Journal of Alzheimer's Disease最新文献

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Neural mechanisms of disease pathology and cognition in young-onset Alzheimer's disease variants. 年轻发病的阿尔茨海默病变异体的疾病病理和认知的神经机制。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 DOI: 10.1177/13872877251344325
Seda Sacu, Catherine F Slattery, Karl J Friston, Ross W Paterson, Alexander Jm Foulkes, Keir Yong, Sebastian Crutch, Jonathan M Schott, Adeel Razi
{"title":"Neural mechanisms of disease pathology and cognition in young-onset Alzheimer's disease variants.","authors":"Seda Sacu, Catherine F Slattery, Karl J Friston, Ross W Paterson, Alexander Jm Foulkes, Keir Yong, Sebastian Crutch, Jonathan M Schott, Adeel Razi","doi":"10.1177/13872877251344325","DOIUrl":"10.1177/13872877251344325","url":null,"abstract":"<p><p>BackgroundLate-onset Alzheimer's disease is consistently associated with alterations in the default-mode network (DMN)-a large-scale brain network associated with self-related processing and memory. However, the functional organization of DMN is far less clear in young-onset Alzheimer's disease (YOAD).ObjectiveThe current study aimed to identify effective connectivity changes in the core DMN nodes between YOAD variants and healthy controls.MethodsWe assessed resting-state DMN effective connectivity in two common YOAD variants (i.e., amnestic variant (n = 26) and posterior cortical atrophy (n = 13) and healthy participants (n = 24) to identify disease- and variant-specific connectivity differences using spectral dynamic causal modelling.ResultsPatients with the amnestic variant showed increased connectivity from prefrontal cortex to posterior DMN nodes relative to healthy controls, whereas patients with posterior cortical atrophy exhibited decreased posterior DMN connectivity. Right hippocampus connectivity differentiated the two patient groups. Furthermore, disease-related connectivity alterations were also predictive of group membership and cognitive performance.ConclusionsThese findings suggest that resting-state DMN effective connectivity provides a new understanding of neural mechanisms underlying the disease pathology and cognition in YOAD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"653-667"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119441","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}
引用次数: 0
Investigating the relationship between visual impairment and cognitive impairment in the older adults using the novel vision screening assessment (VISA) tool. 使用新型视力筛查评估(VISA)工具调查老年人视力障碍与认知障碍之间的关系。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 DOI: 10.1177/13872877251344218
Yue Shi, Ying Tang, Ya Wang, Xiao Fei, Xiaoyan Xu, Yi Zhang
{"title":"Investigating the relationship between visual impairment and cognitive impairment in the older adults using the novel vision screening assessment (VISA) tool.","authors":"Yue Shi, Ying Tang, Ya Wang, Xiao Fei, Xiaoyan Xu, Yi Zhang","doi":"10.1177/13872877251344218","DOIUrl":"10.1177/13872877251344218","url":null,"abstract":"<p><p>BackgroundEarly identification and multimodal treatment of dementia, especially Alzheimer's disease, is a common goal of global efforts.ObjectiveThis study aims to investigate the relationship between visual impairment (VI) and cognitive impairment in older adults using the Vision Screening Assessment (VISA) tool.MethodsA total of 94 healthy older adults from community settings in Changzhou were recruited for the study. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and the Clock Drawing Test (CDT). The VISA tool was employed to evaluate participants' visual acuity, ocular motility, visual fields, and visual attention.ResultsThis study examined 94 participants, identifying 80 with VI, 26 with abnormal visual attention, 58 with cognitive impairment, and 11 with visuospatial dysfunction. Analyses showed: (1) Visual acuity negatively correlated with MMSE and CDT scores; (2) Groups with near vision impairment or visual attention abnormalities had significantly lower MMSE and CDT scores, while cognitively normal participants showed better visual acuity; (3) Logistic regression revealed MMSE scores were primarily influenced by left-eye near vision and visual attention, whereas CDT scores were additionally affected by education level; (4) Mediation analysis indicated left-eye near vision and visual attention may impact cognitive function via visuospatial function.ConclusionsVI is closely associated with cognitive impairment, with left-eye near vision and visual attention potentially affecting cognition through their impact on visuospatial function. The application of the VISA tool may provide scientific evidence for optimizing dementia prevention and control strategies in China.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"562-573"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199163","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}
引用次数: 0
Isolated elevation of 181p-tau in the cerebrospinal fluid is associated with distinct clinical features: Findings from a Danish memory clinic cohort. 脑脊液中181p-tau的孤立升高与独特的临床特征相关:来自丹麦记忆诊所队列的研究结果。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 Epub Date: 2025-05-06 DOI: 10.1177/13872877251339679
Laura Storm Næsborg Andersen, Anja Hviid Simonsen, Asmus Vogel, Oskar Hoffmann McWilliam, Steen Gregers Hasselbalch, Kristian Steen Frederiksen
{"title":"Isolated elevation of 181p-tau in the cerebrospinal fluid is associated with distinct clinical features: Findings from a Danish memory clinic cohort.","authors":"Laura Storm Næsborg Andersen, Anja Hviid Simonsen, Asmus Vogel, Oskar Hoffmann McWilliam, Steen Gregers Hasselbalch, Kristian Steen Frederiksen","doi":"10.1177/13872877251339679","DOIUrl":"10.1177/13872877251339679","url":null,"abstract":"<p><p>BackgroundDeposition of amyloid-β and tau are key pathological events in Alzheimer's disease and may be assessed by cerebrospinal fluid (CSF) biomarkers. It remains uncertain whether patients who display abnormal phosphorylated tau in isolation differ from patients with other biomarker profiles.ObjectiveThe primary objective was to investigate differences in demographics, comorbidities, and cognitive performance in amyloid-β negative phosphorylated tau positive patients. Further, the aim was also to investigate the relationship between cognitive function and phosphorylated tau level.MethodsA total of 1049 consecutive patients from the Copenhagen Memory Clinic Cohort from 2018 to August 2022 were included and divided into four groups based on the CSF biomarkers amyloid-β<sub>42</sub> (A) and phosphorylated tau (T). Data on co-morbidities, abuse, and neuropsychological tests were recorded, and retrospective data analyses were performed across all groups.ResultsA total of 2.8% participants had an A-T+ biomarker profile and were younger (Mean: 65.1 years, SD: 14.2), comprised of more men (65.5%) than the A + T- group and exhibited both more psychiatric illness (p = 0.027) and alcohol and/or drug abuse (p = 0.004) than the A + T+ group. The A-T+ group performed better on both Addenbrooke's Cognitive Examination (p = 0.002) and Mini-Mental State Examination (p = 0.001) as well as immediate (p = 0.026) and delayed recall (p = 0.009) compared to the A + T+ group but showed no difference compared to the A-T- group on all cognitive scores. Further, higher p-tau levels were associated with worse cognitive performance although effects were small.ConclusionsThe findings indicate that patients with the A-T+ biomarker profile have different clinical characteristic that may indicate a non-neurodegenerative background.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"111-119"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025535","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}
引用次数: 0
Altered hemispheres lateralization of brain functional gradients in Alzheimer's disease. 阿尔茨海默病脑功能梯度的半球侧化改变。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 Epub Date: 2025-05-22 DOI: 10.1177/13872877251339761
Hao Liu, Yunfei Li, Zheng Sun, Xiaoyu Xu, Bicong Yan, Yuehua Li, Xiaohu Zhao
{"title":"Altered hemispheres lateralization of brain functional gradients in Alzheimer's disease.","authors":"Hao Liu, Yunfei Li, Zheng Sun, Xiaoyu Xu, Bicong Yan, Yuehua Li, Xiaohu Zhao","doi":"10.1177/13872877251339761","DOIUrl":"10.1177/13872877251339761","url":null,"abstract":"<p><p>BackgroundThe human brain demonstrates intrinsic hemispheric asymmetry across structural, functional, and biochemical domains. While cortical gradients provide a multiscale framework for understanding brain network organization, their hemispheric divergence in Alzheimer's disease (AD) remains unexplored.ObjectiveTo characterize interhemispheric gradient lateralization patterns across the AD continuum and evaluate their clinical correlates.MethodsResting-state fMRI data of 45 normal controls (NC), 45 patients with mild cognitive impairment (MCI), and 45 patients with AD underwent gradient networks processing. Interhemispheric comparisons of mean gradient values were conducted across these groups. A lateralization index (L value) was defined for 17 networks, and differences among the three groups were analyzed using one-way ANOVA. Additionally, correlations between network L values and cognitive scores were examined.ResultsNC and MCI participants exhibited left lateralization of gradient values in the second gradient. In contrast, AD patients showed a loss of interhemispheric lateralization. Notably, AD patients demonstrated reduced lateralization in default mode network (DMN) and control network. The degree of lateralization in DMN was significantly positively correlated with cognitive function.ConclusionsOur findings indicated that patients with AD demonstrated a diminished lateralization in gradient networks. Quantifying gradient laterality may serve as a multimodal biomarker for early AD detection and therapeutic monitoring.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"139-150"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119408","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}
引用次数: 0
Angiogenesis promotion of the transplantation of human amniotic mesenchymal stem cells via the Ang-1/Tie-2 signaling pathways in Alzheimer's disease model. 阿尔茨海默病模型中通过Ang-1/Tie-2信号通路促进人羊膜间充质干细胞移植血管生成
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 DOI: 10.1177/13872877251338687
Rui Wu, Jing Guo, Yang Liu, Sirou Huang, Pingping Wu, Weiping Liu
{"title":"Angiogenesis promotion of the transplantation of human amniotic mesenchymal stem cells via the Ang-1/Tie-2 signaling pathways in Alzheimer's disease model.","authors":"Rui Wu, Jing Guo, Yang Liu, Sirou Huang, Pingping Wu, Weiping Liu","doi":"10.1177/13872877251338687","DOIUrl":"10.1177/13872877251338687","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is a progressive degenerative disease of the central nervous system, leading to cognitive decline, mental symptoms, and behavioral disorders. The comorbidity of cerebrovascular disease in AD patients will accelerate the development of cognitive impairment and dementia. Since the dysfunction of the cerebral vasculature is closely related to neuropathology in AD patients, the protection of cerebral microvascular function and the improvement of cerebral microcirculation may bring a potential path for AD treatment. Human amniotic mesenchymal cells (hAMSCs) as a more advantageous cellular therapy for AD are proven to improve AD model mice's learning and memory abilities significantly, but fewer studies on angiogenesis and blood-brain barrier recovery have been found.ObjectiveThe study aimed to analyze the changes in angiogenesis-related factors of hAMSCs transplantation in the AD model and explore the underlying molecular mechanism.MethodshAMSCs were injected into APP/PS1 and wild type (WT) mice via tail vein, and the hAMSCs distribution in the cerebral tissue and angiogenesis in the hippocampal tissues were observed.ResultshAMSCs were found in the cortex and hippocampal areas of APP/PS1 and WT mice. hAMSCs transplantation significantly increased CD31 and Tie-2 expression in AD mice compared with the control group.ConclusionsThe study indicates that hAMSCs can cross the blood-brain barrier and enter the cerebral tissue of the mouse, transplantation of hAMSCs may promote angiogenesis in the AD model. The Ang-1/Tie-2 signaling pathway may be a therapeutically attractive target for the hAMSCs treatment of AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"646-652"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015415","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}
引用次数: 0
Social isolation, loneliness, genetic risk, and incident dementia in people with type 2 diabetes mellitus: A population-based cohort study. 2型糖尿病患者的社会隔离、孤独、遗传风险和痴呆:一项基于人群的队列研究
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 DOI: 10.1177/13872877251344253
Zhixuan He, Yu Nie, Weijie Zhang, Yue Liu, Yaping Liu, Huachen Xue, Sizhi Ai, Hongliang Feng, Yujing Zhou, Jihui Zhang, Yan Yannis Liang, Yuping Ning
{"title":"Social isolation, loneliness, genetic risk, and incident dementia in people with type 2 diabetes mellitus: A population-based cohort study.","authors":"Zhixuan He, Yu Nie, Weijie Zhang, Yue Liu, Yaping Liu, Huachen Xue, Sizhi Ai, Hongliang Feng, Yujing Zhou, Jihui Zhang, Yan Yannis Liang, Yuping Ning","doi":"10.1177/13872877251344253","DOIUrl":"10.1177/13872877251344253","url":null,"abstract":"<p><p>BackgroundSocial isolation and loneliness, two independent constructs of social disengagement, are becoming increasingly recognized factors for dementia risk.ObjectiveWe aimed to investigate whether these two constructs also associate with dementia risk in individuals with type 2 diabetes mellitus (T2DM), which is becoming more prevalent.MethodsThe longitudinal study included 24,986 participants (mean age: 60.0 ± 6.9 years, median follow-up: 12.0 years) with T2DM at baseline from the UK Biobank. Social isolation and loneliness were assessed using self-reported questionnaires. Genetic risk factors for dementia including polygenic risk score (PRS) and <i>APOE</i> genotype were extracted. We identified incident dementia cases by linking hospital records and death registries.ResultsSocial isolation (most versus least: hazard ratio, HR: 1.46 [95% confidence intervals, CI: 1.22-1.75]) and loneliness (yes versus no: 1.56 [1.25-1.95]) were associated with an increased risk of incident dementia after adjusting for demographic factors; however, such associations attenuated when further adjusting for health behaviors, psychological factors, or diabetes-related characteristics. The social isolation-dementia association was predominantly attributable to health behaviors (48% for the most social isolation), while the loneliness-dementia association was largely explained by psychological factors (46%). Significant modification effects of dementia genetic risk were observed in these associations.ConclusionsSocial isolation and loneliness were associated with a greater risk for incident dementia among T2DM individuals, with differential explanatory factors. The genetic risk for dementia modified these associations. The findings underscore the importance of strengthening social connections to mitigate diabetes-related dementia risk.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"605-619"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173834","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}
引用次数: 0
Therapeutic targets for Alzheimer's disease: Proteome-wide Mendelian randomization and colocalization analyses. 阿尔茨海默病的治疗靶点:蛋白质组范围的孟德尔随机化和共定位分析。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 DOI: 10.1177/13872877251344572
Kefu Yu, Ruiqi Jiang, Dabiao Zhou, Zhigang Zhao
{"title":"Therapeutic targets for Alzheimer's disease: Proteome-wide Mendelian randomization and colocalization analyses.","authors":"Kefu Yu, Ruiqi Jiang, Dabiao Zhou, Zhigang Zhao","doi":"10.1177/13872877251344572","DOIUrl":"10.1177/13872877251344572","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is a major neurodegenerative disorder with limited treatment options.ObjectiveThis study aimed to identify novel therapeutic targets for AD using proteome-wide Mendelian randomization (MR) and colocalization analyses.MethodsWe conducted a large-scale, proteome-wide MR analysis using data from two extensive genome-wide association studies (GWASs) of plasma proteins: the UK Biobank Pharma Proteomics Project (UKB-PPP) and the deCODE Health Study. We extracted genetic instruments for plasma proteins from these studies and utilized AD summary statistics from European Bioinformatics Institute GWAS Catalog. Colocalization analysis assessed whether identified associations were due to shared causal variants. Phenome-wide association studies and drug repurposing analyses were performed to assess potential side effects and identify existing drugs targeting the identified proteins.ResultsOur MR analysis identified significant associations between genetically predicted levels of 9 proteins in the deCODE dataset and 17 proteins in the UKB-PPP dataset with AD risk after Bonferroni correction. Four proteins (BCAM, CD55, CR1, and GRN) showed consistent associations across both datasets. Colocalization analysis provided strong evidence for shared causal variants between GRN, CR1, and AD. PheWAS revealed minimal potential side effects for CR1 but suggested possible pleiotropic effects for GRN. Drug repurposing analysis identified several FDA-approved drugs targeting CR1 and GRN with potential for AD treatment.ConclusionsThis study identifies GRN and CR1 as promising therapeutic targets for AD. These findings provide new directions for AD drug development, but further research and clinical trials are warranted to validate the therapeutic potential of these targets.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"695-702"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199168","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}
引用次数: 0
Thieves in the delusions of theft in patients with Alzheimer's disease living alone: A case series. 小偷在妄想偷窃的阿尔茨海默病患者独居:一个案例系列。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 DOI: 10.1177/13872877251343313
Daiki Ishimaru, Yuto Satake, Hideki Kanemoto, Daiki Taomoto, Maki Hotta, Yuma Nagata, Kunihiko Katsuki, Manabu Ikeda
{"title":"Thieves in the delusions of theft in patients with Alzheimer's disease living alone: A case series.","authors":"Daiki Ishimaru, Yuto Satake, Hideki Kanemoto, Daiki Taomoto, Maki Hotta, Yuma Nagata, Kunihiko Katsuki, Manabu Ikeda","doi":"10.1177/13872877251343313","DOIUrl":"10.1177/13872877251343313","url":null,"abstract":"<p><p>This study explored the phenomenology of theft delusions in four female patients with Alzheimer's disease (AD) living alone, aiming to understand its psychological relevance. Caregivers participated in semi-structured interviews to assess delusion phenomenology, while patients were evaluated on their aging perceptions and life values. In three cases, the primary persecutor was a family member involved in managing finances, whereas the persecutor in the fourth patient who managed finances independently was a specific neighbor. Thieves in the delusion of theft in patients with AD living alone were likely to be persons who helped in the management of money or property.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"518-522"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110522","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}
引用次数: 0
Alzheimer's disease-associated genotypes differentially influence chronic evoked seizure outcomes and antiseizure medicine efficacy in aged mice. 老年小鼠阿尔茨海默病相关基因型对慢性诱发癫痫结果和抗癫痫药物疗效的影响存在差异。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 DOI: 10.1177/13872877251343321
Kevin M Knox, Stephanie Davidson, Leanne M Lehmann, Erica Skinner, Alexandria Lo, Suman Jayadev, Melissa Barker-Haliski
{"title":"Alzheimer's disease-associated genotypes differentially influence chronic evoked seizure outcomes and antiseizure medicine efficacy in aged mice.","authors":"Kevin M Knox, Stephanie Davidson, Leanne M Lehmann, Erica Skinner, Alexandria Lo, Suman Jayadev, Melissa Barker-Haliski","doi":"10.1177/13872877251343321","DOIUrl":"10.1177/13872877251343321","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) patients are at greater risk of focal seizures than similarly aged adults, which may accelerate cognitive decline. Older people with epilepsy generally respond well to antiseizure medications (ASMs). However, whether specific ASMs can differentially control seizures in AD is unknown. The corneal kindled model of chronic seizures allows for precisely timed drug administration studies to expediently evaluate efficacy and tolerability of investigational treatments in AD-associated mouse models.ObjectiveWe hypothesized that mechanistically distinct ASMs would differentially control seizures of aged AD mice (9-14 months), thereby informing rational ASM selection for AD.MethodsPSEN2-N141I and APP<sup>swe</sup>/PS1<sup>dE9</sup> mice underwent corneal kindling at 9-14 months old to quantify latency to kindled criterion versus matched wild-type mice. Dose-related response to commonly prescribed ASMs for older adults with epilepsy (valproic acid, levetiracetam, lamotrigine, phenobarbital, and gabapentin) was then assessed.ResultsSex and AD genotype differentially impacted seizure susceptibility. Male PSEN2-N141I mice required more kindling stimulations to reach criterion (χ<sup>2</sup> = 5.521; p < 0.05). Male APP/PS1 mice were no different in kindling rate versus controls, but did have more severe seizures. There were significant ASM class-specific differences in acute seizure control and dose-related tolerability. APP/PS1 mice were more sensitive to valproic acid, levetiracetam, and gabapentin. PSEN2-N141I mice were more sensitive to valproic acid and lamotrigine.ConclusionsAD genotypes may differentially impact ASMs activity in vivo with advanced biological age. These findings highlight the heterogeneity of seizure risk in AD and suggest that precisely selected ASMs may beneficially control seizures in AD to slow cognitive decline.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"547-561"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12282399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208528","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}
引用次数: 0
Artificial intelligence-driven natural language processing for identifying linguistic patterns in Alzheimer's disease and mild cognitive impairment: A study of lexical, syntactic, and cohesive features of speech through picture description tasks. 人工智能驱动的自然语言处理用于识别阿尔茨海默病和轻度认知障碍的语言模式:通过图片描述任务研究语音的词汇、句法和衔接特征。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 Epub Date: 2025-05-07 DOI: 10.1177/13872877251339756
Cynthia A Nyongesa, Mike Hogarth, Judy Pa
{"title":"Artificial intelligence-driven natural language processing for identifying linguistic patterns in Alzheimer's disease and mild cognitive impairment: A study of lexical, syntactic, and cohesive features of speech through picture description tasks.","authors":"Cynthia A Nyongesa, Mike Hogarth, Judy Pa","doi":"10.1177/13872877251339756","DOIUrl":"10.1177/13872877251339756","url":null,"abstract":"<p><p>BackgroundLanguage deficits often occur early in the neurodegenerative process, yet traditional methods frequently fail to detect subtle changes. Natural language processing (NLP) offers a novel approach to identifying linguistic patterns associated with cognitive impairment.ObjectiveWe aimed to analyze linguistic features that differentiate cognitively unimpaired (CU), mild cognitive impairment (MCI), and Alzheimer's disease (AD) groups.MethodsData was extracted from picture description tasks performed by 336 participants in the DementiaBank datasets. 53 linguistic features aggregated into 4 categories: lexical, structural, syntactic, and discourse domains, were identified using NLP toolkits. With normal diagnostic cutoffs, cognitive function was evaluated with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA).ResultsWith age and education as covariates, ANOVA and post-hoc Tukey's HSD tests revealed that linguistic features such as pronoun usage, syntactic complexity, and lexical sophistication showed significant differences between CU, MCI, and AD groups (p < 0.05). Notably, past tense and personal references were higher in AD than both CU and MCI (p < 0.001), while pronoun usage differed between AD and CU (p < 0.0001). Correlations indicated that higher pronoun rates and lower syntactic complexity were associated with lower MMSE scores and although some features like conjunctions and determiners approached significance, they lacked consistent differentiation.ConclusionsWith the growing adoption of artificial intelligence (AI)-based scribing, these results emphasize the potential of targeted linguistic analysis as a digital biomarker to enable continuous screening for cognitive impairment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"120-138"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12231876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981822","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}
引用次数: 0
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