Alzheimer's & Dementia最新文献

{"title":"Tackling social determinants of dementia will require qualitative research with the public and professionals","authors":"Timothy Daly","doi":"10.1002/alz.70767","DOIUrl":"https://doi.org/10.1002/alz.70767","url":null,"abstract":"<p>In their scoping review, Walsh et al. found varying degrees of evidence for six classes of “social determinants of dementia” (SDOD), upstream features of the physical and social environment that produce, or protect against, dementia risk.<span><sup>1</sup></span> The authors recognize that evidence is strongest for education and lacking for other SDOD, such as housing stability, and they understandably call for further causal research with rigorous methodologies.</p><p>Establishing causal evidence is one piece of the puzzle. However, the authors do not mention the need to integrate quantitative evidence with qualitative research with the public, policy makers, and health-care professionals, which is equally necessary to make a public health approach to SDOD actionable and equitable. As an example, Dykxhoorn et al.<span><sup>2</sup></span> conceptualized mental health priorities alongside members of the public with different levels of exposure to determinants, as well as policy makers and public health practitioners. For all of the known determinants, they asked the public and professionals to rank each determinant according to two criteria: its importance for lived experience, and its amenability to change.<span><sup>2</sup></span> They then used this aggregated list to create a hierarchy of priorities for public mental health.</p><p>This synthesizing of different perspectives is important because the public, particularly those in situations of vulnerability, perceive “a clear hierarchy of influences” of factors influencing their health, which may be incorrectly “listed on par” in academic research.<span><sup>3</sup></span> For instance, in a qualitative study with members of the public on how urban environments could support dementia risk reduction, Susanne Röhr et al.<span><sup>4</sup></span> found that social inclusion and housing—which Walsh et al. found to have significant evidence gaps<span><sup>1</sup></span>—was the primary theme that emerged from interviews. This shows how academic research and lived experience can differ greatly. Moreover, in other qualitative studies, policy makers<span><sup>5</sup></span> recognized the need to address SDOD, whereas general practitioners<span><sup>6</sup></span> tended to stress individual behaviors, highlighting the need to work with different groups simultaneously to prioritize relevant, actionable fulcra for action against SDOD.</p><p>In summary, academic research, health policy making, and the lived experience of exposure to social determinants are very different realities. Just as Walsh et al. have brought together evidence to provide a state-of-the-art review of the academic literature, further research and policy efforts should bring together different groups to establish priorities that address the needs of the public, professionals, and researchers by underlining the evidence, importance, and actionability of SDOD. Quantitative evidence alone cannot answer the question: What are the reason","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.70767","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146864","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":"Slowly crossing the blood–brain barrier takes time","authors":"Walter H. Backes, Damon Verstappen, Joost J. A. de Jong, Jacobus F. A. Jansen","doi":"10.1002/alz.70687","DOIUrl":"https://doi.org/10.1002/alz.70687","url":null,"abstract":"<p>Dear Editor,</p><p>In their publication “Tracer kinetic model detecting heterogeneous blood–brain barrier permeability to water and contrast agent in Alzheimer's disease and dementia with Lewy bodies,” Dr. Xu and colleagues measure the brain tissue uptake of an magnetic resonance imaging (MRI) contrast agent over time in severely compromised patients with dementia and elderly controls.<span><sup>1</sup></span> From the measurements they simultaneously calculate the permeability of the blood–brain barrier (BBB) for gadolinium contrast agent and water molecules.</p><p>We feel this is an important and challenging attempt to assess BBB breakdown in neurodegenerative disease, as it is thought to be one of the key initiating mechanisms of dementia. We compliment the authors with this achievement, but would like to provide a different perspective on the approach and interpretation of the results.</p><p>Leakage of (Magnetic Resonance Imaging) MRI contrast agent from the blood circulation into the brain parenchyma is extremely subtle in neurodegenerative disease. Any MRI measurement in brain tissue is mainly determined by the signal from the gadolinium inside blood vessels. To properly measure the tiny amounts of leaking contrast agent requires long measurement times to let the contrast agent sufficiently accumulate in the brain parenchyma. A recent consensus article recommended acquiring images for at least 15 min and preferably longer.<span><sup>2</sup></span> The approach by Xu et al. only sampled 5 min. Including the first minutes of the multiple (re)circulations of the contrast agent means that for a substantial part of the measurement time, no (dynamic) equilibrium is reached for the distribution of the contrast agent over the blood and parenchyma. Moreover, these early (re)circulations reflect differences in the concentration time-course between the supplying artery and microvessels by delaying and broadening (i.e., dispersion) the concentration time-course profile.<span><sup>3</sup></span> We are concerned that such hemodynamic effects may deteriorate the leakage estimation in such short-term measurements. The calculation of contrast agent leakage is based on differences between arterial and tissue time-courses, and the leakage part is determined predominantly from later signals when the circulation is in the steady-state and sufficient contrast agent has accumulated.</p><p>Investigators applied a tracer kinetic model to the MRI signal and considered three compartments (blood, interstitial, and intracellular space) and calculated various parameters, including the leakage of contrast agent and water exchange rate over the endothelium. The authors meticulously performed computer simulations in which single potentially superfluous parameters were omitted to determine the simplest model with the best fit, very much in line with previous work.<span><sup>4</sup></span> The inclusion of water exchange effects has been intensively debated in the litera","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.70687","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146866","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 association of mild cognitive impairment with outpatient visits for hypertension","authors":"Mellanie V. Springer,&nbsp;Yi Chen,&nbsp;Slim Benloucif,&nbsp;Francine Grodstein,&nbsp;Bryan D. James,&nbsp;Ana W. Capuano,&nbsp;Mousumi Banerjee,&nbsp;Julie P. W. Bynum","doi":"10.1002/alz.70743","DOIUrl":"https://doi.org/10.1002/alz.70743","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Hypertension management is critically important to reduce the risk of conversion of mild cognitive impairment (MCI) to dementia. The degree to which older adults with hypertension and MCI engage in outpatient ambulatory care for hypertension management is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Among older adults with hypertension in the Rush Alzheimer's Disease Center (RADC) cohorts (2011 to 2019), we used repeated measures negative binomial regression to evaluate the association between cognitive status (MCI vs no cognitive impairment [NCI]) and number of annual outpatient clinic visits for hypertension evaluation and management (E&amp;M) (primary outcome).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>MCI (<i>n</i> = 1013 person-years) was associated with 8% fewer outpatient visits for hypertension versus older adults with NCI (<i>n</i> = 4373 person-years) (relative incidence ratio [RIR] 0.92, <i>p</i> &lt; 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Despite the known adverse cognitive effects of hypertension, older adults with MCI may be less likely to engage in outpatient hypertension management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Fewer outpatient hypertension visits among adults with MCI versus NCI.</li>\u0000 \u0000 <li>Fewer primary care hypertension visits among adults with MCI versus without MCI.</li>\u0000 \u0000 <li>Need for interventions to engage adults with hypertension and MCI in outpatient care.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","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.70743","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146865","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 scoping review and comprehensive needs assessment for developing an intergenerational cognitive and physical activity program for MCI patients and their adult children","authors":"Julie Latomme,&nbsp;Tim Van Langenhove,&nbsp;Marijke Miatton,&nbsp;Greet Cardon","doi":"10.1002/alz.70696","DOIUrl":"https://doi.org/10.1002/alz.70696","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Mild cognitive impairment (MCI) is a high-risk state for dementia, marked by cognitive decline with preserved daily functioning. Combined physical and cognitive activity (PA+CA) programs show promising benefits for MCI patients. Involving adult children through intergenerational approaches may enhance participation and impact, yet little is known about tailoring such programs to both generations’ needs. This study aimed to (1) identify cognitive, physical, and psychosocial challenges experienced by MCI patients, and (2) explore the needs, preferences, barriers, and facilitators regarding participation in an intergenerational PA+CA program. A mixed-methods design combined a scoping review of 45 studies with eight semi-structured interviews involving eight MCI patient–adult child dyads. Results highlight challenges such as memory loss, fatigue, social withdrawal, and a desire for meaningful, safe, and structured activities. Barriers included overload, physical limitations, and time constraints; facilitators involved routine, emotional support, and family connection. Findings offer guidance for designing effective intergenerational PA+CA programs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>A scoping review and interviews identified key challenges in mild cognitive impairment (MCI) across domains.</li>\u0000 \u0000 <li>Physical, cognitive, and psychosocial needs were mapped for MCI patients and their children.</li>\u0000 \u0000 <li>Barriers to participation included cognitive overload, low motivation, and time constraints.</li>\u0000 \u0000 <li>Facilitators included emotional safety, routine, and meaningful family connection.</li>\u0000 \u0000 <li>Findings support the design of tailored, intergenerational combined physical and cognitive support programs for MCI.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","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.70696","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Single-nucleus analysis reveals oxidative stress in Down syndrome basal forebrain neurons at birth”","authors":"","doi":"10.1002/alz.70777","DOIUrl":"https://doi.org/10.1002/alz.70777","url":null,"abstract":"<p>West NR, Arachchilage KH, Knaack S, et al. Single-nucleus analysis reveals oxidative stress in Down syndrome basal forebrain neurons at birth. <i>Alzheimers Dement</i>. 2025;21(7):e70445. https://doi.org/10.1002/alz.70445. PMID: 40667939; PMCID: PMC12265022. The data presented in the current publication have been deposited in and are available from the dbGaP database under accession phs004098.v1.p1. Data can also be accessed through the INCLUDE Data Hub at the INCLUDE Data Coordinating Center. For comprehensive guides, documentation, and help in general, you may visit the INCLUDE DCC Help Center. The data can be interactively visualized at https://daifengwanglab.shinyapps.io/DS_basal/.</p><p>At the time of publication, the data were not publicly available. The data is now available.</p><p>We apologize for this error.</p>","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.70777","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146981","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 disease diagnostic progression is associated with cerebrovascular disease and neuroinflammation in adults with Down syndrome","authors":"Natalie C. Edwards,&nbsp;Patrick J. Lao,&nbsp;Mohamad J. Alshikho,&nbsp;Olivia M. Ericsson,&nbsp;Batool Rizvi,&nbsp;Melissa E. Petersen,&nbsp;Sid O'Bryant,&nbsp;Lisi Flores-Aguilar,&nbsp;Sabrina Simoes,&nbsp;Mark Mapstone,&nbsp;Dana L. Tudorascu,&nbsp;Shorena Janelidze,&nbsp;Oskar Hansson,&nbsp;Benjamin L. Handen,&nbsp;Bradley T. Christian,&nbsp;Joseph H. Lee,&nbsp;Florence Lai,&nbsp;H Diana Rosas,&nbsp;Shahid Zaman,&nbsp;Ira T. Lott,&nbsp;Michael A. Yassa,&nbsp;Alzheimer's Biomarkers Consortium–Down Syndrome (ABC-DS) Investigators,&nbsp;José Gutierrez,&nbsp;Donna M. Wilcock,&nbsp;Elizabeth Head,&nbsp;Adam M. Brickman","doi":"10.1002/alz.70726","DOIUrl":"https://doi.org/10.1002/alz.70726","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;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.&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 included 149 participants (mean age [SD] = 44.6 [9]) from the Alzheimer's Biomarkers Consortium–Down Syndrome who had two (&lt;i&gt;n&lt;/i&gt; = 24) or three follow-up visits (&lt;i&gt;n&lt;/i&gt; = 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.&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;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.&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;In DS, markers of CVD and inflammation are independently and synergistically associated with clinical AD progression.&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;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.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;WMH volume and GFAP concentration discriminated between those who progressed and those who did not.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Models including the independent and interactive effects of WMH and GFAP more accurately discriminated between participants who progressed diagnostically from those who did not.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Individuals with evidence of amyloid pathology were more likely to progress if they also had elevated WMH or GFAP.&lt;/li&gt;\u0000 &lt;/ul&gt;\u0000 &lt;/div&gt;\u0000 &lt;/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,&nbsp;Ziming Xu","doi":"10.1002/alz.70686","DOIUrl":"https://doi.org/10.1002/alz.70686","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;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 &gt; 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&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; (15.4 s) investigating subtle leakage.&lt;/p&gt;&lt;p&gt;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”&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; for deconvolution and only “time resolution between 1 and 2 s is acceptable.”&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; 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)&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; and slightly prolonged mean transit time (MTT) (1–2 s)&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; 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,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; which omitted transit effects with long duration, also supporting the effectiveness of our protocol. Moreover, a previous study&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; 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.&lt;/p&gt;&lt;p&gt;Furthermore, long duration is not always better for models neglecting contrast reflux to plasma, such as the commonly used Patlak model.&lt;span&gt;&lt;sup&gt;1, 6&lt;/sup&gt;&lt;/span&gt; Actually, the physiological feature of BBB breakdown is the passive bidirectional BBB permeability.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; The bias (underestimation) introduced by neglecting reflux could be ignored with short durations but will certainly increase as duration becomes longer.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; 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":"Relationship of antihypertensives with late-life cognitive decline and neuropathology","authors":"Ajay Sood,&nbsp;Ana Werneck Capuano,&nbsp;Rupal Mehta,&nbsp;Lisa Laverne Barnes,&nbsp;David Alan Bennett,&nbsp;Zoe Arvanitakis","doi":"10.1002/alz.70739","DOIUrl":"10.1002/alz.70739","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Antihypertensives (AHTs) are commonly used to treat high blood pressure and other conditions, but their associations with cognitive decline and common age-related neuropathologies are not well understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>More than 3300 participants from three harmonized community-based cohorts without baseline dementia were evaluated annually for changes in cognition and &gt; 1800 participants were analyzed for <i>post mortem</i> neuropathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In a linear mixed effect model adjusted for age, sex, education, and race/ethnicity, AHT use was associated with higher baseline global cognition (<i>p</i> &lt; 0.001) and slower decline (<i>p</i> = 0.002) in global cognition, episodic memory, and semantic memory (all <i>p</i> &lt; 0.02) compared to non-use. In the autopsy group AHT use was associated with a lower tau tangle density (<i>p</i> = 0.004), but not with other neurodegenerative or cerebrovascular pathologies. These associations did not change after controlling for blood pressure or other comorbidities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>AHT use is associated with slower cognitive decline and lower tau pathology in late life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>In this prospective study of &gt; 3200 older, community-dwelling, persons followed for a mean of 8.6 years, those who used antihypertensive (AHT) medications during the study had slower cognitive decline, especially in episodic memory and semantic memory, compared to non-users.</li>\u0000 \u0000 <li>Among the &gt; 1800 deceased and autopsied persons, AHT medication use was associated with fewer paired helical filament-positive tau tangles (a marker of Alzheimer's disease) but not with other neurodegenerative or cerebrovascular pathologies, compared to non-users.</li>\u0000 \u0000 <li>Based on observational data from a large dataset, AHT use in older persons was related to slower cognitive decline and less Alzheimer's disease pathology.</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.70739","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134440","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}