Alzheimer's & Dementia最新文献

{"title":"Neuronal ABCA7 deficiency aggravates mitochondrial dysfunction and neurodegeneration in Alzheimer's disease","authors":"Ni Wang,&nbsp;Yining Pan,&nbsp;Skylar C. Starling,&nbsp;Devon H. Haskell,&nbsp;Astrid C. Quintero,&nbsp;Keiji Kawatani,&nbsp;Yasuteru Inoue,&nbsp;Francis Shue,&nbsp;Xiaoye Ma,&nbsp;Tomonori Aikawa,&nbsp;Yuka A. Martens,&nbsp;Aishe Kurti,&nbsp;Tammee M. Parsons,&nbsp;Ralph B. Perkerson,&nbsp;Bhaskar Roy,&nbsp;Ana-Caroline Raulin,&nbsp;Yingxue Ren,&nbsp;Michael DeTure,&nbsp;Dennis W. Dickson,&nbsp;Hanmei Bao,&nbsp;Xianlin Han,&nbsp;Guojun Bu,&nbsp;Takahisa Kanekiyo","doi":"10.1002/alz.70112","DOIUrl":"https://doi.org/10.1002/alz.70112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Loss-of-function variants of the <i>ABCA7</i> gene are associated with an increased risk of Alzheimer's disease (AD). How neuronal ABCA7 contributes to AD pathogenesis is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using neuron-specific <i>Abca7</i> KO mice (n<i>Abca7</i>^−/−) with or without 5×FAD amyloid model background and <i>post mortem</i> AD brains, we investigated AD-related phenotypes through comprehensive approaches including transcriptomics and lipidomics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Lipidomics analysis detected altered lipid profiles in the brains and synaptosomes of 5×FAD; n<i>Abca7</i>^−/− mice compared to controls. Transcriptomics profiling revealed that neuronal ABCA7 deficiency altered the expression of genes and pathways related to mitochondrial homeostasis and apoptosis, particularly in excitatory neurons. Consistently, synaptosomes isolated from 5×FAD; n<i>Abca7</i>^−/− mice showed diminished mitochondria respiration and reduced synaptic protein levels, which is further supported by results from human AD brains.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our findings reveal that neuronal ABCA7 plays a critical role in mitochondrial homeostasis important for neuronal function and survival in the presence of AD pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Neuronal ABCA7 deficiency exacerbates Aβ pathology and neuronal damage in 5×FAD mice.</li>\u0000 \u0000 <li>Neuronal ABCA7 deficiency alters brain transcriptomes and lipidomes of 5×FAD mice.</li>\u0000 \u0000 <li>Neuronal ABCA7 deficiency disturbs mitochondria functions in synaptosomes from 5×FAD mice.</li>\u0000 \u0000 <li>Neuronal <i>ABCA7</i> expression associates with genes and pathways related to mitochondrial homeostasis in AD brains.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707698","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":"World Dementia Council Update Lessons from Treatment: Treatment Series","authors":"","doi":"10.1002/alz.70058","DOIUrl":"https://doi.org/10.1002/alz.70058","url":null,"abstract":"&lt;p&gt;The field of Alzheimer's disease treatment has entered a pivotal new era with the approval and utilization of new disease-modifying treatments across many countries. Although these treatments do not yet offer a cure, they hold promise in slowing disease progression and offering hope to the millions of people around the world affected by this disease. Despite these treatment advances, there are many unknowns related to the global implementation of these therapies as well as issues of equity and accessibility.&lt;/p&gt;&lt;p&gt;To discuss these barriers, successes, and share lessons learned, the World Dementia Council (WDC) held the first of three virtual dialogues focused on the era of treatment on January 23, 2025.&lt;/p&gt;&lt;p&gt;Following opening remarks from Lenny Shallcross, Executive Director of the WDC, session co-chair, Dr. Phillip Scheltens, Emeritus Professor and Head of the Dementia Fund at EQT Life Sciences in Amsterdam, Netherlands, introduced some of the key questions to be addressed in this new era of treatment: Who to treat? When to treat? How to address side effects? When to start treatment? When to stop treatment? These questions, among others, helped guide the subsequent discussion focused on sharing lessons learned across the Alzheimer's disease treatment landscape.&lt;/p&gt;&lt;p&gt;The remainder of the dialogue included reflections from global researchers on early learnings from treatment delivery and a robust full-group discussion on how these lessons can be translated and expanded globally.&lt;/p&gt;&lt;p&gt;Dr. Reisa Sperling, Professor of Neurology at Harvard Medical School and Director of the Center for Alzheimer's Research and Treatment discussed the progress in Alzheimer's disease treatment. She acknowledged that although current treatments are not perfect, the ongoing and upcoming Phase 3 clinical trials, like TRAILBLAZER-ALZ 3, offer promise. She also highlighted the growing interest and opportunity surrounding combination trials, particularly those targeting both amyloid and tau, which could offer even greater benefits.&lt;/p&gt;&lt;p&gt;She addressed an important area of focus for researchers, the side effects of these treatments, most pointedly, ARIA (amyloid-related imaging abnormalities), which can refer to swelling and bleeding in the brain. Understanding the avenues to most effectively manage and avoid ARIA is becoming increasingly important, and recent research exploring adjusting titration of treatment as a way to reduce the risk of ARIA has indicated that progress is being made in the space.&lt;/p&gt;&lt;p&gt;Looking toward the future, Dr. Sperling emphasized the importance of early intervention and primary prevention efforts including clinical trials like the AHEAD Study, which is exploring whether treatment can slow or stop early brain changes due to Alzheimer's disease in cognitively normal adults who are at higher risk of developing the disease in later life. Finally, she called on the research world to take a renewed focus on understanding the inequities of Alzheimer'","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707228","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":"Driving research on successful aging and neuroprotection in Latin America: Insights from the inaugural symposium on brain resilience and healthy longevity","authors":"Yakeel T. Quiroz,&nbsp;David Aguillón,&nbsp;Joseph Arboleda-Velasquez,&nbsp;Yamile Bocanegra,&nbsp;Gloria Patricia Cardona-Gómez,&nbsp;Maria M. Corrada,&nbsp;Ibai Diez,&nbsp;Elkin Garcia-Cifuentes,&nbsp;Kenneth Kosik,&nbsp;Lusiana Martinez,&nbsp;David Pineda-Salazar,&nbsp;Rafael Posada,&nbsp;Norbel Roman,&nbsp;Diego Sepulveda-Falla,&nbsp;Andrea Slachevsky,&nbsp;Marcio Soto-Añari,&nbsp;Evelyn Tabilo,&nbsp;Daniel Vasquez,&nbsp;Andrés Villegas-Lanau","doi":"10.1002/alz.70037","DOIUrl":"https://doi.org/10.1002/alz.70037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Global life expectancy has steadily increased in recent decades, resulting in a significant rise in the number of individuals aged 80 years and older. This trend is also evident in Latin America, where life expectancy is improving, though at varying rates across countries and regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Partnering with the Neurosciences Group of Antioquia (GNA), we launched a Colombian study on resilience in families with autosomal dominant Alzheimer's disease and the oldest-old population. Over the past 2 years, the project has expanded to include participants from Peru, Chile, and Costa Rica.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>This research led to the first symposium on Brain Resilience and Healthy Longevity, held in Medellín, Colombia, in August 2024.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The article summarizes key discussions from the symposium, highlighting the most promising opportunities for brain resilience and prevention research in the region and offering recommendations for future research to promote healthy aging and dementia-free communities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Uncovering the genetic and physiological drivers of cognitive resilience, neurodegeneration resistance, and healthy longevity is essential for maintaining brain function as we age.</li>\u0000 \u0000 <li>“Superagers” and cognitively resilient individuals from Latin American families with Alzheimer's disease offer valuable insights into brain protection mechanisms.</li>\u0000 \u0000 <li>Studying the interplay of socio-environmental and genetic factors in the oldest-old is key to understanding healthy longevity and improving dementia prevention.</li>\u0000 \u0000 <li>The inaugural Brain Resilience and Healthy Longevity Symposium highlights the need for global collaboration to uncover factors that drive cognitive resilience and healthy aging in Latin America, advancing dementia prevention.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707226","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":"Brain structural alterations in young women with premature ovarian insufficiency: Implications for dementia risk","authors":"Shuang Yuan,&nbsp;Yuchen Gong,&nbsp;Yu Zhang,&nbsp;Wenjiao Cao,&nbsp;Liutong Wei,&nbsp;Taotao Sun,&nbsp;Junyan Sun,&nbsp;Lulu Wang,&nbsp;Qiuwan Zhang,&nbsp;Qian Wang,&nbsp;Yu Wei,&nbsp;Zhaoxia Qian,&nbsp;Puming Zhang,&nbsp;Dongmei Lai","doi":"10.1002/alz.70111","DOIUrl":"https://doi.org/10.1002/alz.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Premature ovarian insufficiency (POI), marked by ovarian function loss before age 40, is linked to a higher risk of dementia, including Alzheimer's disease (AD). However, the associated brain structural changes remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We analyzed T1-weighted and diffusion tensor imaging in 33 idiopathic POI women and 51 healthy controls, using voxel-based, surface-based morphometry, and network analyses to assess gray matter volume (GMV), cortical thickness, and brain connectivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Women with POI showed significant GMV and cortical thickness reductions in the frontal, parietal, and temporal regions (<i>p</i> &lt; 0.05), alongside impaired connectivity with key regions such as the hippocampus, thalamus, and amygdala (<i>p</i> &lt; 0.05). Younger POI subgroups exhibited changes in more widespread brain regions. In additionally, notable atrophy was observed in specific hippocampal and thalamic subregions in POI (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This preliminary study suggests early neurodegenerative patterns in POI, potentially contributing to dementia risk. Further research is needed to explore the underlying mechanisms and potential interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We evaluated brain structural changes in participants with idiopathic premature ovarian insufficiency (POI).</li>\u0000 \u0000 <li>The observed brain alterations in POI participants closely resemble those seen in early dementia, including regions specifically associated with Alzheimer's disease (AD).</li>\u0000 \u0000 <li>These findings highlight the critical need for early interventions to reduce the long-term risks of cognitive impairment and dementia in women with POI.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707699","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":"Racial and ethnic differences in white matter hypointensities: The role of vascular risk factors","authors":"Farooq Kamal,&nbsp;Roqaie Moqadam,&nbsp;Cassandra Morrison,&nbsp;Mahsa Dadar","doi":"10.1002/alz.70105","DOIUrl":"https://doi.org/10.1002/alz.70105","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>White matter hypointensities (WMHs) are markers of cerebrovascular pathology associated with cognitive decline. Reports of racial and ethnic differences in WMHs have been inconsistent across studies. This study examined whether race and ethnicity influence WMH burden and whether vascular risk factors explain these differences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Data from the National Alzheimer's Coordinating Center included 7132 Whites, 892 Blacks, 283 Asians, and 661 Hispanics. Baseline and longitudinal WMHs were examined using linear regression and mixed-effects models across racial and ethnic groups, controlling for demographics and vascular risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Adjusting for vascular risk factors reduced WMH burden differences and eliminated differences in temporal regions in Black versus White older adults. For Hispanics, differences became significant after adjusting for vascular risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Although some racial and ethnic WMH disparities are influenced by vascular risk factors, others persist, highlighting the need for multidimensional approaches when targeting WMHs in diverse populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Current research is inconsistent as to whether there are racial differences in white matter hypointensities (WMHs).</li>\u0000 \u0000 <li>Blacks exhibit higher WMH burden than Whites, mediated by vascular factors.</li>\u0000 \u0000 <li>In Hispanics, WMH differences emerged only after adjusting for vascular risk factors.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707660","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 and related disorders in patients with bipolar disorders and other mental disorders: Actual neurodegenerative processes or phenocopies?","authors":"Emmanuel Cognat,&nbsp;Emeline Marlinge,&nbsp;Capucine Blaise,&nbsp;Claire Paquet","doi":"10.1002/alz.70110","DOIUrl":"https://doi.org/10.1002/alz.70110","url":null,"abstract":"<p>Dear Editor,</p><p>We read with great interest the study by Liu et al.<span>¹</span>, which leverages a robust methodological framework in a large sample of nearly 500,000 participants to investigate the association between chronic psychiatric disorders and the risk of late-life neurocognitive diseases.</p><p>The study highlights an increased risk of neurocognitive disorders in patients with mood disorders and especially bipolar disorder (BD), with particular emphasis on Alzheimer's disease (AD). This conclusion is supported by the use of Mendelian randomization, which suggests a causal link between BD and AD. However, the study also uncovers an elevated risk for other types of dementia, including vascular dementia (VD) and frontotemporal dementia (FTD), with hazard ratios exceeding those for AD (AD 2.37 [1.43–3.94], VD 3.82 [2.16–6.75], FTD 5.80 [1.86–18.13]).<span>¹</span> This broader finding is important, as it points to the possibility of multiple underlying mechanisms contributing to late cognitive impairment in BD.</p><p>These observations lead us to commend Liu et al. for their important contribution while also highlighting the complexity of interpreting their findings. The increased risk of neurocognitive disorders in BD, as demonstrated by their study, may include AD but also other dementias, each with distinct pathophysiological underpinnings. This aligns with prior research suggesting an elevated risk of other neurodegenerative conditions, such as Parkinson's disease, among patients with BD.<span>⁸</span></p><p>To advance in the field, it will be essential to determine whether patients with BD and cognitive decline exhibit the characteristic pathological hallmarks of these neurodegenerative diseases or whether the observed associations reflect phenocopies. Such an effort requires the integration of biomarkers and neuropathological data into future studies, as well as the establishment of dedicated cohorts to explore these questions.</p><p>Altogether, these findings resonate with the historical concept of “vesanic dementia” a term that encapsulates the complex interplay between psychiatric disorders and late-life cognitive decline.<span>⁹</span> This also underscores the importance of distinguishing late-life cognitive impairment in patients with BD from the cognitive impairments observed in younger patients, which likely arise from different mechanisms.</p><p>The authors declare no conflicts of interest. Author disclosures are available in the Supporting Information.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707379","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":"Biomarkers of blood–brain barrier and neurovascular unit integrity in human cognitive impairment and dementia","authors":"Scott R. French,&nbsp;Briana P. Meyer,&nbsp;Juan C. Arias,&nbsp;Swati Rane Levendovzsky,&nbsp;Craig C. Weinkauf","doi":"10.1002/alz.70104","DOIUrl":"https://doi.org/10.1002/alz.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Blood–brain barrier (BBB) dysfunction is recognized as an early step in the development of Alzheimer's disease and related dementias (ADRD). Biomarkers are needed to monitor BBB integrity over time, better understand the role of the BBB in neurodegeneration, potentially help define long-term ADRD risk, and monitor effects of therapeutics. In this review, we discuss the current biomarkers used to detect human BBB dysfunction in the context of cognitive decline and dementia. We also discuss promising candidate fluid biomarkers to detect BBB dysfunction in blood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>BBB permeability occurs during normal aging and is further exacerbated in ADRD.</li>\u0000 \u0000 <li>In this review, we discuss in vivo imaging and CSF biomarkers of BBB dysfunction currently used in the setting of aging and ADRD in humans.</li>\u0000 \u0000 <li>We also review promising candidate blood-based biomarkers that may represent BBB dysfunction.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707700","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":"Validation of the CAMCOG-DS-II, a neuropsychological test battery for Alzheimer's disease in people with Down syndrome: A Horizon 21 European Down syndrome Consortium study","authors":"Phoebe Ivain,&nbsp;Asaad Baksh,&nbsp;Fedal Saini,&nbsp;Mina Idris,&nbsp;Miren Tamayo-Elizalde,&nbsp;Jasmine Wells,&nbsp;Bessy Benejam,&nbsp;Sandra Virginia Loosli,&nbsp;Katja Sandkühler,&nbsp;Elisabeth Wlasich,&nbsp;Olivia Wagemann,&nbsp;Johannes Levin,&nbsp;Diane Martet,&nbsp;Silvia Sacco,&nbsp;Ségolène Falquero,&nbsp;Manon Clert,&nbsp;Anne-Sophie Rebillat,&nbsp;Wan Ming Khoo,&nbsp;Madelaine Amelia Smith,&nbsp;Jessica Beresford-Webb,&nbsp;Shahid Zaman,&nbsp;María Carmona-Iragui,&nbsp;Laura Videla,&nbsp;Juan Fortea,&nbsp;Ellen Melbye Langballe,&nbsp;Ingrid Tøndel Medbøen,&nbsp;Frode Kibsgaard Larsen,&nbsp;Eleni Baldimtsi,&nbsp;Raphaella Paradisi,&nbsp;Panagiotis Ntailakis,&nbsp;Magdalini Tsolaki,&nbsp;Georgia Papantoniou,&nbsp;Eimear McGlinchey,&nbsp;Mary McCarron,&nbsp;Seán Kennelly,&nbsp;André Strydom","doi":"10.1002/alz.70071","DOIUrl":"https://doi.org/10.1002/alz.70071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The Cambridge Cognitive Examination modified for use in people with Down syndrome (CAMCOG-DS) is a sensitive cognitive test for Alzheimer's disease (AD)–related decline in people with DS, but needs updates for sensitivity, cultural adaptability, and additional memory/executive function items. This study aimed to develop and validate the CAMCOG-DS-II.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In this multi-language, multi-site study, the psychometric properties of the CAMCOG-DS-II were evaluated against previously validated measures in 223 participants (mean age: 40.18 years) with DS across seven countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The CAMCOG-DS-II had a high completion rate, minimal floor/ceiling effects (compared to the modified Cued Recall Test, the CANTAB Paired Associates Learning, and the Purdue Pegboard), strong validity and reliability, and performance was unaffected by language across sites. It differentiated between those with/without AD and distinguished clinically rated cognitively stable and prodromal individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>The CAMCOG-DS-II is a sensitive measure of cognitive performance in people with DS at risk of AD. Its cross-language and site reliability support its potential use in AD–DS clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Developed and validated the Cambridge Cognitive Examination modified for use in people with Down syndrome (CAMCOG-DS-II) for Alzheimer's disease in Down syndrome.</li>\u0000 \u0000 <li>CAMCOG-DS-II shows increased sensitivity to Alzheimer's disease–related decline in Down syndrome.</li>\u0000 \u0000 <li>Improved applicability across an international and culturally diverse population.</li>\u0000 \u0000 <li>Differentiates Alzheimer's disease status: cognitively stable, prodromal, and clinical.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707214","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":"Updates and future perspectives on neuropsychiatric symptoms in Alzheimer's disease","authors":"Myuri Ruthirakuhan,&nbsp;Dylan X. Guan,&nbsp;Moyra Mortby,&nbsp;Jennifer Gatchel,&nbsp;Ganesh M. Babulal","doi":"10.1002/alz.70079","DOIUrl":"https://doi.org/10.1002/alz.70079","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Neuropsychiatric symptoms (NPS) are common throughout the Alzheimer's disease (AD) continuum and profoundly affect patients, caregivers, and health-care systems. This review synthesizes key research presented in the 2022 and 2023 Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment Neuropsychiatric Syndromes–Professional Interest Area (NPS-PIA) Year-In-Reviews, emphasizing six critical areas: (1) diversity and disparities, (2) diagnostic frameworks, (3) neurobiology of NPS, (4) NPS as a disease marker, (5) the impact of COVID-19, and (6) interventions. NPS accelerates AD progression, increases functional decline, diminishes quality of life, and heightens caregiver burden and institutionalization rates. Current treatments primarily rely on psychotropics, which offer limited efficacy and raise safety concerns. This review aims to inform clinicians and researchers about recent NPS advancements while identifying gaps for future studies to improve outcomes for individuals with AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Research in Alzheimer's disease–related neuropsychiatric symptoms has rapidly increased, indicating heightened interest.</li>\u0000 \u0000 <li>Key areas include: diversity, diagnostics, markers, COVID-19 impact, and treatments.</li>\u0000 \u0000 <li>A road map for future studies, based on the key areas of research, is provided.</li>\u0000 \u0000 <li>This road map includes considerations to improve study applicability and validity.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707215","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":"Novel blood-based proteomic signatures across multiple neurodegenerative diseases","authors":"Robert Durcan,&nbsp;Amanda Heslegrave,&nbsp;Peter Swann,&nbsp;Julia Goddard,&nbsp;Leonidas Chouliaras,&nbsp;Alexander G. Murley,&nbsp;George Savulich,&nbsp;W. Richard Bevan-Jones,&nbsp;Owen Swann,&nbsp;Nicholas J. Ashton,&nbsp;Kaj Blennow,&nbsp;William McEwan,&nbsp;Henrik Zetterberg,&nbsp;James B. Rowe,&nbsp;John T. O'Brien,&nbsp;Maura Malpetti","doi":"10.1002/alz.70116","DOIUrl":"https://doi.org/10.1002/alz.70116","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;Blood-based biomarkers have the potential to support early and accurate diagnoses of neurodegenerative diseases, which are sensitive to molecular pathology and are predictive of outcome. We evaluated a novel multiplex proteomic method in people with diverse neurodegenerative diseases.&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;Serum from people with Alzheimer's disease (&lt;i&gt;N&lt;/i&gt; = 36), Lewy body dementia (&lt;i&gt;N&lt;/i&gt; = 34), frontotemporal dementia (&lt;i&gt;N&lt;/i&gt; = 36), and progressive supranuclear palsy (&lt;i&gt;N&lt;/i&gt; = 36) and age-matched controls (&lt;i&gt;N&lt;/i&gt; = 30) was analyzed with the nucleic acid linked immuno-sandwich assay (NULISA) central nervous system panel (≈ 120 analytes) and inflammation panel (250 analytes). Biomarkers were compared across groups and included as predictors of survival.&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 NULISA panels demonstrated high sensitivity and reliability for detecting multiple biomarkers across neurodegenerative disorders. There were condition-specific proteomic biomarkers, while neurofilament light chain, corticotropin-releasing hormone, CD276, and a data-driven inflammation pattern were significant transdiagnostic outcome predictors.&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 sensitive NULISA multiplex approach supports differential diagnosis and target identification, with prognostically informative dementia-related biomarkers.&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;We tested the novel technology nucleic acid linked immuno-sandwich assay (NULISA) in people with diverse neurodegenerative diseases, which demonstrated high sensitivity and reliability for detecting multiple biomarkers in serum samples.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We compared the NULISA central nervous system serum results to single molecule array (Simoa) plasma assays for phosphorylated tau (p-tau)217, p-tau231, neurofilament light chain (NfL), and glial fibrillary acidic protein, finding strong correlations.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Increased levels of serum NfL were identified across all patient groups and most elevated in the frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP) cohorts, while p-tau epitopes were the most significant markers in patients with Alzheimer's disease (AD) and Lewy body dementia.&lt;/li&gt;\u0000 \u0000 ","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707448","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}