Alzheimer's & Dementia最新文献

{"title":"Joint spatial associations of amyloid beta and tau pathology in Down syndrome and preclinical Alzheimer's disease: Cross-sectional associations with early cognitive impairments","authors":"Jessie Fanglu Fu,&nbsp;Arun Garimella,&nbsp;Alex Lapointe,&nbsp;William W. T. Aye,&nbsp;Charles D. Chen,&nbsp;Joseph H. Lee,&nbsp;Sharon J. Krinsky-McHale,&nbsp;Shahid Zaman,&nbsp;Ira T. Lott,&nbsp;Christy Hom,&nbsp;Beau Ances,&nbsp;Elizabeth Head,&nbsp;Mark Mapstone,&nbsp;Florence Lai,&nbsp;Benjamin L. Handen,&nbsp;Charles M. Laymon,&nbsp;Sigan L. Hartley,&nbsp;Bradley T. Christian,&nbsp;Dorene M. Rentz,&nbsp;Keith A. Johnson,&nbsp;H. Diana Rosas,&nbsp;Julie C. Price,&nbsp;the Alzheimer Biomarkers Consortium–Down Syndrome (ABC-DS)","doi":"10.1002/alz.70424","DOIUrl":"https://doi.org/10.1002/alz.70424","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Individuals with Down syndrome (DS) have elevated risks for Alzheimer's disease (AD) due to amyloid beta (Aβ) precursor protein overexpression, with nearly all developing AD pathology by age 40 at autopsy. This study examined spatial associations between Aβ and tau burden in DS and neurotypical aging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Data included 145 DS (25–67 years) and 191 neurotypical aging individuals (63–89 years). Regional Aβ and tau positron emission tomography outcomes were analyzed using multiset canonical correlation analysis to identify joint Aβ/tau spatial patterns, with regression models assessing associations with age and cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>For a given Aβ burden, cognitively stable DS individuals exhibited relatively higher tau burden than neurotypical aging, while DS mild cognitive impairment/AD individuals exhibited more widespread pathology. Joint Aβ/tau patterns were associated with episodic memory impairment in DS and, as the disease progresses, executive dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>DS exhibits overlapping and distinct AD-related neuropathology features, emphasizing the importance of biomarkers for early detection and intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>There are distinct amyloid beta (Aβ) and tau spatial patterns in Down syndrome (DS): For a given level of Aβ burden, individuals with DS exhibited greater and more widespread tau burden compared to neurotypical aging, even before a clinical diagnosis of dementia.</li>\u0000 \u0000 <li>Aβ-associated tau burden was linked to episodic memory impairment in DS prior to dementia, with executive dysfunction emerging as the disease progressed, highlighting the sequential impact of pathology on cognition.</li>\u0000 \u0000 <li>The unique pattern of early striatal Aβ accumulation in DS supports its use as a potential biomarker for tracking disease progression and guiding clinical trial inclusion criteria for Alzheimer's disease interventions in DS.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70424","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma p-tau231 in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: A cross-sectional and longitudinal cohort study","authors":"Vincent Malotaux,&nbsp;Nicholas J. Ashton,&nbsp;Annika Öhrfelt,&nbsp;Yinghua Chen,&nbsp;Yi Su,&nbsp;Gloria Garcia-Ospina,&nbsp;Claudia Guzman-Martínez,&nbsp;Andres Villegas-Lanau,&nbsp;Johana Gómez-Ramirez,&nbsp;Margarita Giraldo-Chica,&nbsp;David Aguillon,&nbsp;Victoria Tirado,&nbsp;Ana Baena,&nbsp;Claudia Munoz,&nbsp;Natalia Acosta-Baena,&nbsp;Jeremy J. Pruzin,&nbsp;Valentina Ghisays,&nbsp;Silvia Rios-Romenets,&nbsp;Clara Vila-Castelar,&nbsp;Jairo E. Martínez,&nbsp;Averi Giudicessi,&nbsp;Pierre N. Tariot,&nbsp;Henrik Zetterberg,&nbsp;Kaj Blennow,&nbsp;Eric M. Reiman,&nbsp;Yakeel T. Quiroz","doi":"10.1002/alz.70421","DOIUrl":"https://doi.org/10.1002/alz.70421","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Plasma phosphorylated tau (p-tau)-231 is a promising biomarker for Alzheimer's disease (AD), particularly in preclinical stages. We evaluated its diagnostic value in presenilin 1 (<i>PSEN1</i>) E280A mutation carriers versus non-carriers and compared it to p-tau217 and neurofilament light chain (NfL).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We analyzed plasma p-tau231 in 722 carriers and 640 non-carriers (ages 18–75). Longitudinal data from 164 carriers and 132 non-carriers were available, with 137 carriers and 109 non-carriers having p-tau231, p-tau217, and NfL levels. Analyses used linear mixed effects models and restricted cubic splines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>E280A carriers had higher p-tau231 levels than non-carriers (9.0 ± 7.4 vs. 5.2 ± 3.4 pg/mL, <i>P</i> &lt; 0.001). Baseline p-tau231 levels correlated with age, distinguishing carriers at age 23. Rates of change differed at age 19, ≈ 25 years before cognitive impairment. In a subset, p-tau231 changes differentiated carriers by age 20, earlier than p-tau217 and NfL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Plasma p-tau231 is a sensitive biomarker for early AD detection and progression monitoring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Plasma phosphorylated tau (p-tau)231 levels are associated with age in presenilin 1 carriers and non-carriers.</li>\u0000 \u0000 <li>Baseline p-tau231 levels diverged between carriers and non-carriers at age 23.</li>\u0000 \u0000 <li>Plasma p-tau231 changes distinguished carriers by age 19, at very early stages.</li>\u0000 \u0000 <li>P-tau231 longitudinal changes differentiate carriers earlier than p-tau217 or neurofilament light chain.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70421","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520155","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":"Register now for the Alzheimer's Association International Conference®","authors":"","doi":"10.1002/alz.70415","DOIUrl":"https://doi.org/10.1002/alz.70415","url":null,"abstract":"&lt;p&gt;Join distinguished researchers, clinicians, and dementia professionals at the Alzheimer's Association International Conference&lt;sup&gt;®&lt;/sup&gt; (AAIC&lt;sup&gt;®&lt;/sup&gt;) July 27–31 in Toronto, Canada, and online.&lt;/p&gt;&lt;p&gt;At AAIC, the largest international conference on dementia research and clinical practice, attendees at all career stages share theories, breakthroughs, and best practices while exploring opportunities to accelerate their work and elevate their careers. To register for AAIC, visit alz.org/AAIC.&lt;/p&gt;&lt;p&gt;The AAIC scientific program is shaped by the work of researchers, clinicians and dementia professionals and designed to accelerate their work. Review the schedule at a glance and the full conference program (PDF) for a peek at the hundreds of podium presentations and thousands of posters on the latest discoveries, research and practice techniques from around the globe.&lt;/p&gt;&lt;p&gt;The recent U.S. Food and Drug Admin's clearance of the first blood test for Alzheimer's disease is an important step in obtaining an early and accurate diagnosis. The Alzheimer's Association is leading the development of clinical practice guidelines for blood-based biomarker tests, to help guide health care professionals on use of these tests. These guidelines will be presented at AAIC'25.&lt;/p&gt;&lt;p&gt;Plenary speakers for AAIC 2025 include the following:&lt;/p&gt;&lt;p&gt;Sunday, July 27:&lt;/p&gt;&lt;p&gt;Sylvia Villeneuve, PhD, Associate Professor, Department of Psychiatry, McGill University, Canada. Plenary session title: Biomarker and Clinical Trajectories of Preclinical AD.&lt;/p&gt;&lt;p&gt;Monday, July 28:&lt;/p&gt;&lt;p&gt;Katerina Akassoglou, PhD, Professor in the Department of Neurology, University of California, San Francisco, United States. Plenary session title: Neurovascular Interactions in Alzheimer's Disease: From Mechanisms to Treatments.&lt;/p&gt;&lt;p&gt;Maria Grazia Spillantini, PhD, Professor of Molecular Neurology in the Clinical School, University of Cambridge, United Kingdom. Plenary session title: The Multiple Facets of Tau Pathology.&lt;/p&gt;&lt;p&gt;Tuesday, July 29:&lt;/p&gt;&lt;p&gt;Inhee Mook-Jung, PhD, Professor, Department of Biochemistry and Biomedical Sciences, Seoul National University, Korea. Plenary session title: The Gut–Brain Axis in Alzheimer's Disease: Unraveling Pathogenesis and Exploring Novel Therapeutic Strategies.&lt;/p&gt;&lt;p&gt;Juan Fortea, MD, PhD, Memory Unit Director, Hospital de la Santa Creu i Sant Pau, Spain. Plenary session title: Alzheimer's Disease in Down Syndrome.&lt;/p&gt;&lt;p&gt;Wednesday, July 30:&lt;/p&gt;&lt;p&gt;Sharon Naismith, AM, Professor, Leonard P. Ullman Chair in Psychology, Charles Perkins Centre, University of Sydney, Australia. Plenary session title: Waking Up to the Importance of Sleep in MCI and AD.&lt;/p&gt;&lt;p&gt;Katrin Andreasson, MD, Edward F. and Irene Thiele Pimley Professor of Neurology and Neurological Sciences, Stanford University, United States. Plenary session title: Restoring Hippocampal Glucose Metabolism Rescues Cognition Across Alzheimer's Disease Pathologies.&lt;/p&gt;&lt;p&gt;Thursday, July 31:&lt;/p&gt;&lt;p&gt;Gill Livingston, MD, Pr","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70415","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492889","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":"Gait variability as a marker of white matter integrity in individuals with Down syndrome","authors":"Elizabeth M. Leach,&nbsp;David K. Powell,&nbsp;Amanda C. Glueck,&nbsp;Elizabeth Head,&nbsp;Moaz W. Ibrahim,&nbsp;Amelia J. Anderson-Mooney,&nbsp;Kathryn L. Van Pelt,&nbsp;Jordan P. Harp,&nbsp;Frederick A. Schmitt,&nbsp;Ahmed A. Bahrani","doi":"10.1002/alz.70407","DOIUrl":"https://doi.org/10.1002/alz.70407","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Individuals with Down syndrome (DS) face a significant risk of neurodegeneration, and gait variability may serve as a clinical biomarker of neurological health. This longitudinal parent substudy aimed to explore relationships between gait, white matter (WM) integrity, and cognitive function in DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The associations were investigated between magnetic resonance imaging diffusion tensor imaging (DTI), cognition, and self-paced gait data from 22 DS participants (mean age ± SD 37 ± 7.5 years).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>DTI measures, such as lower fractional anisotropy (FA) and higher mean diffusivity, were correlated with greater step time variability but not normalized velocities. Lower cognitive scores on the Vineland Adaptive Behavior Composite, Dementia Questionnaire for People with Learning Disabilities, and Motor Skill subscale were correlated with FA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Gait variability correlates with WM integrity and cognitive function in DS, suggesting that gait and DTI measures may serve as clinical markers of neurological decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Gait variability linked to white matter integrity in individuals with Down syndrome (DS).</li>\u0000 \u0000 <li>Lower fractional anisotropy and higher mean diffusivity are associated with increased step time variability in DS.</li>\u0000 \u0000 <li>Cognitive decline is tied to white matter changes in motor-related brain regions.</li>\u0000 \u0000 <li>Gait analysis alongside diffusion tensor imaging may aid in screening for cognitive impairment in DS.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70407","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503155","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":"Correction to “Machine learning prediction of tau-PET in Alzheimer's disease using plasma, MRI, and clinical data”","authors":"","doi":"10.1002/alz.70433","DOIUrl":"https://doi.org/10.1002/alz.70433","url":null,"abstract":"<p>Karlsson L, Vogel J, Arvidsson I, et al. Machine learning prediction of tau-PET in Alzheimer's disease using plasma, MRI, and clinical data. <i>Alzheimer Dement</i>. 2025;21(2):e14600. doi:10.1002/alz.14600</p><p>In Figure 5, the lower right grayscale confusion matrix is missing two values: 12 in the upper left cell and 19 in the center cell.</p><p>We apologize for this error.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70433","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492932","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":"Targeting dementia prevention with semaglutide: The case for APOE4 homozygotes","authors":"Timothy Daly,&nbsp;Bruno P. Imbimbo","doi":"10.1002/alz.70422","DOIUrl":"https://doi.org/10.1002/alz.70422","url":null,"abstract":"&lt;p&gt;In &lt;i&gt;Alzheimer's &amp; Dementia&lt;/i&gt;, Wang et al. used a target trial emulation approach based on U.S. electronic health records and reported a significant reduction in the first-time diagnosis of Alzheimer's disease (AD) among patients with type 2 diabetes mellitus (T2DM) treated with semaglutide.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; While their findings warrant cautious interpretation due to the potential for unmeasured confounding,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; they contribute to a growing body of evidence—including other target trial emulations&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; and systematic reviews and meta-analyses of randomized controlled trials (RCTs)&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;—supporting the neuroprotective effects of semaglutide.&lt;/p&gt;&lt;p&gt;Importantly, differences in the degree of neuroprotection appear to exist both within the class of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), to which semaglutide belongs,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; and between GLP-1 RAs and other cardioprotective glucose-lowering therapies.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; This suggests that semaglutide's neuroprotective effects are unlikely to be mediated solely by glycemic control, supporting its potential as a neuroprotective agent even in populations without T2DM. Experts commenting on recent findings involving antidiabetic drugs in dementia&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; have emphasized the need for RCTs to mitigate the risks of false positives (i.e., incorrectly concluding a protective effect) and false negatives (i.e., failing to detect a true benefit) inherent in observational studies. One such trial is the ongoing EVOKE and EVOKE+ study, which evaluates semaglutide versus placebo over 3 years in individuals with early symptomatic AD.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;However, the history of AD research has highlighted the importance of presymptomatic interventions and the slow progression to dementia along the AD continuum.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; To generate high-quality data on the neuroprotective effects of semaglutide in dementia prevention among individuals without T2DM, studies should target populations with a non-diabetic genetic risk profile in which conversion to dementia within a normal lifespan is certain or highly probable.&lt;/p&gt;&lt;p&gt;The small population with autosomal dominant AD could serve as one such model,&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; although recruitment would be limited by the rarity of the condition. In contrast, apolipoprotein E4 (&lt;i&gt;APOE4)&lt;/i&gt; homozygotes—who comprise approximately 2% of the general population—represent a group that develops dementia, on average, 7–10 years earlier than non-carriers.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; Furthermore, this population faces an elevated risk of developing serious amyloid-related imaging abnormalities (ARIA) with United States Food and Drug Administration (FDA)-approved lecanemab, rendering them ineligible for treatment in healthcare systems such as the European Union (EU), where lecanemab is contraindicated in &lt;i&gt;APOE4&lt;/i&gt; homozygotes. We ther","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492690","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":"Response to the letter titled “Targeting dementia prevention with semaglutide: the case for APOE4 homozygotes”","authors":"Rong Xu","doi":"10.1002/alz.70423","DOIUrl":"https://doi.org/10.1002/alz.70423","url":null,"abstract":"<p>To the Editor,</p><p>We appreciate the opportunity to address Dr. Daly and colleagues’ comments regarding our study.<span>¹</span> The author raised an interesting question that future studies shall focus on testing semaglutide, on Alzheimer's disease (AD) in high-risk patients with a nondiabetic genetic risk profile—those with apolipoprotein (<i>APOE</i>) ε4 homozygotes. The <i>APOE</i> ε4 allele remains the strongest genetic risk factor for sporadic AD<span>²</span>; however, ≈ 45% of dementia cases have been linked to 14 modifiable non-genetic risk factors, including diet, physical inactivity, diabetes, obesity, hypertension, high low-density lipoprotein cholesterol, smoking, alcohol drinking, sleep disorders, and depression.<span>³</span> Semaglutide has benefits in treating multiple modifiable AD risk factors, including obesity, type 2 diabetes, and cardiovascular and chronic kidney diseases, and appears to be promising for treating smoking and alcohol drinking<span>^4-9</span>. Emerging research suggests that semaglutide has anti-inflammatory and immunological properties<span>^{10, 11}</span> and that it improves vascular function.<span>^{5, 12}</span> Given its ability to target multiple non-genetic risk factors and proximal mechanisms of AD, focusing exclusively on individuals with <i>APOE</i> ε4 homozygotes may overlook important opportunities in other high-risk populations. However, we agree that the benefit and risk profiles of semaglutide may differ in people with different clinical and genetic characteristics, including <i>APOE</i> genotypes; therefore, a precision medicine approach is warranted.</p><p>The author declares no conflicts of interest. Author disclosures are available in the supporting information.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70423","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492694","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":"Synbiotics of Lactobacillus suilingensis and inulin alleviates cognitive impairment via regulating gut microbiota indole-3-lactic acid metabolism in female AD mice","authors":"Cong Yang,&nbsp;Jingxi Sun,&nbsp;Ling Li,&nbsp;Jin Zheng,&nbsp;Chuhan Wang,&nbsp;Yu Zhao,&nbsp;Duo Yun,&nbsp;Mengzhen Jia,&nbsp;Zhinan Wu,&nbsp;Hewei Liang,&nbsp;Wenxi Li,&nbsp;Tongyuan Hu,&nbsp;Rui Guo,&nbsp;Liang Xiao,&nbsp;Yuanqiang Zou,&nbsp;Zhigang Liu","doi":"10.1002/alz.70406","DOIUrl":"https://doi.org/10.1002/alz.70406","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Recent studies have found that gut microbial tryptophan metabolism is altered in Alzheimer's disease (AD) patients. However, the functional consequences of these changes and their therapeutic potential remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The metagenomic data of 49 preclinical AD patients and 115 healthy controls were analyzed. A synbiotic with targeted metabolic functions was formulated based on in vitro testing, and its effect on AD was evaluated using female 5×FAD mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Indole lactic acid (ILA) synthesis was downregulated in AD patients. Synbiotic treatment combining <i>Lactobacillus suilingensis</i> and inulin outperformed probiotic treatment alone in enhancing tryptophan metabolism, and increasing ILA biosynthesis. Increased ILA could reduce Aβ accumulation and significantly alleviate cognitive impairment in female AD mice by inhibiting neuroinflammation through activation of the aryl hydrocarbon receptor (AhR) signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study highlights the therapeutic potential of targeting gut microbial tryptophan metabolism in AD and provides a rationale for future precision strategies aimed at modulating microbiota-derived metabolic pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Gut metagenomic analysis reveals reduced indole lactic acid (ILA) biosynthesis genes in preclinical AD patients.</li>\u0000 \u0000 <li>Screening and formulating ILA-producing synbiotic by using whole-genome analysis.</li>\u0000 \u0000 <li>Synbiotic treatment alleviates cognitive impairment and promotes ILA synthesis in female 5×FAD mice.</li>\u0000 \u0000 <li>ILA alleviates neuroinflammation in female 5×FAD mice by activating aryl hydrocarbon receptor (AhR) in the brain.</li>\u0000 \u0000 <li>Synbiotic targeting tryptophan metabolism provides a novel approach for Alzheimer's intervention.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70406","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492585","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":"Subjective cognitive decline among diverse older adults: Prevalence and associations with objective cognition","authors":"Sarah Tomaszewski Farias,&nbsp;Iris Leng,&nbsp;Kathryn Papp,&nbsp;Anika Mehra,&nbsp;Michelle Chan,&nbsp;Michelle York,&nbsp;Bonnie C. Sachs,&nbsp;Kristin R. Krueger,&nbsp;Athene Lee,&nbsp;Rachel Whitmer,&nbsp;Heather M. Snyder,&nbsp;Laura D. Baker,&nbsp;for the U.S. POINTER Study Group","doi":"10.1002/alz.70432","DOIUrl":"https://doi.org/10.1002/alz.70432","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Subjective cognitive decline (SCD) may precede objective cognitive impairment. We examined prevalence, type of SCD, and associations with neuropsychological measures among diverse older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The sample included older adults from three ethnoracial groups enrolled in the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (POINTER) trial. Everyday Cognition (ECog) measured SCD, and neuropsychological function was assessed using global memory, executive function, and processing speed composites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Hispanic/Latinx participants were more likely to report SCD than non-Hispanic White (NHW) or Black participants, particularly executive function concerns. In the full sample, adjusting for demographics and depression, SCD ratings were associated with most neuropsychological outcomes. In analyses stratified by ethnoracial group, SCD ratings were associated with many of the neuropsychological domains in NHW participants and with processing speed among Black participants; no association was observed in Hispanic/Latinx participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Prevalence, type of SCD, and associations with cognition varied by ethnoracial group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CLINICAL TRIAL REGISTRATION NUMBER</h3>\u0000 \u0000 <p>NCT03688126 (ClinicalTrials.gov).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Hispanic/Latinx participants endorsed greater subjective cognitive decline (SCD) than other ethnoracial groups.</li>\u0000 \u0000 <li>Hispanic/Latinx participants were more likely to endorse executive function concerns.</li>\u0000 \u0000 <li>SCD was associated with several neuropsychological domains in non-Hispanic White participants.</li>\u0000 \u0000 <li>SCD was related to processing speed for Black participants.</li>\u0000 \u0000 <li>SCD was unrelated to objective cognitive performance in Hispanic/Latinx participants.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70432","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492586","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":"Bridging perspectives: The value of collaboration between Traditional Healing Practitioners and Medical Doctors in dementia research and care in South Africa","authors":"Eimear McGlinchey,&nbsp;Kirti Ranchod,&nbsp;Rayne Stroebel,&nbsp;Bongiwe Lusizi,&nbsp;Miriam Galvin,&nbsp;Atholl Valdon Kleinhans,&nbsp;Juan Fortea,&nbsp;Jaco Hoffman,&nbsp;Sinethemba Makanya","doi":"10.1002/alz.70370","DOIUrl":"https://doi.org/10.1002/alz.70370","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;Traditional Healing Practitioners (THPs) provide care to the majority of the population in South Africa. Despite their widespread presence, they remain largely excluded from dementia research and policy. This reinforces healthcare inequities and overlooks the realities of communities where THPs provide care.&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;This paper explores the role of THPs in dementia care by examining literature in South Africa. It identifies key barriers to collaboration between THPs and medical doctors and discusses pathways for integration.&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;Barriers include epistemological historical marginalization, mutual distrust, fragmented care pathways, and language barriers. These challenges hinder knowledge exchange and joint dementia care strategies.&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;Strengthening relationships through structured engagement, bidirectional knowledge exchange, and ethical collaboration could bridge the gap between THPs and Medical Doctors (MDs). A pluralistic, integrated model valuing both systems could lead to more equitable and effective dementia care.&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;The majority of people in South Africa engage with Traditional Healing Practitioners (THPs) as part of their healthcare, yet THPs remain largely excluded from dementia research and policy.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Barriers to collaboration between THPs and Medical Doctors (MDs) include historical marginalization, mutual distrust, fragmented care pathways, and language differences.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Integrating THPs and MDs through structured engagement, bidirectional knowledge exchange, and ethical collaboration could enhance dementia care.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Shifting away from the binary opposition of Indigenous Knowledge Systems (IKS) and biomedical approaches toward a more integrated and collaborative model of dementia care could lead to more equitable and effective healthcare.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The FUNDISA (Framework for Understanding Neurocognitive Disorders via Indigenous Systems in South Africa) project aims to understand how dementia is conceptualized by THPs and foster collaboration between THPs and MDs to support e","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482240","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}