Alzheimer's & Dementia最新文献

{"title":"Plasma p-tau217 identifies cognitively normal older adults who will develop cognitive impairment in a 10-year window","authors":"Yara Yakoub,&nbsp;Fernando Gonzalez-Ortiz,&nbsp;Nicholas J. Ashton,&nbsp;Christine Déry,&nbsp;Cherie Strikwerda-Brown,&nbsp;Frédéric St-Onge,&nbsp;Valentin Ourry,&nbsp;Michael Schöll,&nbsp;Maiya R. Geddes,&nbsp;Simon Ducharme,&nbsp;Maxime Montembeault,&nbsp;Pedro Rosa-Neto,&nbsp;Jean-Paul Soucy,&nbsp;John C. S. Breitner,&nbsp;Henrik Zetterberg,&nbsp;Kaj Blennow,&nbsp;Judes Poirier,&nbsp;Sylvia Villeneuve,&nbsp;PREVENT−AD Research Group","doi":"10.1002/alz.14537","DOIUrl":"https://doi.org/10.1002/alz.14537","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We assessed the prognostic accuracy of plasma p-tau217 in predicting the progression to mild cognitive impairment (MCI) in cognitively unimpaired (CU) individuals over a mean follow-up of 5.65 years after plasma collection (range 1.01–10.47).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We included 215 participants from the PREVENT−AD cohort with plasma Aβ_42/40 and p-tau217, 159 with cerebrospinal fluid (CSF) Aβ_42/40 and p-tau217, and 155 with ¹⁸F-NAV4694 and ¹⁸F-flortaucipir PET scans. MCI progression was determined by multidisciplinary consensus among memory experts blind to biomarker and genetic information.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Cox proportional hazard models indicated a greater progression rate in A+T+_plasma and A−T+_plasma compared to A−T−_plasma individuals (HR = 7.81 [95% CI = 3.92 to 15.59] and HR = 4.25 [1.60–11.31] respectively). Similar results were found with CSF (HR = 3.63 [1.72–7.70]) and PET (HR = 9.30 [3.67–23.55]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Plasma p-tau217 is a prognostic marker for identifying individuals who will develop cognitive impairment within ten years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Elevated plasma p-tau217 levels in CU individuals indicate future clinical progression.</li>\u0000 \u0000 <li>Adding plasma Aβ_42/40 status to p-tau markers did not improve the prediction to MCI.</li>\u0000 \u0000 <li>All individuals with abnormal tau PET measured in a temporal meta-ROI progressed to MCI.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14537","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490052","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":"Prevalence and factors associated with dementia in Lesotho: A cross-sectional, population-based study","authors":"Natalie E. Johnson,&nbsp;Jennifer M. Belus,&nbsp;Felix Gerber,&nbsp;Tristan T. Lee,&nbsp;Irene Ayakaka,&nbsp;Pearl Letsoela,&nbsp;Manthabiseng Molulela,&nbsp;Frédérique Chammartin,&nbsp;Alain Amstutz,&nbsp;Niklaus D. Labhardt","doi":"10.1002/alz.14614","DOIUrl":"https://doi.org/10.1002/alz.14614","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Limited research has examined dementia prevalence and associated factors in Lesotho. This study investigates dementia prevalence and the associated factors in Lesotho.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A survey in Lesotho included 1738 participants screened for dementia and potential associated factors with a focus on modifiable factors. Associations were evaluated using logistic regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The median age was 66 years, with 54.83% women. The prevalence of dementia was 4.89%. Those with depressive symptoms (adjusted odds ratio [aOR]: 3.97, 95% confidence interval [CI]: 1.39–11.30), age ≥ 75 (aOR: 2.68, 95% CI: 1.42–5.04), and underweight (aOR 2.30, 95% CI: 1.23–4.29) had increased odds of dementia. Those with moderate (aOR: 0.32, 95% CI: 0.17–0.58) to high (aOR: 0.35, 95% CI: 0.16–0.77) physical activity and obesity (aOR: 0.30, 95% CI: 0.11–0.80) presented lower odds for dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>This study provides a contemporary estimate of dementia prevalence in Lesotho, highlighting an association with modifiable factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>In Lesotho there is a probable dementia prevalence of 4.89%, aligning with regional estimates for Africa.</li>\u0000 \u0000 <li>Depression, older age, being underweight, and low physical activity were associated with increased odds of dementia.</li>\u0000 \u0000 <li>Moderate to high physical activity and obesity were associated with lower dementia odds.</li>\u0000 \u0000 <li>Further study of the association of dementia with potentially modifiable factors in low- and middle-income countries is warranted.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489872","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":"Mechanisms of comorbidity between Alzheimer's disease and pain","authors":"Kaifang Yao,&nbsp;Shenjun Wang,&nbsp;Zhifang Xu,&nbsp;Zezhi Fan,&nbsp;Zhihan Chen,&nbsp;Peng Jia,&nbsp;Shiwei Tu,&nbsp;Yangyang Liu,&nbsp;Xiaowei Lin,&nbsp;Yuan Xu,&nbsp;Yuxing Fang,&nbsp;Baomin Dou,&nbsp;Yi Guo","doi":"10.1002/alz.14605","DOIUrl":"https://doi.org/10.1002/alz.14605","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Clinical studies have revealed a significant correlation between pain and neurodegenerative diseases, particularly Alzheimer's disease (AD). However, due to cognitive and speech impairments, AD patients, especially those in moderate to severe stages, are often overlooked in pain management. The challenges in obtaining pain-related information from this population exacerbate the issue. Although recent clinical research has increasingly recognized the comorbidity of AD and pain, the pathological alterations and interactive mechanisms underlying this relationship remain inadequately explored. This review provides a comprehensive analysis of the clinical features and pathological mechanisms of AD with and without pain comorbidity. It examines underlying processes, including neuroinflammation, peripheral-central immune interactions, and neurotransmitter dynamics. Furthermore, it highlights current pain assessment and management strategies in AD patients. By offering a theoretical framework, this review aims to support the development of effective pain management approaches and serve as a reference for clinical interventions targeting AD-associated pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The comorbidity between AD and CP encompasses multiple interrelated biological pathways, such as neurodegeneration and inflammatory responses.</li>\u0000 \u0000 <li>The damage to neurons and synapses in AD patients influences the brain regions responsible for processing pain, thereby reducing the pain response.</li>\u0000 \u0000 <li>Neuroinflammation plays a vital role in the development of both AD and CP. Enhanced inflammatory responses have an impact on the CNS and promote sensitization.</li>\u0000 \u0000 <li>Common neurotransmitter alterations exist in the comorbidity of AD and CP, influencing cognition, emotion, and pain perception.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14605","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481351","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 systematic exposure-wide framework leveraging machine learning to identify multidomain exposure factors and their joint influence on cognitive function: Evidence from a neurological cohort","authors":"Jingtao Wu,&nbsp;Bowen Yin,&nbsp;Rui Wen,&nbsp;Huanting Pei,&nbsp;Siqi Zhu,&nbsp;Jiaxin Zhao,&nbsp;Yanbing Li,&nbsp;Ming Yang,&nbsp;Yaoyu Hu,&nbsp;Qun Xu,&nbsp;Ang Li,&nbsp;Yuxia Ma","doi":"10.1002/alz.14624","DOIUrl":"10.1002/alz.14624","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Cognitive decline has become a growing public concern, yet large-scale exposure data identifying the contributing factors remain limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We conducted an exposure-wide association study involving 1142 participants and 207 exposures, using machine learning to assess the relative contribution and joint effects of key factors. Cluster analysis and intervention simulation trials helped identify high-risk subpopulations and the potential benefits of targeted interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In adjusted mixed models, the socioeconomic status domain emerged as the strongest predictor of longitudinal global cognitive score (<i>β</i> = 2.91, <i>p </i>&lt; 0.0001, <i>q</i> &lt; 0.0001), while the dietary domain also played an important role in memory function. The cluster analysis found that the “unfavorable lifestyle” dominated phenotype was associated with the poorest cognitive outcomes. Simulation trials indicated that cognitive scores could improve by shifting individuals from unfavorable to favorable phenotypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Cognitive health requires multidomain interventions, particularly in the socioeconomic and dietary fields, and necessitates collaboration between government and individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The exposure-wide association study design, which assesses a broad range of exposures, is used to identify novel variables and understand their contributions to cognitive function.</li>\u0000 \u0000 <li>The findings from the multidomain analysis indicate that socioeconomic status is the most significant contributor to global cognitive function, while diet plays the largest role in memory function.</li>\u0000 \u0000 <li>Increasing the proportion of favorable phenotypes through multidomain interventions can significantly enhance public cognitive health.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14624","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486360","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 interaction between dysfunction of vasculature and tauopathy in Alzheimer's disease and related dementias","authors":"Chuyao Huang,&nbsp;Zhenwen Wei,&nbsp;Ningxiang Zheng,&nbsp;Jingsi Yan,&nbsp;Jiayu Zhang,&nbsp;Xinyi Ye,&nbsp;Wei Zhao","doi":"10.1002/alz.14618","DOIUrl":"10.1002/alz.14618","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Tauopathy is one of the pathological features of Alzheimer's disease and related dementias (ADRD). At present, there have been many studies on the formation, deposition, and intercellular transmission of tau in neurons and immune cells. The vasculature is an important component of the central nervous system. This review discusses the interaction between vasculature and tau in detail from three aspects. (1) The vascular risk factors (VRFs) discussed in this review include diabetes mellitus (DM), abnormal blood pressure (BP), and hypercholesterolemia. (2) In ADRD pathology, the hyperphosphorylation and deposition of tau interact with disrupted vasculature, such as different cells (endothelial cells, smooth muscular cells, and pericytes), the blood−brain barrier (BBB), and the cerebral lymphatic system. (3) The functions of vasculature are regulated by various signaling transductions. Endothelial nitric oxide synthase/nitric oxide, calcium signaling, Rho/Rho-associated coiled-coil containing Kinase, and receptors for advanced glycation end products are discussed in this review. Our findings indicate that the prevention and treatment of vascular health may be a potential target for ADRD combination therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Persistent VRFs increase early disruption of vascular mechanisms and are strongly associated with tau pathology in ADRD.</li>\u0000 \u0000 <li>Cell dysfunction in the vasculature causes BBB leakage and drainage incapacity of the cerebral lymphatic system, which interacts with tau pathology.</li>\u0000 \u0000 <li>Signaling molecules in the vasculature regulate vasodilation and contraction, angiogenesis, and CBF. Abnormal signaling transduction is related to tau hyperphosphorylation and deposition.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14618","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485875","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 “Incidence of dementia in the German Heinz Nixdorf Recall study over 20 years”","authors":"","doi":"10.1002/alz.70008","DOIUrl":"10.1002/alz.70008","url":null,"abstract":"<p>Schramm S, Rinck C, Krizanovic N, et al. Incidence of dementia in the German Heinz Nixdorf Recall study over 20 years. <i>Alzheimer's Dement</i>. 2025;17(1):e70061. https://doi.org/10.1002/dad2.70061. PMID: 39822293; PMCID: PMC11736620.</p><p>The letter “M” of Prof Hermann's middle name has been lost. The name is Dirk M Hermann.</p><p>We apologize for this error.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485874","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 Nun Study: Insights from 30 years of aging and dementia research","authors":"Kyra M. Clarke,&nbsp;Shahroo Etemadmoghadam,&nbsp;Benjamin Danner,&nbsp;Cole Corbett,&nbsp;Ali Ghaseminejad-Bandpey,&nbsp;Matthew Dopler,&nbsp;Julie Parker-Garza,&nbsp;Mohammad Alhneif,&nbsp;Sahana Babu,&nbsp;Oluwaseun B. Ogunbona,&nbsp;Angelique D. Gonzalez,&nbsp;Arash Salardini,&nbsp;Margaret E. Flanagan","doi":"10.1002/alz.14626","DOIUrl":"https://doi.org/10.1002/alz.14626","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The Nun Study is an iconic longitudinal study of aging and dementia on a cohort of 678 Catholic nuns from the School Sisters of Notre Dame. Participants consented to undergoing annual neuropsychological assessments, allowing researchers access to convent archives and medical records and <i>post mortem</i> brain donation. This study investigated the associations between epidemiological factors, cognitive function, and brain pathology. By examining published literature that reports on or utilizes Nun Study data, we provide an overview of its methodology and key findings, emphasizing its significant contributions to understanding cognitive impairment and related neuropathologies. Seminal findings on early-life factors affecting cognitive health, clinicopathological correlations, and apparent resistance and resilience to neuropathology are discussed. Decades of Nun Study research have made critical contributions to our understanding of Alzheimer's disease and related dementias and highlight continuing objectives for future research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>The uniform lifestyles of participants minimized potential confounds of the study.</li>\u0000 \u0000 <li>Early-life cognitive ability influenced late-life cognitive outcomes.</li>\u0000 \u0000 <li>Some participants with AD pathology did not exhibit dementia.</li>\u0000 \u0000 <li>Neuropathological comorbidities were common and increased the risk of dementia.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14626","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the polygenic risk scores for attention-deficit/hyperactivity disorder in Alzheimer's disease","authors":"Douglas T. Leffa,&nbsp;Guilherme Povala,&nbsp;Bruna Bellaver,&nbsp;João Pedro Ferrari-Souza,&nbsp;Pamela C. L. Ferreira,&nbsp;Firoza Z. Lussier,&nbsp;Cristiano Schaffer Aguzzoli,&nbsp;Carolina Soares,&nbsp;Hussein Zalzale,&nbsp;Francieli Rohden,&nbsp;Guilherme Bauer-Negrini,&nbsp;Sarah Abbas,&nbsp;Maitê Schneider,&nbsp;Joseph Therriault,&nbsp;Oscar L. Lopez,&nbsp;Victor L. Villemagne,&nbsp;William E. Klunk,&nbsp;Dana L. Tudorascu,&nbsp;Ann D. Cohen,&nbsp;Pedro Rosa-Neto,&nbsp;Eduardo R. Zimmer,&nbsp;Thomas K. Karikari,&nbsp;Luis Augusto Rohde,&nbsp;Brooke S. G. Molina,&nbsp;Tharick A. Pascoal,&nbsp;the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/alz.70003","DOIUrl":"https://doi.org/10.1002/alz.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Epidemiological studies indicate a link between attention-deficit/hyperactivity disorder (ADHD) and elevated risk of dementia. However, the impact of ADHD on cognition and Alzheimer's disease (AD) biomarkers in individuals with cognitive impairment remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We computed weighted ADHD polygenic risk scores (ADHD-PRS) in 938 cognitively impaired participants (674 mild cognitive impairment [MCI] and 264 dementia; mean age 73.5 years). A subset underwent cerebrospinal fluid (CSF) analysis for amyloid beta (Aβ) and phosphorylated tau, as well as fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG-PET).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We observed lower executive function in individuals with high ADHD-PRS for both MCI and dementia participants. Higher levels of CSF phosphorylated tau, but not Aβ, were observed in dementia participants with higher ADHD-PRS. Increased ADHD-PRS was associated with glucose hypometabolism in the frontal and parietal cortices.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>ADHD-PRS is associated with a more severe disease presentation in individuals with cognitive impairment due to dementia, characterized by impaired executive function, elevated tau pathology, and hypometabolism in the frontal and parietal cortices.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We calculated the genetic liability for attention-deficit/hyperactivity disorder (ADHD) using polygenic risk scores (ADHD-PRS).</li>\u0000 \u0000 <li>Elevated ADHD-PRS was associated with executive function deficits in individuals with mild cognitive impairment (MCI) or Alzheimer's disease (AD) dementia.</li>\u0000 \u0000 <li>Higher levels of cerebrospinal fluid (CSF) phosphorylated tau, but not amyloid beta (Aβ), were observed in dementia participants with higher ADHD-PRS.</li>\u0000 \u0000 <li>Higher ADHD-PRS was associated with brain hypometabolism in individuals with AD dementia.</li>\u0000 \u0000 <li>Hypometabolism in the parietal cortex mediated the effects of ADHD-PRS on executive function.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481544","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":"Tau pathology is associated with postsynaptic metabotropic glutamate receptor 5 (mGluR5) in early Alzheimer's disease in a sex-specific manner","authors":"Yan Wang,&nbsp;Jie Wang,&nbsp;Xing Chen,&nbsp;Zengping Lin,&nbsp;Zhiwen You,&nbsp;Kun He,&nbsp;Tengfei Guo,&nbsp;Jun Zhao,&nbsp;Qi Huang,&nbsp;Ruiqing Ni,&nbsp;Yihui Guan,&nbsp;Binyin Li,&nbsp;Fang Xie","doi":"10.1002/alz.70004","DOIUrl":"https://doi.org/10.1002/alz.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>To investigate the associations of metabotropic glutamate receptor 5 (mGluR5) with tau deposition and cognitive ability in patients with early Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Twenty-six cognitively impaired (CI) and 14 cognitively unimpaired (CU) individuals underwent mGluR5 positron emission tomography (PET) ([¹⁸F]PSS232), amyloid PET ([¹⁸F]florbetapir), and tau PET ([¹⁸F]MK6240), and neuropsychological assessment. The relationships among mGluR5 availability, tau deposition, and neuropsychological assessment were analyzed using Spearman's correlation and mediation analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>CI patients had lower mGluR5 in the hippocampus than CU (standardized uptake value ratio [SUVr]: 2.03 ± 0.25 vs 1.79 ± 0.17, <i>p</i> = 0.003). Hippocampal mGluR5 was negatively associated with hippocampal tau deposition (<i>r</i> = −.46, <i>p</i> = 0.003) and positively associated with cognitive performance, but only in women. Hippocampal tau deposition mediated the effect of mGluR5 on cognitive performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Reduced hippocampal mGluR5 is negatively related with tau deposition in most cortical regions and positively associated with cognitive performance, making it a promising biomarker for AD diagnosis and therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Cognitively impaired (CI) patients exhibited lower metabotropic glutamate receptor 5 (mGluR5) availability in the hippocampus than cognitively unimpaired (CU) subjects.</li>\u0000 \u0000 <li>Hippocampal mGluR5 availability was negatively associated with tau deposition in widespread cortex.</li>\u0000 \u0000 <li>Hippocampal mGluR5 availability was positively associated with cognitive performance.</li>\u0000 \u0000 <li>The close association of mGluR5 with tau and cognition performance exists only in females.</li>\u0000 \u0000 <li>Tau pathology mediated the relationship between mGluR5 availability and cognition.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481543","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":"Identification of 16 novel Alzheimer's disease loci using multi-ancestry meta-analyses","authors":"Julian Daniel Sunday Willett,&nbsp;Mohammad Waqas,&nbsp;Younjung Choi,&nbsp;Tiffany Ngai,&nbsp;Kristina Mullin,&nbsp;Rudolph E. Tanzi,&nbsp;Dmitry Prokopenko","doi":"10.1002/alz.14592","DOIUrl":"https://doi.org/10.1002/alz.14592","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is the most prevalent form of dementia. While many AD-associated genetic determinants have been identified, few studies have analyzed individuals of non-European ancestry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We conducted a multi-ancestry genome-wide association study (GWAS) of clinically diagnosed AD and AD-by-proxy using whole genome sequencing data from the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS), National Institute of Mental Health, UK Biobank (UKB), and All of Us (AoU) consisting of 49,149 cases (12,074 clinically diagnosed and 37,075 AD-by-proxy) and 383,225 controls. Nearly half of NIAGADS and AoU participants were of non-European ancestry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>For clinically diagnosed AD, we identified 14 new loci—five common (FBN2/SCL27A6, AC090115.1, DYM, KCNG1/AL121785.1, TIAM1) and nine rare (VWA5B1, RNU6-755P/LMX1A, MOB1A, MORC1-AS1, LINC00989, PDE4D, RNU2-49P/CDO1, NEO1, and SLC35G3/AC022916.1). Meta-analysis of UKB and AoU AD-by-proxy cases yielded two new rare loci (RPL23/LASP1 and CEBPA/AC008738.6), also nominally significant in NIAGADS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>In summary, we provide evidence for 16 novel AD loci and advocate for more studies using whole genome sequencing–based GWAS of diverse cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We used whole-genome sequencing data from large and diverse cohorts.</li>\u0000 \u0000 <li>We found novel genome-wide association study findings based on whole-genome data.</li>\u0000 \u0000 <li>We performed a multiancestry meta-analysis and incorporated results from underrepresented groups.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14592","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481633","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}