Associations of Accelerated Biological Aging With Dementia and the Mediation Role of Brain Structure: Findings From a Longitudinal Study

生物衰老加速与痴呆的关联及脑结构的中介作用：一项纵向研究的发现

The association between biological aging and dementia, as well as the underlying mechanism, remains limited. The aim of this study was to investigate the relationships of biological age (BA) with incident dementia and examine the underlying neurobiological mechanisms. Advanced BA may be a potential risk factor of incident dementia. The risk is possibly mediated through the widespread reduction of brain structures.

生物衰老与痴呆之间的关联及其潜在机制仍有待进一步研究。本研究旨在探讨生物年龄（BA）与新发痴呆的关系，并研究其潜在的神经生物学机制。生物年龄超前可能是新发痴呆的一个潜在危险因素。这种风险可能是通过广泛的脑结构萎缩来介导的。

REF: Bo Y, Sun L, Hou S, et al. Associations of Accelerated Biological Aging With Dementia and the Mediation Role of Brain Structure: Findings From a Longitudinal Study. Neurology. 2025;104(10):e213616. doi:10.1212/WNL.0000000000213616 PMID: 40305743

Long-Term Follow-Up Results of Antiseizure Medication Withdrawal in Grade 2 and 3 Glioma Patients: A Prospective Observational Study

2级和3级胶质瘤患者停用抗癫痫药物的长期随访结果：一项前瞻性观察性研究

The aim of this study was to evaluate the long-term results of seizure recurrence after antiseizure medication (ASM) withdrawal vs continuation in patients with diffuse glioma, grades 2 and 3. Risk of recurrent seizure when withdrawing ASM was not statistically significantly higher in patients continuing ASM. However, a clinically relevant higher percentage of patients had a recurrent seizure in the ASM withdrawal group compared with the ASM continuation group. The lack of a statistical difference may be explained by the small sample size. Larger studies are needed to confirm these findings. Our results suggest that ASM withdrawal should be initiated cautiously and only when necessary.

本研究旨在评估 2 级和 3 级弥漫性胶质瘤患者停用与继续使用抗癫痫药物（ASM）后癫痫复发的长期结果。继续使用 ASM 的患者停用 ASM 时癫痫复发风险并无统计学显著升高。然而，与继续使用 ASM 组相比，停用 ASM 组有临床意义的癫痫复发患者比例更高。缺乏统计学差异可能是由于样本量较小。需要更大规模的研究来证实这些发现。我们的研究结果表明，应谨慎启动 ASM 停药，且仅在必要时进行。

REF: van der Meer PB, Kerkhof M, Dirven L, et al. Long-Term Follow-Up Results of Antiseizure Medication Withdrawal in Grade 2 and 3 Glioma Patients: A Prospective Observational Study. Neurology. 2025;104(10):e213590. doi:10.1212/WNL.0000000000213590 PMID: 40300122 PMCID: PMC12042096

Survival Differences Between Individuals With Typical and Atypical Phenotypes of Alzheimer Disease

典型和非典型阿尔茨海默病表型个体之间的生存差异

Survival estimates for individuals with Alzheimer disease (AD) are informative to understand the disease trajectory, but precise estimates for atypical AD variants are scarce. Atypical AD variants are characterized by nonamnestic phenotypes, an early onset, and lower prevalence of APOEε4 carriership, which affect the AD trajectory. We aimed to provide survival estimates for posterior cortical atrophy (PCA), logopenic variant primary progressive aphasia (lvPPA), and behavioral AD (bvAD) and to evaluate the effect of these atypical AD diagnoses beyond known mortality determinants. Survival in atypical AD (PCA, lvPPA, bvAD) was shorter compared with typical AD. These atypical variants are associated with increased mortality beyond age, sex, education, APOEε4 carriership, and disease severity. Future studies are required to address generalizability of these findings and to identify factors that explain the observed survival differences.

对阿尔茨海默病（AD）患者的生存情况进行估计有助于了解疾病的发展轨迹，但针对非典型AD变异型的精确估计却很匮乏。非典型AD变异型的特征为非遗忘型表型、发病早以及载脂蛋白Eε4（APOEε4）携带率较低，这些因素会影响AD的发展进程。我们旨在提供后皮质萎缩（PCA）、进行性失语症Logopenic变异型（lvPPA）和行为变异型AD（bvAD）的生存估计值，并评估这些非典型AD诊断在已知死亡决定因素之外的影响。与典型AD相比，非典型AD（PCA、lvPPA、bvAD）患者的生存期更短。除年龄、性别、受教育程度、APOEε4携带情况和疾病严重程度外，这些非典型变异型还与死亡风险增加相关。未来需要开展研究以确定这些研究结果的可推广性，并找出导致所观察到的生存差异的因素。

REF: Bader I, Groot C, Van Der Flier WM, Pijnenburg YAL, Ossenkoppele R. Survival Differences Between Individuals With Typical and Atypical Phenotypes of Alzheimer Disease. Neurology. 2025;104(10):e213603. doi:10.1212/WNL.0000000000213603 PMID: 40294367 PMCID: PMC12042099

Impact of Brain Frailty on Clinical Presentation and Neurologic Recovery in Acute Ischemic Stroke Patients Undergoing Thrombectomy

脑衰弱对接受取栓治疗的急性缺血性脑卒中患者临床表现及神经功能恢复的影响

Brain frailty impairs the ability to compensate for brain dysfunction and is linked to worse outcomes after stroke. Stroke severity at presentation is a key determinant of outcomes in acute ischemic stroke. This study aimed to examine the impact of brain frailty on initial stroke severity and recovery in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT). This study highlights the association of brain frailty with the clinical presentation and recovery trajectory of patients with AIS undergoing EVT. Specifically, cortical atrophy was independently associated with baseline stroke severity, and the total burden of brain frailty was independently associated with NIHSS recovery trajectories. The results emphasize the importance of considering brain frailty in acute stroke management and prognostication.

脑脆弱性会损害大脑对功能障碍的代偿能力，并且与中风后更差的预后相关。就诊时的中风严重程度是急性缺血性中风预后的关键决定因素。本研究旨在探讨脑脆弱性对接受血管内血栓切除术（EVT）的急性缺血性中风（AIS）患者初始中风严重程度和恢复情况的影响。本研究强调了脑脆弱性与接受EVT的AIS患者的临床表现和恢复轨迹之间的关联。具体而言，皮质萎缩与基线中风严重程度独立相关，而脑脆弱性的总负担与美国国立卫生研究院卒中量表（NIHSS）恢复轨迹独立相关。研究结果强调了在急性中风管理和预后评估中考虑脑脆弱性的重要性。

REF: Fladt J, Benali F, Jaroenngarmsamer T, et al. Impact of Brain Frailty on Clinical Presentation and Neurologic Recovery in Acute Ischemic Stroke Patients Undergoing Thrombectomy. Neurology. 2025;104(10):e213619. doi:10.1212/WNL.0000000000213619 PMID: 40294371

Effect of Thrombolytics on Delayed Reperfusion After Incomplete Thrombectomy: Target Trial Emulation

溶栓药物对血栓部分切除术后延迟再灌注的影响：目标试验模拟

More than half of the endovascularly treated ischemic stroke patients with incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] <3) show delayed reperfusion (DR) on 24-hour perfusion imaging, which is associated with favorable clinical outcome. The effect of intravenous thrombolysis (IVT) on the rates of DR remains unclear. This study aimed to assess the treatment effect of IVT on the occurrence of DR. Exposure to thrombolytics showed independent treatment effect on the occurrence of DR among patients with incomplete reperfusion after thrombectomy who undergo perfusion imaging at the 24-hour follow-up. The effect of thrombolytics on DR was observed if there was a high chance of therapeutic concentrations of thrombolytics at the time point when the proximal vessel was recanalized, but distal occlusions persisted and/or occurred.

超过一半接受血管内治疗但再灌注不完全（扩展的脑梗死溶栓分级[eTICI] <3）的缺血性卒中患者在24小时灌注成像中显示出延迟再灌注（DR），这与良好的临床结局相关。静脉溶栓（IVT）对延迟再灌注发生率的影响尚不清楚。本研究旨在评估静脉溶栓对延迟再灌注发生的治疗效果。在接受取栓术后再灌注不完全且在24小时随访时进行灌注成像的患者中，接触溶栓药物对延迟再灌注的发生显示出独立的治疗效果。如果在近端血管再通但远端仍存在和/或出现阻塞的时间点有很大机会达到溶栓药物的治疗浓度，则可观察到溶栓药物对延迟再灌注的影响。

REF: Mujanovic A, Yogendrakumar V, Ng FC, et al. Effect of Thrombolytics on Delayed Reperfusion After Incomplete Thrombectomy: Target Trial Emulation. Neurology. 2025;104(10):e213641. doi:10.1212/WNL.0000000000213641 PMID: 40294370 PMCID: PMC12042098

Investigating Plasma Metabolomics and Gut Microbiota Changes Associated With Parkinson Disease: A Focus on Caffeine Metabolism

探究与帕金森病相关的血浆代谢组学和肠道微生物群变化：聚焦咖啡因代谢

Coffee intake is linked to a reduced risk of Parkinson disease (PD), but whether this effect is mediated by gut microbiota and metabolomic changes remains unclear. This study examines PD-associated metabolomic shifts, caffeine metabolism, and their connection to gut microbiome alterations in a multicenter study. This study identifies PD-related changes in microbial-caffeine metabolism compared with controls. Our findings offer insights for future functional research on caffeine-microbiome interactions in PD.

咖啡摄入与降低帕金森病（PD）风险有关，但这种效应是否由肠道微生物群和代谢组学变化介导仍不清楚。本项多中心研究探讨了与帕金森病相关的代谢组学变化、咖啡因代谢及其与肠道微生物组改变的关联。本研究确定了与对照组相比，帕金森病患者在微生物 - 咖啡因代谢方面的相关变化。我们的研究结果为未来关于帕金森病中咖啡因 - 微生物组相互作用的功能研究提供了见解。

REF: Chen CC, Chiu JY, Tan AH, et al. Investigating Plasma Metabolomics and Gut Microbiota Changes Associated With Parkinson Disease: A Focus on Caffeine Metabolism. Neurology. 2025;104(10):e213592. doi:10.1212/WNL.0000000000213592 PMID: 40273394 PMCID: PMC12022887

Association Between Metabolic Syndrome and Young-Onset Dementia: A Nationwide Population-Based Study

代谢综合征与早发型痴呆的关联：一项全国性基于人群的研究

Young-onset dementia (YOD) poses substantial societal and health care burdens. Although metabolic syndrome (MetS) is recognized as a contributor to late-onset dementia, its effect on YOD remains unclear. This study aimed to determine whether MetS and its individual components increase the risk of YOD, including all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD). In this large Korean cohort, MetS and its individual components were significantly associated with an increased risk of YOD. These findings suggest that interventions targeting MetS may help mitigate YOD risk. However, the observational design precludes definitive causal inferences, and reliance on claims data could introduce misclassification bias. Future research using longitudinal designs and comprehensive data collection is needed to validate and expand on these associations.

早发性痴呆（YOD）给社会和医疗保健带来了沉重负担。尽管代谢综合征（MetS）被认为是晚发性痴呆的一个致病因素，但其对早发性痴呆的影响仍不明确。本研究旨在确定代谢综合征及其各组成成分是否会增加早发性痴呆（包括全因痴呆、阿尔茨海默病（AD）和血管性痴呆（VaD））的发病风险。在这个大型韩国队列研究中，代谢综合征及其各组成成分与早发性痴呆发病风险增加显著相关。这些研究结果表明，针对代谢综合征的干预措施可能有助于降低早发性痴呆的发病风险。然而，由于本研究为观察性研究设计，无法得出明确的因果推断，且依赖索赔数据可能会引入分类错误偏差。未来需要开展采用纵向设计和全面数据收集的研究，以验证并拓展这些相关性。

REF: Lee JY, Han K, Kim J, Lim JS, Cheon DY, Lee M. Association Between Metabolic Syndrome and Young-Onset Dementia: A Nationwide Population-Based Study. Neurology. 2025;104(10):e213599. doi:10.1212/WNL.0000000000213599 PMID: 40267374

Multiple Sclerosis–Specific Reference Curves for Brain Volumes to Explain Disease Severity

用于解释疾病严重程度的多发性硬化症特定脑体积参考曲线

Brain atrophy is relevant for understanding disease progression and treatment response in people with multiple sclerosis (pwMS). Automatic brain volume-reporting tools often rely on healthy control (HC) reference curves to interpret brain volumes, whereas brain volume loss is different in pwMS. This observational study aimed to develop an MS-specific reference model for brain volumes and evaluate its performance compared with HC-based curves, as a proof-of-concept. NBV values derived from an MS-specific reference model offer improved relevance for assessing disease severity compared with curves derived from age-specific and sex-specific HC reference models. Improving the model toward application in individual people could enhance clinical implementation.

脑萎缩与理解多发性硬化症患者（pwMS）的疾病进展和治疗反应相关。自动脑容量报告工具通常依靠健康对照（HC）参考曲线来解读脑容量，而pwMS患者的脑容量丢失情况有所不同。这项观察性研究旨在开发一种针对多发性硬化症的脑容量参考模型，并作为概念验证评估其与基于HC的曲线相比的性能。与从年龄特异性和性别特异性HC参考模型得出的曲线相比，从多发性硬化症特异性参考模型得出的脑实质体积（NBV）值在评估疾病严重程度方面具有更高的相关性。对该模型进行改进以应用于个体患者，可能会促进其临床应用。

REF: van Nederpelt DR, Bos L, Mattiesing RM, et al. Multiple Sclerosis-Specific Reference Curves for Brain Volumes to Explain Disease Severity. Neurology. 2025;104(10):e213618. doi:10.1212/WNL.0000000000213618 PMID: 40267375 PMCID: PMC12012623

Comparison of the Clinical Spectrum of Juvenile- and Adult-Onset Huntington Disease: A National Cohort and Enroll-HD Observational Study

青少年和成人起病型亨廷顿病临床谱的比较：一项全国性队列研究和 Enroll - HD 观察性研究

Differences in clinical characteristics between juvenile-onset Huntington disease (JHD) and adult-onset HD (AHD) are hypothesized but not directly compared. This study compares clinical characteristics occurrence and severity across age-at-onset (AO) subtypes. This study highlights distinct clinical patterns in JHD subtypes compared with AHD. Stratification by age at onset-defined HD subtypes is needed in future studies.

目前有假设认为青少年型亨廷顿病（JHD）和成人型亨廷顿病（AHD）在临床特征上存在差异，但尚未进行直接比较。本研究比较了不同发病年龄（AO）亚型的临床特征出现情况和严重程度。本研究凸显了与成人型亨廷顿病相比，青少年型亨廷顿病亚型具有独特的临床模式。未来的研究需要按发病年龄对亨廷顿病亚型进行分层。

REF: Bakels HS, van der Zwaan KF, Van Zwet E, et al. Comparison of the Clinical Spectrum of Juvenile- and Adult-Onset Huntington Disease: A National Cohort and Enroll-HD Observational Study. Neurology. 2025;104(10):e213525. doi:10.1212/WNL.0000000000213525 PMID: 40262071 PMCID: PMC12015966