Alzheimer's & Dementia最新文献

{"title":"Alzheimer's disease and dementia in Japan: Epidemiological trends, regional disparities, and future projections","authors":"Deepak Kumar Behera,&nbsp;Dil B. Rahut,&nbsp;Snehasish Tripathy","doi":"10.1002/alz.70444","DOIUrl":"https://doi.org/10.1002/alz.70444","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease and other dementias (ADOD) are a growing public health concern in Japan. This study examines historical ADOD burden trends, identifies contributing risk factors, and forecasts future projections using time-series modeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This study uses the Global Burden of Disease (GBD) study 2021 data to analyze ADOD trends in Japan, and assess incidence, mortality, and Disability-adjusted life years (DALYs). Regression analysis identifies risk factors, and an Autoregressive Integrated Moving Average (ARIMA) model is employed to forecasts the burden from 2021 to 2030.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>ADOD cases have steadily increased, with projections indicating continued growth by 2030. Aging and life expectancy are major contributors, with urban areas like Kantō and Kansai region experiencing higher prevalence than Tōhoku and Kyūshū. High fasting plasma glucose, obesity, and smoking are significant modifiable risk factors. The ARIMA model forecasts an ongoing upward trend, highlighting a rising public health challenge.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Targeted policies, early interventions, and equitable health care access are vital to mitigating Japan's growing ADOD burden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Alzheimer's disease and other dementias (ADOD) are rising in Japan due to an aging population.</li>\u0000 \u0000 <li>Key risk factors include high fasting plasma glucose, obesity, and smoking.</li>\u0000 \u0000 <li>Kantō and Kansai region have higher ADOD prevalence than other region</li>\u0000 \u0000 <li>ARIMA modeling predicts a continuous increase in ADOD cases through 2030.</li>\u0000 \u0000 <li>Targeted health care policies and preventive measures are crucial to mitigate the burden.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582316","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":"Discrepancies between CSF biomarker and PET determinations of elevated brain amyloid and their prognostic significance","authors":"David S. Knopman,&nbsp;Stephen D. Weigand,&nbsp;Heather J. Wiste,&nbsp;Jonathan Graff-Radford,&nbsp;Neill R. Graff-Radford,&nbsp;Ronald C. Petersen,&nbsp;Bradley F. Boeve,&nbsp;Clifford R Jack Jr,&nbsp;Val J. Lowe,&nbsp;Mary M. Machulda,&nbsp;Julie A. Fields,&nbsp;Vijay K. Ramanan,&nbsp;Hugo Botha,&nbsp;Stuart J. McCarter,&nbsp;David T. Jones,&nbsp;Bryan J. Neth,&nbsp;Gregory S. Day,&nbsp;Kejal Kantarci,&nbsp;Alicia Algeciras-Schimnich,&nbsp;Joshua A. Bornhorst,&nbsp;Derek R. Johnson,&nbsp;and the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/alz.70468","DOIUrl":"https://doi.org/10.1002/alz.70468","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>When cerebrospinal fluid (CSF) and positron emission tomography (PET) measurements for amyloid-beta-peptide (Aβ) related pathology are discordant, therapeutic decision-making becomes uncertain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using data from patients with mild cognitive impairment (<i>n</i> = 541) from the Alzheimer's Disease Neuroimaging Initiative, we examined baseline characteristics and longitudinal clinical outcomes in persons grouped according to normal/abnormal Aβ via concurrent CSF and PET determinations using standard cutpoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Discordant groups for brain Aβ status (CSF+/PET− and CSF−/PET+) each represented about 5% of the mild cognitive impairment (MCI) population. Longitudinally, neither discordant group declined more than the CSF−/PET− group on either a memory measure or the Clinical Dementia Rating Sum of Boxes scores over a median 4 years of observation, while the CSF+/PET+ group exhibited worsening on both measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>In contrast to the clinical decline observed in the CSF+/PET+ group, persons with MCI and CSF+/PET− or CSF−/PET+ brain amyloid patterns did not exhibit incipient decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Discrepant abnormal cerebrospinal fluid (CSF) and positron emission tomography (PET) brain amyloid indicators are uncommon in mild cognitive impairment (MCI).</li>\u0000 \u0000 <li>CSF-PET discrepant persons with MCI tend to have less abnormal values initially.</li>\u0000 \u0000 <li>CSF-PET discrepant persons with MCI have a benign prognosis at 4 years.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582317","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 Alzheimer's disease-associated complement receptor 1 variant confers risk by impacting glial phagocytosis","authors":"Nikoleta Daskoulidou,&nbsp;Bethany Shaw,&nbsp;Wioleta Milena Zelek,&nbsp;Bryan Paul Morgan","doi":"10.1002/alz.70458","DOIUrl":"https://doi.org/10.1002/alz.70458","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Genome-wide association studies have implicated complement in Alzheimer's disease (AD). The <i>CR1*2</i> variant of complement receptor 1 (CR1; CD35), confers increased AD risk. We confirmed CR1 expression on glial cells; however, how CR1 variants influence AD risk remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Induced pluripotent stem cell-derived microglia and astrocytes were generated from donors homozygous for the common CR1 variants (CR1*1/CR1*1;CR1*2/CR1*2). CR1 expression was quantified and phagocytic activity assessed using diverse targets (<i>Escherichia coli</i> bioparticles, amyloid β aggregates, and synaptoneurosomes), with or without serum opsonization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Expression of CR1*1 was significantly higher than CR1*2 on glial lines. Phagocytosis for all targets was markedly enhanced following serum opsonization, attenuated by Factor I-depletion, demonstrating CR1 requirement for C3b processing. CR1*2-expressing glia showed significantly enhanced phagocytosis of all opsonized targets compared to CR1*1-expressing cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>CR1 is critical for glial phagocytosis of opsonized targets. CR1*2, despite lower expression, enhances glial phagocytosis, providing mechanistic explanation of increased AD risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Induced pluripotent stem cell (iPSC)-derived glia from individuals expressing the Alzheimer's disease (AD) risk variant complement receptor (CR) 1*2 exhibit lower CR1 expression compared to those from donors expressing the non-risk form CR1*1.</li>\u0000 \u0000 <li>The iPSC-derived glia from individuals expressing the AD risk variant CR1*2 exhibit enhanced phagocytic activity for opsonized bacterial particles, amyloid-β aggregates and human synaptoneurosomes compared to those from donors expressing the non-risk form CR1*1.</li>\u0000 \u0000 <li>We suggest that expression of the CR1*2 variant confers risk of AD by enhancing the phagocytic capacity of glia for opsonized targets.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70458","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582315","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":"Leptin levels are associated with body mass index and Alzheimer's disease in Down syndrome","authors":"Lorena Sordo,&nbsp;Annie Du,&nbsp;Vinutha Sandadi,&nbsp;Farheen B. Dustagheer,&nbsp;Jesse Pascual,&nbsp;Phong Ngo,&nbsp;Christy L. Hom,&nbsp;Eric Doran,&nbsp;Elizabeth Head","doi":"10.1002/alz.70448","DOIUrl":"https://doi.org/10.1002/alz.70448","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Higher body mass index (BMI) is linked to greater risk of Alzheimer's disease (AD) and elevated plasma leptin levels correlate with cognitive decline and AD. Since obesity is a frequent feature in individuals with Down syndrome (DS), we investigated the association between obesity, the leptin pathway, and AD neuropathology in people with DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Plasma concentrations of leptin and AD biomarkers were measured in 40 individuals (aged controls, Down syndrome and Alzheimer's disease [DSAD], and AD participants). Frontal cortex leptin, leptin receptors (LepRs), and leptin-associated proteins were measured in 73 individuals with DS, DSAD, and AD, and compared to age-matched controls using immunohistochemistry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Individuals with DSAD had the highest plasma leptin levels, as well as the highest leptin resistance index and brain leptin deficiency. Plasma leptin levels were significantly associated with staging of AD neuropathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Leptin has the potential to be an early indicator and therapeutic target for AD in people with and without DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Plasma leptin levels are increased in Down syndrome and Alzheimer's disease (DSAD).</li>\u0000 \u0000 <li>Leptin resistance and brain leptin deficiency are present in Down syndrome (DS) and DSAD.</li>\u0000 \u0000 <li>Plasma leptin levels are positively associated with staging of Alzheimer's disease (AD) neuropathology.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589537","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":"Comprehensive characterization of the RNA editing landscape in the human aging brains with Alzheimer's disease","authors":"Amit Kumar Gupta,&nbsp;William Martin,&nbsp;Andrew A. Pieper,&nbsp;Yinsheng Wang,&nbsp;Andrew J. Saykin,&nbsp;Feixiong Cheng","doi":"10.1002/alz.70452","DOIUrl":"https://doi.org/10.1002/alz.70452","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;While RNA editing has been linked to Alzheimer's disease (AD), its specific impact on the transcriptomic landscape in human AD brains remains under explored.&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;We conducted a comprehensive analysis of RNA editing across nine human brain regions affected by AD, utilizing RNA-seq data and matched whole-genome sequencing data from three human brain biobanks, adjusting for age, &lt;i&gt;post mortem&lt;/i&gt; interval, sex, and apolipoprotein E4 (&lt;i&gt;APOE4)&lt;/i&gt; status.&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;RNA-editing events were identified in both AD and healthy control aging brains, highlighting 127 genes with significant RNA editing loci. AD exhibited elevated RNA editing in the parahippocampal gyrus and cerebellar cortex. We also discovered 147 colocalized genome-wide association studies (GWAS) and &lt;i&gt;cis&lt;/i&gt;-edQTL (± 1 MB) signals in 48 likely causal genes encompassing &lt;i&gt;CLU&lt;/i&gt;, &lt;i&gt;BIN1&lt;/i&gt;, and &lt;i&gt;GRIN3B&lt;/i&gt;, primarily allied to amyloid and tau pathology, and neuroinflammation.&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;Our findings delineate RNA editing regulatory signatures in human AD, providing novel insights into AD pathophysiology and potential biomarkers and therapeutic targets.&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;span&gt;· &lt;/span&gt;We discovered genome-wide landscape of RNA editing signals from 4208 (1364 Alzheimer's disease [AD] cases vs. 742 healthy controls) RNA-seq data across nine human brain regions from three large brain biobanks (Mount Sinai Brain Bank [MSBB], Mayo Clinic [MAYO] Religious Order Study and Memory and Aging Project [ROSMAP]) tied with AD, including in sex-specific and apolipoprotein E4 (APOE4) -specific manner adjusting for age, &lt;i&gt;post mortem&lt;/i&gt; interval (PMI), sex, and APOE4 status.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;&lt;span&gt;· &lt;/span&gt;We emphasize 127 genes, including &lt;i&gt;SYT11&lt;/i&gt;, &lt;i&gt;KCNIP4&lt;/i&gt;, &lt;i&gt;NRG3&lt;/i&gt;, &lt;i&gt;ANKS1B&lt;/i&gt;, and &lt;i&gt;RALYL&lt;/i&gt;, exhibiting significant RNA editing loci shared by multiple brain tissues, mainly implicated in synaptic plasticity, signaling and transmission, neuronal development, and morphogenesis.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;&lt;span&gt;· &lt;/span&gt;Brain-wide tissue-specific &lt;i&gt;cis&lt;/i&gt;-regulatory variants (&lt;i&gt;cis&lt;/i&gt;-edQTLs) were inspected using matched genotyping data from 3627 samples from a","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70452","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582318","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 racialization on neuroimaging and plasma biomarkers of Alzheimer's disease","authors":"Alexandra Gogola,&nbsp;Xuemei Zeng,&nbsp;Lilcelia A. Williams,&nbsp;Theresa Chapple-McGruder,&nbsp;Anum Saeed,&nbsp;Brian J Lopresti,&nbsp;Beth Snitz,&nbsp;Dana Tudorascu,&nbsp;Davneet Minhas,&nbsp;Milos D. Ikonomovic,&nbsp;Julia Kofler,&nbsp;Cristy Matan,&nbsp;Tharick A. Pascoal,&nbsp;Howard Aizenstein,&nbsp;Henrik Zetterberg,&nbsp;Kaj Blennow,&nbsp;Oscar Lopez,&nbsp;Victor L Villemagne,&nbsp;Thomas K. Karikari,&nbsp;Ann D Cohen","doi":"10.1002/alz.70463","DOIUrl":"https://doi.org/10.1002/alz.70463","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Given the predominance of imaging and plasma biomarkers in Alzheimer's disease observational studies and clinical trials, it is critical to understand the differences between these biomarkers across racialized groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A total of 260 older adults without dementia racialized as Black and/or African American (AA) and non-Hispanic white (NHW), ranging in age from 50 to 90 years (68.8 ± 9.1 years), were evaluated for differences in plasma amyloid-β (Aβ) 42/Aβ40, p-tau181, p-tau217, p-tau231, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) as well as Aβ positron emission tomography (PET) and magnetic resonance (MR) imaging-derived cortical thickness using Mann–Whitney U tests and analysis of covariance (ANCOVA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Both Mann–Whitney tests and ANCOVA found significant differences between groups racialized as AA or NWH with respect to global ¹¹[C]-Pittsburgh Compound B (PiB) standardized uptake value ratio (SUVR), cortical thickness values, p-tau181, and p-tau231 values (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Racialization should be given more consideration in AD clinical research, particularly when biomarker results are used for inclusion or exclusion criteria for clinical trials and qualification in clinical practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Global ¹¹[C]-Pittsburgh compound B (PiB) standardized uptake value ratio (SUVR), cortical thickness, p-tau181, and p-tau231 differed between groups</li>\u0000 \u0000 <li>Differences were unaffected by age, sex, apolipoprotein E *4 (APOE*4), education, and Mini-Mental State Examination (MMSE) score</li>\u0000 \u0000 <li>Racialization needs more consideration in Alzheimer's disease clinical research</li>\u0000 \u0000 <li>Additional work is needed to understand the sources of biomarker differences</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70463","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582332","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":"Subcortical gray matter volumes and 5-year dementia risk in individuals with subjective cognitive decline or mild cognitive impairment: A multi-cohort analysis","authors":"Mathijs T. Rosbergen,&nbsp;Pieter van der Veere,&nbsp;Jacqueline J. Claus,&nbsp;Tavia E. Evans,&nbsp;Vikram Venkatraghavan,&nbsp;Frederik Barkhof,&nbsp;Argonde C. van Harten,&nbsp;M. Arfan Ikram,&nbsp;Wiesje M. van der Flier,&nbsp;Meike W. Vernooij,&nbsp;Frank J. Wolters","doi":"10.1002/alz.70413","DOIUrl":"https://doi.org/10.1002/alz.70413","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The prognostic value of subcortical gray matter structures for dementia beyond the hippocampus remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We included participants with subjective cognitive decline or mild cognitive impairment from two memory clinic-based cohorts (Amsterdam Dementia Cohort and National Alzheimer's Coordinating Center) and one population-based cohort (Rotterdam Study). We assessed volumes of subcortical structures on magnetic resonance imaging and determined 5-year dementia risk using Cox models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Of 7076 participants (mean age: 66–69 years, 58.8%–61.0% women; <i>N</i>_SCC = 5425, <i>N</i>_MCI = 1661), 622 developed dementia within 5 years. Smaller volumes of the hippocampus and amygdala were consistently associated with increased dementia risk, independent of other subcortical structures. Smaller hippocampal volume was predominantly associated with the clinical diagnosis of Alzheimer's disease, but the prognostic value did not differ by amyloid status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Hippocampal and amygdalar volume are consistently associated with dementia risk in individuals with subjective cognitive decline or mild cognitive impairment, which may hold potential for personalized prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Seven thousand seventy-six participants from three large longitudinal cohorts were followed for a maximum of 5 years.</li>\u0000 \u0000 <li>Hippocampal volume is associated with 5-year risk of dementia in subjective cognitive decline (SCD) or mild cognitive impairment (MCI).</li>\u0000 \u0000 <li>Amygdalar volume is associated with a 5-year risk of dementia in SCD or MCI.</li>\u0000 \u0000 <li>Stratifying by SCD and MCI revealed no consistent major differences.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582186","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":"Longitudinal tau aggregation, atrophy, and cognitive decline in Alzheimer's disease","authors":"Ellen Hanna Singleton,&nbsp;Niklas Mattsson-Carlgren,&nbsp;Alexa Pichet Binette,&nbsp;Erik Stomrud,&nbsp;Olof Strandberg,&nbsp;Sebastian Palmqvist,&nbsp;Rik Ossenkoppele,&nbsp;Oskar Hansson","doi":"10.1002/alz.70435","DOIUrl":"https://doi.org/10.1002/alz.70435","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The independent contributions of baseline and longitudinal tau positron emission tomography (PET) and magnetic resonance imaging (MRI) to cognitive decline remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We included <i>n</i> = 761 amyloid-positive individuals from the Swedish BioFINDER-2 study with [¹⁸F]RO948-tau-PET, 3-Tesla structural-MRI, and cognition (<i>n</i> = 322 with longitudinal imaging data). Linear-mixed-models with random-intercepts and -slopes or linear-regressions were adjusted for age, sex, education, diagnosis, and other-imaging-modality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Tau-PET showed stronger associations with cognitive decline than MRI, showing the strongest associations in a neocortical-composite-region with a cognitive composite (β = −0.25 ± 0.02, <i>p</i> &lt; 0.001) for baseline and longitudinal tau-PET (β = −0.62 ± 0.05, <i>p</i> &lt; 0.001). Baseline tau-PET explained the largest proportion of cognitive decline (54.0%–94.0%), with modest mediation effects for longitudinal tau-PET or MRI pathways (2.0%–15.0%). Simulated reductions of tau-PET-slopes (up to 100%) were associated with marginally altered cognitive trajectories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The strong associations between baseline tau-PET and longitudinal cognition, with marginal contributions of longitudinal tau-PET and MRI, emphasize the importance of baseline tau aggregates for prognostics and treatments in Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Baseline and longitudinal regional tau-PET uptake were more closely associated than structural MRI with longitudinal cognitive decline.</li>\u0000 \u0000 <li>Baseline tau-PET was a stronger determinant of longitudinal cognitive decline than longitudinal tau-PET.</li>\u0000 \u0000 <li>Simulated reductions of tau-PET accumulation showed limited alterations of cognitive trajectories, with potential implications for tau-targeting therapies.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70435","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581870","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":"Neuroinflammation and amyloid load in different age groups of individuals with Down syndrome: A PET imaging study","authors":"Dimitri B. A. Mantovani,&nbsp;Laura C. Oliveira,&nbsp;Lidia E. W. Spelta,&nbsp;Claudia L. Carvalho,&nbsp;Orestes V. Forlenza,&nbsp;Suely K. N. Marie,&nbsp;Carlos A. Buchpiguel,&nbsp;Artur M. Coutinho,&nbsp;Daniele de Paula Faria","doi":"10.1002/alz.70449","DOIUrl":"10.1002/alz.70449","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Down syndrome (DS) is associated with early-onset Alzheimer's disease (AD). This study evaluated neuroinflammation and amyloid beta (Aβ) load in individuals with DS of different ages, using positron emission tomography (PET) imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>DS (<i>n</i> = 29) and age-matched non-DS (<i>n</i> = 35) individuals underwent [¹¹C]PK11195 and [¹¹C]PiB (Pittsburgh compound B) PET scans, for assessment of neuroinflammation and Aβ load, respectively. Voxel-wise and region-based analyses were conducted, and associations between [¹¹C]PK11195 binding and Aβ load were investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Individuals with DS exhibited increased [¹¹C]PK11195 binding compared to non-DS controls, with most pronounced differences in older (≥50 years) adults, followed by younger (20–34 years), and intermediate (35–49 years) ages. Among DS participants, 13 individuals were amyloid positive. Associations were observed between [¹¹C]PK11195 binding and global Aβ load.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Neuroinflammation in DS follows a region-specific pattern, partially associated with amyloid deposition, and may contribute to the early progression of AD-related pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Neuroinflammation is elevated in Down syndrome (DS) versus age-matched non-DS controls.</li>\u0000 \u0000 <li>Neuroinflammation in DS shows a different pattern depending on the brain region.</li>\u0000 \u0000 <li>[¹¹C]PK11195 uptake has a positive monotonic association with amyloid burden.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568435","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":"Synthetic control methods for n-of-1 and parallel-group trials in Alzheimer's disease: A proof-of-concept study using the I-CONECT","authors":"Chao-Yi Wu,&nbsp;Liu Chen,&nbsp;John R. Dickson,&nbsp;Bo Zhang,&nbsp;Steven E. Arnold,&nbsp;Hiroko H. Dodge","doi":"10.1002/alz.70460","DOIUrl":"10.1002/alz.70460","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;With the advent of Alzheimer's disease (AD)-modifying and symptomatic treatments of demonstrated efficacy, enrolling participants as concurrent placebo controls in trials can become increasingly difficult. Synthetic controls have been proposed as a viable alternative to concurrent control groups, but their feasibility and reliability remain untested in AD studies.&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;I-CONECT trial, which evaluates conversational interactions on cognition, was used to test synthetic control methods. Data from the National Alzheimer's Coordinating Center-Uniform Data Set was used to create synthetic-controls for I-CONECT participants using two methods: 1) case mapping and 2) case modeling. Efficacy estimates were compared between original versus synthetic-controlled trials.&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;In parallel-group designs, treatment effect sizes for the primary outcome were closely aligned between the original trial (β = 1.67) and synthetic control analyses (β = 1.40–1.65). For n-of-1 designs, the two methods showed high agreement in identifying treatment responders (Kappa = 0.75–0.82).&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;Synthetic control methods are feasible and reliable to create alternative controls in AD studies.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; CLINICAL TRIAL REGISTRATION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;NCT02871921.&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;Synthetic control methods are feasible and suitable for evaluating treatment effects in various trial designs such as n-of-1, single-arm, and parallel groups.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Synthetic control methods can help replicate early-phase Alzheimer's trials, informing go/no-go decisions for larger-scale studies.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The choice of similarity algorithms is critical as it affects the quality of historical case mapping.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The National Alzheimer's Coordinating Center-Uniform Data Set (NACC-UDS) provided an ideal pool for identifying historical cases with similar demographic, biological, and social characteristics to participants in trials, enabling the creation of synthetic control groups for Alzheimer's clinical res","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568431","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}