Frontiers in dementia最新文献

{"title":"Evidence that cholinergic mechanisms contribute to hyperexcitability at early stages in Alzheimer's disease.","authors":"Helen E Scharfman, Korey Kam, Áine M Duffy, John J LaFrancois, Paige Leary, Elissavet Chartampila, Stephen D Ginsberg, Christos Panagiotis Lisgaras","doi":"10.3389/frdem.2025.1513144","DOIUrl":"https://doi.org/10.3389/frdem.2025.1513144","url":null,"abstract":"<p><p>A long-standing theory for Alzheimer's disease (AD) has been that deterioration of synapses and depressed neuronal activity is a major contributing factor. We review the increasing evidence, in humans and in mouse models, that show that there is often neuronal hyperactivity at early stages rather than decreased activity. We discuss studies in mouse models showing that hyperexcitability can occur long before plaque deposition and memory impairment. In mouse models, a generator of the hyperactivity appears to be the dentate gyrus. We present evidence, based on mouse models, that inhibition of muscarinic cholinergic receptors or medial septal cholinergic neurons can prevent hyperactivity. Therefore, we hypothesize the novel idea that cholinergic neurons are overly active early in the disease, not depressed. In particular we suggest the medial septal cholinergic neurons are overly active and contribute to hyperexcitability. We further hypothesize that the high activity of cholinergic neurons at early ages ultimately leads to their decline in function later in the disease. We review the effects of a prenatal diet that increases choline, the precursor to acetylcholine and modulator of many other functions. In mouse models of AD, maternal choline supplementation (MCS) reduces medial septal cholinergic pathology, amyloid accumulation and hyperexcitability, especially in the dentate gyrus, and improves cognition.</p>","PeriodicalId":520000,"journal":{"name":"Frontiers in dementia","volume":"4 ","pages":"1513144"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing an overview Theory of Change for a multi-component support community for people affected by rare dementia.","authors":"Mary Pat Sullivan, Paul M Camic, Emma Harding, Joshua Stott, Gill Windle, Ian Davies-Abbott, Sebastian J Crutch","doi":"10.3389/frdem.2025.1565277","DOIUrl":"10.3389/frdem.2025.1565277","url":null,"abstract":"<p><strong>Introduction: </strong>There is growing awareness of people living with diverse dementia syndromes, many of whom are younger in age, with distinct support needs. Planning for increasing numbers of people living with dementia and subsequent models of support has largely overlooked this population. To address this gap, the aim was to design a Theory of Change for multi-component rare dementia support.</p><p><strong>Methods: </strong>Intervention development frameworks underpinned the construction of a Theory of Change informed by research evidence on rare dementia support and an iterative consultation process with people with lived experience, researchers, educators and health and social care practitioners.</p><p><strong>Results: </strong>The Theory of Change illustrates pathways to activities for continuous and tailored support solutions, education and knowledge production. Characteristic features include relationship, connection and continuity for people with lived experience, training and networking for professionals, and relational support with a commitment to ongoing learning for the rare dementia support team.</p><p><strong>Conclusion: </strong>The Theory of Change is positioned to flexibly support people affected by rare dementia, strengthen capacity within all sectors, improve service quality whilst maintaining a commitment to knowledge production and mobilization.</p>","PeriodicalId":520000,"journal":{"name":"Frontiers in dementia","volume":"4 ","pages":"1565277"},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meaningful inclusion of people with dementia in interview research: adopting the \"intentional stance\".","authors":"Emma O'Shea, Suzanne Timmons, Kate Irving","doi":"10.3389/frdem.2025.1596393","DOIUrl":"10.3389/frdem.2025.1596393","url":null,"abstract":"<p><p>Engaging people living with dementia in interview research presents unique ethical, methodological, and practical challenges. In recent years there is an increased recognition of the importance and value of meaningfully including people with dementia in research, and of the epistemic injustice of systematic exclusion. While there are a growing number of research papers suggesting strategies for fostering ethical and meaningful inclusion, this area is still very much in development, theoretically and methodologically. This paper outlines how a theoretical perspective on selfhood in dementia, which incorporates the concept of the \"Intentional Stance\" (as per Sabat), may be a useful means of reaching people with dementia in a meaningful way via open, curious and personhood-supporting interactions. Embodying the \"intentional stance\" refers to operating under the assumption that all behavior and interactions do have meaning(s), even if it is not immediately or intuitively evident to the researcher what the meaning(s) are. Here, we draw on excerpts from an interview I conducted with a person living with dementia about his experiences of and perspectives on respite and day services, using the intentional stance, in conjunction with a range of other strategies for maximizing reciprocal communication. The analysis highlights instances where the intentional stance was central to connecting with the person, and temporarily entering their lifeworld. Adopting this stance is a means of reducing the epistemic injustice that people with dementia have faced, through longstanding omission and exclusion from research, and from social spheres more broadly.</p>","PeriodicalId":520000,"journal":{"name":"Frontiers in dementia","volume":"4 ","pages":"1596393"},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in risk factors for Alzheimer dementia encephalopathy patients.","authors":"Connor John O'Brien, James Wayne Patterson, Dami Taiwo Ojo, Nathan Gerhard Faulstich, Killian Joseph Bucci, Philip Cole Brewer, Adebobola Imeh-Nathaniel, Emmanuel I Nathaniel, Laurie Roley, Richard Goodwin, Thomas I Nathaniel","doi":"10.3389/frdem.2025.1593788","DOIUrl":"10.3389/frdem.2025.1593788","url":null,"abstract":"<p><strong>Background: </strong>The objective is to identify risk factors that contribute to sex differences in Alzheimer dementia (AD) patients with encephalopathy (ADEN) and determine whether these factors are different between male and female ADEN patients. This is the first large-scale study comparing sex-specific ADEN risk profiles.</p><p><strong>Methods: </strong>Our retrospective cohort study analyzed data collected from February 2016 to August 2020. It included a total of 128,769 AD patients, among whom 41,266 AD patients also presented with encephalopathy, compared to 87,503 AD patients that did not. The univariate analysis was used to determine differences in risk factors for male and female AD patients. Multivariate analysis predicted specific risk factors associated with male and female ADEN patients.</p><p><strong>Result: </strong>In the adjusted analysis, males presented with hypertension (OR = 1.144, 95% CI, 1.094-1.197, <i>p</i> < 0.001), peripheral vascular disease (OR = 1.606, 95% CI, 1.485-1.737, <i>p</i> < 0.001), atrial fibrillation (OR = 1.555, 95% CI, 1.443-1.676, <i>p</i> < 0.001), hallucinations (OR = 1.406, 95% CI, 1.119-1.766, <i>p</i> = 0.003), and traumatic head injury (OR = 3.211, 95% CI, 2.346-4.395, <i>p</i> < 0.001). Females presented with osteoporosis (OR = 0.307, 95% CI, 0.278-0.340, <i>p</i> < 0.001), unspecified cancer (OR = 0.615, 95% CI, 0.512-0.740, <i>p</i> < 0.001), anxiety (OR = 0.609, 95% CI, 0.565-0.655, <i>p</i> < 0.001), urinary tract infections (UTI) (OR = 0.451, 95% CI, 0.423-0.481, <i>p</i> < 0.001), upper respiratory infections (URI) (OR = 0.531, 95% CI, 0.432-0.653, <i>p</i> < 0.001) and gastrointestinal ulceration (OR = 0.338, 95% CI, 0.269-0.424, <i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>Our analysis identified risk factors that contribute to sex differences in ADEN. This difference was fully mediated by peripheral vascular disease, atrial fibrillation, hallucinations, and traumatic head injury for males and unspecified cancer, anxiety, urinary tract infections, upper respiratory infections, and gastrointestinal ulceration for females. These findings provide valuable insights into the risk factors that can be managed to improve the care of male and female ADEN patients.</p>","PeriodicalId":520000,"journal":{"name":"Frontiers in dementia","volume":"4 ","pages":"1593788"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From inclusion to empowerment: advancing equity through co-research with people living with dementia.","authors":"Lillian Hung, Joey Wong, Karen Lok Yi Wong, Emily Ong, Granville Johnson, Helen Rochford-Brennan, Jim Mann, Lester Gierach, Lynn Jackson, Mario Gregorio, Mary Beth Wighton, Phyllis Fehr","doi":"10.3389/frdem.2025.1600162","DOIUrl":"10.3389/frdem.2025.1600162","url":null,"abstract":"<p><p>Too often, people living with dementia are spoken for rather than spoken with. This reflects deeply embedded assumptions/biases about people living with dementia in our society. This article explores the experiences and insights of individuals with dementia, positioning empowerment as a foundational strategy to advance social citizenship and equity. We collaboratively on more than a decade of shared work in research and advocacy. Our collective analysis identifies three key dimensions essential for meaningful empowerment: (a) recognizing strengths and building capacities, (b) equitable leadership, and (c) supportive environments and learning together. Our findings demonstrate that intentional, respectful collaboration produces extensive social, political, and healthcare benefits, actively challenging inequities and fostering a deeper sense of belonging and contribution.</p>","PeriodicalId":520000,"journal":{"name":"Frontiers in dementia","volume":"4 ","pages":"1600162"},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurogenesis drives hippocampal formation-wide spatial transcription alterations in health and Alzheimer's disease.","authors":"Zachery D Morrissey, Pavan Kumar, Trongha X Phan, Mark Maienschein-Cline, Alex Leow, Orly Lazarov","doi":"10.3389/frdem.2025.1546433","DOIUrl":"https://doi.org/10.3389/frdem.2025.1546433","url":null,"abstract":"<p><p>The mechanism by which neurogenesis regulates the profile of neurons and glia in the hippocampal formation is not known. Further, the effect of neurogenesis on neuronal vulnerability characterizing the entorhinal cortex in Alzheimer's disease (AD) is unknown. Here, we used <i>in situ</i> sequencing to investigate the spatial transcription profile of neurons and glia in the hippocampal circuitry in wild-type mice and in familial AD (FAD) mice expressing varying levels of neurogenesis. This approach revealed that in addition to the dentate gyrus, neurogenesis modulates the cellular profile in the entorhinal cortex and CA regions of the hippocampus. Notably, enhancing neurogenesis in FAD mice led to partial restoration of neuronal and cellular profile in these brain areas, resembling the profile of their wild-type counterparts. This approach provides a platform for the examination of the cellular dynamics in the hippocampal formation in health and in AD.</p>","PeriodicalId":520000,"journal":{"name":"Frontiers in dementia","volume":"4 ","pages":"1546433"},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proposing a multi-method phenomenological approach in exploring the perceived daily life experiences of people with dementia in their dementia care environments and immediate outdoor settings.","authors":"Alexia Mercieca, Iain Scott, Catharine Ward Thompson, Heather Wilkinson","doi":"10.3389/frdem.2025.1502911","DOIUrl":"https://doi.org/10.3389/frdem.2025.1502911","url":null,"abstract":"<p><p>The environment in this study is presented primarily drawing on the theoretical definition of home, and its experience and meaning to the individual with dementia, with an interest in access to outdoors. Notions of perception, cognitive image and affordance are central to the sense of home, and in turn the sense of self that this may inform and support. This theoretical framework informs the multi-method phenomenological approach proposed, through themes of spatial legibility, cultural appropriateness, fascination, user-centredness and personalisation. The novelty of the methodological toolkit lies in the incorporation of methods that have been traditionally used in research with people with dementia as the basis of the framework, but which are supplemented by additional layers developed from conventional architectural tools to create a more visual representation of the environmental experience. Despite its apparent complexity, the methodology yields a very clear and precise image of the person's presence in her surroundings, at once providing a location in space and time, her mood and engagement, as well as a layering of the affordances that may have informed her behavior. This method was developed as part of this research, and remains unique to it. Its innovation lies in the progression of the DCM tool, the integration of the notion of affordances and architectural mapping techniques to propose a holistic depiction of the care experience of people with dementia.</p>","PeriodicalId":520000,"journal":{"name":"Frontiers in dementia","volume":"4 ","pages":"1502911"},"PeriodicalIF":0.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report: Behavioral variant FTD confounding a language variant FTD in a case of PSP-CBS.","authors":"Alexandra V Jürs, Elisabeth Kasper, Manuela Neumann, Jens Kurth, Bernd J Krause, Daniel Cantré, Johannes Prudlo","doi":"10.3389/frdem.2025.1540519","DOIUrl":"10.3389/frdem.2025.1540519","url":null,"abstract":"<p><p>Frontotemporal dementia (FTD) occurs in two main clinical subtypes, which can transition into one another: the behavioral variant (bvFTD) and the language variant (primary progressive aphasia; PPA). It is common for the latter, as primary progressive aphasia (PPA), to transition into bvFTD; however, the opposite development, where bvFTD is followed by \"secondary progressive aphasia,\" has received little attention. This constellation is particularly challenging to recognize as frontal dysexecutive syndrome can confound subsequent progressive aphasia as impulsive behavior, a lack of inhibition, and apathy can lead to non-aphasic communication disturbances, including impoverished syntax, reduced cognitive flexibility, and insufficient error monitoring. A 78-year-old patient, with a disease duration of 10 years, was initially diagnosed in the 3rd year of the disease with corticobasal syndrome (CBS) with frontal behavioral-spatial syndrome (CBS-FBS) and subsequently with CBS with progressive non-fluent aphasia (CBS-PNFA) in the 4th year. Severe ophthalmoplegia was the reason for changing the diagnosis in the seventh year to progressive supranuclear palsy with CBS predominance type (PSP-CBS). The pathological diagnosis was FTLD-tau in the form of a PSP subtype. The MRI showed asymmetric atrophy, particularly of the left insular cortex and the left inferior frontal gyrus. The 2-[¹⁸F]FDG-PET revealed left-accentuated bifrontal glucose hypometabolism. This case report highlights how progressive neurodegenerative aphasia can occur in FTD not only as a primary language phenomenon (in the sense of PPA) but also as a secondary phenomenon (following a primary behavioral disorder with a non-aphasic communication disorder). Dysexecutive syndrome can mask aphasia. Therefore, incorporating spontaneous speech tasks into standard neuropsychological language tests, in addition to MRI and PET imaging techniques, could help better recognize such secondary aphasias, even in the presence of dysexecutive syndrome, and thus broaden our understanding of the natural history of FTD.</p>","PeriodicalId":520000,"journal":{"name":"Frontiers in dementia","volume":"4 ","pages":"1540519"},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wayfinding behavioral patterns of seniors with dementia: two exploratory case studies.","authors":"Leonie van Buuren, Daantje Derks, Masi Mohammadi, Bernard Colenbrander","doi":"10.3389/frdem.2025.1524425","DOIUrl":"10.3389/frdem.2025.1524425","url":null,"abstract":"<p><strong>Introduction: </strong>While wayfinding is vital for quality of life, it is also a declining skill for people with dementia. Understanding wayfinding behavioral patterns of people with dementia helps to improve the nursing home corridor designs to facilitate autonomously conducting activities of daily life. However, a comprehensive image of these patterns is lacking.</p><p><strong>Methods: </strong>An empirical qualitative study was conducted, studying seven wayfinding behavioral patterns of people with advanced dementia (<i>n</i> = 8) in two nursing home corridors where they live, using fly-on-the-wall observation.</p><p><strong>Results: </strong>The data show that the most frequent wayfinding behavioral patterns observed were \"movements\" followed by \"looking at\", \"stops on the route\", and \"verbal navigational cues\".</p><p><strong>Discussion: </strong>These behaviors occurred often at crossroads; i.e., places in which participants should make a decision concerning continuing their route. Spatially, these places have high-visibility values and many things to see for people with dementia. Contradictory, these places might cause more confusion for people with dementia. Therefore, special attention should be paid to the design of these spaces.</p>","PeriodicalId":520000,"journal":{"name":"Frontiers in dementia","volume":"4 ","pages":"1524425"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum: Differentiation of Alzheimer's disease from other neurodegenerative disorders using chemiluminescence immunoassays measuring cerebrospinal fluid biomarkers.","authors":"Philipp Arendt, Katharina Römpler, Britta Brix, Viola Borchardt-Lohölter, Mandy Busse, Stefan Busse","doi":"10.3389/frdem.2025.1568275","DOIUrl":"https://doi.org/10.3389/frdem.2025.1568275","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/frdem.2024.1455619.].</p>","PeriodicalId":520000,"journal":{"name":"Frontiers in dementia","volume":"4 ","pages":"1568275"},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}