Alzheimer's & Dementia最新文献

{"title":"Sociodemographic modifiers of effects of statin initiation on dementia incidence: An emulated trial design in a large health care member population with 10+ years of follow-up","authors":"Minhyuk Choi,&nbsp;Scott C. Zimmerman,&nbsp;Chen Jiang,&nbsp;Jingxuan Wang,&nbsp;Kaitlin Swinnerton,&nbsp;Thomas J. Hoffmann,&nbsp;Akinyemi Oni-Orisan,&nbsp;Erin L. Ferguson,&nbsp;Travis Meyers,&nbsp;Vidhu Choudhary,&nbsp;Rachel A. Whitmer,&nbsp;Neil Risch,&nbsp;Ronald M. Krauss,&nbsp;Catherine M. Schaefer,&nbsp;M. Maria Glymour,&nbsp;Paola Gilsanz","doi":"10.1002/alz.14627","DOIUrl":"https://doi.org/10.1002/alz.14627","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Mixed evidence on how statin use affects risk of Alzheimer's disease and related dementias (ADRD) may reflect heterogeneity across sociodemographic factors. Few studies have sufficient power to evaluate effect modifiers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Kaiser Permanente Northern California (KPNC) members (<i>n</i> = 705,061; <i>n</i> = 202,937 with sociodemographic surveys) who initiated statins from 2001 to 2010 were matched on age and low-density lipoprotein cholesterol (LDL-C) with non-initiators and followed through 2020 for incident ADRD. Inverse probability-weighted Cox proportional hazards models were used to evaluate effect modification by age, gender, race/ethnicity, education, marital status, income, and immigrant generation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Statin initiation (vs non-initiation) was not associated with ADRD incidence in any of the 32 subgroups (<i>p</i> &gt; .05). Hazard ratios ranged from 0.964 (95% CI: 0.923 to 1.006) among Asian-identified participants to 1.122 (95% CI: 0.995 to 1.265) in the highest income category.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Sociodemographic heterogeneity appears to have little to no influence on the relationship between statin initiation and dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The study includes a large and diverse cohort from Kaiser Permanente (<i>N</i> = 705,061).</li>\u0000 \u0000 <li>An emulated trial design of statin initiation on dementia incidence was used.</li>\u0000 \u0000 <li>Effect modification by sociodemographic factors was assessed.</li>\u0000 \u0000 <li>There were no significant Alzheimer's disease and related dementias (ADRD) risk differences in 32 sociodemographic subgroups (<i>p</i> &gt; 0.05).</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14627","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726832","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":"Accountable care organizations and Medicare payments for residents with ADRD in disadvantaged neighborhoods","authors":"Seyeon Jang,&nbsp;Jie Chen","doi":"10.1002/alz.70067","DOIUrl":"https://doi.org/10.1002/alz.70067","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Accountable care organizations (ACOs) are well positioned to promote care coordination. However, robust evidence of ACOs’ impact on Medicare payments for residents with Alzheimer's disease and related dementias (ADRD) in disadvantaged neighborhoods remains limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using a 2016 to 2020 longitudinal dataset, we examined the effects of ACO enrollment on Medicare payments for people newly diagnosed with ADRD, focusing on the neighborhood Social Vulnerability Index (SVI) and its subcategories. Multivariable generalized estimating equation (GEE) models were applied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>ACO enrollment was associated with significantly reduced total payments across all SVI subcategories. The highest cost savings were observed among ADRD patients living in neighborhoods with high proportions of racial and ethnic minorities. Results also showed that higher quality ACOs were associated with lower total payments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>ACOs have a great potential to save health-care costs for beneficiaries with ADRD living in socially vulnerable neighborhoods, particularly for those residing in areas with higher proportions of racial and ethnic minority populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Accountable care organizations (ACOs) reduced Medicare payments for Alzheimer's disease and related dementias across neighborhood disadvantage levels.</li>\u0000 \u0000 <li>The cost reductions varied by specific indicators of social vulnerability.</li>\u0000 \u0000 <li>Highest cost savings were found among residents living with high proportion of racial/ethnic minorities.</li>\u0000 \u0000 <li>Cost savings were the greatest among the highest quality ACOs.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726854","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 biomarkers distinguish Boston Criteria 2.0 cerebral amyloid angiopathy from healthy controls","authors":"Ryan T. Muir,&nbsp;Sophie Stukas,&nbsp;Jennifer G. Cooper,&nbsp;Andrew E. Beaudin,&nbsp;Cheryl R. McCreary,&nbsp;Myrlene Gee,&nbsp;Krista Nelles,&nbsp;Nikita Nukala,&nbsp;Janina Valencia,&nbsp;Kristopher M. Kirmess,&nbsp;Sandra E. Black,&nbsp;Michael D. Hill,&nbsp;Richard Camicioli,&nbsp;Cheryl L. Wellington,&nbsp;Eric E. Smith","doi":"10.1002/alz.70010","DOIUrl":"https://doi.org/10.1002/alz.70010","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Cerebral amyloid angiopathy (CAA) is characterized by the deposition of beta-amyloid (Aβ) in small vessels leading to hemorrhagic stroke and dementia. This study examined whether plasma Aβ_42/40, phosphorylated-tau (p-tau), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) differ in CAA and their potential to discriminate Boston Criteria 2.0 probable CAA from healthy controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Plasma Aβ_42/40, p-tau-181, NfL, and GFAP were quantified using single molecule array (Simoa) and Aβ_42/40 was also independently quantified using immunoprecipitation liquid chromatography mass-spectrometry (IPMS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Forty-five participants with CAA and 47 healthy controls had available plasma. Aβ_42/40 ratios were significantly lower in CAA than healthy controls. While p-tau-181 and NfL were elevated in CAA, GFAP was similar. A combination of Aβ_42/40 (Simoa), p-tau-181, and NfL resulted in an area under the curve of 0.90 (95% confidence interval: 0.80, 0.95).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Plasma Aβ_42/40, p-tau-181, and NfL differ in those with CAA and together can discriminate CAA from healthy controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Participants with CAA had reduced plasma Aβ_42/40 ratios compared to controls.</li>\u0000 \u0000 <li>Plasma p-tau-181 and NfL concentrations are elevated in CAA compared to controls.</li>\u0000 \u0000 <li>Plasma GFAP was similar in CAA and controls.</li>\u0000 \u0000 <li>Together, plasma Aβ_42/40, p-tau-181, and NfL had excellent discriminability for CAA.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726814","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":"A look at caregivers for community-living persons with dementia: Implications for the GUIDE model","authors":"Julia G. Burgdorf,&nbsp;Vicki A. Freedman,&nbsp;Jennifer L. Wolff","doi":"10.1002/alz.70013","DOIUrl":"https://doi.org/10.1002/alz.70013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Medicare's new Guiding an Improved Dementia Experience (GUIDE) model funds integrated dementia care and related caregiver supports for community-living persons with dementia (PwD). Caregiver strain is a factor in provider payment and performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We examined national survey data on community-living PwD and their caregivers to identify which caregivers would receive support under GUIDE and characterize caregiver strain and use of supportive services.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Half of GUIDE-eligible PwD received care from multiple caregivers and high strain was common even among caregivers considered “low-complexity” under GUIDE. Use of role-related training, respite care, and support groups were low (11%, 18%, and 4%, respectively) and did not vary with caregiver strain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Caregiver identification and assessment standards under GUIDE may overlook a significant number of caregivers. To maximize impact, innovative models like GUIDE should align caregiver engagement and services with the unique realities of care networks for PwD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Half of GUIDE-eligible persons with dementia have multiple caregivers.</li>\u0000 \u0000 <li>32% of caregivers for community-living PwD report high strain.</li>\u0000 \u0000 <li>11% of caregivers for community-living PwD received training and 18% used respite care.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726827","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":"Unraveling temporal patterns of diagnostic markers and comorbidities in Alzheimer's disease: Insights from large-scale data","authors":"Bayard Rogers","doi":"10.1002/alz.14564","DOIUrl":"https://doi.org/10.1002/alz.14564","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;Comorbid conditions associated with Alzheimer's disease (AD) are poorly understood regarding timing and potential impact on disease onset and progression.&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;Medical Information Mart for Intensive Care-IV electronic health records from 2008 to 2019 were examined. The study identified 2527 AD patients (34.9% male, mean age 80.27 years) among 299,712 patients. We examined the timing of 12 cardiovascular and metabolic diseases relative to AD diagnosis. Data from the National Alzheimer's Coordinating Center validated the findings.&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;Hypertension was the most common comorbidity, diagnosed 1.09 years before AD. Depression was the only comorbidity diagnosed after AD start, 0.16 years on average. AD patients had greater rates of hypertension, hypercholesterolemia, and depression compared to the general population.&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;The findings emphasize early detection and therapy of AD-related comorbidities, notably cardiovascular and metabolic diseases. The temporal link between these diseases and AD suggests opportunities for preventive strategies and improved care pathways.&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;&lt;b&gt;Temporal analysis of comorbidities&lt;/b&gt;: The study reveals hypertension and hyperlipidemia as leading precursors to AD, typically diagnosed 1 to 1.3 years prior to AD onset, while depression emerges predominantly after diagnosis.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;&lt;b&gt;Unique data integration&lt;/b&gt;: Large-scale datasets from MIMIC-IV (&lt;i&gt;n&lt;/i&gt; = 299,712) and NACC (&lt;i&gt;n&lt;/i&gt; = 51,836) were leveraged to identify chronological patterns in 12 key comorbid conditions relative to AD diagnosis.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;&lt;b&gt;Sex- and age-specific insights&lt;/b&gt;: AD prevalence peaks at 80 to 86 years, with females exhibiting higher rates of LOAD compared to males.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;&lt;b&gt;Depression as a post-diagnostic marker&lt;/b&gt;: Unlike other comorbidities, depression's post-diagnostic mean onset (0.16 years after AD diagnosis) highlights the need for targeted mental health interventions in AD patients.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;&lt;b&gt;Implications for early detection&lt;/b&gt;: Findings suggest that managing hypertension, hyperli","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14564","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726829","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":"Diagnostic accuracy of plasma p-tau217/Aβ42 for Alzheimer's disease in clinical and community cohorts","authors":"Jun Wang,&nbsp;Shan Huang,&nbsp;Guoyu Lan,&nbsp;Yu-Jie Lai,&nbsp;Qing-Hua Wang,&nbsp;Yang Chen,&nbsp;Zhong-Song Xiao,&nbsp;Xiao Chen,&nbsp;Xian-Le Bu,&nbsp;Yu-Hui Liu,&nbsp;Fan Zeng,&nbsp;Laihong Zhang,&nbsp;Anqi Li,&nbsp;Yue Cai,&nbsp;Pan Sun,&nbsp;Zhengbo He,&nbsp;Vincent Doré,&nbsp;Jurgen Fripp,&nbsp;Pierrick Bourgeat,&nbsp;Qin Chen,&nbsp;Jin-Tai Yu,&nbsp;Yi Tang,&nbsp;Henrik Zetterberg,&nbsp;Colin L. Masters,&nbsp;Tengfei Guo,&nbsp;Yan-Jiang Wang,&nbsp;for the Translational Biomarker Research of AgIng and Neurodegeneration (TBRAIN)","doi":"10.1002/alz.70038","DOIUrl":"https://doi.org/10.1002/alz.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>This study was undertaken to evaluate the diagnostic performance of a novel plasma phosphorylated tau (p-tau) 217/amyloid beta (Aβ) 42 ratio test for Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The diagnostic performance of the Lumipulse G plasma p-tau217/Aβ42 ratio was evaluated using Aβ and tau positron emission tomography (PET) as reference standards in a clinic cohort (<i>n</i> = 391) and a community cohort (<i>n</i> = 121).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Plasma p-tau217/Aβ42 exhibited high performance for abnormal statuses of Aβ PET (area under the curve [AUC]: 0.963 to 0.966) and tau PET (AUC: 0.947 to 0.974), which were clinically equivalent to those of cerebrospinal fluid (CSF) p-tau181/Aβ42 and Aβ42/Aβ40 and higher than those of blood p-tau217, Aβ42/Aβ40, p-tau181, and p-tau181/Aβ42 in both clinic and community cohorts. Applying a two-cutoff approach improved the specificity without reducing sensitivity. The p-tau217/Aβ42 ratio had a lower intermediate percentage than p-tau217 alone in both clinic (10.6% vs 13.0%) and community (16.5% vs 31.4%) cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Plasma p-tau217/Aβ42 has high performance in detecting cerebral AD pathologies, thus offering a promising tool for clinical diagnosis and community screening of AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Lumipulse G plasma p-tau217 and the p-tau217/Aβ42 ratio accurately identified abnormal Aβ and tau PET statuses in both clinical and community cohorts.</li>\u0000 \u0000 <li>The performance of plasma p-tau217 and p-tau217/Aβ42 ratio were equivalent to CSF tests.</li>\u0000 \u0000 <li>Plasma p-tau217/Aβ42 ratio outperformed p-tau217 alone in identifying Aβ PET positivity, and this superiority is more obvious in the community cohort, suggesting an advantage in the early diagnosis of AD.</li>\u0000 \u0000 <li>Two cut points of p-tau217/Aβ42 were established in the Chinese population for clinical laboratory and community screening uses.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726831","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":"Multi-omics delineate growth factor network underlying exercise effects in an Alzheimer's mouse model","authors":"Xin Li,&nbsp;Chaozhong Liu,&nbsp;Wenbo Li,&nbsp;Guantong Qi,&nbsp;Yanwan Dai,&nbsp;Chaohao Gu,&nbsp;Yuxiang Sun,&nbsp;Wenjun Zhou,&nbsp;Veronica C. Ciliberto,&nbsp;Jing Liang,&nbsp;Udhaya Kumar S,&nbsp;Dongyin Guan,&nbsp;Zhaoyong Hu,&nbsp;Hui Zheng,&nbsp;Zhandong Liu,&nbsp;Hu Chen,&nbsp;Ying-Wooi Wan,&nbsp;Zheng Sun","doi":"10.1002/alz.70024","DOIUrl":"https://doi.org/10.1002/alz.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Physical exercise is a primary defense against age-related cognitive decline and Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We conducted single-nucleus transcriptomic and chromatin accessibility analyses (snRNA-seq and snATAC-seq) on the hippocampus of mice carrying mutations in the amyloid precursor protein gene (APP^NL-G-F) following prolonged voluntary wheel-running exercise.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Exercise mitigates amyloid-induced changes in transcriptome and chromatin accessibility through cell type–specific regulatory networks converging on growth factor signaling, particularly the epidermal growth factor receptor (EGFR) signaling. The beneficial effects of exercise on neurocognition can be blocked by pharmacological inhibition of EGFR and its downstream PI3K signaling. Exercise leads to elevated levels of heparin-binding EGF (HB-EGF), and intranasal administration of HB-EGF enhances memory function in sedentary APP^NL-G-F mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings offer a panoramic delineation of cell type–specific hippocampal transcriptional networks activated by exercise and suggest EGFR signaling as a druggable contributor to exercise-induced memory enhancement to combat AD-related cognitive decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>snRNA-seq and snATAC-seq analysis of APP^NL-G-F mice after prolonged wheel-running.</li>\u0000 \u0000 <li>Exercise counteracts amyloid-induced transcriptomic and accessibility changes.</li>\u0000 \u0000 <li>Networks converge on the activation of EGFR and insulin signaling.</li>\u0000 \u0000 <li>Pharmacological inhibition of EGFR and PI3K blocked cognitive benefits of exercise.</li>\u0000 \u0000 <li>Intranasal HB-EGF administration enhances memory in sedentary APP^NL-G-F mice.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726830","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":"Primary care preparedness to care for patients with ADRD: A national survey study","authors":"Joseph Januszewicz,&nbsp;Nicole R. Fowler,&nbsp;Matthew B. Mackwood,&nbsp;Elliott Fisher,&nbsp;Alice O. Andrews,&nbsp;Rachel O. Schmidt,&nbsp;Ellesse-Roselee L. Akré,&nbsp;Karen E. Schifferdecker","doi":"10.1002/alz.70064","DOIUrl":"https://doi.org/10.1002/alz.70064","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>It is unknown how prepared primary care practices are to deliver recommended dementia care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A nationally representative survey of US primary care practices focused on care delivery processes, including those for patients with Alzheimer's disease and related dementias (ADRD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>A total of 1245 of 3498 practices (36%) responded. Most practices reported systems to detect patients with ADRD (67%) and refer patients for diagnostic testing (75%). Fewer required ADRD-related training (45%–46%) or maintained an ADRD registry (29%). Practices that scored higher on ADRD care preparedness were more likely to be smaller, receive a higher proportion of revenue from Medicare, and have other important practice capabilities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Primary care practices have mixed preparedness to care for patients with ADRD. Efforts to boost ADRD preparedness, including providing adequate infrastructure and resources directly to primary care, should be a priority to address disparities in diagnosis and to optimize the patient and caregiver journey.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Mixed ADRD preparedness identified in primary care practices across the United States.</li>\u0000 \u0000 <li>Practices often lack ADRD-specific registries and staff training initiatives.</li>\u0000 \u0000 <li>Medicare-reliant and larger physician-owned groups show higher ADRD preparedness.</li>\u0000 \u0000 <li>FQHCs reported lower ADRD preparedness, highlighting potential gaps in care.</li>\u0000 \u0000 <li>Cultural awareness and other support services correlate with better ADRD readiness.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726828","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 protein risk scores for mild cognitive impairment and Alzheimer's disease in the Framingham heart study","authors":"Habbiburr Rehman,&nbsp;Ting Fang Alvin Ang,&nbsp;Qiushan Tao,&nbsp;Rhoda Au,&nbsp;Lindsay A. Farrer,&nbsp;Wei Qiao Qiu,&nbsp;Xiaoling Zhang,&nbsp;for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/alz.70066","DOIUrl":"https://doi.org/10.1002/alz.70066","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>It is unclear whether aggregated plasma protein risk scores (PPRSs) could be useful in predicting the risks of mild cognitive impairment (MCI) and Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The Cox proportional hazard model with the Least Absolute Shrinkage and Selection Operator penalty was used to build the PPRSs for MCI and AD in 1515 Framingham Heart Study Generation 2 with 1128 proteins measured in plasma at exam 5 (cognitively normal [CN] = 1258, MCI = 129, AD = 128).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>MCI PPRS had a hazard ratio (HR) of 6.97 [5.34, 9.12], with a discriminating power (C-index = 82.52%). AD PPRS had a HR of 5.74 [4.67, 7.05] (C-index = 88.15%). Both PPRSs were also significantly associated with cognitive changes, brain atrophy, and plasma AD biomarkers. Proteins in the MCI and AD PPRSs were involved in several pathways related to leukocyte, chemotaxis, immunity, inflammation, and cellular migration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study suggests that PPRSs serve well to predict the risk of developing MCI and AD as well as cognitive changes and AD-related pathogenesis in the brain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>PPRSs were developed for the risk of AD and AD preclinical stage, MCI.</li>\u0000 \u0000 <li>PPRSs were developed for MCI and AD associated with cognitive changes, loss of brain volume, and increasing level of plasma AD biomarkers.</li>\u0000 \u0000 <li>Leukocyte, chemotaxis, immunity, inflammation, and cellular migration enriched in proteins were identified as being involved in MCI and AD PPRSs.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726833","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":"Social cognition in mild cognitive impairment and dementia: A systematic review and meta-analysis","authors":"Puyu Shi,&nbsp;Hannah Chapman,&nbsp;Lisa Liu,&nbsp;Fern Rodgers,&nbsp;Jasmine Shaw,&nbsp;Gill Livingston,&nbsp;Katherine P. Rankin,&nbsp;Jason D. Warren,&nbsp;Andrew Sommerlad","doi":"10.1002/alz.70076","DOIUrl":"https://doi.org/10.1002/alz.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Social cognition is impaired in people with dementia but the differences in social cognitive impairment between mild cognitive impairment (MCI) and dementia and its subtypes remain unclear. We therefore aimed to systematically review and meta-analyze differences in emotion recognition, theory of mind (ToM), and empathy between individuals with MCI and dementia. Across 28 cross-sectional studies (<i>n</i> = 2409), people with MCI had better emotion recognition (Cohen's <i>d</i> = 0.69) and ToM (<i>d</i> = 0.70) than individuals with Alzheimer's disease (AD) dementia, and larger effect sizes were observed for people with frontotemporal dementia (FTD) (emotion recognition (<i>d</i> = 2.09), ToM (<i>d</i> = 1.49), but emotional empathy was higher in AD than in MCI in included studies. Our findings suggest a progressive decline of aspects of social cognition across the MCI–dementia continuum. Longitudinal studies should investigate the diagnostic role of social cognition deficits in MCI progression to dementia, and interventions for social cognition in MCI should be developed and tested.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>First systematic review and meta-analysis comparing social cognition between mild cognitive impairment (MCI) and dementia subtypes.</li>\u0000 \u0000 <li>Findings from 28 studies with 2409 participants show people with MCI outperform those with Alzheimer's disease (AD) and frontotemporal dementia (FTD) in emotion recognition and theory of mind.</li>\u0000 \u0000 <li>Empathy appears intact in AD dementia, suggesting that this cognitive domain is preserved throughout disease progression.</li>\u0000 \u0000 <li>Evaluation of social cognition should be built into dementia assessment as it may hold diagnostic value.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707446","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}