Alzheimer's & Dementia最新文献

{"title":"Cross-cultural validation of plasma p-tau217 and p-tau181 as precision biomarkers for amyloid PET positivity: An East Asian study in Taiwan and Korea","authors":"Yung-Shuan Lin,&nbsp;Hyuk Sung Kwon,&nbsp;Wei-Ju Lee,&nbsp;Mina Hwang,&nbsp;Jee Hyang Jeong,&nbsp;Seong-Ho Koh,&nbsp;Seong Hye Choi,&nbsp;Jong-Ling Fuh","doi":"10.1002/alz.14565","DOIUrl":"10.1002/alz.14565","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Plasma phosphorylated tau (p-tau) biomarkers have improved Alzheimer's disease (AD) diagnosis, but data from diverse Asian populations are limited. This study evaluated plasma p-tau217 and p-tau181 levels in Korean and Taiwanese populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>All participants (<i>n</i> = 270) underwent amyloid positron emission tomography (PET) and blood tests. Plasma p-tau model-derived probabilities of amyloid PET positivity (amyloid beta [Aβ]+) classified participants into low-, intermediate-, or high-risk groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In both cohorts, plasma p-tau217 outperformed p-tau181, especially in cognitively unimpaired participants (area under the curve = 0.921 [p-tau217] vs. 0.769 [p-tau181], <i>P</i>_difference= 0.022). Including apolipoprotein E status and glial fibrillary acidic protein improved model fit. The negative predictive value of the low-risk group and positive predictive value of the high-risk group were 97.5% and 86.0%, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Plasma p-tau217 and p-tau181 effectively predict Aβ+ among culturally different Asian populations. P-tau217 performed better, especially in the early stages of AD. Plasma p-tau217–based models reduced intermediate-risk classifications, suggesting fewer amyloid PET scans needed to confirm the diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The efficacy of plasma phosphorylated tau (p-tau)217 and p-tau181 was analyzed in two Asian populations.</li>\u0000 \u0000 <li>Plasma p-tau217 performs better in predicting amyloid positron emission tomography positivity, especially in cognitively unimpaired subjects.</li>\u0000 \u0000 <li>Adding apolipoprotein E and glial fibrillary acidic protein to p-tau improved model accuracy.</li>\u0000 \u0000 <li>The models from each cohort were confirmed in the other cohort.</li>\u0000 \u0000 <li>Plasma p-tau–based risk stratification may reduce the need for confirmatory tests.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14565","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055316","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 higher benefit of lecanemab in males compared to females in CLARITY AD is probably due to a real sex effect","authors":"Daniel Andrews,&nbsp;Simon Ducharme,&nbsp;Howard Chertkow,&nbsp;Maria Pia Sormani,&nbsp;D. Louis Collins,&nbsp;for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/alz.14467","DOIUrl":"10.1002/alz.14467","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The phase 3 trial CLARITY AD found lecanemab slowed cognitive decline by 27%. However, subgroup analyses indicated a significant 31% sex difference in the effect and suggested no or limited effectiveness in females. We used simulations constrained by the trial design to determine whether that difference reflects a pre-existing sex difference in Alzheimer's disease progression or was a random event.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Simulations were generated using linear mixed models of cognitive decline fit to data from Alzheimer's Disease Neuroimaging Initiative participants satisfying CLARITY AD inclusion criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The statistically non-significant 7.9% smaller cognitive decline rate in our cohort's males versus females does not explain CLARITY AD's 31% sex difference in lecanemab's effect. A ≥ 31% difference occurred randomly in only 12 of our 10,000 simulations (0.0012 probability).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>CLARITY AD's sex difference was probably not random. Lecanemab is likely less effective in females than males, but we cannot conclude the drug is ineffective in females.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Lecanemab is more clinically effective in males than in females.</li>\u0000 \u0000 <li>Forest plots should only report subgroup-specific effects in well-powered subgroups.</li>\u0000 \u0000 <li>Trial simulations based on real data enable investigation of subgroup drug effects.</li>\u0000 \u0000 <li>We cannot conclude that lecanemab is clinically ineffective in females.</li>\u0000 \u0000 <li>A sex difference in lecanemab's efficacy could be linked to its action mechanism.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056494","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":"Regional brain iron correlates with transcriptional and cellular signatures in Alzheimer's disease","authors":"Aocai Yang,&nbsp;Jixin Luan,&nbsp;Manxi Xu,&nbsp;Lei Du,&nbsp;Kuan Lv,&nbsp;Pianpian Hu,&nbsp;Ni Shu,&nbsp;Zhen Yuan,&nbsp;Amir Shmuel,&nbsp;Guolin Ma","doi":"10.1002/alz.14459","DOIUrl":"10.1002/alz.14459","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The link between overload brain iron and transcriptional/cellular signatures in Alzheimer's disease (AD) remains inconclusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Iron deposition in 41 cortical and subcortical regions of 30 AD patients and 26 healthy controls (HCs) was measured using quantitative susceptibility mapping (QSM). The expression of 15,633 genes was estimated in the same regions using transcriptomic data from the Allen Human Brain Atlas (AHBA). Partial least square (PLS) regression was used to identify the association between the healthy brain gene transcription and aberrant regional QSM signal in AD. The biological processes and cell types associated with the linked genes were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Gene ontological analyses showed that the first PLS component (PLS1) genes were enriched for biological processes relating to the “protein phosphorylation” and “metal ion transport”. Additionally, these genes were expressed in microglia (MG) and glutamatergic neurons (GLUs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our findings provide mechanistic insights from transcriptional and cellular signatures into regional iron accumulation measured by QSM in AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Spatial patterns of iron deposition changes in AD correlate with cortical spatial expression genes in healthy subjects.</li>\u0000 \u0000 <li>The identified gene transcription profile underlies aberrant iron accumulation in AD was enriched for biological processes relating to “protein phosphorylation” and “metal ion transport”.</li>\u0000 \u0000 <li>The related genes were predominantly expressed in MG and GLUs.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055308","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":"Iron-associated lipid peroxidation in Alzheimer's disease is increased in lipid rafts with decreased ferroptosis suppressors, tested by chelation in mice","authors":"Max A. Thorwald,&nbsp;Jose A. Godoy-Lugo,&nbsp;Gilberto Garcia,&nbsp;Justine Silva,&nbsp;Minhoo Kim,&nbsp;Amy Christensen,&nbsp;Wendy J. Mack,&nbsp;Elizabeth Head,&nbsp;Peggy A. O'Day,&nbsp;Bérénice A. Benayoun,&nbsp;Todd E. Morgan,&nbsp;Christian J. Pike,&nbsp;Ryo Higuchi-Sanabria,&nbsp;Henry Jay Forman,&nbsp;Caleb E. Finch","doi":"10.1002/alz.14541","DOIUrl":"10.1002/alz.14541","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Iron-mediated cell death (ferroptosis) is a proposed mechanism of Alzheimer's disease (AD) pathology. While iron is essential for basic biological functions, its reactivity generates oxidants which contribute to cell damage and death.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>To further resolve mechanisms of iron-mediated toxicity in AD, we analyzed <i>post mortem</i> human brain and ApoEFAD mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>AD brains had decreased antioxidant enzymes, including those mediated by glutathione (GSH). Subcellular analyses of AD brains showed greater oxidative damage and lower antioxidant enzymes in lipid rafts, the site of amyloid processing, than in the non-raft membrane fraction. Apolipoprotein E ε4 carriers had lower lipid raft yield with greater membrane oxidation. The hypothesized role of iron in AD pathology was tested in ApoEFAD mice by iron chelation with deferoxamine, which decreased fibrillar amyloid and lipid peroxidation, together with increased GSH-mediated antioxidants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These novel molecular pathways highlight iron-mediated damage to lipid rafts during AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlghts</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Alzheimer's disease (AD) brains have numerous markers for ferroptosis, including increased lipid peroxidation, reduced antioxidant levels, and increased iron storage.</li>\u0000 \u0000 <li>Lipid rafts in AD cases have increased oxidative damage and reduced antioxidant enzyme levels and activity which are most severe in apolipoprotein E ε4 carriers.</li>\u0000 \u0000 <li>Neuronal markers are correlated with lipid peroxidation, antioxidant defense, and iron signaling proteins suggesting that neuronal loss is linked to these events.</li>\u0000 \u0000 <li>Chelation of iron in the early-onset familial AD model reduces iron-mediated lipid peroxidation and fibrillar amyloid.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055309","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":"Sleep spindles and slow oscillations predict cognition and biomarkers of neurodegeneration in mild to moderate Alzheimer's disease","authors":"Arsenio Páez,&nbsp;Sam O. Gillman,&nbsp;Shahla Bakian Dogaheh,&nbsp;Anna Carnes,&nbsp;Faride Dakterzada,&nbsp;Ferran Barbé,&nbsp;Thien Thanh Dang-Vu,&nbsp;Gerard Piñol Ripoll","doi":"10.1002/alz.14424","DOIUrl":"10.1002/alz.14424","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Changes in sleep physiology can predate cognitive symptoms by decades in persons with Alzheimer's disease (AD), but it remains unclear which sleep characteristics predict cognitive and neurodegenerative changes after AD onset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using data from a prospective cohort of mild to moderate AD (<i>n</i> = 60), we analyzed non-rapid eye movement sleep spindles and slow oscillations (SOs) at baseline and their associations with baseline amyloid beta (Aβ) and tau and with cognition from baseline to 3-year follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Higher spindle and SO activity predicted significant changes in Aβ and tau at baseline, lower Alzheimer's Disease Assessment Scale Cognitive Subscale (better cognitive performance) score, and higher Mini-Mental State Examination score from baseline to 36 months. Spindles and SOs mediated the effect of phosphorylated tau 181 (pTau181)/Aβ42 on cognition, while pTau181/aβ42 moderated the effect of spindles and SOs on cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our findings demonstrate that spindle and SO activity during sleep constitute predictive and non-invasive biomarkers of neurodegeneration and cognition in AD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Sleep spindles predict long-term cognitive performance in AD.</li>\u0000 \u0000 <li>Sleep spindle and SOs can be predictive, non-invasive biomarkers for AD.</li>\u0000 \u0000 <li>Sleep may be one of the most important modifiable risk factors for AD progression.</li>\u0000 \u0000 <li>Sleep microarchitecture is a novel therapeutic target for preserving brain heath.</li>\u0000 \u0000 <li>Sleep physiology can provide novel therapeutic targets to slow AD progression.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14424","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055149","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":"AAIC® Satellite Symposium slated for May 14 to 15 in Lima, Peru","authors":"","doi":"10.1002/alz.14569","DOIUrl":"10.1002/alz.14569","url":null,"abstract":"&lt;p&gt;Hosted in collaboration with the Global Brain Health Institute (GBHI) and the Atlantic Fellows for Equity in Brain Health, the annual Alzheimer's Association International Conference&lt;sup&gt;®&lt;/sup&gt; (AAIC&lt;sup&gt;®&lt;/sup&gt;) Satellite Symposium will take place May 14 to 15 in Lima, Peru, and online.&lt;/p&gt;&lt;p&gt;The AAIC Satellite Symposium convenes local and international leaders to discuss brain health and dementia risk; developments in clinical research; the role of psychosocial, care, and non-pharmacological interventions in Alzheimer's and other dementias; epidemiology; advances in biomarkers; emerging areas of investigation; and more in a particular region of the world. Previous symposia brought key elements of AAIC to Mexico, Argentina, Bulgaria, India, Brazil, South Africa, and Australia.&lt;/p&gt;&lt;p&gt;There is widespread recognition that the unique cultural, demographic, and economic characteristics of individual countries demand country- and culture-specific plans to address the burden of the disease and gaps in research. By more broadly sharing locally conducted research and statistics at events such as the AAIC Satellite Symposium, the international research community can better collaborate and find commonalities.&lt;/p&gt;&lt;p&gt;Also promoting understanding will be the numerous abstracts to be featured at the symposium. Abstract themes will include basic science and pathogenesis, biomarkers, clinical manifestations, public health, drug development, and dementia care. Abstracts will be considered for posters or lightning talks. As part of the abstract submission process, presenting authors may apply for a conference fellowship. Full (registration, airfare, and housing) and partial packages will be awarded based on application materials and financial need.&lt;/p&gt;&lt;p&gt;Satellite Symposium details, including the program and how to register, will be available soon at alz.org.&lt;/p&gt;&lt;p&gt;The Alzheimer's Association is committed to supporting global research initiatives through convening, funding, and advocating on behalf of the international research community. We are dedicated to identifying ways the global Alzheimer's research community can collaborate across international borders toward the mutual goal of finding better methods of treatment, prevention, and, ultimately, a cure.&lt;/p&gt;&lt;p&gt;The Alzheimer's Association, the Global Brain Health Institute (GBHI), and the UK-based Alzheimer's Society have announced the newest recipients of the Pilot Awards for Global Brain Health Leaders, a competitive funding initiative dedicated to fostering leadership in brain health and dementia care.&lt;/p&gt;&lt;p&gt;“Alzheimer's disease and other dementia are growing global health issues,” said Stefania Forner, PhD, Alzheimer's Association director of medical and scientific relations. As such, local customs and culture, attitudes and perceptions regarding health and disease, and available resources and health systems all must be taken into account in the development of effective dementia-related interventions, s","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14569","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050836","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":"Identifying gait differences between Alzheimer's disease and dementia with Lewy bodies and their associations with regional amyloid deposition","authors":"Salma Elasfar,&nbsp;Hajr Hameed,&nbsp;Bradley F. Boeve,&nbsp;Julie A. Fields,&nbsp;Clifford R. Jack Jr.,&nbsp;Kejal Kantarci,&nbsp;Erik K. St. Louis,&nbsp;Val J. Lowe,&nbsp;Ronald C. Petersen,&nbsp;Farwa Ali,&nbsp;Kaylena Ehgoetz Martens","doi":"10.1002/alz.14351","DOIUrl":"10.1002/alz.14351","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We aimed to compare gait between individuals with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and cognitively unimpaired (CU) individuals and to evaluate the association between gait and regional amyloid beta (Aβ) burden in AD and DLB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We included 420 participants (70 AD, 70 DLB, 280 CU) in the Mayo Clinic Study of Aging (MCSA). Gait was assessed using a pressure-sensor walkway. Aβ deposition was analyzed with Pittsburgh compound B (PiB) positron emission topography (PET).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The DLB group had reduced stride velocity, step length, and stride width variability, as well as increased double support percentage (%DS) and variability in step length, swing time, and step time compared to the AD and CU groups. Aβ burden was not associated with any gait outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study provides additional evidence that gait differs between AD and DLB. Larger studies are needed to investigate associations between Aβ burden and gait outcomes in dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Gait was more impaired in dementia than in cognitively unimpaired (CU) controls.</li>\u0000 \u0000 <li>Compared with Alzheimer's disease (AD), Dementia with Lewy bodies (DLB) had more impaired pace, variability, and postural control.</li>\u0000 \u0000 <li>Step length and double support (%) distinguished DLB and AD with moderate accuracy.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044350","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":"Investing in equitable healthy aging: Why Africa must reform social pension schemes to improve Alzheimer's disease and dementia outcomes","authors":"Cyprian M. Mostert,&nbsp;Najat EL Mekkaoui,&nbsp;Shehzad Ali,&nbsp;Dominic Trepel,&nbsp;Kirti Randcord,&nbsp;Chinedu Udeh-Momoh,&nbsp;Olivera Nesic,&nbsp;Karen Blackmon,&nbsp;Mary Karanja,&nbsp;Thomas Thesen,&nbsp;David Andai,&nbsp;Rym Ayadi,&nbsp;Harris Eyre,&nbsp;Zul Merali","doi":"10.1002/alz.14527","DOIUrl":"10.1002/alz.14527","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The eligibility criteria for social pension schemes in Africa hinder equitable and healthy aging. In 2019, women in 14 sub-Saharan African countries had an average life expectancy of 67 years but a healthy life expectancy of only 57 years, leaving them 5 years in poor health before receiving a pension at age 62. Men had a similar situation—a life expectancy of 62 years and a healthy life expectancy of 53 years, spending 10 years in poor health before becoming eligible for pensions at age 63. Many men do not receive pensions due to early death. Delays and low pension payouts contribute to a 2.5% increase in the death rate from Alzheimer's disease and dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Eligibility criteria for social pension schemes in Africa hinder equitable and healthy aging.</li>\u0000 \u0000 <li>Delays and low pension payouts are associated with worsening death rates from dementia.</li>\u0000 \u0000 <li>Average health life expectancy for both genders should serve as a basis for initiating pension payouts.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044415","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":"Exploring the role of T cells in Alzheimer's and other neurodegenerative diseases: Emerging therapeutic insights from the T Cells in the Brain symposium","authors":"Wassim Elyaman,&nbsp;Lawrence J. Stern,&nbsp;Ning Jiang,&nbsp;Dallin Dressman,&nbsp;Philip Bradley,&nbsp;David Klatzmann,&nbsp;Elizabeth M. Bradshaw,&nbsp;Donna L. Farber,&nbsp;Sally C. Kent,&nbsp;Shahab Chizari,&nbsp;Kristen Funk,&nbsp;Davangere Devanand,&nbsp;Kiran T. Thakur,&nbsp;Towfique Raj,&nbsp;Osama Al Dalahmah,&nbsp;Rani A. Sarkis,&nbsp;Howard L. Weiner,&nbsp;Neil A. Shneider,&nbsp;Serge Przedborski","doi":"10.1002/alz.14548","DOIUrl":"10.1002/alz.14548","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>This proceedings article summarizes the inaugural “T Cells in the Brain” symposium held at Columbia University. Experts gathered to explore the role of T cells in neurodegenerative diseases. Key topics included characterization of antigen-specific immune responses, T cell receptor (TCR) repertoire, microbial etiology in Alzheimer's disease (AD), and microglia–T cell crosstalk, with a focus on how T cells affect neuroinflammation and AD biomarkers like amyloid beta and tau. The symposium also examined immunotherapies for AD, including the Valacyclovir Treatment of Alzheimer's Disease (VALAD) trial, and two clinical trials leveraging regulatory T cell approaches for multiple sclerosis and amyotrophic lateral sclerosis therapy. Additionally, single-cell RNA/TCR sequencing of T cells and other immune cells provided insights into immune dynamics in neurodegenerative diseases. This article highlights key findings from the symposium and outlines future research directions to further understand the role of T cells in neurodegeneration, offering innovative therapeutic approaches for AD and other neurodegenerative diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Researchers gathered to discuss approaches to study T cells in brain disorders.</li>\u0000 \u0000 <li>New technologies allow high-throughput screening of antigen-specific T cells.</li>\u0000 \u0000 <li>Microbial infections can precede several serious and chronic neurological diseases.</li>\u0000 \u0000 <li>Central and peripheral T cell responses shape neurological disease pathology.</li>\u0000 \u0000 <li>Immunotherapy can induce regulatory T cell responses in neuroinflammatory disorders.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14548","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between adult child education and cognitive functioning among older parents: A cross-national comparison of diverse contexts","authors":"Emma Nichols,&nbsp;Karla R. Flores Romero,&nbsp;Dipti Govil,&nbsp;Jinkook Lee,&nbsp;Jaqueline M. Torres","doi":"10.1002/alz.14562","DOIUrl":"10.1002/alz.14562","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The association between adult child educational attainment and older parent's cognitive health may vary across diverse contexts but cross-national comparisons have been limited by differences in outcome assessment, study design, and analytic choices.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We used harmonized data with comprehensive cognitive assessments from the United States (<i>N</i> = 3088), India (<i>N</i> = 3828), and Mexico (<i>N</i> = 1875) to estimate associations between adult child education and older adults’ cognitive functioning using linear regression models adjusted for respondent and family-level socio-economic status (SES) in each study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Each additional year of offspring education was associated with 0.02 (Longitudinal Aging Study in India – Diagnostic Assessment of Dementia [LASI-DAD]) to 0.04 (Health and Retirement Study Harmonized Cognitive Assessment Protocol Survey [HRS-HCAP], Mexican Health and Aging Study Cognitive Aging Ancillary Study [Mex-Cog]) standard deviation (SD) units higher cognitive score (pooled estimate: 0.032 [95% confidence interval [CI]: 0.018–0.046]), comparable to about 1/3–1/4 of the association with respondents’ own years of education. Differences by respondent gender were heterogeneous across contexts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Consistent overall estimates despite differences in context and potential confounding structures underscore the importance of offspring education for cognitive outcomes among older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The harmonized study design allows for fair comparisons across diverse contexts.</li>\u0000 \u0000 <li>Effect sizes were largely consistent across the United States, India, and Mexico, despite differences in confounding structures.</li>\u0000 \u0000 <li>The pooled association between adult child education and parental cognitive functioning was about 1/3–1/4 of the association with respondent's own years of education.</li>\u0000 \u0000 <li>Heterogeneity in gender differences point to the potential effects of local culture and context.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14562","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044412","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}