Journal of Alzheimer's Disease最新文献

{"title":"Red flags for remote cognitive diagnostic assessment: A Delphi expert consensus study by the Canadian Consortium on Neurodegeneration in Aging.","authors":"Nathan Hm Friedman, Sophie Hallot, Inbal Itzhak, Richard Camicioli, Alex Henri-Bhargava, Jacqueline A Pettersen, Linda Lee, John D Fisk, Paula McLaughlin, Vladimir Khanassov, Zahinoor Ismail, Morris Freedman, Howard Chertkow, Philippe Desmarais, Megan E O'Connell, Maiya R Geddes","doi":"10.1177/13872877251338186","DOIUrl":"10.1177/13872877251338186","url":null,"abstract":"<p><p>Despite the potential benefits of remote cognitive assessment for dementia, it is not appropriate for all clinical encounters. Our aim was to develop guidance on determining a patient's suitability for comprehensive remote cognitive diagnostic assessment for dementia. A multidisciplinary expert workgroup was convened under the auspices of the Canadian Consortium on Neurodegeneration in Aging. We applied the Delphi method to determine 'red flags' for remote cognitive assessment of dementia. This resulted in 14 red flags that met the predetermined consensus criteria. We then developed a novel clinical decision-making infographic that integrated these findings to support multidisciplinary clinicians in determining a patient's readiness to undergo comprehensive remote cognitive assessment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"527-536"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal relationships between plasma proteins and Alzheimer's disease using bidirectional Mendelian randomization.","authors":"Yichen Li, Yu-Lin Yao, Yong Wu","doi":"10.1177/13872877251345151","DOIUrl":"10.1177/13872877251345151","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is influenced by a complex interplay of genetic, immune, and metabolic factors. Identifying plasma proteins causally linked to AD could help clarify these pathways and uncover potential therapeutic targets.ObjectiveThis study aims to investigate the causal relationships between AD and plasma proteins.MethodsWe conducted a two-stage, two-sample Mendelian randomization (MR) analysis to explore the causal relationships between plasma protein levels and AD risk. In both stages, we used non-overlapping genome-wide association study datasets for exposures (plasma protein levels) and outcome (AD) to ensure robust and independent analyses. We examined both forward (from plasma proteins to AD risk) and reverse (from AD to plasma protein expression) causal effects to elucidate potential bidirectional relationships.ResultsOur MR analysis identified 25 plasma proteins with causal associations to AD, with many implicated in immune and lipid metabolic pathways. These findings reinforce the roles of inflammation and lipid metabolism in AD pathogenesis and offer novel insights into specific proteins that may serve as biomarkers or therapeutic targets.ConclusionsThis study provides further support for the relationship between immune and lipid metabolic dysregulation and AD, advancing our understanding of the molecular mechanisms underlying disease progression and highlighting key proteins for future research and therapeutic development.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"765-773"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Porphyromonas gingivalis</i>-lipopolysaccharide and amyloid-β: A dangerous liaison for impairing memory?","authors":"Sim K Singhrao","doi":"10.1177/13872877251343317","DOIUrl":"10.1177/13872877251343317","url":null,"abstract":"<p><p>Alzheimer's disease is characterized by declining memory and the presence of insoluble amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain. Gui et al.¹ studied the effects of low levels of <i>Porphyromonas gingivalis</i>-lipopolysaccharide (<i>P. gingivalis</i>-LPS) and soluble Aβ on synaptic proteins, synapsin1 (SYN1) and post-synaptic density protein-95 (PSD-95). Their study revealed increased proinflammatory cytokine production in microglial cells (MG6) treated with <i>P. gingivalis</i>-LPS and Aβ, while neuronal cells, N2a, exposed to MG6-conditioned medium showed SYN1 and PSD-95 loss. This suggests that excessive neuroinflammation may contribute to synaptic protein and memory loss, offering mechanistic insights into <i>P. gingivalis</i>-LPS-mediated inflammatory pathways in periodontitis.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"537-539"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pterosin D-activated protein kinase A mitigates Alzheimer's disease in 5xFAD mice.","authors":"Ha Na Kim, Won Hee Jang, Nam Sook Kang, Sungsub Kim, Kwang-Eun Choi, Anand Balupuri, Seong Su Hong, Yun-Hyeok Choi, Eun-Jae Lee, Lynkyung Choi, Jae-Young Koh, Gil Hong Park","doi":"10.1177/13872877251344627","DOIUrl":"10.1177/13872877251344627","url":null,"abstract":"<p><p>BackgroundProtein kinase A (PKA) is a key activator of cAMP response element-binding protein signaling; it plays a pivotal role in cognition, memory, and adult neurogenesis. Phosphodiesterase (PDE) inhibitors that indirectly activate PKA through cAMP are promising candidates for Alzheimer's disease (AD) therapeutics.ObjectiveWe examined whether pterosins bind directly to PKA as activators and enhance cognition and memory.MethodsWe investigated PKA phosphorylation and performed <i>in silico</i> docking analysis using the cAMP-binding domains (CBD1, CBD2) of bovine PKA. Our focus was on exploring the effects of oral pterosin D on learning and memory in a 5xFAD mouse model of AD.ResultsWe demonstrated that C3-hydroxylated pterosins directly activated PKA in neuronal cells but not in astrocytes and did not affect intracellular cAMP levels or inhibit PDE. <i>In silico</i> modeling implied that C3-hydroxylated pterosins fitted the CBD of PKA. Pterosins enhanced long-term potentiation mossy fiber-CA1 in the mouse hippocampus without affecting normal synaptic transmission. Pterosins more potently accelerate neuronal proliferation and neurite outgrowth in primary mouse cortical neurons than dibutyryl-cAMP does. Pterosin D significantly restored cognition and memory in 5xFAD mice on the Morris water maze.ConclusionsC3-hydroxylated pterosins, as activators of PKA, have substantial potential as disease-modifying/-slowing therapeutic agent for AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"726-738"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward a person-centered return of research results of dementia risk: A pluralistic, constructive expansion.","authors":"Bilal Irfan, Elijah Wiseman, J Wesley Boyd, Jonathan Reader, Annalise Rahman-Filipiak","doi":"10.1177/13872877251343319","DOIUrl":"10.1177/13872877251343319","url":null,"abstract":"<p><p>Graham et al.'s article offers a thoughtful account of why disclosing modifiable dementia risk factors to cognitively unimpaired research participants may be ethically defensible. In this Ethics Response, we seek to engage constructively with their arguments, affirming value in a person-centered approach, while also expanding on how cultural, communal, and religious contexts can further illuminate the ethics of returning individual research results. Drawing on emerging ethical issues and examples from diverse settings, this response highlights how stigmatization, religious worldviews, family care traditions, and broader socioeconomic factors may influence the perceived meaning and impact of dementia risk communication.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"540-546"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging role of the circadian rhythm in the blood-brain barrier dysfunction associated with cerebral small vessel disease.","authors":"Yorito Hattori","doi":"10.1177/13872877251337775","DOIUrl":"10.1177/13872877251337775","url":null,"abstract":"<p><p>The relationship between circadian rhythm and cerebrovascular disease has recently emerged as a fascinating area of research. It has been found that the circadian rhythm could affect the development and exacerbation of cerebral small vessel disease (CSVD). Dysfunction of the blood-brain barrier (BBB) is one of the key players in the mechanisms of CSVD. This is thought to be regulated by circadian oscillations of clock genes, which control transporter function, regulating the permeability of the BBB endothelial cells, tight junction proteins, and pericytes. Understanding the interaction between circadian genes and BBB components may contribute to the development of promising treatments for CSVD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"47-50"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain and Ocular Nutrition Conference 2025, Lecture Abstracts June 17th - 20th 2025, Endicott College, Massachusetts, USA.","authors":"","doi":"10.1177/13872877251345099","DOIUrl":"https://doi.org/10.1177/13872877251345099","url":null,"abstract":"","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":"106 1_suppl","pages":"S1-S33"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in cognitive trajectories and practice effects in a cohort of older Londoners: The role of risk factors.","authors":"Sima Toopchiani, Shireen Sindi, Neil Poulter, Sujin Kang, Chi Udeh-Momoh, Geraint Price, Miia Kivipelto, Lefkos Middleton, Oliver Robinson","doi":"10.1177/13872877251339833","DOIUrl":"10.1177/13872877251339833","url":null,"abstract":"<p><p>BackgroundSex differences in cognitive abilities have been reported; however, the underlying reasons remain unclear.ObjectiveTo (i) investigate sex differences in cognitive performance, (ii) evaluate the contributions of established dementia risk factors to these differences, and (iii) examine the role of non-modifiable risk factors on sex differences in cognitive performance.MethodsAmong 964 cognitively unimpaired participants (aged 60-85) of the UK CHARIOT-PRO Main Study, we assessed cross-sectional and longitudinal associations, over up to 3 years of follow-up, between sex and cognitive performance, using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).ResultsSex differences, mostly favoring women were observed at baseline across almost all RBANS indices including the total scale (Cohen's d = 0.3, adjusted mean difference in score = -5.4, p < 0.001). Sex differences were observed in Practice effects (PEs), with men showing less PE in almost all cognitive domains including the total scale (adjusted 1.3, p = 0.002). Greater sex differences in PEs, were documented among the 'older' participants in two out of five cognitive domains including the immediate memory index (mean difference: older (69-85 years) group = -3.2, p = 0.002); younger (60-68 years) group = -0.8, p = 0.4). Sex differences were more pronounced among 'Apolipoprotein-Ꜫ4 -carriers' in three out of five domains including the total scale (mean difference in carriers = -2.6, p = 0.002); non-carriers = -0.7, p = 0.3).ConclusionsSex differences in cognition and PE were observed after adjusting for risk factors associated with Alzheimer's disease. Future studies should also consider the effects of sex on non-modifiable risk factors and PEs to identify potential 'masked' neuropathology.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"230-244"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12231851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How can we define a brain health chart? A narrative review and a proposal.","authors":"Luca Tagliafico, Elena Bogliacino, Stefano Raffa, Nicola Girtler, Andrea Brugnolo, Pietro Mattioli, Dario Arnaldi, Valentina Marozzi, Gabriele Giacomini, Alessio Nencioni, Gianluca Serafini, Paolo Nozza, Fabio Gotta, Paola Mandich, Stefano Pretta, Ilaria Gandoglia, Massimo Del Sette, Luca Sofia, Mehrnaz Hamedani, Luca Roccatagliata, Mattia Losa, Gabriella Biffa, Lucia Argenti, Paola Castellini, Lorenzo Lombardo, Luigi Lorenzini, Carlo Serrati, Martina Pulze, Gianmario Sambuceti, Giulia Bozzo, Silvia Daniela Morbelli, Angelo Schenone, Federico Massa, Virginia Pelagotti, Wendy Kreshpa, Fiammetta Monacelli, Beatrice Orso, Matteo Pardini","doi":"10.1177/13872877251343233","DOIUrl":"10.1177/13872877251343233","url":null,"abstract":"<p><p>In recent years, there has been a significant change in the type of patients referred to memory clinics, characterized by an increase in mildly symptomatic individuals and potentially even healthy people at risk of cognitive decline due to Alzheimer's disease and other neurodegenerative diseases in this context. Additionally, there is growing interest in developing health services focused on brain health throughout the lifespan, particularly within a primary prevention framework. This effort has led to proposing dedicated \"brain health services\" for dementia risk reduction. However, in the context of cognitive disorders, distinguishing between primary and secondary prevention poses significant challenges, particularly in identifying individuals within the general population who may exhibit subtle cognitive decline or early-stage neurodegeneration. We propose seven key dimensions for assessing \"brain health\": cognitive reserve along with social and functional status, cognitive decline, mood and sleep disorders, general dementia risk factors, geriatric syndromes in older adults, structural brain damage, and neurodegenerative proteinopathies. Together, these dimensions form a comprehensive \"brain health chart\". We review the known evidence for each dimension's role in assessing brain health, emphasizing approaches that can be applied in a community setting. We believe that by identifying broadly applicable assessment methods for these dimensions, the development of personalized strategies for maintaining brain health could be facilitated.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"427-442"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Finger motor skills and related brain regions in patients with cognitive disorder.","authors":"Shota Suzumura, Junpei Sugioka, Keita Sakurai, Aiko Osawa, Taisei Matsubayashi, Masaki Kamiya, Yuko Sano, Akihiko Kandori, Tomohiko Mizuguchi, Yoshiharu Uchida, Hitoshi Kagaya, Izumi Kondo","doi":"10.1177/13872877251344223","DOIUrl":"10.1177/13872877251344223","url":null,"abstract":"<p><p>BackgroundMotor impairment precede cognitive impairment and may be early biomarkers for dementia. We have previously reported an association between finger tapping and cognitive function; however, the link between finger motor movements and associated brain regions is unclear.ObjectiveIn this study, finger tapping movements were used to identify brain regions strongly associated with finger motor dexterity in individuals with Alzheimer's disease (AD) and mild cognitive impairment (MCI).MethodsThis exploratory, cross-sectional study included individuals with AD or MCI who underwent finger motor movement measurements and 3D magnetic resonance imaging (MRI). Voxel-based morphometry analysis was conducted using Statistical Parametric Mapping 12 and Computational Anatomy Toolbox 12 to assess gray matter volume. Correlations between MRI and finger motor parameters were analyzed using intracranial volume, Mini-Mental State Examination score, age, and sex as covariates.ResultsWe included 136 individuals (AD, 71; MCI, 65). The number of taps and the number of freezing calculated from acceleration significantly correlated with gray matter volume in motor and sensory regions, including the primary motor (BA4) and primary somatosensory (BA3, 1, 2) cortices. Many correlations with the left hemisphere were found in both left- and right-handed bimanual alternating tapping tasks.ConclusionsFinger motor dexterity in individuals with cognitive impairment is associated with gray matter volume in specific brain regions, with a pronounced correlation in the left hemisphere. These findings suggest that finger motor skills may be linked to structural brain changes.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"634-645"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}