Journal of Alzheimer's Disease最新文献_第4页

High-intensity transcranial alternating current stimulation improves sleep quality in patients with mild Alzheimer's disease: Findings from the TRANSFORM-AD study. 高强度经颅交流电刺激改善轻度阿尔茨海默病患者的睡眠质量：来自TRANSFORM-AD研究的发现

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2026-10-10 DOI: 10.1177/13872877261492561

Yuchen Qiao, Hong Chen, Kaiting Fan, Xuan Yang, Yueyi Yu, Rui Wang, Yi Xing, Yi Tang

{"title":"High-intensity transcranial alternating current stimulation improves sleep quality in patients with mild Alzheimer's disease: Findings from the TRANSFORM-AD study.","authors":"Yuchen Qiao, Hong Chen, Kaiting Fan, Xuan Yang, Yueyi Yu, Rui Wang, Yi Xing, Yi Tang","doi":"10.1177/13872877261492561","DOIUrl":"https://doi.org/10.1177/13872877261492561","url":null,"abstract":"BackgroundHigh-intensity transcranial alternating current stimulation (Hi-tACS) has shown beneficial effects on cognitive function in Alzheimer's disease (AD). However, data on the effects of hi-tACS on sleep quality and emotional state in patients with AD are still limited.ObjectiveThis study aimed to investigate the influences of hi-tACS on sleep quality and emotional state in AD.MethodsThe TRANSFORM-AD study was a double-blind, randomized-controlled trial that enrolled individuals with mild AD. Participants were randomized to receive hi-tACS group or sham stimulation group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 consecutive days. Pittsburgh sleep quality index (PSQI), Hamilton anxiety Rating Scale (HAMA), Hamilton depression Rating Scale (HAMD) and Quality of life in Alzheimer's Disease scale (QOL-AD) were evaluated at baseline, and the end of the intervention.ResultsAmong 43 participants with complete baseline and post-intervention assessments, Hi-tACS reduced post-intervention PSQI scores compared with sham after adjustment for baseline PSQI (adjusted mean difference, -2.34 points; 95% CI, -3.63 to -1.05; p < 0.001). Baseline-adjusted effects for HAMA (-1.43; 95% CI, -2.89 to 0.02), HAMD (0.44; 95% CI, -1.28 to 2.15), and QOL-AD (2.07; 95% CI, -1.57 to 5.70) were imprecise and included the null.ConclusionHi-tACS improved subjective sleep quality in patients with mild AD. The present secondary analysis did not provide conclusive evidence of effects on anxiety, depression, or quality of life; these exploratory outcomes require confirmation in larger, adequately powered trials.Trial registration:ClinicalTrials.gov, NCT03920826.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261492561"},"PeriodicalIF":3.4,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169756","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

Single-cell gene networks nominate IKZF1 as an Alzheimer's disease microglial regulator. 单细胞基因网络提名IKZF1作为阿尔茨海默病的小胶质调节因子。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2026-10-10 DOI: 10.1177/13872877261496918

Çağrı Özkurt

{"title":"Single-cell gene networks nominate IKZF1 as an Alzheimer's disease microglial regulator.","authors":"Çağrı Özkurt","doi":"10.1177/13872877261496918","DOIUrl":"https://doi.org/10.1177/13872877261496918","url":null,"abstract":"BackgroundMicroglia drive neuroinflammation in Alzheimer's disease (AD), yet no approved therapy targets this compartment. Human genome-wide association studies consistently implicate innate immune loci in AD risk, establishing microglial transcriptional programs as therapeutically relevant but pharmacologically underexploited targets.ObjectiveWe sought to identify transcription factors (TFs) governing microglial state transitions computationally and to nominate structurally tractable drug repurposing candidates.MethodsWe applied trajectory inference (PAGA), pseudobulk DESeq2, pySCENIC gene regulatory network (GRN) inference, CellChat, and virtual screening of 1962 approved compounds to 236,002 microglial nuclei from 84 donors (SEA-AD atlas).ResultsIKZF1 was the sole target TF retained under cisTarget v10 motif constraints, with peak regulon activity in LateAD-DAM (pseudotime ρ = + 0.309) and replication in an independent bulk cohort (GSE95587; adjusted p = 0.004). CellChat identified SLIT2→ROBO2 from multiple neuron subtypes (predominantly inhibitory interneurons) as the top predicted pathway to microglia. Tafamidis (→IRF8) and diflunisal (→PPARG) were top virtual screening hits; all evaluated compounds failed the pre-specified selectivity threshold.ConclusionsIKZF1 is prioritized as a candidate late-disease microglial TF, supported by six convergent evidence dimensions including independent bulk replication. Tafamidis and diflunisal are low-confidence repurposing hypotheses requiring experimental validation.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261496918"},"PeriodicalIF":3.4,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167199","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

Baseline and longitudinal trajectories of peak expiratory flow in relation to incident cognitive impairment among older adults: Evidence from CHARLS. 老年人呼气流量峰值的基线和纵向轨迹与偶发性认知障碍的关系：来自CHARLS的证据。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2026-10-10 DOI: 10.1177/13872877261494159

Peijian Wang, Lijun Ge, Beiyao Gao, Shan Jiang, Siyuan Wang

{"title":"Baseline and longitudinal trajectories of peak expiratory flow in relation to incident cognitive impairment among older adults: Evidence from CHARLS.","authors":"Peijian Wang, Lijun Ge, Beiyao Gao, Shan Jiang, Siyuan Wang","doi":"10.1177/13872877261494159","DOIUrl":"https://doi.org/10.1177/13872877261494159","url":null,"abstract":"BackgroundPrevious studies, including CHARLS analyses, have linked lower peak expiratory flow (PEF) with cognitive decline. Evidence regarding incident score-based cognitive impairment, longitudinal PEF patterns, and incremental prediction remains limited.ObjectiveTo examine associations of baseline PEF and exploratory PEF trajectories with incident score-based cognitive impairment and evaluate the incremental predictive value of PEF.MethodsThe primary analysis included 2604 CHARLS participants aged ≥60 years without score-based cognitive impairment at baseline. Cognitive impairment was defined as a global cognitive score ≥1 SD below the wave- and age-specific mean and was not a clinical diagnosis of mild cognitive impairment or dementia. Cox models, sensitivity analyses, prediction analyses, and exploratory trajectory modeling were performed.ResultsOver a median follow-up of 9.0 years, 636 participants developed score-based cognitive impairment. Each 1-SD increase in PEF was associated with lower risk in fully adjusted models (HR = 0.801, 95% CI 0.728-0.880) and after adjustment for baseline cognition (HR = 0.846, 95% CI 0.768-0.930). Nine-year cumulative incidence decreased from 35.6% to 16.6% across PEF quartiles. Adding PEF modestly improved 9-year AUC (ΔAUC = 0.011, p = 0.042). In the exploratory trajectory analysis, the moderate PEF group was not significantly associated with risk versus the high group (HR = 1.294, 95% CI 0.860-1.948), whereas the low PEF group had higher risk (HR = 1.817, 95% CI 1.172-2.817), with no clear graded pattern.ConclusionsLower baseline PEF was associated with wave-specific score-based cognitive impairment, but not under stricter definitions requiring subsequent confirmation with wave-specific or fixed thresholds. PEF trajectories were exploratory, and incremental predictive value was limited.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261494159"},"PeriodicalIF":3.4,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167488","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

The problem with Alzheimer's disease. 阿尔茨海默病的问题。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2026-10-09 DOI: 10.1177/13872877261491987

Amos D Korczyn

引用次数: 0

Benzodiazepine use, incident dementia and Alzheimer's disease, and progression to severe dementia: A nationwide Korean cohort study. 苯二氮卓类药物的使用，痴呆和阿尔茨海默病的发病率，以及向严重痴呆的进展：一项全国性的韩国队列研究

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2026-10-09 DOI: 10.1177/13872877261492672

Hyunkee Kim, Jiyeong Kim, Hojin Choi, Young Seo Kim

{"title":"Benzodiazepine use, incident dementia and Alzheimer's disease, and progression to severe dementia: A nationwide Korean cohort study.","authors":"Hyunkee Kim, Jiyeong Kim, Hojin Choi, Young Seo Kim","doi":"10.1177/13872877261492672","DOIUrl":"https://doi.org/10.1177/13872877261492672","url":null,"abstract":"BackgroundThe association between benzodiazepine (BZD) use and dementia risk remains controversial owing to conflicting observational findings and incomplete adjustment for confounders.ObjectiveTo examine the association between BZD use and incident dementia, including Alzheimer's disease (AD), and to determine whether BZD use accelerates progression to severe dementia, using nationwide claims data with detailed comorbidity adjustment.MethodsWe conducted a matched cohort study using Korean National Health Insurance Service data, comparing 132,805 BZD users with 132,805 age- and sex-matched controls. Incident dementia (AD [F00], vascular dementia [F01], and other subtypes) was defined by ≥3 diagnostic claims within one year, and severe cases by national special-registration codes. Hazard ratios (HRs) were estimated using Cox models adjusted for the Charlson Comorbidity Index (CCI) and clinical covariates.ResultsDementia incidence was 382.4/100,000 person-years in BZD users versus 280.7 in controls. BZD users had higher multimorbidity (CCI ≥7: 42.5% versus 26.5%) and psychiatric comorbidity (e.g., anxiety disorders: 42.6% versus 2.7%). After full adjustment, the HR for overall dementia attenuated from 1.43 to 1.15 (95% CI, 1.09-1.22), with similar attenuation for AD and severe dementia. The risk of progression from dementia to severe dementia was not increased among BZD users (adjusted HR, 0.98; 95% CI, 0.84-1.14), with no dose- or duration-response observed.ConclusionsBZD use showed only a modest association with incident dementia, largely attributable to the higher multimorbidity burden among users, and was not associated with accelerated progression to severe dementia.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261492672"},"PeriodicalIF":3.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136698","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

Beyond the cerebrospinal fluid: Preclinical and clinical evidence on central nervous system penetration and functional activity of oral rapamycin (sirolimus). 脑脊液之外：口服雷帕霉素（西罗莫司）中枢神经系统渗透和功能活性的临床前和临床证据。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2026-10-09 DOI: 10.1177/13872877261495936

Jeffrey M Melin, Nancy A Young, Joseph Camardo

{"title":"Beyond the cerebrospinal fluid: Preclinical and clinical evidence on central nervous system penetration and functional activity of oral rapamycin (sirolimus).","authors":"Jeffrey M Melin, Nancy A Young, Joseph Camardo","doi":"10.1177/13872877261495936","DOIUrl":"https://doi.org/10.1177/13872877261495936","url":null,"abstract":"Rapamycin, a potent mTORC1 inhibitor, is a leading candidate for treating age-related neurodegenerative disease. Numerous studies demonstrate beneficial effects in a variety of diseases that affect the brain. Yet a persistent belief among researchers is that rapamycin cannot penetrate brain tissue, citing as evidence its absence of detection in cerebrospinal fluid (CSF). This narrative review synthesizes clinical and preclinical evidence challenging this \"CSF misconception.\" In humans, direct tissue sampling in glioblastoma detects rapamycin in brain at mTORC1-inhibitory concentrations, while functional measures-tumor regression and seizure control in tuberous sclerosis complex, cerebral metabolic preservation on PET in Alzheimer's disease, increased cerebral blood flow in APOE4 carriers, and prolonged antidepressant response-demonstrate incontrovertible activity in the brain. In mice, LC-MS/MS confirms dose-dependent brain accumulation, and rapamycin modulates mTORC1 signaling, autophagy, and synaptic, epigenetic, and inflammatory pathways. Rapamycin cannot be reliably detected in CSF because of four pharmacological factors-high lipophilicity with parenchymal sequestration, extreme red-cell and protein binding, P-glycoprotein efflux at the blood-CSF barrier, and assay insensitivity-none of which supports the contention that rapamycin fails to enter brain tissue. We flag the field's central gap: direct measurement of parent drug in intact human brain parenchyma at therapeutic doses is lacking. CSF concentration is a flawed proxy for rapamycin's CNS penetration. Alzheimer's disease and related dementias (ADRD) trials should instead track surrogate markers of mTORC1 inhibition, functional neuroimaging, clinical outcomes, and ADRD fluid biomarkers. These pharmacodynamics measurements are essential to the rational design and interpretation of prevention trials for the aging brain.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261495936"},"PeriodicalIF":3.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136725","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

The Alzheimer's Association 2024 diagnostic criteria: Generalizability of supporting autopsy evidence. 阿尔茨海默病协会2024诊断标准：支持尸检证据的普遍性。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2026-10-09 DOI: 10.1177/13872877261496550

Gayatri Devi

引用次数: 0

Beyond WEIRD populations: Interpreting the gap between subjective cognitive complaints and objective impairment. 超越怪异人群：解释主观认知抱怨和客观损害之间的差距。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2026-10-09 DOI: 10.1177/13872877261497234

Isabel Manica, Marcelo D Mendonça

引用次数: 0

Accelerated forgetting in memory clinic patients with subjective cognitive decline: Results from a 7-day follow-up long-term retrieval assessment. 主观认知能力下降的记忆临床患者的加速遗忘：来自7天随访长期检索评估的结果。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2026-10-09 DOI: 10.1177/13872877261490478

Ingo Frommann, Selina Vogel, Lena Jansen, Dix Meiberth, Ann-Katrin Schild, Frank Jessen, Susanne Zank, Anja Schneider, Cornelia McCormick, Michael Wagner

{"title":"Accelerated forgetting in memory clinic patients with subjective cognitive decline: Results from a 7-day follow-up long-term retrieval assessment.","authors":"Ingo Frommann, Selina Vogel, Lena Jansen, Dix Meiberth, Ann-Katrin Schild, Frank Jessen, Susanne Zank, Anja Schneider, Cornelia McCormick, Michael Wagner","doi":"10.1177/13872877261490478","DOIUrl":"https://doi.org/10.1177/13872877261490478","url":null,"abstract":"BackgroundSubjective cognitive decline (SCD) is recognized as an early indicator of preclinical Alzheimer's disease (AD). However, individuals with SCD do not exhibit cognitive impairment on standard neuropsychological tests. Accelerated forgetting (AF) has been reported in individuals with preclinical AD and is characterized by intact learning and early retention but impaired retrieval after several days. Currently, AF is not captured by standard neuropsychological testing.ObjectiveThe present study investigated recall performance in memory clinic patients with SCD, without impairment on standard cognitive tests, during a 7-day follow-up telephone assessment for detecting AF.MethodsOne week after completing the neuropsychological assessment, participants underwent a structured telephone-based follow-up interview. This included various measures of verbal and visual memory. AF was operationalized as the rate of forgetting between initial recall and 7-day delayed recall.ResultsData from 35 individuals with SCD, who showed no cognitive impairment on standard tests, and 54 healthy controls (HC) were analyzed. Although there were no significant differences between the groups in learning and short-delay memory performance, after seven days, the SCD group showed lower recall and a higher forgetting rate on the FCSRT-IR free and total recall measures compared to the HC group.ConclusionsAF can be detected using a brief, telephone-based assessment in cognitively unimpaired participants with SCD. It could bridge the gap between subjective and objective memory decline. Further research is necessary to improve potential follow-up assessments in neuropsychological testing and to investigate the link between AF and AD biomarkers and memory decline.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261490478"},"PeriodicalIF":3.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136727","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

The ACOD1-itaconate axis in anti-neuroinflammation and protection against neurodegenerative diseases. acod1 -衣康酸轴在抗神经炎症和保护神经退行性疾病中的作用。

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2026-10-09 DOI: 10.1177/13872877261495587

Dahui Wang, Jensen G Weedor, Natasha M Weah, Stephane Koda, Cleopatra Martricia Quayon, Wei Pan, Yinghua Yu

{"title":"The ACOD1-itaconate axis in anti-neuroinflammation and protection against neurodegenerative diseases.","authors":"Dahui Wang, Jensen G Weedor, Natasha M Weah, Stephane Koda, Cleopatra Martricia Quayon, Wei Pan, Yinghua Yu","doi":"10.1177/13872877261495587","DOIUrl":"https://doi.org/10.1177/13872877261495587","url":null,"abstract":"Chronic neuroinflammation mediated by activated microglia constitutes a central pathogenic mechanism underlying neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Despite substantial progress in elucidating disease mechanisms, effective disease-modifying therapies remain elusive. Recent investigations have identified the aconitate decarboxylase 1 (ACOD1)-itaconate axis, a mitochondrial enzyme-metabolite pathway, as a critical immunometabolic checkpoint that regulates inflammation across diverse pathological contexts. This pathway exerts immunomodulatory effects through multiple mechanisms, including succinate dehydrogenase inhibition, nuclear factor erythroid 2-related factor 2 activation via Kelch-like ECH-associated protein 1 alkylation, and suppression of the NOD-like receptor protein 3 inflammasome. Emerging evidence has demonstrated that ACOD1-derived itaconate and its cell-permeable derivatives modulate neuroinflammation, preserve synaptic integrity, and ameliorate cognitive deficits in preclinical models of neurodegenerative diseases. This review critically synthesizes current evidence on the ACOD1-itaconate axis in central nervous system pathology, with particular emphasis on its roles in AD, PD, MS, and metabolic cognitive dysfunction. We further summarize the mechanistic insights and therapeutic potential of targeting this pathway in neuroinflammation-driven cognitive impairment. Additionally, this review uniquely integrates infection-induced and diet-induced cognitive impairment models and provides a critical perspective on translating this pathway from the bench to the bedside.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877261495587"},"PeriodicalIF":3.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136911","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