Alzheimer's & Dementia最新文献

{"title":"Characterizing financial risk from out-of-pocket expenditures across dementia stages","authors":"Patricia G. Synnott,&nbsp;Yingying Zhu,&nbsp;Angie Mae Rodday,&nbsp;Pei-Jung Lin","doi":"10.1002/alz.70666","DOIUrl":"10.1002/alz.70666","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Older adults with dementia incur considerable out-of-pocket (OOP) health care expenses, but it is unclear how their financial burden differs by dementia stage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We identified 2939 respondents aged ≥65 with dementia in the 2018 Health and Retirement Study, representing 9.8 million individuals on weighted analysis. We grouped respondents into four severity stages and examined their OOP expenditures, prevalence of financial risk (i.e., catastrophic or impoverishing levels of health care spending), and factors associated with financial risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Individuals with severe dementia had significantly higher OOP costs, with 21% experiencing catastrophic expenditures and 12% falling below poverty thresholds due to these costs. Regression analyses indicated nursing home residence, poor subjective health, advanced age, and other factors are associated with an increased odds of financial risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Financial risk increases in advanced dementia stages, likely reflecting more complex care needs and poorer overall health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Out-of-pocket health care costs increase with dementia severity.</li>\u0000 \u0000 <li>Twenty-one percent of people with severe dementia spend at least 40% of their income on health care.</li>\u0000 \u0000 <li>The risk of impoverishment from health care costs increases in severe dementia.</li>\u0000 \u0000 <li>Care needs, poor health, and nursing home residence may contribute to financial risk.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70666","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062386","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":"Impact of cardiometabolic conditions on the progression from mild cognitive impairment to dementia: A large cohort study","authors":"Filippos Anagnostakis,&nbsp;Michail Kokkorakis,&nbsp;Christos Asvestis,&nbsp;Ilias Papadimopoulos,&nbsp;Shrihari Nagarajan,&nbsp;Konrad Talbot,&nbsp;Lu Li,&nbsp;Yong Chen,&nbsp;Ilya M. Nasrallah,&nbsp;Junhao Wen,&nbsp;Christos Davatzikos","doi":"10.1002/alz.70692","DOIUrl":"10.1002/alz.70692","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study investigates the impact of cardiometabolic conditions, including type 2 diabetes, hyperlipidemia, hypertension, and obesity, on the progression of mild cognitive impairment (MCI) to dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The cohort included adults ≥ 50 years old with MCI and a cardiometabolic condition identified through electronic health records. Propensity score matching was applied to control for confounders, and Kaplan–Meier analysis was used to assess time-to-event outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>During a 7-year median follow-up, type 2 diabetes was associated with the highest risk of all-cause dementia (hazard ratio [HR] 1.18, 95% confidence interval [CI]: 1.06 to 1.31), followed by hypertension and hyperlipidemia. For vascular dementia, type 2 diabetes conferred the greatest risk (HR 1.33, 95% CI: 1.07 to 1.64). Hyperlipidemia was the sole cardiometabolic factor significantly associated with Alzheimer's disease (AD) risk (HR 1.21, 95% CI: 1.11 to 1.32).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSIONS</h3>\u0000 \u0000 <p>Hyperlipidemia is primarily associated with AD dementia risk, while type 2 diabetes is the major contributor to vascular dementia and all-cause risk in individuals with MCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Type 2 diabetes, hypertension, and hyperlipidemia are associated with a high risk of developing all-cause dementia in participants already diagnosed with mild cognitive impairment (MCI).</li>\u0000 \u0000 <li>Type 2 diabetes was shown to pose a high risk for the progression from MCI to vascular dementia.</li>\u0000 \u0000 <li>Hyperlipidemia was associated with Alzheimer's disease progression in individuals with MCI.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70692","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062385","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":"Investigating the oxidative stress–vascular brain injury axis in mild cognitive impairment of the Alzheimer's type","authors":"Flavie E. Detcheverry,&nbsp;Sneha Senthil,&nbsp;Winnie L. K. Motue,&nbsp;Chris Hosein,&nbsp;Rozie Arnaoutelis,&nbsp;David Araujo,&nbsp;Dumitru Fetco,&nbsp;Haz-Edine Assemlal,&nbsp;Samson Antel,&nbsp;Douglas L. Arnold,&nbsp;Jamie Near,&nbsp;Hyman M. Schipper,&nbsp;AmanPreet Badhwar,&nbsp;Sridar Narayanan","doi":"10.1002/alz.70456","DOIUrl":"10.1002/alz.70456","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Oxidative stress may contribute to brain injury in the Alzheimer's disease (AD) continuum. The antioxidant glutathione (GSH) can be assessed with magnetic resonance spectroscopy (MRS). Because the relationship between GSH and vascular brain injury is unknown in the AD continuum, we address this gap in mild cognitive impairment (MCI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>3T Magnetic resonance imaging (MRI)/MRS data were obtained from 31 patients with MCI. GSH and total <i>N</i>-acetylaspartate (tNAA; neuroaxonal integrity marker) were measured in posterior cingulate cortex (PCC) and frontal white matter (FWM). Cerebrovascular injury was assessed using white matter hyperintensity (WMH) volume. Global and regional brain tissue integrity were assessed using normalized brain (NBV) and hippocampal volumes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Significant associations were reported in FWM between GSH/total creatine (tCr) and tNAA/tCr, and between GSH and both WMH and NBV. tNAA, GSH/tCr, and tNAA/tCr were higher in PCC than in FWM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our results suggest that oxidative stress contributes to vascular brain injury in MCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Neuronal, vascular, and oxidative injuries occur in the Alzheimer's disease (AD) spectrum.</li>\u0000 \u0000 <li>Glutathione (GSH) is the main endogenous antioxidant in the brain.</li>\u0000 \u0000 <li>Brain GSH can be measured with magnetic resonance spectroscopy (MRS).</li>\u0000 \u0000 <li>We measured brain GSH level in people with mild cognitive impairment (MCI).</li>\u0000 \u0000 <li>Low GSH level was associated with vascular brain injury, neuroaxonal damage, and atrophy.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062694","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":"Co-pathology in Alzheimer's disease and Lewy body disease and its association with neuropsychiatric symptoms","authors":"Lucy L. Gibson,&nbsp;Lea T. Grinberg,&nbsp;Victor R. Paes,&nbsp;Christoph Mueller,&nbsp;Renata E. P. Leite,&nbsp;Paula Villela Nunes,&nbsp;Alberto F. O. Justo,&nbsp;Carlos A. Pasqualucci,&nbsp;Eduardo Ferriolli,&nbsp;Dag Aarsland,&nbsp;Claudia K. Suemoto","doi":"10.1002/alz.70693","DOIUrl":"10.1002/alz.70693","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>Mixed neuropathology is common in dementia, but the clinical implications for neuropsychiatric symptoms (NPSs) are not well characterized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In a population-based <i>post mortem</i> study, cases with Alzheimer's disease neuropathological change (ADNC) and Lewy body disease (LBD) were identified with any comorbid neuropathology (limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy neuropathological change (LATE-NC), cerebrovascular disease, LBD, and ADNC, respectively). <i>Post mortem</i> interviews collected information regarding NPSs and cognition to explore associations between each co-pathology and NPSs across the whole cohort, as well as in participants without dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Co-existing neuropathology was frequent, even among individuals without clinical dementia. In cases with ADNC, comorbid neocortical LBD pathology was associated with hallucinations, regardless of cognitive status. However, ADNC co-pathology in LBD was linked to a greater NPS burden in the full cohort but not in individuals without dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Lewy bodies are associated with hallucinations independent of cognitive impairment, whereas ADNC co-pathology may contribute to NPS only when widespread and associated with cognitive dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Neuropathological heterogeneity is high even in clinical stages without dementia.</li>\u0000 \u0000 <li>Neocortical but not limbic or brainstem LBD co-pathology is associated with hallucinations.</li>\u0000 \u0000 <li>LBs are associated with hallucinations independent of cognitive status.</li>\u0000 \u0000 <li>ADNC co-pathology is not associated with NPSs in LBD without dementia.</li>\u0000 \u0000 <li>LATE co-pathology is associated with increased risk of dementia but not NPS.</li>\u0000 \u0000 <li>Vascular co-pathology is associated with increased risk of delusions in ADNC.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70693","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062788","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 iADRS as an integrated measure of cognition and function: Psychometric evidence from recent clinical trials in early symptomatic Alzheimer's disease","authors":"Alexandra S. Atkins,&nbsp;Sarah Marquis,&nbsp;Kristin Creel,&nbsp;Juliette Meunier,&nbsp;Stefan Cano,&nbsp;Laure Delbecque,&nbsp;Mingyang Shan,&nbsp;Alette M. Wessels","doi":"10.1002/alz.70656","DOIUrl":"10.1002/alz.70656","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Psychometric evaluation of the integrated Alzheimer's Disease Rating Scale (iADRS) was performed using data from three randomized clinical trials (RCTs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Traditional measurement properties of the iADRS were assessed using classical test theory (CTT). Rasch Measurement Theory (RMT) analyses evaluated response properties of cognitive and functional items across the disease severity continuum. Crosswalks between iADRS, Clinical Dementia Rating – Sum of Boxes (CDR-SB), and Mini-Mental State Examination (MMSE) were developed to provide estimates of score equivalence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>CTT results confirm good psychometric properties of the iADRS, including reliability (Cronbach's alpha 0.79–0.84), concurrent validity with CDR-SB (range: −0.64–0.70), and sensitivity to change. RMT findings demonstrate improved reliability of the integrated scale (person-separation index [PSI] = 0.92) compared to components and highlight concurrent and overlapping progression of cognitive and functional decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The findings confirm the psychometric strength of the iADRS as a fit-for-purpose integrated endpoint for RCTs in early symptomatic Alzheimer's disease (AD). Crosswalk tables facilitate interpretation of clinical trial findings in clinical practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Findings confirm integrated Alzheimer's Disease Rating Scale (iADRS) total score reliability, validity, and sensitivity.</li>\u0000 \u0000 <li>Using the Rasch Measurement Theory (RMT), iADRS item set shows improved reliability relative to its component subscales.</li>\u0000 \u0000 <li>iADRS item thresholds are well distributed along the disease severity continuum.</li>\u0000 \u0000 <li>iADRS shows sensitivity to concurrent progression of cognitive and functional impairment.</li>\u0000 \u0000 <li>Crosswalk tables provide direct translation between iADRS, Clinical Dementia Rating – Sum of Boxes (CDR-SB), and Mini-Mental State Examination (MMSE).</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70656","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062656","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":"Harmonizing genotype array data to understand genetic risk for brain amyloid burden in the AMYPAD PNHS Consortium","authors":"Emma S. Luckett,&nbsp;Yasmina Abakkouy,&nbsp;Luigi Lorenzini,&nbsp;Lyduine E. Collij,&nbsp;David Vallez Garcia,&nbsp;Pieter Jelle Visser,&nbsp;Anouk den Braber,&nbsp;Craig Ritchie,&nbsp;Mercè Boada,&nbsp;Patricia Genius,&nbsp;Natàlia Vilor-Tejedor,&nbsp;Juan Domingo Gispert,&nbsp;Rik Vandenberghe,&nbsp;Frederik Barkhof,&nbsp;Isabelle Cleynen,&nbsp;the AMYPAD Consortium","doi":"10.1002/alz.70376","DOIUrl":"10.1002/alz.70376","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We sought to harmonize genotype data from the predementia AMYPAD (Amyloid Imaging to Prevent Alzheimer's Disease) Consortium, compute polygenic risk scores (PRS), and determine their association with global amyloid deposition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Genetic data from five AMYPAD parent cohorts were harmonized, and PRS were computed for Alzheimer's disease (AD) susceptibility, cerebrospinal fluid (CSF) amyloid beta (Aβ)42, and CSF phosphorylated tau181. Cross-sectional amyloid (Centiloid [CL]) burden was available for all participants, and regression models determined if PRS were associated with CL burden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>After harmonization, data for 867 participants showed that high CL burden was most strongly predicted by CSF Aβ42 PRS compared to traditional AD susceptibility PRS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This work emphasizes the importance of data harmonization and pooling of cohorts for large-powered studies. Findings suggest a genetic predisposition to amyloid pathology that may predispose individuals early in the AD continuum. This validates the potential use of PRS in clinical (trial) settings as a non-invasive tool to assess AD risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We developed a robust harmonization pipeline for multi-cohort genotype array data.</li>\u0000 \u0000 <li>Cerebrospinal fluid amyloid beta (Aβ)-specific polygenic risk scores (PRS) more strongly predicted global Aβ positron emission tomography burden than other PRS.</li>\u0000 \u0000 <li>Results suggest a strong genetic predisposition to early Aβ pathology.</li>\u0000 \u0000 <li>This work highlights the need for robust data harmonization and data pooling.</li>\u0000 \u0000 <li>This work also validates the potential use of PRS as a non-invasive tool to assess Alzheimer's disease risk.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062657","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":"Randomized phase 2a trial assessing a novel septin molecular glue in Alzheimer's disease","authors":"Mieke Nuytten,&nbsp;Marieke Voets,&nbsp;Eveline Debroux,&nbsp;Katrien Princen,&nbsp;Lentel Pringels,&nbsp;Marc Fivaz,&nbsp;Eline Byl,&nbsp;Steven Ramael,&nbsp;Koen De Witte,&nbsp;Mercé Boada,&nbsp;Xavier Morató,&nbsp;Juan Pablo Tartari,&nbsp;Asunción Lafuente,&nbsp;Emilio Franco Macias,&nbsp;Jordi A. Matias-Guiu,&nbsp;Everard Vijverberg,&nbsp;Charlotte E. Teunissen,&nbsp;Peter Anderer,&nbsp;Vincent Staggs,&nbsp;Vincent Hayman,&nbsp;Anne Corbett,&nbsp;Clive Ballard,&nbsp;John E. Harrison,&nbsp;Manfred Windisch,&nbsp;Ann Brinkmalm Westman,&nbsp;Henrik Zetterberg,&nbsp;Sam Dickson,&nbsp;Craig Mallinckrodt,&nbsp;Suzanne Hendrix,&nbsp;Jeffrey Cummings,&nbsp;Gerard Griffioen","doi":"10.1002/alz.70537","DOIUrl":"10.1002/alz.70537","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Pharmacological restoration of septin filament integrity has the potential to provide symptomatic benefit and disease modification in Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>REM127, a septin modulator, was assessed in mild-to-moderate AD (EudraCT: 2022-000080-43) in a phase 2a trial (<i>n</i> = 14). Primary endpoints: safety and tolerability; exploratory endpoints: pharmacokinetics, cerebrospinal fluid (CSF) biomarkers, electroencephalography (EEG), and functional outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In participants on active therapy, dose-dependent increases in serum aminotransferase were observed, leading to study discontinuation. CSF hyperphosphorylated tau (P-tau181), endpoints reflecting synaptic function and cognitive outcomes, were changed significantly (<i>p</i> &lt; 0.05) to normal compared to placebo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>REM127 triggers off-target liver adverse effects. Anticipated on-target outcomes suggest septin modulation has symptomatic benefit and modifies processes underlying AD. Results are considered exploratory as statistical power is constrained due to the small sample size caused by early termination. Further investigation of the therapeutic concept using an optimized septin molecular glue with an improved safety profile is warranted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Septin 6/7 molecular glue REM127 was assessed in symptomatic participants with Alzheimer's disease (AD).</li>\u0000 \u0000 <li>REM127 triggers off-target effects suggesting liver adverse effects.</li>\u0000 \u0000 <li>REM127 brain exposure was consistent with saturated target engagement.</li>\u0000 \u0000 <li>Biomarker and cognitive outcomes were changed consistent with therapeutic benefit.</li>\u0000 \u0000 <li>Septin modulation may restore synaptic function and mitigate pathology in AD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70537","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038341","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":"Reflecting upon Session 8 of the 2023 dementia care summit: Diversity beyond outreach, recruitment, and retention","authors":"Crystal M. Glover","doi":"10.1002/alz.70661","DOIUrl":"10.1002/alz.70661","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Informal dementia caregivers play essential roles in their families, communities, and our society. Furthermore, their research participation is paramount to fully understanding dementia experiences and aging trajectories. In this Perspective, I reflect upon Session 8 of the National Institute on Aging (NIA) National Research Summit on Care, Services, and Supports for Persons Living with Dementia and Their Care Partners/Caregivers. I assert that the field prioritizes outreach, recruitment, and retention regarding the inclusion of informal dementia caregivers from diverse backgrounds in research. Fully characterizing heterogeneous caregiver experiences and examining the impacts of dementia caregiving requires centering informal caregivers in the complete context of study design, beginning with research questions. I offer three critical areas of research questions for consideration within aging and dementia research. These questions may serve as a foundation for future Summits and, ultimately, as a pathway to facilitate optimal health and aging for all informal dementia caregivers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Research engagement and recruitment are critical components of dementia studies.</li>\u0000 \u0000 <li>These components must align with study design, especially research questions.</li>\u0000 \u0000 <li>Three critical areas of research questions will advance the field of dementia.</li>\u0000 \u0000 <li>Examining these research questions will provide evidence for policy and strategy.</li>\u0000 \u0000 <li>Questions focus on post-death caregiving, aging trajectories, and clinical trials.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70661","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038342","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":"Specialists’ perceptions of clinical instruments, practices, and staging of DS-AD: Results from an international survey","authors":"Hampus Hillerstrom,&nbsp;Amit Das,&nbsp;Matthew P. Janicki,&nbsp;Natalia S. Rozas,&nbsp;Stephanie L. Santoro","doi":"10.1002/alz.70356","DOIUrl":"10.1002/alz.70356","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Diagnosing and staging Down syndrome–associated Alzheimer's disease (DS-AD) is hindered by the lack of standardized criteria, complicating clinical decision making, trial participation, and access to advanced therapies. This study aimed to explore perceptions of these issues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHOD</h3>\u0000 \u0000 <p>An international survey of 42 clinicians and researchers specializing in DS-AD gathered perspectives on instruments, symptomatic staging, clinical practices, and research priorities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Respondents noted that key domains of impairment in mild cognitive impairment in Down syndrome and DS-AD dementia included memory, executive functioning, personality, social behavior, attention, mood, and language. Among the 10 assessment tools evaluated, informant-based interviews were noted as critical for individuals with severe intellectual disability (ID), while direct assessments were noted as useful for those with mild to moderate ID. Common diagnostic confounders like hypothyroidism and sleep disorders were identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Behavioral assessments provide a valuable function; however, future efforts should integrate behavioral assessments with biomarkers and develop standardized staging frameworks to improve diagnostic reliability, care planning, and treatment strategies for DS-AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Personality, social behavior, language, mood/affect, memory, executive functioning, and attention are recognized as key domains of impairment in both mild cognitive impairment in Down syndrome (MCI-DS) and Down syndrome–associated Alzheimer's disease (DS-AD).</li>\u0000 \u0000 <li>Ten prominent informant and direct assessment tools were noted as appropriate for individuals with DS and mild to moderate intellectual disability (ID) for identifying both MCI-DS and DS-AD; however, for individuals with severe/profound ID, there was less assurance of applicability.</li>\u0000 \u0000 <li>Harmonizing recommended tools in a standardized list was identified as a strategy to promote consistency across clinical and research contexts.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70356","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038343","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":"Ancestral genomic functional differences in oligodendroglia: implications for Alzheimer's disease","authors":"Aura M. Ramirez,&nbsp;Luciana Bertholim Nasciben,&nbsp;Sofia Moura,&nbsp;Lauren Coombs,&nbsp;Farid Rajabli,&nbsp;Brooke A. DeRosa,&nbsp;Patrice L. Whitehead,&nbsp;Larry D. Adams,&nbsp;Takiyah D. Starks,&nbsp;Pedro R. Mena,&nbsp;Maryenela Illanes-Manrique,&nbsp;Sergio Tejada,&nbsp;Goldie S. Byrd,&nbsp;Allison Caban-Holt,&nbsp;Michael L Cuccaro,&nbsp;Katalina McInerney,&nbsp;Mario R. Cornejo-Olivas,&nbsp;Briseida E. Feliciano-Astacio,&nbsp;Liyong Wang,&nbsp;Maria C. Robayo,&nbsp;Wanying Xu,&nbsp;Fulai Jin,&nbsp;Margaret A. Pericak-Vance,&nbsp;Anthony J. Griswold,&nbsp;Juan I. Young,&nbsp;Derek M. Dykxhoorn,&nbsp;Jeffery M. Vance","doi":"10.1002/alz.70593","DOIUrl":"10.1002/alz.70593","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study investigates ancestry-specific changes in induced pluripotent stem cell (iPSC)-derived oligodendroglia genomic regulation in Alzheimer's disease (AD), addressing diversity gaps by including African, Amerindian, and European ancestries in the analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We generated 12 iPSC lines from AD patients and controls with different apolipoprotein E (<i>APOE</i>) genotypes, <i>APOE ε3/ ε3</i> and <i>APOE ε</i><i>4/ ε4</i>, across three ancestries. Lines were differentiated into neural spheroids containing oligodendrocyte lineage cells and analyzed by single-nucleus RNA sequencing, Assay for Transposase-Accessible Chromatin with sequencing (ATACseq)APO, and High-throughput Chromosome Conformation Capture (Hi-C).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We identified ancestry-specific differences in gene expression and chromatin accessibility of AD genome-wide association study candidate genes. <i>APOE ε4/ ε4</i> carriers across all ancestries showed upregulated cholesterol biosynthesis genes with decreased myelination markers. iPSC-derived oligodendrocytes demonstrated high correlation (<i>R</i>² &gt; 0.85) with human brain transcriptomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our findings highlight the importance of studying diverse ancestries in AD research and suggest early <i>APOE ε4</i> effects on cholesterol metabolism. The validated iPSC model provides a valuable tool for investigating ancestry-specific disease mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>First study comparing iPSC-derived oligodendroglia across three ancestries.</li>\u0000 \u0000 <li><i>APOE ε4</i> carriers show upregulated cholesterol synthesis in oligodendroglia.</li>\u0000 \u0000 <li>Reduced myelin gene expression observed in <i>APOE ε4/ε4</i> oligodendroglia.</li>\u0000 \u0000 <li>Ancestry-specific differences found in AD GWAS genes and chromatin states.</li>\u0000 \u0000 <li>Novel insights into oligodendrocyte biology relevant to Alzheimer’s disease.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70593","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038340","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}