Alzheimer's & Dementia最新文献

{"title":"Pathways underlying selective neuronal vulnerability in Alzheimer's disease: Contrasting the vulnerable locus coeruleus to the resilient substantia nigra","authors":"Alexander J. Ehrenberg,&nbsp;Cathrine Sant,&nbsp;Felipe L. Pereira,&nbsp;Song Hua Li,&nbsp;Jessica Buxton,&nbsp;Sonali Langlois,&nbsp;Marena Trinidad,&nbsp;Ian Oh,&nbsp;Renata Elaine Paraizo Leite,&nbsp;Roberta Diehl Rodriguez,&nbsp;Vitor Ribeiro Paes,&nbsp;Carlos Agusto Pasqualucci,&nbsp;William W. Seeley,&nbsp;Salvatore Spina,&nbsp;Claudia K. Suemoto,&nbsp;Sally Temple,&nbsp;Daniela Kaufer,&nbsp;Lea T. Grinberg","doi":"10.1002/alz.70087","DOIUrl":"https://doi.org/10.1002/alz.70087","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) selectively affects certain brain regions, yet the mechanisms of selective vulnerability remain poorly understood. The neuromodulatory subcortical system, which includes nuclei exhibiting a range of vulnerability and resilience to AD-type degeneration, presents a framework for uncovering these mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We leveraged transcriptomics and immunohistochemistry in paired samples from human <i>post mortem</i> tissue representing a vulnerable and resilient region—the locus coeruleus (LC) and substantia nigra (SN). These regions have comparable anatomical features but distinct vulnerability to AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We identified significant differences in cholesterol homeostasis, antioxidant pathways, KRAS signaling, and estrogen signaling at a bulk transcriptomic level. Notably, evidence of sigma-2 receptor upregulation was detected in the LC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our findings highlight pathways differentiating the LC and SN, potentially explaining the LC's selective vulnerability in AD. Such pathways offer potential targets of disease-modifying therapies for AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Intraindividual comparative RNAseq was used to study selective vulnerability.</li>\u0000 \u0000 <li>Metallothionein genes are significantly enriched in the substantia nigra.</li>\u0000 \u0000 <li>Cholesterol homeostatic genes are significantly enriched in the locus coeruleus.</li>\u0000 \u0000 <li>The locus coeruleus is likely more susceptible to toxic amyloid beta oligomers.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698957","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":"Generalizability of tau and amyloid plasma biomarkers in Alzheimer's disease cohorts of diverse genetic ancestries","authors":"Anthony J. Griswold,&nbsp;Farid Rajabli,&nbsp;Tianjie Gu,&nbsp;Jamie Arvizu,&nbsp;Charles G. Golightly,&nbsp;Patrice L. Whitehead,&nbsp;Kara L. Hamilton-Nelson,&nbsp;Larry D. Adams,&nbsp;Jose J. Sanchez,&nbsp;Pedro R. Mena,&nbsp;Takiyah D. Starks,&nbsp;Maryenela Illanes-Manrique,&nbsp;Concepcion Silva,&nbsp;William S. Bush,&nbsp;Michael L. Cuccaro,&nbsp;Jeffery M. Vance,&nbsp;Mario R. Cornejo-Olivas,&nbsp;Briseida E. Feliciano-Astacio,&nbsp;Goldie S. Byrd,&nbsp;Gary W. Beecham,&nbsp;Jonathan L. Haines,&nbsp;Margaret A. Pericak-Vance","doi":"10.1002/alz.14367","DOIUrl":"https://doi.org/10.1002/alz.14367","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Plasma phosphorylated threonine 181 of tau (pTau181) and amyloid beta (Aβ) are biomarkers for differential diagnosis and preclinical detection of Alzheimer disease (AD). Given differences in AD risk across diverse populations, the generalizability of existing biomarker data is not assured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In 2086 individuals of diverse genetic ancestries (African American, Caribbean Hispanic, and Peruvian), we measured plasma pTau181 and Aβ42/Aβ40. Differences in biomarkers between cohorts and clinical diagnosis groups and the potential discriminative performance of the two biomarkers were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>pTau181 and Aβ42/Aβ40 were consistent across cohorts. Higher levels of pTau181 were associated with AD, while Aβ42/Aβ40 had minimal differences. Correspondingly, pTau181 had a greater predictive value than Aβ42/Aβ40; however, the area under the curve differed between cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>pTau181 as a plasma biomarker for clinical AD is generalizable across genetic ancestries, but its predictive value may vary. Combining genomic and biomarker data from diverse individuals will increase understanding of genetic risk and refine clinical diagnoses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>This is a diverse ancestry study of plasma biomarkers for AD.</li>\u0000 \u0000 <li>Plasma biomarkers were assessed in African Americans, Caribbean Hispanics, and Peruvians.</li>\u0000 \u0000 <li>Biomarker levels were consistent across the diverse cohorts.</li>\u0000 \u0000 <li>Plasma phosphorylated tau was higher in AD in all cohorts.</li>\u0000 \u0000 <li>Plasma biomarker findings in diverse cohorts largely generalize with existing European studies.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14367","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698708","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":"Carbonic anhydrase inhibitors prevent presymptomatic capillary flow disturbances in a model of cerebral amyloidosis","authors":"Eugenio Gutiérrez-Jiménez,&nbsp;Peter Mondrup Rasmussen,&nbsp;Irene Klærke Mikkelsen,&nbsp;Sreekanth Kura,&nbsp;Signe K. Fruekilde,&nbsp;Brian Hansen,&nbsp;Luca Bordoni,&nbsp;Jasper Carlsen,&nbsp;Johan Palmfeldt,&nbsp;David A. Boas,&nbsp;Sava Sakadžić,&nbsp;Sergei Vinogradov,&nbsp;Mirna El Khatib,&nbsp;Jaime Ramos-Cejudo,&nbsp;Boris Wied,&nbsp;Desiree Leduc-Galindo,&nbsp;Elisa Canepa,&nbsp;Adam C. Mar,&nbsp;Begona Gamallo-Lana,&nbsp;Silvia Fossati,&nbsp;Leif Østergaard","doi":"10.1002/alz.70023","DOIUrl":"https://doi.org/10.1002/alz.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Disturbances in microvascular flow dynamics are hypothesized to precede the symptomatic phase of Alzheimer's disease (AD). However, evidence in presymptomatic AD remains elusive, underscoring the need for therapies targeting these early vascular changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We employed a multimodal approach, combining in vivo optical imaging, molecular techniques, and ex vivo magnetic resonance imaging, to investigate early capillary dysfunction in C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax (Tg-SwDI) mice without memory impairment. We also assessed the efficacy of carbonic anhydrase inhibitors (CAIs) in preventing capillary flow disturbances.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Our study revealed capillary flow disturbances associated with alterations in capillary morphology, adhesion molecule expression, and amyloid beta (Aβ) load in 9- to 10-month-old Tg-SwDI mice without memory impairment. CAI treatment ameliorated these capillary flow disturbances, enhanced oxygen availability, and reduced Aβ load.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings underscore the importance of capillary flow disturbances as early biomarkers in presymptomatic AD and highlight the potential of CAIs for preserving vascular integrity in the early stages of AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Uncovered early capillary dysfunction in a presymptomatic Alzheimer's disease (AD) mouse model.</li>\u0000 \u0000 <li>Evidence linking capillary stalls and capillary dysfunction with oxygen delivery issues in AD.</li>\u0000 \u0000 <li>Novel use of carbonic anhydrase inhibitors to prevent early capillary flow disturbances in AD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698707","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":"Decreased practice effects in cognitively unimpaired amyloid betapositive individuals: a multicenter, longitudinal, cohort study","authors":"Adrià Tort-Merino,&nbsp;Agnès Pérez-Millan,&nbsp;Neus Falgàs,&nbsp;Sergi Borrego-Écija,&nbsp;Diana Esteller,&nbsp;Bea Bosch,&nbsp;Magdalena Castellví,&nbsp;Jordi Juncà-Parella,&nbsp;Andrea del Val-Guardiola,&nbsp;Guadalupe Fernández-Villullas,&nbsp;Anna Antonell,&nbsp;María Belén Sanchez-Saudinós,&nbsp;Sara Rubio-Guerra,&nbsp;Nuole Zhu,&nbsp;María García-Martínez,&nbsp;Ana Pozueta,&nbsp;Ainara Estanga,&nbsp;Mirian Ecay-Torres,&nbsp;Carolina López de Luis,&nbsp;Mikel Tainta,&nbsp;Miren Altuna,&nbsp;Eloy Rodríguez-Rodríguez,&nbsp;Pascual Sánchez-Juan,&nbsp;Pablo Martínez-Lage,&nbsp;Alberto Lleó,&nbsp;Juan Fortea,&nbsp;Ignacio Illán-Gala,&nbsp;Mircea Balasa,&nbsp;Albert Lladó,&nbsp;Lorena Rami,&nbsp;Raquel Sánchez-Valle","doi":"10.1002/alz.70016","DOIUrl":"https://doi.org/10.1002/alz.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We aimed to determine whether cognitively unimpaired (CU) amyloid- beta-positive (Aβ+) individuals display decreased practice effects on serial neuropsychological testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We included 209 CU participants from three research centers, 157 Aβ− controls and 52 Aβ+ individuals. Participants underwent neuropsychological assessment at baseline and annually during a 2-year follow-up. We used linear mixed-effects models to analyze cognitive change over time between the two groups, including time from baseline, amyloid status, their interaction, age, sex, and years of education as fixed effects and the intercept and time as random effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The Aβ+ group showed reduced practice effects in verbal learning (β = −1.14, SE = 0.40, <i>p </i>= 0.0046) and memory function (β = −0.56, SE = 0.19, <i>p </i>= 0.0035), as well as in language tasks (β = −0.59, SE = 0.19, <i>p </i>= 0.0027).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Individuals with normal cognition who are in the Alzheimer's continuum show decreased practice effects over annual neuropsychological testing. Our findings could have implications for the design and interpretation of primary prevention trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>This was a multicenter study on practice effects in asymptomatic Aβ+ individuals.</li>\u0000 \u0000 <li>We used LME models to analyze cognitive trajectories across multiple domains.</li>\u0000 \u0000 <li>Practice-effects reductions might be an indicator of subtle cognitive decline.</li>\u0000 \u0000 <li>Implications on clinical and research settings within the AD field are discussed.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699019","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":"Association update","authors":"","doi":"10.1002/alz.14554","DOIUrl":"https://doi.org/10.1002/alz.14554","url":null,"abstract":"&lt;p&gt;Registration is open for the 2025 Tau Global Conference, which brings together three major tau-focused conferences (Global Tau, EuroTau, and CurePSP Neuro) and is hosted by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation. Taking place April 24–25 in London, UK, and online, the Tau Global Conference plays a critical role in bringing together interdisciplinary researchers and perspectives to move tau research forward.&lt;/p&gt;&lt;p&gt;The hybrid conference provides a forum for members of academia, industry, philanthropy, and government to explore tau-related biology, biomarkers, therapeutics, and phenotypes; enhance interdisciplinary collaboration and alignment to address challenges in tau research; and foster talent development and secure funding for the study of tauopathies.&lt;/p&gt;&lt;p&gt;The program aims to provide a deeper understanding of research advancements in tauopathies, including primary tauopathies such as progressive supranuclear palsy (PSP), cortical basal degeneration (CBD), and frontotemporal dementia (FTD), as well as key issues impacting the tau research community.&lt;/p&gt;&lt;p&gt;Questions about the Tau Global Conference may be sent to &lt;span&gt;[email protected]&lt;/span&gt;.&lt;/p&gt;&lt;p&gt;In early December 2024, the bipartisan BOLD Reauthorization Act was signed into law. The bill, which passed unanimously out of Congress, reauthorizes the Building Our Largest Dementia (BOLD) Infrastructure for Alzheimer's Act (P.L.115-406) and will enable public health departments to implement effective dementia interventions.&lt;/p&gt;&lt;p&gt;“In the 5 years since the initial BOLD Act was signed into law, public health departments across the country have been making a real-world impact by successfully implementing effective Alzheimer's interventions, such as increasing early detection and diagnosis and reducing risk,” said Robert Egge, Alzheimer's Impact Movement (AIM) president and Alzheimer's Association chief public policy officer. “Today's reauthorization will build on this progress and expand the law's impact further into communities.”&lt;/p&gt;&lt;p&gt;The BOLD Reauthorization Act was championed by Sens. Susan Collins (R-Maine), Catherine Cortez Masto (D-Nev.), Shelley Moore Capito (R-W. Va.), and Tim Kaine (D-Va.) in the Senate, and Reps. Brett Guthrie (R-Ky.), Paul Tonko (D-N.Y.), Chris Smith (R-N.J.), and Maxine Waters (D-Calif.) in the House.&lt;/p&gt;&lt;p&gt;“We are grateful to the bill's sponsors for their tremendous bipartisan leadership in introducing the bipartisan BOLD Reauthorization Act, and their steadfast commitment to the Alzheimer's and dementia community,” continued Egge.&lt;/p&gt;&lt;p&gt;The BOLD Act has been essential to creating and growing a public health infrastructure for dementia across the country. Through the law, the Centers for Disease Control and Prevention (CDC) has provided funding to state, local, and tribal public health departments to help them improve brain health in their communities. Since 2018, the CDC has made 66 awards to 45 state, local, and tribal publi","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14554","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698709","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":"Blood DNA methylation signature for incident dementia: Evidence from longitudinal cohorts","authors":"Wei Zhang,&nbsp;Juan I. Young,&nbsp;Lissette Gomez,&nbsp;Michael A. Schmidt,&nbsp;David Lukacsovich,&nbsp;Brian W. Kunkle,&nbsp;X. Steven Chen,&nbsp;Eden R. Martin,&nbsp;Lily Wang","doi":"10.1002/alz.14496","DOIUrl":"https://doi.org/10.1002/alz.14496","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Distinguishing between molecular changes that precede dementia onset and those resulting from the disease is challenging with cross-sectional studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We studied blood DNA methylation (DNAm) differences and incident dementia in two large longitudinal cohorts: the Offspring cohort of the Framingham Heart Study (FHS) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. We analyzed blood DNAm samples from &gt; 1000 cognitively unimpaired subjects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Meta-analysis identified 44 CpGs and 44 differentially methylated regions consistently associated with time to dementia in both cohorts. Our integrative analysis identified early processes in dementia, such as immune responses and metabolic dysfunction. Furthermore, we developed a methylation-based risk score, which successfully predicted future cognitive decline in an independent validation set, even after accounting for age, sex, apolipoprotein E ε4, years of education, baseline diagnosis, and baseline Mini-Mental State Examination score.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>DNAm offers a promising source as a biomarker for dementia risk assessment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Blood DNA methylation (DNAm) differences at individual CpGs and differentially methylated regions are significantly associated with incident dementia.</li>\u0000 \u0000 <li>Pathway analysis revealed DNAm differences associated with incident dementia are significantly enriched in biological pathways involved in immune responses and metabolic processes.</li>\u0000 \u0000 <li>Out-of-sample validation analysis demonstrated that a methylation-based risk score successfully predicted future cognitive decline in an independent dataset, even after accounting for age, sex, apolipoprotein E ε4, years of education, baseline diagnosis, and baseline Mini-Mental State Examination score.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14496","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698710","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":"Dementia in a resource-constrained sub-Saharan African setting: A comprehensive retrospective analysis of prevalence, risk factors, and management at the only neuropsychiatric facility in Northeastern Nigeria","authors":"Ibrahim Abdu Wakawa,&nbsp;Umar Baba Musami,&nbsp;Suleiman Hamidu Kwairanga,&nbsp;Placidus Nwankuba Ogualili,&nbsp;Mohammed Yusuf Mahmood,&nbsp;Muhammad Abba Fugu,&nbsp;Mohammed Mala Gimba,&nbsp;Muktar Mohammed Allamin,&nbsp;Zaharadeen Umar Abbas,&nbsp;Muhammad Kawu Sunkani,&nbsp;Zainab Bukar Yaganami,&nbsp;Fatima Mustapha Kadau,&nbsp;Nasir Muhammad Sani,&nbsp;Peter Danmallam,&nbsp;Luka Nanjul,&nbsp;Larema Babazau,&nbsp;Zaid Muhammad,&nbsp;Baba Waru Goni,&nbsp;Babagana Kundi Machina,&nbsp;Celeste M. Karch,&nbsp;Chinedu Udeh-Momoh,&nbsp;Thomas K. Karikari,&nbsp;Chiadi U. Onyike,&nbsp;Mahmoud Bukar Maina","doi":"10.1002/alz.14538","DOIUrl":"10.1002/alz.14538","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Dementia prevalence is increasing in sub-Saharan Africa, potentially due to population growth and aging. Resource-constrained settings such as Northeastern Nigeria face challenges in dementia management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We assessed dementia burden and management at the Federal Neuropsychiatric Hospital Maiduguri, the only neuropsychiatric facility in Northeastern Nigeria. This retrospective analysis included patient records from 1999 to 2023 for individuals 60 year of age and older with a dementia diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Of the 1216 cases reported, Alzheimer's disease (60.5%) was the most common subtype, followed by vascular dementia (24.5%). Hypertension (41.6%) was the most frequent comorbidity. Memory loss was present in all cases, whereas behavioral symptoms like agitation presented in some cases. Treatments included cognitive enhancers (donepezil), supplements (gingko biloba), and non-drug therapies (psychoeducation).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The increasing burden of dementia at this sole facility highlights the urgent need for targeted interventions and further research to understand the underlying factors contributing to dementia in this population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Dementia trends and management in a neuropsychiatric facility serving over 26 million people in Northeastern Nigeria.</li>\u0000 \u0000 <li>Alzheimer's disease accounted for 60.5% of the dementia cases reported, with hypertension as the leading comorbidity.</li>\u0000 \u0000 <li>There is an urgent need for improved diagnostic tools and health care infrastructure to address dementia in resource-constrained settings.</li>\u0000 \u0000 <li>The findings lay the foundation for developing a dementia cohort as part of the Northern Nigeria Dementia Research Group.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14538","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660312","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":"Fibrillar tau alters cerebral endothelial cell metabolism, vascular inflammatory activation, and barrier function in vitro and in vivo","authors":"Roberto Guzmán-Hernández,&nbsp;Silvia Fossati","doi":"10.1002/alz.70077","DOIUrl":"10.1002/alz.70077","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The presence of tau aggregates in and around the brain vasculature in Alzheimer's disease (AD) and tauopathies suggests its possible pathogenicity to cerebral endothelial cells (ECs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We used an in vitro model of the blood–brain barrier (BBB) to understand the mechanisms of fibrillar tau–mediated cerebral EC and BBB pathology, confirming our findings in 3-month-old P301S mice brains and extracted microvessels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Protofibrillar and fibrillar tau species induce endothelial barrier permeability through an increase in glycolysis, which activates ECs toward a pro-inflammatory phenotype, inducing loss of junction protein expression and localization. The Warburg-like metabolic shift toward glycolysis and increased vascular pathological phenotypes are also present in young P301S mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>In sum, our work reveals that fibrillar tau species, by enhancing endothelial glycolytic metabolism, promote vascular inflammatory phenotypes and loss of BBB function, highlighting the importance of addressing and targeting early tau-mediated neurovascular damage in AD and tauopathies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We improve the understanding of the mechanisms of vascular pathology in tauopathies.</li>\u0000 \u0000 <li>Fibrillar tau mediates vascular metabolic changes, inflammation, and blood–brain barrier (BBB) dysfunction.</li>\u0000 \u0000 <li>These events are replicated at early stages in a tauopathy mouse model.</li>\u0000 \u0000 <li>Inhibiting altered glycolysis reduces BBB permeability and endothelial activation.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660621","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":"Association of neighborhood disadvantage with cognitive function and cortical disorganization in an unimpaired cohort: An exploratory study","authors":"Apoorva Safai,&nbsp;William R Buckingham,&nbsp;Erin M Jonaitis,&nbsp;Rebecca E Langhough,&nbsp;Sterling C. Johnson,&nbsp;W. Ryan Powell,&nbsp;Amy J. Kind,&nbsp;Barbara B. Bendlin,&nbsp;Pallavi Tiwari","doi":"10.1002/alz.70095","DOIUrl":"10.1002/alz.70095","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Neighborhood disadvantage has been shown to impact health and cognitive outcomes, while morphological similarity network (MSN) can elucidate structural morphological patterns underlying cognitive functions. We hypothesized MSNs could provide cortical patterns linked with neighborhood disadvantage and cognitive function, explaining the potential risk of cognitive impairment in disadvantaged neighborhoods.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;For cognitively unimpaired participants from the Wisconsin Alzheimer's Disease Research Center or Wisconsin Registry for Alzheimer's Prevention (&lt;i&gt;n&lt;/i&gt; = 524), and the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (&lt;i&gt;n&lt;/i&gt; = 100), neighborhood disadvantage was obtained using Area Deprivation Index (ADI) and its association with cognitive performance and MSN features was analyzed using linear regression and mediation analysis.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Neighborhood disadvantage was associated with worse cognitive performance on memory, executive function, processing speed, and preclinical Alzheimer's tests on both datasets. Local morphological organization of predominantly the frontal and temporal regions showed association trends with ADI.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Morphological patterns associated with ADI, in-part, may explain the risk for poor cognitive functioning in a neighborhood disadvantaged population.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Social determinants of health such as neighborhood context can be studied using ADI.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;High neighborhood disadvantage was related to worse performance on category fluency, implicit learning speed, story recall memory and pre-clinical Alzheimer's cognitive composite.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;In this exploratory study, using morphological brain networks that indicate similarity in distribution of cortical thickness between regions, we observed that centrality of predominantly frontal and temporal regions was marginally linked with neighborhood disadvantage status and also partially mediated its association with preclinical Alzheimer's composite test.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;There is a potential role for considering neighborhood status in early screening of cognitive impairment ","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660306","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":"Distinct medical and substance use histories associate with cognitive decline in Alzheimer's disease","authors":"Clayton Mansel,&nbsp;Diego R. Mazzotti,&nbsp;Ryan Townley,&nbsp;Mihaela E. Sardiu,&nbsp;Russell H. Swerdlow,&nbsp;Robyn A. Honea,&nbsp;Olivia J. Veatch","doi":"10.1002/alz.70017","DOIUrl":"10.1002/alz.70017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Phenotype clustering reduces patient heterogeneity and could be useful when designing precision clinical trials. We hypothesized that the onset of early cognitive decline in patients would exhibit variance predicated on the clinical history documented prior to an Alzheimer's disease (AD) diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Self-reported medical and substance use history (i.e., problem history) was used to cluster participants from the National Alzheimer's Coordinating Center (NACC) into distinct subtypes. Linear mixed effects modeling was used to determine the effect of problem history subtype on cognitive decline over 2 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Two thousand seven hundred fifty-four individuals were partitioned into three subtypes: minimal (<i>n</i> = 1380), substance use (<i>n</i> = 1038), and cardiovascular (<i>n</i> = 336). The cardiovascular problem history subtype had significantly worse cognitive decline over a 2 year follow-up period (<i>p</i> = 0.013).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our study highlights the need to account for problem history to reduce heterogeneity of outcomes in AD clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Clinical data were used to identify subtypes of patients with Alzheimer's disease (AD) in the National Alzheimer's Coordinating Center dataset.</li>\u0000 \u0000 <li>Three problem history subtypes were found: minimal, substance use, and cardiovascular.</li>\u0000 \u0000 <li>The mean change in Clinical Dementia Rating Sum of Boxes (CDR-SB) was assessed over a 2 year follow-up.</li>\u0000 \u0000 <li>The cardiovascular subtype was associated with the worst cognitive decline.</li>\u0000 \u0000 <li>The magnitude of change in CDR-SB was similar to recent AD clinical trials.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660324","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}