The Journal of Prevention of Alzheimer's Disease最新文献

{"title":"Validation of the multi-day Boston remote assessment of neurocognitive health (BRANCH) among cognitively impaired & unimpaired older adults.","authors":"Emma L Weizenbaum, Stephanie Hsieh, Cassidy Molinare, Daniel Soberanes, Caitlyn Christiano, Andrea M Román Viera, Juliana A U Anzai, Stephanie Moreno, Emily C Campbell, Hyun-Sik Yang, Gad A Marshall, Reisa A Sperling, Kathryn V Papp, Rebecca E Amariglio","doi":"10.1016/j.tjpad.2025.100057","DOIUrl":"10.1016/j.tjpad.2025.100057","url":null,"abstract":"<p><strong>Background: </strong>The multi-day Boston Remote Assessment of Neurocognitive Health (BRANCH) is a remote, web-based assessment designed to capture the earliest cognitive changes in the preclinical stage of Alzheimer's disease (AD). It has been validated in unimpaired older adults, but as individuals progress on the AD continuum, assessments need to remain feasible and valid at different clinical stages. The focus of this study was to assess feasibility and validity of multi-day BRANCH in participants with and without cognitive impairment.</p><p><strong>Methods: </strong>For seven days participants completed the BRANCH paradigm to capture a muti-day learning curve score. Participants also completed the mini-mental-status-exam (MMSE) and the Quick Dementia Rating Scale (QDRS). The primary cohort included 81 older adults: 38 with cognitive impairment (CI) and 43 cognitively-unimpaired (CU). A complementary replication cohort included 16 participants with consensus-defined mild cognitive impairment (MCI) and 47 demographically-matched cognitively unimpaired participants.</p><p><strong>Results: </strong>Multi-day BRANCH was feasibile with 92 % or participants completing all seven days of testing. More CI than CU reported nervousness and found tasks slightly less enjoyable on Day 1, but ratings increased at a similar rate in both groups. Convergent validity was confirmed by a positive association between BRANCH and total MMSE and QDRS scores. There was a large effect size of group status on BRANCH (CI vs. CU; Cohen's d = 0.83) and per logistic regression, BRANCH significantly predicted group status (β = -1.49, p < 0.001); even more so between MCI and CU in the replication cohort.</p><p><strong>Conclusions: </strong>Findings suggest that a remotely administered web-based assessment of multi-day learning is feasible and valid in participants with and without cognitive impairment.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100057"},"PeriodicalIF":4.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hearing loss, diet, and cognitive decline: interconnections for dementia prevention.","authors":"Xiaoran Liu, Uzma S Akhtar, Todd Beck, Kyle Dennis, Denis A Evans, Kumar B Rajan","doi":"10.1016/j.tjpad.2024.100052","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100052","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hearing loss poses a significant global public health concern associated with cognitive decline. Among the many risk factors associated with Alzheimer's disease and related dementia (ADRD), hearing loss is the most prevalent sensory impairment in older adults and has emerged as a significant, yet often overlooked, modifiable risk factor for dementia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To access 1) the association between diet and risk of hearing loss in older adults and 2) the modifying effect of diet on the impact of hearing loss on cognitive decline in an aging population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Prospective cohort study SETTING: The Chicago Health and Aging Project, a community-based cohort study PARTICIPANTS: A total of 5,145 older adults (62 % non-Hispanic Black, 63 % female).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Measurements: &lt;/strong&gt;Self-reported hearing ability was assessed during each cycle of data collection. Diet was assessed by a 144-item Food Frequency Questionnaire. Diet quality was evaluated using a 144-item Food Frequency Questionnaire, focusing on adherence to dietary patterns such as Dietary Approaches to Stop Hypertension (DASH), Mediterranean, and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND). Cognitive function assessment was conducted during the in-home visits at each cycle. Four cognitive tests, including the East Boston tests of immediate and delayed recall, the mini-mental State Examination, and the Symbol Digit Modalities test, were included. We used linear mixed effect models to examine 1) the association of hearing loss and cognitive decline and 2) the association of diet on cognitive decline through modifying risk hearing loss. Discrete-time survival analysis examined the association between dietary patterns and the time to hearing impairment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 5,145 participants included in the analyses, 747 (14.5 %) reported hearing loss, including 207 Black adults and 199 White adults. Each unit increase in the DASH, MedDiet, and MIND scores was associated with 19 % (95 % CI: 0.79, 0.94, P &lt; 0.001), 11 % (95 % CI: 0.79, 1.00, P = 0.05), and 13 % (95 % CI: 0.87, 0.99, P &lt; 0.05) lower risk for hearing loss, respectively. High adherence to the Western diet was associated with an earlier onset of hearing loss up to 14 months (P &lt; 0.05). Participants had an increased rate of cognitive decline after reporting hearing loss. During follow-up, participants in the highest tertile of the DASH diet score who reported hearing loss experienced a 17 % faster cognitive decline (β = -0.07 ± 0.01) compared to those without hearing loss (β = -0.06 ± 0.003). However, this decline was significantly slower than that of participants observed in the lowest tertile of the DASH diet, who exhibited a 67 % faster cognitive decline (β = -0.10 ± 0.012, P = 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Healthy dietary patterns, particularly the DASH diet, was associated with a reduced risk of","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 3","pages":"100052"},"PeriodicalIF":4.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative efficacy and safety of antidiabetic agents in Alzheimer's disease: A network meta-analysis of randomized controlled trials.","authors":"Zixin Cai, Jiaxin Zhong, Guanghui Zhu, Jingjing Zhang","doi":"10.1016/j.tjpad.2025.100111","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100111","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatment options. Emerging evidence suggests that antidiabetic agents may offer neuroprotective effects by targeting shared pathophysiological mechanisms such as insulin resistance and neuroinflammation. However, the comparative efficacy, and safety of these agents in the treatment of AD remain unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This study aimed to systematically evaluate and compare the efficacy and safety of antidiabetic agents for improving cognitive outcomes, reducing amyloid-β (Aβ) deposition, and managing adverse effects in patients with AD, using a network meta-analysis of randomized controlled trials (RCTs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A comprehensive literature search was conducted across multiple databases to identify RCTs examining the effects of antidiabetic agents in patients with AD. The primary outcomes included cognitive performance (e.g., MMSE scores), Aβ deposition (measured via CSF biomarkers), and safety/adverse effects. A network meta-analysis was performed to integrate direct and indirect evidence, ranking interventions using Surface Under the Cumulative Ranking (SUCRA) probabilities. Risk of bias was assessed using the Cochrane risk-of-bias tool.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 26 studies, involving 7,361 participants, were included in the analysis. The interventions evaluated included insulin detemir (both low-dose and high-dose), liraglutide, exenatide, metformin, and pioglitazone. Both low-dose insulin detemir (mean difference: 2.10, 95 % CI: 1.04 to 3.15), high-dose insulin detemir (mean difference: 1.40, 95 % CI: -0.07 to 2.88), exenatide (mean difference: 1.19, 95 % CI: 0.06 to 2.32), and metformin combined with exenatide (mean difference: 1.06, 95 % CI: -1.68 to 3.80) showed cognitive improvements compared to placebo. Among these, low-dose insulin detemir demonstrated the most significant improvement. In terms of reducing Aβ deposition, metformin ranked highest in effectiveness, with the highest SUCRA score (84.6), followed by high-dose insulin detemir (SUCRA: 54.1). Low-dose insulin detemir (SUCRA: 51.1) also demonstrated moderate efficacy. Low-dose insulin detemir showed some reduction in Aβ deposition (mean difference: -0.31, 95 % CI: -2.82 to 2.20), although statistical significance was limited. Liraglutide exhibited the highest rate of study treatment withdrawal (mean difference: 1.97, 95 % CI: -0.07 to 4.00), while pioglitazone demonstrated the lowest withdrawal rates (mean difference: 0.07, 95 % CI: -0.03 to 0.17).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This network meta-analysis provides valuable insights into the comparative efficacy and safety of antidiabetic agents in AD. Low-dose insulin detemir demonstrated the most significant cognitive improvement and a moderate effect on reducing Aβ deposition. Metformin emerged as the most effective agent for reducing Aβ levels, thou","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100111"},"PeriodicalIF":4.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative single-cell RNA sequencing and mendelian randomization analysis reveal the potential role of synaptic vesicle cycling-related genes in Alzheimer's disease.","authors":"Junfeng Zeng, Ruihua Zhang, Huihua Xu, Chengwu Zhang, Li Lu","doi":"10.1016/j.tjpad.2025.100097","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100097","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) involves alterations in synaptic vesicle cycling (SVC), which significantly affect neuronal communication and function. Therefore, a thorough investigation into the potential roles of SVC-related genes (SVCRGs) in AD can enhance the identification of critical biomarkers that may influence disease progression and treatment responses.</p><p><strong>Methods: </strong>The datasets used in this study were sourced exclusively from public databases. By integrating differential expression analysis with Mendelian randomization (MR), we identified SVCRGs as biomarkers for AD. Functional characterization of these biomarkers was performed, followed by integration into a nomogram. Further investigation of immune infiltration in AD patients and healthy individuals was carried out. Ultimately, the potential cellular mechanisms of AD were explored through single-cell RNA sequencing (scRNA-seq) analysis.</p><p><strong>Results: </strong>ATP6V1D, ATP6V1G2, CLTB, and NSF were identified as biomarkers, exhibiting a positive correlation with each other and a downregulated expression in AD. These markers were pinpointed as protective factors for AD [odds ratio (OR) < 1, P < 0.05], with potential to reduce the risk of the disease. Integrated into a nomogram, they demonstrated satisfactory diagnostic performance and clinical utility, surpassing the use of single gene. They were collectively enriched in pathways related to \"interferon gamma response\", \"inflammatory response\", and \"TNFα signaling via NFκB\". Additionally, an increase in infiltration of 17 immune cell types in AD was noted, particularly cells associated with neuroinflammation such as activated CD8 T cells and various dendritic cells (DCs), suggesting an inflammatory milieu in AD while also displaying a negative correlation with the biomarkers. The cell types were further annotated, revealing specific expressions of biomarkers and uncovering the heterogeneity of excitatory neurons. A significant reduction in the overall number of excitatory neurons under AD conditions was observed, alongside consistent expression of biomarkers during the developmental stages of excitatory neurons.</p><p><strong>Conclusion: </strong>By using MR, we firstly identified four SVCRGs as protective factors for AD, functioning through pathways associated with mitochondrial dysfunction, chronic inflammation, immune dysregulation, and neuronal damage. These genes had the potential to modulate immune cell infiltration activated in AD patients and exhibited cell-type-specific expression profiles within AD-related cellular contexts. Their findings provide novel insights and valuable references for future research on AD pathogenesis and therapeutic strategies.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100097"},"PeriodicalIF":4.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility and acceptability of remote APOE-genotyping among research volunteers of an online recruitment registry (The Dutch Brain Research Registry).","authors":"L Waterink, S J van der Lee, D Nijland, F I van der Zee, L N C Visser, Y A L Pijnenburg, S A M Sikkes, W M van der Flier, M D Zwan","doi":"10.1016/j.tjpad.2025.100099","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100099","url":null,"abstract":"<p><strong>Background: </strong>Participant recruitment for preclinical Alzheimer's disease (AD) prevention studies is challenging. Online registries facilitate large scale prescreening of individuals at risk for AD to accelerate recruitment. APOE-prescreening has the potential to better identify at-risk individuals. This study investigated the feasibility and acceptability of at-home APOE-genotyping in cognitively-normal registrants of an online registry.</p><p><strong>Methods: </strong>We invited 9,287 cognitively-normal registrants of Dutch Brain Research Registry (DBRR) aged 50 to 75 for at-home APOE-genotype testing, without receiving the results. Feasibility was measured by participation ratio (participation/interested), swab-return ratio (returned-swabs/participation), and genotyping-success ratio (analyzed swabs/returned swabs). Acceptability was measured with online questions about information provision and project scope. We explored prescreening questions potentially reducing screen-failures.</p><p><strong>Results: </strong>Feasibility was high with an 0.89 participation ratio (2,886/3,251), 0.90 swab-return ratio (2,886/2,597), 0.99 genotyping-success ratio (2,558/2,597). Acceptability was high, as participants were content with the information provision (87 %-97 %, n= 1,709-1,894), which was also well understood (91 %-93 %, n = 1,772-1,802). Among successful-analyzed swabs (n = 2,558), 27 % participants were APOE-ε4 heterozygote (n = 703), and 2 % homozygote (n = 60). Prescreening on a positive family history leads to a third reduction in the number of invitations needed to identify one APOE-ε4 carrier.</p><p><strong>Conclusion: </strong>Our results suggest that APOE-ɛ4 genotyping in participants of an online research registry is feasible, well received and could be used to prescreen individuals at risk for AD for prevention studies. Adding a positive family history before invitation for APOE-genotyping, would further improve the prescreening process and reduce screen failures when identifying carriers.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100099"},"PeriodicalIF":4.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143504036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multisensory stimulation reduces neuropsychiatric symptoms and enhances cognitive function in older adults with dementia: A meta-analysis of randomized controlled trials.","authors":"Tiara Octary, Melati Fajarini, Hidayat Arifin, Ruey Chen, Chien-Mei Sung, Li-Fang Chang, Chia-Hui Wang, Kondwani Joseph Banda, Kuei-Ru Chou","doi":"10.1016/j.tjpad.2025.100091","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100091","url":null,"abstract":"<p><strong>Objective: </strong>Multisensory stimulation defined as engaging multiple senses (visual, olfactory, auditory, gustatory, and tactile), has been demonstrated to improve older adults' general health. However, its effectiveness in mitigating neuropsychiatric symptoms (NPSs) and cognitive deficits in older adults with dementia remains unclear. This meta-analysis evaluated the efficacy of multisensory stimulation in ameliorating NPSs and improving overall cognitive function in older adults with dementia.</p><p><strong>Methods: </strong>We searched eight databases to September 2024 without restriction. Older adults with all stages of dementia aged 65 years and above were included. To estimate the pooled effect size, Hedge's g (g) values were calculated using a random-effects model. Heterogeneity was assessed using the Q, I², and τ² statistics. Subgroup and meta-regression analyses were performed to identify moderators. Publication bias was assessed using Begg and Mazumdar's rank correlation and Egger's linear regression tests.</p><p><strong>Results: </strong>This review included 16 studies (974 patients). Multisensory stimulation significantly reduced agitation (g= -0.96; 95 %CI= -1.44, -0.48), apathy (g= -1.27; 95 %CI= -2.08, -0.46), and depression (g= -0.28; 95 %CI= -0.48, -0.07). Moreover, the intervention significantly improved overall cognitive function (g= 0.30; 95 %CI= 0.09, 0.52). However, multisensory stimulation had no significant effect on anxiety (g= -0.81; 95 %CI= -1.79, 0.17). Significant heterogeneity was observed in agitation, apathy, and anxiety. Moreover, meta-regression analyses by educational level (junior high school and above) revealed significant moderators in agitation.</p><p><strong>Conclusions: </strong>Multisensory stimulation shows promise as a non-pharmacological intervention for older adults with dementia. It may effectively mitigate NPSs and improve cognitive function into clinical practice as an alternative therapeutic.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100091"},"PeriodicalIF":4.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interactions of physical activity and lung function on cognitive health in older adults: Joint association and mediation analysis.","authors":"Peng Hu, Dan Song, Tian Heng, Ling-Ling Yang, Chuan-Chuan Bai, Rui He, Tao Liu, Ya-Xi Luo, Xiu-Qing Yao","doi":"10.1016/j.tjpad.2025.100090","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100090","url":null,"abstract":"<p><strong>Background: </strong>Maintaining cognitive health in old adults has become a significant public health challenge, with lung function and physical activity (PA) as essential modifiable factors. However, the joint and mediation effects of these two factors with cognition remain unclear.</p><p><strong>Objectives: </strong>This study assesses the joint association and mediation effects of lung function and PA with cognition.</p><p><strong>Design, setting, and participants: </strong>We utilized cross-sectional data from the 2011-2012 U.S. National Health and Nutrition Examination Survey, including adults aged 60-79 assessed for lung function, PA, and cognition.</p><p><strong>Main outcomes and measures: </strong>Lung function included forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), peak expiratory flow (PEF) and FEV₁/FVC. PA was assessed using the Global Physical Activity Questionnaire, covering occupational PA (OPA), transportation-related PA (TPA), and leisure-time PA (LTPA). Cognition was evaluated using the Digit Symbol Substitution Test, Animal Fluency Test, Delayed Recall Test and Immediate Recall Test. Weighted multiple linear regression models were used to analyze the separate and joint associations of lung function and PA with cognition, while also exploring potential mediation effects between these factors.</p><p><strong>Results: </strong>A total of 927 participants, representing 35,525,782 U.S. residents, were included, with a weighted median age of 65 (IQR, 63 -71) years, and 53.6 % were female. The results showed a significant positive association between lung function and cognitive function, with FEV₁, FVC, and PEF all positively correlated, while the FEV₁/FVC showed no notable link. Further analysis revealed the best cognitive performance observed in participants with active LTPA and the highest quartile of lung function, indicating a joint association of LTPA and lung function with cognition. Mediation analysis indicated that lung function mediated 24.1 % (95 %CI: 6.3 % - 47.0 %, P = 0.03) of the relationship between LTPA and cognition, while cognition mediated 10.2 % (95 %CI: 0.5 % - 27.0 %, P = 0.04) of the relationship between LTPA and lung function.</p><p><strong>Conclusion: </strong>Lung function and cognition may have a bidirectional relationship. The combination of active LTPA and better lung function was strongly associated with higher cognition, highlighting the need to strengthen exercise focused on lung function to maintain cognitive health in older adults.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100090"},"PeriodicalIF":4.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic and discriminative accuracy of plasma phosphorylated tau 217 for symptomatic Alzheimer's disease in a Chinese cohort.","authors":"Li-Min Li, Ping Che, Dequan Liu, Yu Wang, Jia Li, Dian He, Tao Liu, Nan Zhang","doi":"10.1016/j.tjpad.2025.100092","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100092","url":null,"abstract":"<p><strong>Background: </strong>Plasma phosphorylated tau at threonine 217 (p-tau217) measured with an ultrasensitive immunoassay method has been demonstrated to be an optimal biomarker for Alzheimer's disease (AD).</p><p><strong>Objectives: </strong>The aim of this study was to establish the reference interval for plasma p-tau217 in Chinese individuals and evaluate its diagnostic value in symptomatic AD.</p><p><strong>Design, setting, participants: </strong>We recruited 150 cognitively unimpaired (CU) individuals, 60 patients with AD dementia, 30 patients with mild cognitive impairment (MCI) due to AD, 40 patients with frontotemporal lobar degeneration (FTLD), and 70 patients with subcortical ischaemic vascular dementia (SIVD).</p><p><strong>Measurements: </strong>The concentrations of plasma p-tau217, total tau, amyloid-beta (Aβ)42 and Aβ40 were measured with a single-molecule array.</p><p><strong>Results: </strong>Plasma p-tau217 outperformed other biomarkers in discriminating AD patients from CU controls, FTLD patients, and SIVD patients (AUC = 0.983, 0.936, 0.892) and discriminating MCI patients from CU controls (AUC = 0.943). The plasma p-tau217 level was negatively correlated with memory in patients with symptomatic AD.</p><p><strong>Conclusion: </strong>The diagnostic accuracy of plasma p-tau217 was exceptional for AD, even at early stages, in the Chinese population.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100092"},"PeriodicalIF":4.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interaction between circadian syndrome and genetic susceptibility in the risk of incident dementia: A longitudinal cohort study.","authors":"Linling Yu, Wei Liu, Chenqi Liao, Na Shen, Anding Liu, Liming Cheng, Xiong Wang","doi":"10.1016/j.tjpad.2025.100089","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100089","url":null,"abstract":"<p><strong>Background: </strong>Despite growing interest in circadian disturbances as potential triggers for dementia, the specific impact of circadian syndrome (CircS) on dementia incidence remains poorly understood. Moreover, the role of genetic susceptibility modulating these effects remains to be explored.</p><p><strong>Methods: </strong>Dementia-free participants from the UK Biobank cohort were included in the analysis. To evaluate the association between CircS and the incidence of dementia, as well as the modifying influence of genetic susceptibility on this relationship, Cox proportional hazards models were utilized.</p><p><strong>Results: </strong>During a median follow-up period of 14.55 years, 3,965 incident dementia cases were documented. CircS was found to significantly increased the risk of incident dementia, with a hazard ratio (HR) of 1.401 (95 % confidence interval [CI]: 1.296, 1.516). Compared to a CircS score of ≤3, mild CircS (HR: 1.259, 95 % CI: 1.146-1.383), moderate CircS (HR: 1.667, 95 % CI: 1.461-1.903), and severe CircS (HR: 2.028, 95 % CI: 1.397-2.944) were all significantly associated with an elevated risk of dementia. There were significant multiplicative interactions between CircS and genetic susceptibility (P_interaction<0.001). Participants with both a high polygenic risk score (PRS) and CircS had the highest risk of incident dementia (HR: 2.551, 95 % CI: 2.169, 3.001), compared to those with a low PRS and no CircS.</p><p><strong>Conclusions: </strong>CircS was associated with an increased risk of dementia, which might be aggravated by genetic susceptibility.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100089"},"PeriodicalIF":4.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LMTK2 and CRB1 are two novel risk genes for Alzheimer's disease in Han Chinese.","authors":"Xuewen Xiao, Hui Liu, Rui Yao, Yunni Li, Xinxin Liao, Yingzi Liu, Yafang Zhou, Junling Wang, Beisha Tang, Bin Jiao, Jinchen Li, Lu Shen, Shilin Luo","doi":"10.1016/j.tjpad.2025.100087","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100087","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is the most prevalent neurodegenerative disease with a substantial genetic background. However, its underlying genetic architecture remains to be elucidated.</p><p><strong>Methods: </strong>In this study, we performed whole-exome sequencing in 282 familial and/or early-onset AD patients and 1086 cognitively normal controls in the Han Chinse populations. According to minor allele frequency, variants were divided into common variants (MAF ≥ 0.01) and rare variants (MAF < 0.01). Common variant-based association analysis and gene-based association test aggregating rare variants were performed by PLINK 1.9 and Sequence Kernel Association Test-Optimal, respectively. We replicated the significant results by using the same AD samples and controls from whole genome sequencing (n = 1879). Furthermore, we determined the functions of the novel AD risk genes in vitro.</p><p><strong>Results: </strong>Common variants association analysis revealed that APOE rs429358 reached statistical whole-exome significance. Gene-level aggregation testing identified that rare damaging variants in LMTK2 and CRB1 conferred risk to AD. All variants are located in highly conserved amino acid regions and are predicted to be damaging. Furthermore, functional studies showed that LMTK2 rare damaging variants (R234P and S974G) enhanced tau phosphorylation levels, tau aggregates formation, and Aβ generation. Meanwhile, the CRB1 Y556X variant caused incomplete translation of CRB1 protein and increased the Aβ42 level and Aβ42/Aβ40 ratio.</p><p><strong>Conclusion: </strong>Our findings indicated that LMTK2 and CRB1 are two novel AD risk genes in Han Chinese, which may provide promising targets for diagnosis and intervention.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100087"},"PeriodicalIF":4.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}