Alzheimer's & Dementia最新文献

{"title":"Association of genetic risk score for Alzheimer's disease with late-life body mass index in all of us: Evaluating reverse causation","authors":"Minhyuk Choi,&nbsp;Scott C. Zimmerman,&nbsp;Peter T. Buto,&nbsp;Jingxuan Wang,&nbsp;Willa D. Brenowitz,&nbsp;Thomas J. Hoffmann,&nbsp;Adina Zeki Al Hazzouri,&nbsp;Katrina Kezios,&nbsp;M. Maria Glymour","doi":"10.1002/alz.14598","DOIUrl":"https://doi.org/10.1002/alz.14598","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Decreases in body mass index (BMI) may be early consequences of Alzheimer's disease (AD) pathophysiological changes. Previous research in the UK Biobank estimated that AD-related genes began affecting BMI around age 47. We assessed whether this result could be replicated using longitudinal data in an independent cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using All of Us (AOU) (<i>N</i> = 197,619, aged 30+) data, we estimated linear mixed models for associations of <i>Z</i>-scored AD-Genetic Risk Score (AD-GRS) with BMI, stratified by decade of age. We calculated the earliest age at which AD-GRS was associated with differences in BMI using cross-validated models adjusted for demographics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Higher AD-GRS was statistically associated with lower BMI in participants aged 60–70 (<i>b</i> = −0.060 [−0.113, −0.007]). Best fitting models suggested the inverse association of AD-GRS and BMI emerged beginning at ages 47–54.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>AD genes accelerate age-related weight loss starting in middle age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Understanding when physiological changes from amyloid pathology begin is key for AD prevention.</li>\u0000 \u0000 <li>Our findings indicate that AD-associated genes accelerate midlife weight loss, starting between 47 and 54 years.</li>\u0000 \u0000 <li>AD prevention research should consider that disease pathology likely begins by middle age.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14598","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787034","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":"Platelets mirror changes in the frontal lobe antioxidant system in Alzheimer's disease","authors":"Huriye Ercan,&nbsp;Christina Maria Reumiller,&nbsp;Jacqueline Mühlberger,&nbsp;Felicia Hsu,&nbsp;Georg Johannes Schmidt,&nbsp;Ellen Umlauf,&nbsp;Ingrid Miller,&nbsp;Eduard Rappold,&nbsp;Johannes Attems,&nbsp;Rudolf Oehler,&nbsp;Maria Zellner","doi":"10.1002/alz.70117","DOIUrl":"https://doi.org/10.1002/alz.70117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Blood biomarkers reflecting Alzheimer's disease (AD) pathophysiology can improve diagnosis and treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We applied top-down proteomics to compare frontal lobe from 17 AD cases and 11 controls to blood platelets from a second independent study group of 124 AD patients, 61 with mild cognitive impairment (MCI), and 168 controls. Findings were immunologically validated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Sixty AD-associated proteoforms were identified in frontal lobe, with 26 identically represented in platelets. Validation in platelet samples confirmed elevated glutathione S-transferase omega 1 (GSTO1) levels linked to single nucleotide polymorphism (SNP) rs4925 and increased superoxide dismutase 1 (SOD1) levels in AD. Bioinformatics revealed copper chaperone for superoxide dismutase (CCS) and glutathione peroxidase 1 (GPX1) as integral partners of these antioxidant enzymes. Both were detected to be reduced in frontal lobes and platelets in AD. SOD1 and CCS are already changed in MCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These four novel blood biomarkers, integrated with traditional AD biomarkers, may facilitate patient risk assessment and treatment, with SOD1 and CCS alterations in MCI offering early diagnostic potential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Platelets mirror several Alzheimer's disease (AD)–dependent neuronal changes, valuable for blood tests.</li>\u0000 \u0000 <li>As a start, 60 AD-associated frontal lobe proteins were identified by top-down proteomics.</li>\u0000 \u0000 <li>Fifty percent of these 60 AD-affected brain proteins are represented identically in platelets.</li>\u0000 \u0000 <li>Among these, glutathione S-transferase omega 1 (GSTO1), superoxide dismutase 1 (SOD1), copper chaperone for superoxide dismutase (CCS), and glutathione peroxidase 1 (GPX1) are identically AD related in brain and platelets.</li>\u0000 \u0000 <li>SOD1 and its crucial activating partner CCS are altered in the platelets of patients with mild cognitive impairment.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786774","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 striatum is an early, accurate indicator of amyloid burden using [11C]PiB in Down syndrome: Comparison of two radiotracers","authors":"Max McLachlan,&nbsp;Brecca Bettcher,&nbsp;Andrew McVea,&nbsp;Alexandra DiFilippo,&nbsp;Matthew Zammit,&nbsp;Lisette LeMerise,&nbsp;Jeremy Rouanet,&nbsp;Julie Price,&nbsp;Dana Tudorascu,&nbsp;Charles Laymon,&nbsp;David Keator,&nbsp;Patrick Lao,&nbsp;Adam M. Brickman,&nbsp;Tim Fryer,&nbsp;Sigan Hartley,&nbsp;Beau M. Ances,&nbsp;H. Diana Rosas,&nbsp;Sterling Johnson,&nbsp;Tobey Betthauser,&nbsp;Charles K. Stone,&nbsp;Shahid Zaman,&nbsp;Benjamin Handen,&nbsp;Elizabeth Head,&nbsp;Mark Mapstone,&nbsp;Bradley T. Christian,&nbsp;ABC-DS Investigators","doi":"10.1002/alz.70141","DOIUrl":"https://doi.org/10.1002/alz.70141","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Adults with Down syndrome demonstrate striatum-first amyloid accumulation with [¹¹C]Pittsburgh Compound-B (PiB) positron emission tomography (PET) imaging, which has not been replicated with [¹⁸F]florbetapir (FBP). Early striatal accumulation has not been temporally quantified with respect to global cortical measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Longitudinal PiB (<i>n</i> = 175 participants) and FBP (<i>n</i> = 92 participants) data from the Alzheimer Biomarkers Consortium-Down Syndrome (ABC-DS) were used to measure cortical and striatal binding. Generalized temporal models for cortical and striatal amyloid accumulation were created using the sampled iterative local approximation (SILA) method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>PiB demonstrated greater striatal-to-cortical ratios than FBP. SILA analysis revealed striatal amyloid burden occurs 3.40 (2.39) years earlier than the cortex in PiB. There was no difference between the cortex and striatum in FBP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Among adults with Down syndrome, the striatum consistently accumulates amyloid earlier than the cortex when measured with PiB. This suggests the striatum is more sensitive to the onset of PiB PET-detectable amyloid in Down syndrome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Striatal amyloid is detectable 3.4 years before the cortex using PiB PET in DS.</li>\u0000 \u0000 <li>Florbetapir PET does not detect early striatal amyloid accumulation in DS.</li>\u0000 \u0000 <li>White matter can be used as reference region in longitudinal florbetapir PET.</li>\u0000 \u0000 <li>SILA trajectory models can be used to compare regional estimates for age of onset.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787304","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":"Deciding on genetic testing for familial dementia: Perspectives of patients and families","authors":"Jetske van der Schaar,&nbsp;Sven J. van der Lee,&nbsp;Eva C. A. Asscher,&nbsp;Yolande A. L. Pijnenburg,&nbsp;Christa M. de Geus,&nbsp;Annelien L. Bredenoord,&nbsp;Wiesje M. van der Flier,&nbsp;Mariette A. van den Hoven,&nbsp;Ellen M. A. Smets,&nbsp;Leonie N. C. Visser","doi":"10.1002/alz.70140","DOIUrl":"https://doi.org/10.1002/alz.70140","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We explored patients’ and families’ interest in, predictors of, and considerations regarding genetic testing for monogenic causes of dementia in a diagnostic setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This mixed-methods study evaluated 519 consecutive Alzheimer Center Amsterdam patients for monogenic testing eligibility. Among those qualifying, differences between testers and non-testers were analyzed. Thirty-three patients completed questionnaires. Additionally, we conducted 21 semi-structured interviews with 15 patients and 18 relatives. Verbatim transcripts were analyzed inductively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Of 138 (27%) eligible patients (46% female, age 61 ± 8 years, Mini-Mental State Examination [MMSE] 22 ± 6), 75 (54%) underwent genetic testing. Testers had better cognition, higher quality of life, and more often undetermined diagnoses than non-testers (all <i>p </i>&lt; 0.05). Decisions were guided by intuitive, value-driven judgments: testers sought to provide heredity information to relatives, enhance actionability, and reduce uncertainty, while non-testers worried about psychosocial impact on family, or unfavorable timing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The substantial interest in genetic testing for monogenic causes of dementia underscores the need for further research into the implications of disclosing test results to memory clinic patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Half of memory clinic patients’ who met eligibility criteria proceeded with genetic testing.</li>\u0000 \u0000 <li>Those tested were more likely to have an undetermined diagnosis, better cognition, and higher quality of life.</li>\u0000 \u0000 <li>Decisions were motivated less by deliberation of factual information, and more by quick, intuitive judgments.</li>\u0000 \u0000 <li>Motivations pro included providing information, enhancing actionability, and resolving uncertainty.</li>\u0000 \u0000 <li>Motivations con comprised concerns about the emotional burden and disruptive impact on their family.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787030","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":"Quantification of perforant path fibers for early detection of Alzheimer's disease","authors":"Yuto Uchida,&nbsp;Zhipeng Hou,&nbsp;Laura Gomez-Isaza,&nbsp;Maria Luongo,&nbsp;Juan C. Troncoso,&nbsp;Michael I. Miller,&nbsp;Susumu Mori,&nbsp;Kenichi Oishi","doi":"10.1002/alz.70142","DOIUrl":"https://doi.org/10.1002/alz.70142","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The entorhinal cortex (ERC) and perforant path (PP) fibers are critical structures in the pathology of Alzheimer's disease (AD). This study aims to explore these regions using high-field magnetic resonance imaging (MRI), with the goal of identifying reliable biomarkers based on histopathological observations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Twenty <i>post mortem</i> brain specimens were scanned with 11.7T MRI, including diffusion tensor imaging and tractography, and were cut for subsequent histological examinations. The entorhinal cortical thickness and number of PP fibers derived from MRI were compared across neuropathological and <i>premortem</i> clinical diagnoses of AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The entorhinal cortical thickness and number of PP fibers decreased along with severities of neurofibrillary tangles in the ERC. Meanwhile, a reduction in the number of PP fibers, but not the entorhinal cortical thickness, was observed during the preclinical stage of AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSIONS</h3>\u0000 \u0000 <p>Degeneration of PP fibers was observed in early AD and progressed along with neuropathological changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>\u0000 <p>Twenty <i>post mortem</i> brain tissues were scanned with 11.7T MRI.</p>\u0000 </li>\u0000 \u0000 <li>\u0000 <p>Degeneration of PP fibers was observed at 250 µm isotropic resolution.</p>\u0000 </li>\u0000 \u0000 <li>\u0000 <p>PP fiber indices were linked with severities of NFTs.</p>\u0000 </li>\u0000 \u0000 <li>\u0000 <p>The number of PP fibers was decreased in preclinical AD.</p>\u0000 </li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787305","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":"Limited generalizability and high risk of bias in multivariable models predicting conversion risk from mild cognitive impairment to dementia: A systematic review","authors":"Robin Jeanna Vermeulen,&nbsp;Vebjørn Andersson,&nbsp;Jimmy Banken,&nbsp;Gerjon Hannink,&nbsp;Tim Martin Govers,&nbsp;Maroeska Mariet Rovers,&nbsp;Marcel Gerardus Maria Olde Rikkert","doi":"10.1002/alz.70069","DOIUrl":"https://doi.org/10.1002/alz.70069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Prediction models have been developed to identify mild cognitive impairment (MCI) cases likely to convert to dementia. This systematic review summarizes multi-source prediction models for MCI to dementia conversion. PubMed and Embase were searched for model development and validation studies from inception up to January 18 2024. Models were assessed for included predictors, predictive performance, risk of bias, and generalizability. 62 studies were included: 41 machine learning models, 11 regression models, and 5 disease state indexes. The number of predictors in the models ranged from 2 to 60; magnetic resonance imaging (MRI) and cognitive scores were the most common sources. Performance measures indicate reasonable predictive capabilities (area under the curve [AUC] range: 0.58–0.98, accuracy range: 66.1–96.3%); however, most studies are at high risk of bias and 47 studies lack external validation. Currently, no highly valid prediction model is available for MCI to dementia conversion risk due to limited generalizability and high risk of bias in most studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Numerous models have been developed to predict the likelihood of conversion to dementia in individuals with MCI.</li>\u0000 \u0000 <li>Prediction models seem to have a reasonably good performance in predicting conversion to dementia, however, external validation and generalizability is often lacking.</li>\u0000 \u0000 <li>There is no prediction model available with a low risk for bias and that has been externally validated to accurately predict the risk of MCI to dementia conversion.</li>\u0000 \u0000 <li>For MCI to dementia conversion prediction models, more emphasis should be directed towards external validation, generalizability, and clinical applicability.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786768","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":"Exposure to neighborhood concentrated poverty is associated with faster decline in episodic memory among midlife women","authors":"Jinshil Hyun,&nbsp;Mary Schiff,&nbsp;Charles B. Hall,&nbsp;Bradley M. Appelhans,&nbsp;Emma Barinas-Mitchell,&nbsp;Rebecca C. Thurston,&nbsp;Carrie A. Karvonen-Gutierrez,&nbsp;Monique M. Hedderson,&nbsp;Imke Janssen,&nbsp;Carol A. Derby","doi":"10.1002/alz.70139","DOIUrl":"https://doi.org/10.1002/alz.70139","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Neighborhood-level socioeconomic status (nSES) is associated with risk for cognitive impairment, but prior studies assessed nSES within an individual's own residential area without considering the distribution of nSES among adjacent areas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using up to 14 years of data from the Study of Women's Health Across the Nation (<i>N</i> = 1391, mean age = 54), we examined whether geographic clustering of concentrated neighborhood poverty was associated with cognitive decline over midlife.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Greater neighborhood concentrated poverty was associated with faster decline in episodic memory but not in processing speed or working memory. Living in high concentrated poverty areas was linked to a 7% episodic memory decline per decade (both immediate and delayed recall), with Black women experiencing the steepest decline at 10% per decade (delayed recall).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Women living in concentrated poverty areas exhibited accelerated decline in episodic memory during midlife. Neighborhood concentrated poverty may impact risk for future cognitive impairment and ADRD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Living in concentrated poverty areas predicted a more rapid episodic memory decline.</li>\u0000 \u0000 <li>This pattern was most pronounced among Black women.</li>\u0000 \u0000 <li>The cohort was a racially/ethnically diverse cohort of midlife women across the US.</li>\u0000 \u0000 <li>Neighborhood concentrated poverty may contribute to the risk of ADRD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787303","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":"Trends in the use of advance care planning and cognitive assessment and care planning service visits: moving toward a palliative-informed approach for ambulatory care of community-dwelling persons with dementia and their caregivers","authors":"Jennifer B. Seaman,&nbsp;Yurun Cai,&nbsp;Dianxu Ren","doi":"10.1002/alz.70074","DOIUrl":"https://doi.org/10.1002/alz.70074","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Both the advance care planning (ACP) visit and cognitive assessment and care planning service (CAACPS) visit offer palliative-oriented care for persons with Alzheimer's disease and related dementias (ADRD); however, the rate of ACP visits remains low, and little has been reported regarding CAACPS visits. Furthermore, few reports describe use of either visit among Medicare Advantage (MA) beneficiaries. This study describes provision of ACP and CAACPS visits to community-dwelling older adult MA beneficiaries with ADRD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using deidentified Optum Clinformatics Data Mart claims data, we evaluated ambulatory care visits for community-dwelling older adult MA beneficiaries with ADRD for the years 2018 to 2019.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>For 2018 and 2019, 3.5% and 5.4% received ACP visits, and 0.4% and 0.5% received CAACPS visits, similar to use reported elsewhere.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Few MA beneficiaries with ADRD received ACP or CAACPS visits, and the delivery of CAACPs visits is similar to that reported for non-MA beneficiaries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Most persons with dementia are community-dwelling and disproportionately disadvantaged.</li>\u0000 \u0000 <li>Access to palliative care is limited for community-dwelling persons with dementia.</li>\u0000 \u0000 <li>CAACPS visits may address this gap.</li>\u0000 \u0000 <li>Our findings show the use of CAACPS visits is very low.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White matter hyperintensity spatial patterns: Risk factors and clinical correlates","authors":"Frauke Beyer,&nbsp;Ami Tsuchida,&nbsp;Aicha Soumaré,&nbsp;Hema Sekhar Reddy Rajula,&nbsp;Aniket Mishra,&nbsp;Fabrice Crivello,&nbsp;Cécile Proust-Lima,&nbsp;Markus Loeffler,&nbsp;Christophe Tzourio,&nbsp;Philippe Amouyel,&nbsp;Arno Villringer,&nbsp;Markus Scholz,&nbsp;Hélène Jacqmin-Gadda,&nbsp;Marc Joliot,&nbsp;A. Veronica Witte,&nbsp;Carole Dufouil,&nbsp;Stéphanie Debette","doi":"10.1002/alz.70053","DOIUrl":"https://doi.org/10.1002/alz.70053","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>White matter hyperintensities (WMHs), a major cerebral small vessel disease (cSVD) marker, may arise from different pathologies depending on their location. We explored clinical and genetic correlates of agnostically derived spatial WMH patterns in two longitudinal population-based cohorts (Three-City Study [3C]-Dijon, LIFE-Adult).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We derived seven WMH spatial patterns using Bullseye segmentation in 2878 individuals aged 65+ and explored their associations with vascular and genetic risk factors, cognitive performance, dementia and stroke incidence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>WMHs in the frontoparietal and anterior periventricular region were associated with blood pressure traits, WMH genetic risk score (GRS), baseline and decline in general cognitive performance, incident all-cause dementia, and ischemic stroke. Juxtacortical-deep occipital WMHs were not associated with vascular risk factors and WMH GRS, but with incident all-cause dementia and intracerebral hemorrhage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Accounting for WMH spatial distribution is key to deciphering mechanisms underlying cSVD subtypes, an essential step towards personalized therapeutic approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We studied spatial patterns of WMHs in 2878 participants.</li>\u0000 \u0000 <li>Blood pressure was associated with frontoparietal and anterior PV WMHs.</li>\u0000 \u0000 <li>Anterior PV WMHs predicted dementia and stroke risk.</li>\u0000 \u0000 <li>Juxtacortical-deep occipital WMH burden was not associated with blood pressure or WMH genetic risk.</li>\u0000 \u0000 <li>Juxtacortical-deep occipital WMH burden predicted dementia and intracerebral hemorrhage.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786767","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":"Tauopathy after long-term cervical lymphadenectomy","authors":"Chenrui Wu,&nbsp;Jiangyuan Yuan,&nbsp;Yu Tian,&nbsp;Youlin Wang,&nbsp;Xianghui He,&nbsp;Ke Zhao,&nbsp;Jinhao Huang,&nbsp;Rongcai Jiang","doi":"10.1002/alz.70136","DOIUrl":"https://doi.org/10.1002/alz.70136","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study examined the effects of long-term cervical lymphadenectomy (cLE) on cognitive and Alzheimer's disease (AD)–like tauopathy changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Male C57BL/6 mice were used to assess cLE impacts on sleep, brain pathways, and pathologies. RNA sequencing and proteomics analyzed gene/protein changes, with results verified by western blotting and immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>CLE led to sleep and psychiatric disorders, linked to mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) pathway activation. Activation of ERK may interfere with autophagy and is associated with phosphorylated tau accumulation. Peripheral blood analysis shows decreased brain waste in the peripheral blood post-cLE, implicating impaired lymphatic drainage and brain waste build-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings suggest a potential connection between cLE and AD-like tauopathy, potentially influencing surgical decisions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Cervical lymphadenectomy (cLE) is the cornerstone of head and neck cancers, affecting millions of people each year. We provide the first evidence of mildly impaired cognitive functioning with significant anxiety–depressive disorders in mice after long-term cLE.</li>\u0000 \u0000 <li>Long-term cLE not only directly impairs brain wastes (amyloid beta, phosphorylated tau [p-tau]) drainage, but also activates the Erk1/2 signaling pathway leading to attenuation of autophagy.</li>\u0000 \u0000 <li>We found for the first time that long-term cLE accelerated the deposition of p-tau in young mice.</li>\u0000 \u0000 <li>Patients after clinical cervical lymph node dissection showed reduced brain waste in peripheral blood consistent with mouse models. This study suggests the need for further evaluation of the neurologic effects of cervical lymph node dissection, a procedure that affects millions of people each year.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787027","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}