Alzheimer's & Dementia最新文献

{"title":"Alzheimer's disease diagnostic progression is associated with cerebrovascular disease and neuroinflammation in adults with Down syndrome","authors":"Natalie C. Edwards, Patrick J. Lao, Mohamad J. Alshikho, Olivia M. Ericsson, Batool Rizvi, Melissa E. Petersen, Sid O'Bryant, Lisi Flores-Aguilar, Sabrina Simoes, Mark Mapstone, Dana L. Tudorascu, Shorena Janelidze, Oskar Hansson, Benjamin L. Handen, Bradley T. Christian, Joseph H. Lee, Florence Lai, H Diana Rosas, Shahid Zaman, Ira T. Lott, Michael A. Yassa, Alzheimer's Biomarkers Consortium–Down Syndrome (ABC-DS) Investigators, José Gutierrez, Donna M. Wilcock, Elizabeth Head, Adam M. Brickman","doi":"10.1002/alz.70726","DOIUrl":"https://doi.org/10.1002/alz.70726","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Despite having few vascular risk factors, people with Down syndrome (DS) have MRI evidence of cerebrovascular disease (CVD) and neuroinflammation that worsens with Alzheimer's disease (AD) severity. We investigated whether markers of CVD and inflammation are associated with AD-related diagnostic progression in people with DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We included 149 participants (mean age [SD] = 44.6 [9]) from the Alzheimer's Biomarkers Consortium–Down Syndrome who had two (<i>n</i> = 24) or three follow-up visits (<i>n</i> = 125). We derived white matter hyperintensity (WMH) volume and plasma biomarker (glial fibrillary acidic protein [GFAP], amyloid beta [Aβ]42/Aβ40, hyperphosphorylated tau-217 [p-tau217], and neurofilament light [NfL]) concentrations at baseline and examined their association with progression in clinical diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Higher baseline WMH volume and higher GFAP were associated with a greater likelihood of diagnostic progression. Combining WMH and GFAP with p-tau217 improved clinical conversion classification accuracy over AD biomarkers alone. Among individuals with evidence of amyloidosis, both WMH and GFAP were associated with clinical progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>In DS, markers of CVD and inflammation are independently and synergistically associated with clinical AD progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Higher baseline white matter hyperintensity (WMH) volume and plasma glial fibrillary acidic protein (GFAP) concentration were associated with a higher likelihood of progressing from cognitively stable to either mild cognitive impairment or clinical Alzheimer's disease in Down syndrome.</li>\u0000 \u0000 <li>WMH volume and GFAP concentration discriminated between those who progressed and those who did not.</li>\u0000 \u0000 <li>Models including the independent and interactive effects of WMH and GFAP more accurately discriminated between participants who progressed diagnostically from those who did not.</li>\u0000 \u0000 <li>Individuals with evidence of amyloid pathology were more likely to progress if they also had elevated WMH or GFAP.</li>\u0000 </ul>\u0000 </div>\u0000 </sec","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70726","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146980","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 letter to the editor","authors":"Huijun Chen, Ziming Xu","doi":"10.1002/alz.70686","DOIUrl":"https://doi.org/10.1002/alz.70686","url":null,"abstract":"<p>Dear Editor,</p><p>We appreciate the compliment of our effort from Backes et al. and their meaningful thoughts regarding the possible explanations of the results. In our study, the clinical constraints forced us to use a dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) protocol with shorter duration, especially the high possibility of severely declined image quality due to the limited tolerance to long scans for elderly participants (average age > 70 years). To fulfill the aim of our study, whole brain coverage and relatively high spatial resolution were chosen, resulting in a temporal resolution of 11.7 s, better than a commonly used protocol<span><sup>1</sup></span> (15.4 s) investigating subtle leakage.</p><p>We understand the concern of vascular transit effects. However, the sampling rate of our data precludes the possibility of performing the suggested deconvolution, since “a high sample rate is of paramount importance”<span><sup>2</sup></span> for deconvolution and only “time resolution between 1 and 2 s is acceptable.”<span><sup>2</sup></span> The reason is that the first pass (especially the peak) of the time courses, when the vascular transit effects are mostly obvious but still subtle, can hardly be well captured with a 5 times lower sampling rate than needed, given the reported similar arterial transit time (ATT)<span><sup>3</sup></span> and slightly prolonged mean transit time (MTT) (1–2 s)<span><sup>4</sup></span> compared with aged controls. Due to the same reason, those transit effects, which were buried in the variance introduced by low-rate sampling, should not systematically affect the results. Our study showed increased blood–brain barrier (BBB) permeability similar to that in a previous study,<span><sup>1</sup></span> which omitted transit effects with long duration, also supporting the effectiveness of our protocol. Moreover, a previous study<span><sup>5</sup></span> investigating water exchange in multiple sclerosis (MS) patients with subtle BBB leakage scenarios using only 115 s duration also ignored the transit effects. Notably, even if the data have a sufficient sampling rate, differentiating coexisting leakage and transit effects is almost impossible by deconvolution, which assumes only transit effects exists. This is because the inevitably existing leakage can also mimic transit effects, thereby leading to biased estimation.</p><p>Furthermore, long duration is not always better for models neglecting contrast reflux to plasma, such as the commonly used Patlak model.<span><sup>1, 6</sup></span> Actually, the physiological feature of BBB breakdown is the passive bidirectional BBB permeability.<span><sup>7</sup></span> The bias (underestimation) introduced by neglecting reflux could be ignored with short durations but will certainly increase as duration becomes longer.<span><sup>8</sup></span> The contrast in tissue may even dissipate rather than “accumulate” when the duration becomes so long that the re","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70686","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146979","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 companion dog as a translational model for Alzheimer's disease: Development of a longitudinal research platform and post mortem protocols","authors":"Stephanie McGrath,&nbsp;Emily Hull,&nbsp;Matthew D. Dunbar,&nbsp;Jena Prescott,&nbsp;Amber J. Keyser,&nbsp;Evan MacLean,&nbsp;Martin Darvas,&nbsp;Caitlin Latimer,&nbsp;Julie Moreno,&nbsp;Michael J. MacCoss,&nbsp;Mandy Kauffman,&nbsp;Paul Litwin,&nbsp;Marta Castelhano,&nbsp;Matt Kaeberlein,&nbsp;C. Dirk Keene,&nbsp;Dog Aging Project Consortium","doi":"10.1002/alz.70630","DOIUrl":"10.1002/alz.70630","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Canine cognitive dysfunction is a valuable model for Alzheimer's disease (AD) and Alzheimer's disease related dementias (ADRD) due to condensed lifespan, naturally occurring clinical signs, genetic diversity, shared environment with humans, and similar molecular and neuropathological hallmarks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>The objective of the Brain Health Study was to build infrastructure to support a diverse national cohort of companion dogs for in-depth, longitudinal analysis of brain and cognitive health over their lifespan. A complex and well-maintained research platform was critical to facilitate enrollment, retention, and biobanking of biofluids and postmortem tissue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The research infrastructure is in place for longitudinal data collection, annual biospecimen collection and postmortem sample collection. The team has conducted 21 postmortem exams.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Although most of the 500 enrolled subjects remain alive, biomarker identification, neuropathology, and proteomics analysis is underway. Future outcomes will benefit the worldwide research community through an Open Data sharing platform.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The dog serves as a novel translational large animal model for Alzheimer's disease (AD) and ad and related dementias.</li>\u0000 \u0000 <li>A large research platform supports collection of biofluids and <i>post mortem</i> tissue.</li>\u0000 \u0000 <li>The companion dog has key molecular and neuropathological hallmarks of AD.</li>\u0000 \u0000 <li>The Brain Health Study research platform has successfully enrolled 500 dogs across the United States.</li>\u0000 \u0000 <li><i>Post mortem</i> biofluid and tissue has been donated from 21 enrolled dogs.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70630","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134438","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 methods for Alzheimer's cognitive status prediction with deep learning","authors":"Houjun Liu,&nbsp;Alyssa Mae Weakley,&nbsp;Hiroko H. Dodge,&nbsp;Xin Liu","doi":"10.1002/alz.70488","DOIUrl":"10.1002/alz.70488","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Prediction of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) using machine learning has primarily focused on short-term predictions spanning 1–3 years. This study aimed to develop a new machine learning technique to extend predictions of cognitive status over 3–10 years from their last visit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We leveraged deep learning to analyze two longitudinal feature sets: (1) neuropsychological data and (2) neuropsychological data with the addition of patient history data. We also introduce two modeling techniques: (1) to separate normalized baseline features and deviations from baseline, and (2) a new linear attention-based imputation method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We demonstrate (1) our technique achieves high 1vA accuracy, representing 81.65% for Control, 72.87% for aMCI, and 86.52% for AD on a 3- to 10-year horizon, and (2) the new method is more accurate than previously proposed approaches for this time horizon.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This work offers a new set of techniques for big-data analysis of longitudinal dementia data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Develops a new method for the prediction using deep learning of longitudinally verified amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) using the National Alzheimer's Coordinating Center NACC) database.</li>\u0000 \u0000 <li>Demonstrates comparable performance on the 3- to 10-year prediction horizon, which is significantly more challenging to predict than using the previous approach that only used a 1- to 3-year prediction horizon.</li>\u0000 \u0000 <li>Highlights that even the prediction of verified 3- to 10-year aMCI that eventually leads to AD is still a challenging task.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70488","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134441","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":"Neuroimaging markers of dementia across race/ethnicity and sex/gender using an intersectional approach within the HABS-HD cohort","authors":"Michelle R. Caunca,&nbsp;Amber Bahorik,&nbsp;Xiaqing Jiang,&nbsp;Meredith N. Braskie,&nbsp;Sid O'Bryant,&nbsp;Kristine Yaffe","doi":"10.1002/alz.70733","DOIUrl":"10.1002/alz.70733","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Racial/ethnic and sex/gender differences in neuroimaging markers of dementia have been previously explored, but rarely with an intersectional approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using data from the Health and Aging Brain Study–Health Disparities cohort, we examined neuroimaging markers of dementia using both interaction between race/ethnicity and sex/gender and effect modification of race/ethnicity by sex/gender.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We analyzed data from 3433 dementia-free participants with either magnetic resonance imaging or positron emission tomography (PET) data at baseline (mean [standard deviation] age: 65 [9] years, 36% non-Hispanic White [NHW], 27% Black, 37% Hispanic, and 63% women). Compared to NHW, Black men had lower global amyloid PET standardized uptake value ratio (SUVR; β [95% confidence interval]: –0.32 [–0.53, –0.11]), and Hispanic (0.65 [0.39, 0.91]) and Black women had greater medial temporal lobe tau SUVR (0.49 [0.30, 0.69]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>We observed that the distribution of neuroimaging markers of dementia differed across racial/ethnicity groups by sex/gender. An intersectional approach can aid in tailoring research and clinical efforts in preventing and treating dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Hispanic and Black women had greater medial temporal lobe tau deposition, compared to their non-Hispanic White counterparts.</li>\u0000 \u0000 <li>Black men had lower global amyloid deposition compared to non-Hispanic White men.</li>\u0000 \u0000 <li>Black men and women had higher burden of cerebral small vessel disease compared to their non-Hispanic White counterparts, with stronger associations in Black men.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70733","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127349","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":"Multimodal prognostic modeling of individual cognitive trajectories to enhance trial efficiency in preclinical Alzheimer's disease","authors":"Viswanath Devanarayan,&nbsp;Michael C. Donohue,&nbsp;Reisa A. Sperling,&nbsp;Keith A. Johnson,&nbsp;Yuanqing Ye,&nbsp;Arnaud Charil,&nbsp;Thomas Doherty,&nbsp;Lu Tian,&nbsp;Rema Raman,&nbsp;Paul S. Aisen,&nbsp;Lynn D. Kramer,&nbsp;Michael C. Irizarry,&nbsp;Shobha Dhadda","doi":"10.1002/alz.70702","DOIUrl":"10.1002/alz.70702","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;Cognitive decline in asymptomatic preclinical Alzheimer's disease (AD) is slow and variable, limiting detection of treatment effects. This study developed models to forecast trajectories and improve trial efficiency.&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;Models were trained on longitudinal Preclinical Alzheimer's Cognitive Composite (PACC) data up to 240 weeks from the Phase III A4 study of solanezumab. Baseline inputs included demographics, apolipoprotein E (&lt;i&gt;APOE&lt;/i&gt;) ε4, clinical scores, amyloid positron emission tomography (PET), plasma pTau217, magnetic resonance imaging (MRI), and tau PET (sub-study). Stochastic gradient boosting was used, with evaluation via cross-validation and trial simulations.&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;The best model without tau PET used pTau217, clinical, and MRI data (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.32; area under the receiver operating characteristic curve (AUROC) for classifying a 0.5-point PACC decline = 78.6%). Replacing MRI with tau PET improved performance (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.42; AUROC = 83.1%). Predicted trajectories as a prognostic covariate reduced sample sizes by 35% and increased power from 80% to 94.7%.&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;Prognostic models can predict decline in preclinical AD and improve trial efficiency.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; CLINICALTRIALS.GOV IDENTIFIERS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;NCT02008357 (Clinical Trial of Solanezumab for Older Individuals Who May be at Risk for Memory Loss (A4))&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;Models forecast 4.5-year cognitive decline in amyloid-positive preclinical Alzheimer's disease (AD).&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Plasma pTau217 and tau positron emission tomography (PET) standardized uptake value ratios (SUVRs) in early-accumulating regions are key predictors.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Tau PET improves prediction beyond plasma, magnetic resonance imaging (MRI), and clinical measures.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Forecasted decline as a prognostic covariate improves power and cuts sample size in trial simulations.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Alternative models underperform yet retain practical utility wh","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70702","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127331","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":"Sociodemographic traits as early indicators of AD, FTD, and VaD up to 10 years before diagnosis","authors":"Ave Kivisild,&nbsp;Iina Rinnankoski,&nbsp;Mikko Aaltonen,&nbsp;Kalle Aho,&nbsp;Sami Heikkinen,&nbsp;Adolfina Lehtonen,&nbsp;Laura Leppänen,&nbsp;Helmi Soppela,&nbsp;Laura Tervonen,&nbsp;Kaijus Ervasti,&nbsp;Päivi Hartikainen,&nbsp;Annakaisa Haapasalo,&nbsp;Kasper Katisko,&nbsp;Johanna Krüger,&nbsp;Eino Solje","doi":"10.1002/alz.70616","DOIUrl":"10.1002/alz.70616","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;We aimed to investigate early differences in sociodemographic factors before the onset of Alzheimer's disease (AD), frontotemporal dementia (FTD), vascular dementia (VaD), and mixed dementia (AD + VaD).&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;Lifetime sociodemographic factors were collected from Statistics Finland for 1238 AD, 274 FTD, 343 VaD, and 402 AD + VaD patients with a diagnosis and visit at Kuopio and Oulu University Hospitals between January 2010 and December 2021. Comparisons were performed between dementia groups and matched controls.&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;All patient groups showed decreased employment status compared to controls already 10 years prior to diagnosis. In particular, individuals with early-onset FTD (EOFTD; 66.9% vs. 77.6%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and early-onset VaD (EOVaD; 49.0% vs. 76.5%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) had significantly lower employment rates than controls. Similarly, 10 years prior to diagnosis the proportion of married individuals was lower in the VaD (60.1% vs. 65.2%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and EOVaD (50.0% vs. 61.6%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) groups versus controls, while single status was more common in early-onset AD (EOAD; 23.2% vs. 17.0%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) versus controls. Patients with VaD and AD + VaD had lower levels of education than controls: basic education only in 51.9% of VaD (vs. 45.0%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and 65.7% of AD + VaD (vs. 60.2%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05).&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 may aid in the early recognition or potential risk factor evaluation for different types of dementia. Screening cognitive symptoms in individuals with unexplained long-term unemployment may help detect prodromal dementia.&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;Employment rates were already reduced 10 years before the diagnosis of Alzheimer's disease, frontotemporal dementia, and vascular dementia.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The association between education level and dementia risk appears to be subtype specific.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Lower employment may serve as an early “social marker” of subtle cognitive decline.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Social markers could help inform models predicting progression to cognitive impairment.&lt;/li&gt;\u0000 &lt;/ul&gt;","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70616","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127317","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":"Everyday functioning in young onset dementia: differences between diagnostic groups","authors":"Emma Weltings,&nbsp;Merel C. Postema,&nbsp;Maureen van Dam,&nbsp;Mark A. Dubbelman,&nbsp;Mukrabe E. Tewolde,&nbsp;Flora H. Duits,&nbsp;Afina W. Lemstra,&nbsp;The LEADS consortium,&nbsp;Bradford C. Dickerson,&nbsp;Maria C. Carrillo,&nbsp;Gil D. Rabinovici,&nbsp;Dustin B. Hammers,&nbsp;Wiesje M. Van der Flier,&nbsp;Liana G. Apostolova,&nbsp;Yolande A. L. Pijnenburg,&nbsp;Sietske A. M. Sikkes","doi":"10.1002/alz.70711","DOIUrl":"10.1002/alz.70711","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>The aim of this study was to examine differences in Instrumental Activities of Daily Living (IADL) among young-onset dementia (YOD) diagnoses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Participants were included from Amsterdam Dementia and Longitudinal Early-Onset Alzheimer's Disease (LEADS) cohorts, with diagnoses of typical Alzheimer's disease (AD), behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), posterior cortical atrophy (PCA), or dementia with Lewy bodies (DLB) established in multidisciplinary meetings. We compared overall IADL scores and item level scores between groups using multiple regression analyses, adjusted for cohort, demographics, and disease severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We included 582 YOD patients (58.4 ± 4.2 years; 59%F), with overall moderate IADL problems (47.5 ± 8.57). DLB patients showed the most IADL difficulties (41.8 ± 7.8) compared to PCA, typical AD, bvFTD, and PPA (adjusted β range 4.62 to 14.14, all <i>p</i> &lt; 0.01), whereas PPA patients showed the least IADL difficulties (55.8 ± 9.83), with item-specific differences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>We found differences in everyday functioning between YOD types. Understanding IADL in YOD types will assist in care planning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Patients with DLB showed the most IADL difficulties compared to PCA, typical AD, bvFTD, and PPA</li>\u0000 \u0000 <li>Patients with PPA showed the least IADL difficulties compared to DLB, PCA, typical AD, and bvFTD</li>\u0000 \u0000 <li>We identified diagnostic group-specific activity challenges. While ‘working’ was among the most commonly impaired activities across al groups, distinct functional challenges emerged per diagnosis: for example, DLB had high impairment in financial tasks, PCA patients in visual-spatial tasks, and bvFTD with planning and organizational activities (e.g. making appointments).</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70711","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129844","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 Brain Health Index: Integrating vulnerability, resilience, and cognitive function into a unified measure of cognitive health and risk of neurodegenerative disease","authors":"Michael J. Kleiman,&nbsp;Gregory Gibbs,&nbsp;Mahesh S. Joshi,&nbsp;James E. Galvin","doi":"10.1002/alz.70723","DOIUrl":"10.1002/alz.70723","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;Assessing brain health and identifying cognitive impairment risk remains challenging, with only 11.4% of MCI cases receiving timely diagnoses. We developed the Brain Health Index (BHI), integrating the Vulnerability Index, Resilience Index, and Number Symbol Coding Task into a unified metric.&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 evaluated 469 participants (258 congnitively normal [CN], 140 mild cognitive impairment [MCI], 49 Alzheimer's disease and related dementias [ADRD]) using comprehensive clinical, cognitive, and biomarker assessments. After empirically-derived weighting, BHI thresholds were developed. Cross-sectional associations and longitudinal analyses were performed, with threshold validation for risk stratification.&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;BHI demonstrated strong correlations with cognitive (Montreal Cognitive Assessment [MoCA] &lt;i&gt;r&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.408), functional (Functional Activities Questionnaire [FAQ] &lt;i&gt;r&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.278), and biomarker (neurofilament light chain [NfL] &lt;i&gt;r&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.073) measures. Complete mediation was observed for NfL and glial fibrillary acidic protein (GFAP) changes over 1 year. Threshold analysis revealed 89.2% of low BHI participants had cognitive impairment, with only one ADRD case in the high BHI group.&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 BHI provides a brief, validated, comprehensive brain health metric with clinical utility for risk stratification and intervention monitoring.&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;Assessing brain health status and identifying individuals at risk for cognitive impairment remains a significant challenge, particularly in early prodromal and symptomatic stages when current therapies may be most effective and patients may be eligible for clinical trials.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We created a unified metric, the Brain Health Index (BHI), combining resilience and vulnerability factors with cognitive performance that divided individuals into high, indeterminant, and low risk groups.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The BHI demonstrated strong correlations with cognitive, functional, and biomarker measures.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The BHI had a 16-fold increase in identifying individuals who were likely to have ","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70723","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127347","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":"Alzheimer's Association releases its first clinical practice guideline for blood-based biomarker tests","authors":"","doi":"10.1002/alz.70701","DOIUrl":"10.1002/alz.70701","url":null,"abstract":"&lt;p&gt;At the Alzheimer's Association International Conference 2025, the Association released release of its first clinical practice guideline (CPG) on the use of blood-based biomarker (BBM) tests.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The CPG provides clear, evidence-based, brand-agnostic recommendations to support more accurate and accessible diagnosis of Alzheimer's using BBM tests. The recommendations are linked to a systematic review using a robust and transparent methodology and will be updated regularly as evidence evolves.&lt;/p&gt;&lt;p&gt;“This is a pivotal moment in Alzheimer's care,” said Maria C. Carrillo, PhD, Alzheimer's Association chief science officer and medical affairs lead, and a co-author of the guideline. “For the first time, we have a rigorously evidence-based guideline that empowers clinicians to use blood biomarker tests confidently and consistently. Adoption of these recommendations will lead to quicker, more accessible, more accurate diagnoses — and better outcomes for individuals and families affected by Alzheimer's.”&lt;/p&gt;&lt;p&gt;The guideline cautions that there is significant variability in diagnostic test accuracy and many commercially available BBM tests do not meet these thresholds.&lt;/p&gt;&lt;p&gt;“Not all BBM tests have been validated to the same standard or tested broadly across patient populations and clinical settings, yet patients and clinicians may assume these tests are interchangeable; they are not,” said Rebecca M. Edelmayer, PhD, Alzheimer's Association vice president of scientific engagement and a co-author of the guideline. “This guideline helps clinicians apply these tools responsibly, avoid overuse or inappropriate use, and ensure that patients have access to the latest scientific advancements.”&lt;/p&gt;&lt;p&gt;Compared to standard-of-care PET imaging and CSF tests, BBM tests are typically less costly, more accessible, and more acceptable to patients. The guideline emphasizes that BBM tests do not substitute for a comprehensive clinical evaluation by a health care professional, and should be ordered and interpreted by a health care professional in the context of clinical care.&lt;/p&gt;&lt;p&gt;This is the first evidence-based guideline in the Alzheimer's space that uses Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The use of GRADE ensures a transparent, structured, and evidence-based process for evaluating the certainty of evidence and formulating recommendations. This strengthens the credibility and reproducibility of the guideline and allows for explicit linkage between evidence and recommendations.&lt;/p&gt;&lt;p&gt;This guideline's primary audience is specialists involved in the diagnostic evaluation of cognitive impairment in specialized care settings. A specialist is defined as a health care provider, typically in neurology, psychiatry, or geriatrics, who cares for adults with cognitive impairment or dementia. It also applies to primary care providers, nurse practitioners, and physician assistants in specialized care settings.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127321","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}