Journal of Alzheimer's Disease最新文献

{"title":"Real-world clinical profile of individuals with cerebrospinal fluid Aβ^-/pTau181<sup />.","authors":"Ophir Keret, Tianxu Xia, Sara Wilkins, Liqhwa Nokukhanya Lubimbi Ncube, Briella Smaw, Yuguang Xiong, Sam Gandy, Ana Pereira, Naasan Georges, Fanny M Elahi","doi":"10.1177/13872877261445561","DOIUrl":"https://doi.org/10.1177/13872877261445561","url":null,"abstract":"<p><p>BackgroundCerebrospinal fluid (CSF) pTau181 is used to support Alzheimer's disease (AD) diagnosis but can also rise in amyloid-negative individuals. This CSF profile (Aβ^-/pTau181⁺) lies outside the AD continuum and complicates real-world etiologic diagnosis of neurocognitive disorders.ObjectiveTo determine the prevalence and clinical phenotype associated with the Aβ^-/pTau181⁺ CSF biomarker profile in a real-world memory clinic population.MethodsWe screened the Mount Sinai Hospital database (2015-2024) for patients who underwent ADmark CSF biomarker testing. An Aβ^-/pTau181⁺ group was classified using assay cutoffs (Amyloid-Total-Tau Index>1.2, pTau181 > 54 pg/mL) and compared to an Aβ⁺ group (Amyloid-Total-Tau Index<0.8) matched for pTau181 and total-Tau. Clinical variables were extracted via chart review, limited to notes preceding CSF and blinded to CSF results.ResultsThe Aβ^-/pTau181⁺ group included 25 individuals (10.1% of the cohort) and had equally impaired cognition but fewer episodic memory complaints. Diagnosis was more often Lewy body or frontotemporal dementia. On neuroimaging, Aβ^-/pTau181⁺ exhibited less white matter hyperintensity burden and temporoparietal atrophy.ConclusionsCSF Aβ^-/pTau181⁺ is frequent in real-world evaluations of cognitive impairment and presents with fewer AD phenotypic features. Further research is required to clarify Aβ^-/pTau181⁺ underlying biology and clinical trajectory.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261445561"},"PeriodicalIF":3.1,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856402","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":"Early diagnosis of Alzheimer's disease through handwriting analysis and deep learning: A review.","authors":"Qizhe Tang, Jiaxi Liu, Chuanhao Fan, Xiaoya Zhang, Chu Zhang, Hengnian Qi","doi":"10.1177/13872877261446573","DOIUrl":"https://doi.org/10.1177/13872877261446573","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders worldwide, requiring early identification for timely intervention and to slow disease progression. However, existing diagnostic approaches, while effective at later stages, remain limited in detecting early-stage AD. Handwriting analysis has recently emerged as a non-invasive, cost-effective, and ecologically valid digital behavioral biomarker that reflects neurocognitive impairment. This review examines the role of handwriting as a neurocognitive marker for AD, focusing on integrating deep learning methodologies to enhance early diagnostic accuracy. It also elucidates the neurocognitive mechanisms linking handwriting behavior and AD, addressing current methodological and translational challenges. We performed a PRISMA-informed structured literature search and narrative synthesis of handwriting- and drawing-based studies for detecting AD/mild cognitive impairment (MCI), including offline handwriting images and online pen-stroke kinematics captured by digital devices. Task paradigms, data dimensions, preprocessing pipelines, modeling strategies (traditional machine learning and deep learning), evaluation practices, and translational considerations were summarized, and studies were organized by detection purpose and analytic approach. Our findings show that handwriting-based models generally discriminate AD/MCI from healthy controls with accuracy exceeding 80%, while deep learning models (e.g., convolutional neural network and multimodal Transformer fusion) approach 90% in structured tasks like clock drawing and figure copying. Online kinematic markers (e.g., reduced velocity, prolonged in-air time, increased pausing, and pressure instability) recur across studies, and multimodal integration with speech, gait, or facial signals can further improve sensitivity and ecological validity, although most studies are small and single-center.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261446573"},"PeriodicalIF":3.1,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856356","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":"Cognitive function in immigrants from Mexico and Latin America: The role of age at migration.","authors":"Cindy E Tsotsoros, Carmín A Centeno Román, Alexandra L Clark, Ileana De Anda-Duran, Kristine J Ajrouch, Irving E Vega","doi":"10.1177/13872877261446976","DOIUrl":"https://doi.org/10.1177/13872877261446976","url":null,"abstract":"<p><p>BackgroundLatino immigrants in the United States represent diverse national origins, with Mexicans comprising the largest group. Cognitive health disparities among Latino immigrants may reflect differences in migration experiences, including age at migration, socioeconomic differences, and acculturation. Whether Mexican immigrants differ from Latin American immigrants in cognitive outcomes remains unclear.ObjectiveThis study examined the independent and interactive effects of Mexican origin and age at migration on cognitive levels and decline compared to other Latin American immigrants. We also test whether socioeconomic and acculturation factors help explain differences in cognitive outcomes.MethodsData came from 2077 Latino immigrants in the Health and Retirement Study (2014-2020). Cognition was assessed using the Telephone Interview for Cognitive Status. Mixed-effects models evaluated the main and interaction effects of origins and age at migration on age-related decline, controlling for demographic, health-related, socioeconomic, and acculturation covariates.ResultsMexican immigrants had significantly lower cognitive levels than Latin American immigrants. However, after adjusting for socioeconomic indicators and language acculturation, Mexican immigrants demonstrated higher cognitive scores. Among Mexicans, late-life migration was associated with significantly poorer cognitive levels, which persisted after accounting for socioeconomic and acculturation factors. No significant differences were observed in rates of cognitive decline by origin or age at migration.ConclusionsLate-life migration is associated with poorer cognitive outcomes among Mexican immigrants. Findings indicate that socioeconomic and acculturation factors mask underlying differences in cognitive performance between Mexican and Latin American immigrants, underscoring the need to consider both migration experiences and social context when evaluating cognitive disparities.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261446976"},"PeriodicalIF":3.1,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856327","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":"A novel synaptic compartmentalization failure framework for neurodegeneration.","authors":"Baikuntha Panigrahi","doi":"10.1177/13872877261449379","DOIUrl":"https://doi.org/10.1177/13872877261449379","url":null,"abstract":"<p><p>Synaptic plasticity relies on precise spatial and temporal compartmentalization of signaling within dendritic spines, presynaptic terminals, and axonal domains. This compartmentalization is usually reinforced through activity-dependent remodeling of spine geometry, cytoskeletal scaffolds, calcium handling, and local protein synthesis, allowing plasticity signals to remain localized and terminate appropriately. Here, a unifying framework is proposed in which neurodegenerative diseases emerge when the capacity to maintain and renew these compartments declines. Ageing and glial dysregulation may act as major biological drivers of this process by altering dendritic spine structure, calcium homeostasis, metabolic support, neurotransmitter clearance, and activity-dependent synaptic remodeling. In this state, plasticity induction remains largely preserved, but signaling becomes spatially diffuse and temporally prolonged, imposing chronic structural and energetic stress on synapses and axons. Proteins such as tau and alpha synuclein, which normally support cytoskeletal organization and dynamic phase separated assemblies, may become destabilized under these conditions leading to pathological aggregation. This framework provides an explanation for early synaptic dysfunction, selective neuronal vulnerability, long presymptomatic phases, network-level disease propagation, the protective effects of education and cognitive engagement, and the limited efficacy of proteinopathy centric therapeutic strategies. Neurodegeneration may be conceptualized as a failure of synaptic compartmentalization, with protein aggregation arising downstream of this primary vulnerability.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261449379"},"PeriodicalIF":3.1,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856376","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":"Association between the Dietary Index for Gut Microbiota and cognitive function among older adults in the United States.","authors":"Ke Si, Cunwei Sun, Han Guo, Chuanqin Shi, Yangang Wang","doi":"10.1177/13872877261449420","DOIUrl":"https://doi.org/10.1177/13872877261449420","url":null,"abstract":"<p><p>BackgroundThe Dietary Index for Gut Microbiota (DI-GM) is a novel index reflecting diet quality relative to gut microbiota health.ObjectiveThe study aims to investigate the relationship between DI-GM and cognitive function in older adults.MethodsData were obtained from 2629 participants aged ≥60 years in the National Health and Nutrition Examination Surveys (NHANES) (2011-2014). Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency Test (AFT), the Digit Symbol Substitution Test (DSST), and a global z score. Multivariable linear regression, restricted cubic splines (RCS), and subgroup analysis were performed. Predictive utility of DI-GM was assessed via the receiver operating characteristic (ROC) analysis against a baseline model. Mediation analysis examined relationships among DI-GM, the Dietary Inflammatory Index (DII), and cognitive outcomes.ResultsHigher DI-GM was associated with higher AFT, DSST, and the global z scores (p < 0.001). After full adjustment, participants with DI-GM (≥ 6) showed higher AFT score (β = 1.11, 95% CI 0.46∼1.75), DSST score (β = 4.95, 95% CI 3.05∼6.86) and z score (β = 0.19, 95% CI 0.10∼0.28), compared to those with DI-GM (0-3). No significant direct association was observed with CERAD (β = 0.45, 95% CI -0.29∼1.18, p = 0.233). RCS indicated linear relationships between DI-GM and cognitive function scores. DI-GM had excellent predictive performances based on the ROC. No significant interactions were detected by subgroup analysis. Furthermore, DII partly mediated the relationship between DI-GM and cognitive function.ConclusionsThe DI-GM showed a linear positive correlation with cognitive function in older adults.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261449420"},"PeriodicalIF":3.1,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856350","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":"Association of mitochondrial genome variants with Alzheimer's disease in a Chinese population.","authors":"Xiaoli Hao, Bin Jiao, Yijing Wang, Tianyan Xu, Qijie Yang, Yuan Zhu, Yiliang Liu, Cong Zhang, Xiaoyan Liang, Yafang Zhou, Xinxin Liao, Shilin Luo, Beisha Tang, Jinchen Li, Xuewen Xiao, Lu Shen","doi":"10.1177/13872877261442231","DOIUrl":"https://doi.org/10.1177/13872877261442231","url":null,"abstract":"<p><p>BackgroundResearch on the mitochondrial genome variants of Alzheimer's disease (AD) in Chinese populations is lacking.ObjectiveThe study aimed to identify mitochondrial DNA (mtDNA) variants associated with AD risk and explore the relationship between mtDNA variants and plasma biomarkers in AD patients.MethodsWhole genome sequencing was performed in 1509 AD patients and 2010 controls from the Chinese population. mtDNA variants were called according to GATK's best practice mitochondrial pipeline. We evaluated the association of AD risk with mtDNA variants and mitochondrial haplogroup. Common variant (MAF≥0.01) based association analysis and gene-based tests of rare variants (MAF<0.01) were carried out with PLINK 1.9 and SKAT-O, respectively. Spearman correlation analysis was performed to assess the association between the burden of mtDNA variants and plasma biomarker levels.ResultsThe frequency of mitochondrial haplogroup G in AD group was nominally higher than control group (p = 0.019, OR = 1.48). Rare variants of <i>MT-CYB</i> gene were significantly enriched in controls compared to AD patients (p = 2.81 × 10^-4, OR = 0.886). Besides, the control group exhibited considerably lower mRNA expression of <i>MT-CYB</i> in brain regions compared to AD patients in GEO database. Furthermore, the number of mtDNA indel variants per individual correlated positively with plasma Aβ42 levels.ConclusionsMitochondrial haplogroup G may serve as a risk factor for AD, while rare variants of <i>MT-CYB</i> gene acted as protective factor against AD in mainland China. Moreover, mtDNA variants were related to AD plasma biomarker levels. Our findings highlighted the role of mitochondrial genome variants in the pathogenesis of AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261442231"},"PeriodicalIF":3.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856404","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":"Corrigendum to \"Early cognitive screening for individuals on the dementia continuum: A novel approach amid current trends\".","authors":"","doi":"10.1177/13872877261447686","DOIUrl":"https://doi.org/10.1177/13872877261447686","url":null,"abstract":"","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261447686"},"PeriodicalIF":3.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838195","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":"Methodological considerations on the network meta-analysis of brexpiprazole dosing for agitation in Alzheimer's disease.","authors":"Anderson Matheus Pereira da Silva, Diogo Haddad Santos","doi":"10.1177/13872877261449394","DOIUrl":"https://doi.org/10.1177/13872877261449394","url":null,"abstract":"","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261449394"},"PeriodicalIF":3.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838202","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":"A snapshot of Italian nursing homes for people with dementia: A national survey of 1671 facilities.","authors":"Roberta Vaccaro, Patrizia Lorenzini, Francesco Giaquinto, Fabio Matascioli, Emanuela Salvi, Giulia Carnevale, Nicoletta Locuratolo, Nicola Vanacore, Ilaria Bacigalupo","doi":"10.1177/13872877261442226","DOIUrl":"https://doi.org/10.1177/13872877261442226","url":null,"abstract":"<p><p>BackgroundNursing homes (NHs) that provide for people with dementia (PWD) are responsible for meeting the needs of patients and their families through medical, personal, and rehabilitative care. However, little is known regarding the Italian facilities.ObjectiveTo describe the characteristics of NHs and to detail the care services and treatments provided.MethodsIn 2023, the Italian National Institute of Health conducted a national survey to assess dementia care services and update the Dementia Observatory's online Map of Services through a detailed facility questionnaire.ResultsOverall, 1671 NHs accommodating PWD participated, representing 46.3% of facilities and 53.1% of beds. Significant disparities emerged when estimating the number of PWD per available NH across macro-area (North 214; Centre 332; South/Islands 850).R2D classification was more frequent in southern than central and northern facilities (28%, 10.9%, and 13.1%, respectively; p<0.001). Northern facilities had more rooms (North: 46, Centre: 28, South and Islands: 29; p<0.001) and beds (North: 87, Centre: 55, South and Islands: 58; p<0.001). Southern NHs had shorter admission wait times and longer stays. Conversely, Northern facilities had more staff, better training, and more digital systems and were more often integrated with day care centers and palliative care services.ConclusionsThis is the first national study assessing the accessibility and affordability of Italian NHs housing PWD. The lack of special units, tailored environments and uneven services distribution and staff highlight the fragmentation of Italy's long-term care system. NH geographical distribution is inconsistent with epidemiological estimates of PWD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261442226"},"PeriodicalIF":3.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838169","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":"Health behavior mechanisms linking childhood socioeconomic status to Alzheimer's disease and related dementia risk: Exploring gender and racial/ethnic differences.","authors":"Suyoung Nah, Carmen Jw Chek, Ana Montoya, Audrey Duarte, Lindsay H Ryan, William J Chopik","doi":"10.1177/13872877251394317","DOIUrl":"https://doi.org/10.1177/13872877251394317","url":null,"abstract":"<p><p>BackgroundLower childhood socioeconomic status (cSES) has been linked to a higher risk of Alzheimer's disease and related dementia (ADRD). Yet, the mechanisms underlying this association remain unclear.ObjectiveThis study examined whether poorer health behaviors in adulthood mediate the association between lower cSES and ADRD risk. We further explored whether the mediating effects of health behaviors vary by gender or race/ethnicity.MethodsData were drawn from 26,631 participants in the Health and Retirement Study (<i>M_age</i> = 61.18 years). Cox proportional hazard models were used to estimate the association between cSES and ADRD risk, as well as the mediating effects of health behaviors, including smoking, heavy drinking, physical activity, and influenza vaccination.ResultsLower cSES was associated with a higher risk of ADRD (hazard ratio = 1.06, [1.02, 1.09]). Lower physical activity mediated this association, accounting for 17.1% of the total effect of cSES on ADRD risk. Subgroup analyses revealed that this mediation was consistent across all gender and racial/ethnic groups, except for foreign-born Hispanics. Smoking mediated the association only for men, explaining 4.2% of the total effect.ConclusionsThese findings suggest that lower cSES may be a risk factor for ADRD partially through lower physical activity across most demographic groups. Interventions promoting physical activity in adulthood could help mitigate the adverse effect of low cSES on ADRD risk. Furthermore, smoking prevention programs may be particularly beneficial for men from lower socioeconomic backgrounds.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251394317"},"PeriodicalIF":3.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838216","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}