morris","doi":"10.1002/alz.70459","DOIUrl":"10.1002/alz.70459","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Ethnoracial groups face the highest risk for Alzheimer's disease and related dementias (ADRD) but remain underrepresented in research, exacerbating health disparities. Understanding barriers and effective recruitment strategies is critical for fostering inclusivity. The aim of this study was to synthesize evidence on strategies to engage, recruit, and retain historically minoritized groups in ADRD research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A systematic review was conducted using PubMed-MEDLINE, EMBASE, SCOPUS, and WEB OF SCIENCE. Studies focusing on ADRD research recruitment and retention among minoritized populations in the United States were included.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Thirty-three studies identified key barriers, including mistrust, logistical challenges, and low awareness. Effective strategies involved long-term community engagement, culturally tailored education, participatory methods, and logistical support.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Addressing systemic barriers through culturally competent strategies, digital tools, and community partnerships is essential for equitable research participation. Researchers and policy-makers must prioritize inclusive approaches to enhance representation and improve ADRD outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The study examined strategies for engaging, recruiting, and retaining historically underrepresented ethnoracial groups in ADRD.</li>\u0000 \u0000 <li>Successful engagement strategies encompass building trust through long-term community involvement, utilizing culturally tailored educational materials, and forming partnerships with community-based organizations.</li>\u0000 \u0000 <li>The study advocates for enhancing cultural competency, leveraging accessible digital tools, fostering community partnerships, addressing logistical barriers, and ensuring diverse representation in biomarker research.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568433","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":"Unravelling the plasma proteome: Pioneering biomarkers for differential dementia diagnosis","authors":"Haşim Gezegen,&nbsp;Merve Alaylıoğlu,&nbsp;Erdi Şahin,&nbsp;Owen Swann,&nbsp;Elena Veleva,&nbsp;Gamze Güven,&nbsp;Umran Yaman,&nbsp;Derviş A. Salih,&nbsp;Başar Bilgiç,&nbsp;Haşmet Hanağası,&nbsp;Hakan Gürvit,&nbsp;Murat Emre,&nbsp;Duygu Gezen-Ak,&nbsp;Erdinç Dursun,&nbsp;Henrik Zetterberg,&nbsp;John Hardy,&nbsp;Amanda Heslegrave,&nbsp;Maryam Shoai,&nbsp;Bedia Samanci","doi":"10.1002/alz.70162","DOIUrl":"https://doi.org/10.1002/alz.70162","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Diagnosing Alzheimer's disease (AD) is challenging due to overlapping symptoms with other dementias and the invasiveness of current biomarkers. This study introduces the NULISA platform, a novel proteomics technology, to evaluate diagnostic accuracy of known biomarkers and uncover novel biomarkers underlying different dementias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We analyzed plasma and cerebrospinal fluid (CSF) samples from 248 participants diagnosed with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and mild cognitive impairment (MCI). Plasma biomarkers were evaluated using regression models, receiver operating characteristics curve (ROC) analysis, and pathway enrichment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Plasma phosphorylated Tau217 (pTau217) demonstrated the highest diagnostic accuracy for AD, DLB, and FTD (area under the curve [AUCs]: 0.9, 0.84, and 0.79, respectively). CXCL1 (fractalkine), synaptosomal-associated protein 25 (SNAP25), triggering receptor expressed on myeloid cells 1 (TREM1), β-synuclein, and tyrosine kinase (TEK) are expressed differently in DLB and FTD than AD. Ingenuity pathway analyses revealed astrocytic, synaptic, and inflammatory pathways as shared and distinct mechanisms across these dementia types.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>Our findings establish plasma pTau217 as a robust diagnostic marker. This study provides new plasma biomarkers for differential diagnosis of dementias with a noninvasive method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Plasma pTau217 showed high diagnostic accuracy for AD, DLB, and FTD.</li>\u0000 \u0000 <li>CXCL1, SNAP25, TREM1, β-synuclein, and TEK are novel markers distinguishing other dementias from AD.</li>\u0000 \u0000 <li>Noninvasive plasma biomarkers enable diagnosis and differentiation of dementias.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551235","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":"Estimating the impact of risk factor reduction on dementia prevalence in New Zealand","authors":"Etuini Ma'u,&nbsp;Naaheed Mukadam,&nbsp;Gill Livingston,&nbsp;Sebastian Walsh,&nbsp;Susanne Röhr,&nbsp;Carol Brayne,&nbsp;Gary Cheung,&nbsp;Sarah Cullum","doi":"10.1002/alz.70440","DOIUrl":"https://doi.org/10.1002/alz.70440","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We aimed to estimate the prevention potential associated with a reduction in risk factor prevalence and the subsequent impact on dementia prevalence projections over time</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We calculated potential impact fraction (PIF) of a 15% and 25% proportional reduction in risk factor prevalence for 12 modifiable dementia risk factors for New Zealand, and individually for the four main ethnic groups, then modeled this over a 30-year period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The PIF for the total NZ population following a 15% risk factor reduction was 14.6% (95% confidence interval: 7.7–21.1) Modeled projections demonstrated prevalence reduction over time, from 1.0% at 10 years to 4.2% at 30 years. PIF and modeled reductions at all time points were higher for Māori and Pacific peoples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The projected impact of interventions targetting risk factor reduction increases over a 30-year time horizon and the benefit is potentially higher in ethnic groups with higher risk factor prevalence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Achievable risk factor reductions have significant prevention potential.</li>\u0000 \u0000 <li>The projected impact of risk factor interventions increase with time.</li>\u0000 \u0000 <li>We need to consider longer time horizons when assessing proposed interventions.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70440","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550840","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":"Enhancing early detection of cognitive impairment in primary care with the TabCAT-BHA","authors":"Andrew G. Breithaupt,&nbsp;Alissa Bernstein Sideman,&nbsp;Collette Goode,&nbsp;Laura Hill-Sakurai,&nbsp;Mukund Premkumar,&nbsp;Aaron W. Scheffler,&nbsp;Anna Chodos,&nbsp;Elena Tsoy,&nbsp;Katherine P. Rankin,&nbsp;Joel H. Kramer,&nbsp;Nhat Bui,&nbsp;Sabrina Jarrott,&nbsp;Leslie Gaynor,&nbsp;Odmara L. Barreto Chang,&nbsp;Christopher Chow,&nbsp;James G. Kahn,&nbsp;Katherine L. Possin","doi":"10.1002/alz.70437","DOIUrl":"https://doi.org/10.1002/alz.70437","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>As dementia cases increase and new therapies become available, timely diagnosis is critical yet challenging in primary care. We evaluated the TabCAT-Brain Health Assessment (TabCAT-BHA) digital paradigm to assist with early detection and diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This implementation study involved 21 primary care providers (PCPs) serving 2733 eligible patients in a family medicine clinic. PCPs initiated cognitive screening using the TabCAT-BHA, administered by medical assistants, with results integrated into the electronic health record. The study assessed changes in PCP cognitive diagnoses, specialist referrals, and implementation metrics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>TabCAT-BHA was adopted by 95% of PCPs, who were more likely to diagnose cognitive disorders (adjusted odds ratio: 1.72, 95% confidence interval: 1.13–2.62, <i>p</i> = 0.01). Practice-wide diagnosis rates remained elevated after research support ended. PCPs reported increased confidence, reduced stress in diagnosing dementia, and preferred TabCAT-BHA over traditional assessments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>TabCAT-BHA was well accepted and sustained, offering a scalable solution for cognitive impairment diagnosis in primary care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>A digital test paradigm increased cognitive impairment diagnoses in primary care.</li>\u0000 \u0000 <li>Increased diagnoses across minority groups may mitigate healthcare disparities.</li>\u0000 \u0000 <li>Clinicians preferred the digital cognitive assessment over alternative tests.</li>\u0000 \u0000 <li>The paradigm decreased clinician stress and increased confidence around diagnosis.</li>\u0000 \u0000 <li>Integration with clinic staff workflow yielded high adoption and sustainability.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551260","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":"Interconnections of insulin/IGF-1 signaling and autophagy abnormalities in Alzheimer's disease","authors":"Wang Liao,&nbsp;Jinfeng Xuan,&nbsp;Woo-In Ryu,&nbsp;Mariana K. Bormann,&nbsp;Yoon Lee,&nbsp;Haley Dion,&nbsp;Elizabeth Evangelista,&nbsp;Ruiyi Li,&nbsp;Lucas Trambaiolli,&nbsp;Jun Liu,&nbsp;Arthur J. Siegel,&nbsp;Brent P. Forester,&nbsp;Bruce M. Cohen,&nbsp;Kai-Christian Sonntag","doi":"10.1002/alz.70099","DOIUrl":"https://doi.org/10.1002/alz.70099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Impaired insulin (INS) and insulin-like growth factor 1 (IGF-1) signaling are features of both brain aging and late-onset Alzheimer's disease (LOAD). However, their exact underlying mechanisms and cause-and-effect linkages, including the downstream regulation of endocytosis and autophagy, are still not well understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We investigated INS/IGF-1 signaling and its connection with endocytic and autophagic processes in fibroblasts from LOAD patients and healthy young or old control individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Compared to control old-age cells, protein levels in the INS/IGF-1 signaling cascade were elevated in LOAD cells, but activation of AKT was reduced. The activation of the INS/IGF-1/AKT/FOXO1 or mTOR axes and associated endo- and autophagic processes were largely intact in old-age but disrupted in LOAD fibroblasts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our results suggest that reduced AKT activation, in the context of altered INS/IGF-1 signaling, and connected alterations of endocytosis and autophagy are features of LOAD pathology but not aging, per se.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Levels of insulin/insulin-like growth factor 1 (INS/IGF-1) factors in late-onset Alzheimer's disease (LOAD) cells are higher than in healthy old controls.</li>\u0000 \u0000 <li>AKT activation by INS/IGF-1 signaling is specifically diminished in LOAD cells.</li>\u0000 \u0000 <li>INS/IGF-1/AKT/forkhead box protein O1/mechanistic target of rapamycin kinase related endocytosis/autophagy are disrupted in LOAD cells.</li>\u0000 \u0000 <li>Intracellular endocytic/autophagic structure distribution is altered in LOAD cells.</li>\u0000 \u0000 <li>INS/IGF-1 reverses endocytic/autophagic processes in LOAD versus old control cells.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551261","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":"Tau burden is best captured by magnitude and extent: Tau-MaX as a measure of global tau","authors":"Christopher A. Brown,&nbsp;Sandhitsu R. Das,&nbsp;Katheryn A. Q. Cousins,&nbsp;Thomas F. Tropea,&nbsp;Alice-Chen Plotkin,&nbsp;John A. Detre,&nbsp;Paul A. Yushkevich,&nbsp;Corey T. McMillan,&nbsp;Edward B. Lee,&nbsp;Leslie M. Shaw,&nbsp;Ilya M. Nasrallah,&nbsp;for the Alzheimer's Disease Neuroimaging Initiative,&nbsp;David A. Wolk","doi":"10.1002/alz.70346","DOIUrl":"https://doi.org/10.1002/alz.70346","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Tau burden consists of both spatial spread and local accumulation, but no study has combined these measures into a single metric to capture overall global tau burden. Here we investigate a new measure combining magnitude and extent—Tau-MaX—as a marker of Alzheimer's disease (AD) severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A total of 1077 ¹⁸F-flortaucipir positron emission tomography scans were analyzed using Gaussian mixture models to identify tau+ regions and quantify magnitude of accumulation. We assessed Tau-MaX across the AD spectrum and compared associations of plasma biomarkers and cognition to global Tau-MaX, extent, and magnitude.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Tau-MaX dynamically captured an early shift in spatial spreading to later tau accumulation across the disease spectrum. Tau-MaX had robust associations with plasma biomarkers and cross-sectional and longitudinal cognition. Global Tau-MaX was equivalent to or superior to magnitude or extent measures alone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Tau-MaX provides a region-agnostic measure of global tau burden that can be used to track disease progression across the AD continuum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We measured tau extent, magnitude, and a new combination of these metrics, Tau-MaX.</li>\u0000 \u0000 <li>Extent increases early in disease, while magnitude increases in later disease stages.</li>\u0000 \u0000 <li>Tau-MaX captures this shift and is closely associated with phosphorylated tau217 and cognition.</li>\u0000 \u0000 <li>Global Tau-MaX performed similarly to or better than meta-region of interest tau magnitude or extent.</li>\u0000 \u0000 <li>Tau-MaX provides a region-agnostic measure of tau burden to track progression.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551236","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 novel approach to resilience and its links with education and Alzheimer's disease genetics","authors":"Maria Carrigan,&nbsp;Diana I. Bocancea,&nbsp;Jacob Vogel,&nbsp;Anna C. van Loenhoud,&nbsp;Niccoló Tesi,&nbsp;Frederik Barkhof,&nbsp;Paul J. Lucassen,&nbsp;Wiesje M. van der Flier,&nbsp;Harm J. Krugers,&nbsp;Sven J. Van der Lee,&nbsp;Rik Ossenkoppele","doi":"10.1002/alz.70379","DOIUrl":"https://doi.org/10.1002/alz.70379","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Cognitive resilience refers to maintaining cognitive function despite Alzheimer's disease (AD) pathophysiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We analyzed amyloid-positive individuals across clinical stages of AD in two cohorts: the Amsterdam Dementia Cohort (ADC, <i>N</i> = 1036) and Alzheimer's Disease Neuroimaging Initiative (ADNI, <i>N</i> = 685). Cognitive resilience was conceptualized from a canonical correlation analysis of magnetic resonance imaging and neuropsychological data in each cohort separately. Model validation involved education as a resilience proxy and key genetic factors (apolipoprotein E [<i>APOE</i>] ε4 and <i>APOE</i> ε2) of AD. We explored associations between 83 AD risk loci and cognitive resilience.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Resilience was correlated with education (ADC: β = 0.144, <i>p</i> &lt; 0.001; ADNI: β = 0.149, <i>p</i> &lt; 0.001) and <i>APOE</i> ε4 (β_{meta-analysis}= –0.052, <i>p</i> = 0.014). Exploratory single nucleotide polymorphism meta-analysis identified potential involvement of genetic variants around genes <i>UNC5CL</i>, <i>USP6NL</i>, and <i>TPCN1</i> in lower, and genes <i>COX7C</i> and <i>MINDY2</i> in higher resilience.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our novel resilience approach showed conceptual validity and potential for future discovery of resilience-related genetic variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li><span>· </span>We define a novel approach to resilience using canonical correlation analysis (CCA).</li>\u0000 \u0000 <li><span>· </span>Apolipoprotein E ε4 is linked to lower resilience, suggesting increased vulnerability.</li>\u0000 \u0000 <li><span>· </span>Genetic loci around <i>COX7C</i> and <i>MINDY2</i> are potentially involved in higher resilience.</li>\u0000 \u0000 <li><span>· </span>This novel approach may be used for multi-cohort studies such as genome-wide association studies in the future.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70379","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551237","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":"Evaluation of plasma p-tau217 for detecting amyloid pathology in a heterogeneous community-based cohort","authors":"Marc D. Rudolph,&nbsp;Courtney L. Sutphen,&nbsp;Thomas C. Register,&nbsp;Samuel N. Lockhart,&nbsp;Melissa M. Rundle,&nbsp;Timothy M. Hughes,&nbsp;James R. Bateman,&nbsp;Kiran K. Solingapuram Sai,&nbsp;Christopher T. Whitlow,&nbsp;Suzanne Craft,&nbsp;Michelle M. Mielke","doi":"10.1002/alz.70426","DOIUrl":"https://doi.org/10.1002/alz.70426","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Studies suggest excellent performance of plasma phosphorylated tau 217 (p-tau217) for detecting amyloid pathology, though studies in more representative populations are needed to validate previously determined cutpoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Plasma p-tau217 utility for detecting amyloid pathology (Aβ) via amyloid positron emission tomography (PET) was assessed in a heterogeneous, community-based cohort in the Wake Forest Alzheimer's Disease Research Center (WFADRC). Participants with baseline plasma data (<i>n </i>= 598) were 21% Black; 313 cognitive unimpaired (CU), 214 mild cognitive impairment (MCI), and 64 dementia (DEM); 49% prediabetic, 44% hypertensive, 29% overweight/obese; and 64% had mild-to-moderate kidney disease. Gaussian-mixture models, logistic regression, and receiver operating curve analyses were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Plasma p-tau217 was associated with elevated Aβ deposition and accurately classified Aβ-positive participants (PET [<i>n </i>= 307]: area under the curve [AUC] = 94%–97%, cutpoint ≥ 0.338 pg/mL).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Plasma p-tau217 is an accurate indicator of amyloid pathology in a heterogeneous cohort and is superior to other plasma biomarkers assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The Wake Forest Alzheimer's Disease Research Center (WFADRC) is a heterogeneous cohort.</li>\u0000 \u0000 <li>p-tau217 levels were lower, on average, in cognitively unimpaired participants, females, and Black participants.</li>\u0000 \u0000 <li>Plasma p-tau217 classified amyloid positron emission tomography (PET)-positive individuals with high precision and performed better than p-tau181.</li>\u0000 \u0000 <li>Cutpoints and reference ranges of plasma p-tau217 were lower compared to recently published thresholds.</li>\u0000 \u0000 <li>Combining cutpoint approaches, a four-tier system captured cohort heterogeneity.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70426","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551238","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}